Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease.

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Nylund, Cade M; Goudie, Anthony; Garza, Jose M; Crouch, Gary; Denson, Lee A

2013-05-01

Adults with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events (TEs). We sought to evaluate the risk for TE in children and adolescents with IBD using a large population database. The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database was used in a retrospective cohort study of hospitalized children in the United States across 1997, 2000, 2003, 2006, and 2009. Billing codes were used to identify discharges with Crohn disease, ulcerative colitis, pulmonary embolism, deep vein thrombosis, thrombophlebitis, thrombosis of intracranial venous sinus, Budd-Chiari syndrome, and portal vein thrombosis. A logistic regression model was fitted to quantify the increased risk of TE in children with IBD, while adjusting for other risk factors of thrombosis. The total weighted number of pediatric discharges was 7,448,292, and 68,394 (0.92%) were identified with IBD. The incidence of any TE in a hospitalized child or adolescent with IBD was 117.9/10,000 with a relative risk (95% confidence interval) of 2.36 (2.15-2.58). The adjusted odds ratio for any TE in a patient with IBD without surgery was 1.22 (1.08-1.36). Risk factors for TE among patients with IBD include older age, central venous catheter, parenteral nutrition, and an identified hypercoagulable condition. There is an increasing trend of TE in both the IBD and non-IBD patients. Hospitalized children and adolescents with IBD are at increased risk for TE. Conservative methods of TE prevention including hydration, mobilization, or pneumatic devices should be considered in hospitalized patients with IBD.

Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy.

Science.gov (United States)

Mariotte, Eric; Azoulay, Elie; Galicier, Lionel; Rondeau, Eric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; de Maistre, Emmanuel; Provôt, François; Delmas, Yahsou; Perez, Pierre; Benhamou, Ygal; Stepanian, Alain; Coppo, Paul; Veyradier, Agnès

2016-05-01

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 [91%] cases), whereas non-idiopathic diseases were

PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

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Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

2018-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

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Tongfang Tang

Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

Science.gov (United States)

Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

2013-01-01

Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

Coma in thrombotic thrombocytopenic purpura

NARCIS (Netherlands)

F.J. de Jong (Fransina); P.A.W. te Boekhorst (Peter); D.W.J. Dippel (Diederik); B.C. Jacobs (Bart)

2010-01-01

textabstractThrombotic thrombocy topenic purpura (TTP) is characterised by a thrombotic, haemolytic microangiopathy leading to microvascular occlusion, haemolysis and ischaemic dysfunction of various organs including the brain. TTP may present with a variety of neurological symptoms, including

Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations.

Science.gov (United States)

Nahar, Pragati P; Slitt, Angela L; Seeram, Navindra P

2015-07-01

Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low solubility and stability in the digestive tract, limits its therapeutic applications. Recent studies have demonstrated increased bioavailability and health-promoting effects of a novel solid lipid particle formulation of curcumin (Curcumin SLCP, Longvida(®)). The goal of this study was to evaluate the aqueous solubility and in vitro anti-inflammatory effects of solid lipid curcumin particle (SLCP) formulations using lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages. SLCPs treatment significantly decreased nitric oxide (NO) and prostaglandin-E2 (PGE2) levels at concentrations ranging from 10 to 50 μg/mL, and reduced interleukin-6 (IL-6) levels in a concentration-dependent manner. Transient transfection experiments using a nuclear factor-kappa B (NF-κB) reporter construct indicate that SLCPs significantly inhibit the transcriptional activity of NF-κB in macrophages. Taken together, these results show that in RAW 264.7 murine macrophages, SLCPs have improved solubility over unformulated curcumin, and significantly decrease the LPS-induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-κB.

Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura

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Karlos Z. Oregel

2013-01-01

Full Text Available A 21-year-old male presented to the emergency department after a 5-day history of recurrent vomiting and decreased urine output. History revealed ingestion of ibuprofen. During the diagnostic workup, the following was identified: white blood cell count 13.4 (x10(3/mcL, hemoglobin 11.9 (x10(6/mcL with an MCV of 73 fL, hematocrit 34% and platelets were 31,000/mcL, sodium of 130 mmol/L, potassium of 5.1 mmol/L, chloride of 83 mmol/L, bicarbonate of 21 mmol/L, blood urea nitrogen of 184 mg/dL and creatinine of 19.1 mg/dL. He was later diagnosed with thrombotic thrombocytopenic purpura (TTP based on the fact that he presented with most components of the TTP pentad (except for fever, which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy. The patient then received plasma exchange, oral corticosteroids, and hemodialysis, which led to a full recovery of platelet count and renal function.

Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses.

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Iwabuchi, Kazuhisa

2015-01-01

Glycosphingolipids (GSLs) are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. GSLs cluster with cholesterol in cell membranes to form GSL-enriched lipid rafts. Biochemical analyses have demonstrated that GSL-enriched lipid rafts contain several kinds of transducer molecules, including Src family kinases. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, is highly expressed on the plasma membranes of human phagocytes, and forms lipid rafts containing the Src family tyrosine kinase Lyn. LacCer-enriched lipid rafts mediate immunological and inflammatory reactions, including superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. LacCer also serves as a signal transduction molecule for functions mediated by CD11b/CD18-integrin (αM/β2-integrin, CR3, Mac-1), as well as being associated with several key cellular processes. LacCer recruits PCKα/ε and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and their adhesion to endothelial cells, as well as regulating β1-integrin clustering and endocytosis on cell surfaces. This review describes the organizational and inflammation-related functions of LacCer-enriched lipid rafts.

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

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Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

2018-01-01

The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

[New marker in thrombotic thrombocytopenic purpura

DEFF Research Database (Denmark)

Hillarp, A.; Lindblom, A.; Bjork, P.

2008-01-01

Thrombotic microangiopathy can be caused by several conditions which are difficult to diagnose from the clinical presentation alone. Deficient enzyme activity of a newly-discovered enzyme, ADAMTS-13, can lead to thrombotic thrombocytopenic purpura (TTP). Lack of ADAMTS-13 activity causes increased...

Correction of Free Radical Lipid Oxidation in Internal Female Genital Inflammatory Diseases

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A. D. Belyaevsky

2008-01-01

Full Text Available The paper descries a specific view on the mechanism responsible for development of the resistance of an inflammatory process in the female genital tract to drugs and on the role of a free radical process activation factor in the pathogenesis of the disease. Emphasis is laid on the importance of measures to diminish cell membrane permeability, by correcting their structural and functional states with antioxidants. Key words: inflammatory processes in the female genital organs, lipid peroxidation, antioxidative defense, cell membrane structural and functional state.

Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Science.gov (United States)

2018-02-12

Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

Impact of low- or high-flux haemodialysis and online haemodiafiltration on inflammatory markers and lipid profile in chronic haemodialysis patients.

Science.gov (United States)

Akoglu, Hadim; Dede, Fatih; Piskinpasa, Serhan; Falay, Mesude Y; Odabas, Ali Riza

2013-01-01

We aimed to evaluate the impact of low- or high-flux haemodialysis (HD) and online haemodiafiltration (OL-HDF) on inflammation and the lipid profile in HD patients. 50 HD patients were assigned to two groups for HD with low-flux (n = 25) or high-flux (n = 25) polysulphone dialysers for 6 weeks. Subsequently, all patients were haemodialysed with a low-flux polysulphone dialyser for 6 weeks, then transferred to OL-HDF for another 6 weeks. Blood samples for lipids and inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP) were obtained at baseline and every 6 weeks. Changes in inflammatory markers and lipids from baseline to the 6-week dialysis period did not differ between low- and high-flux groups. When patients were transferred from low-flux HD to OL-HDF, IL-6, IL-8, and TNF-α levels significantly decreased whereas HDL and LDL cholesterol significantly increased. Low- and high-flux polysulphone membranes had similar effects on lipids and inflammatory markers, whereas OL-HDF potently reduced pro-inflammatory cytokines. Copyright © 2013 S. Karger AG, Basel.

Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura: How Close Is Close Enough?

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Cesar A. Perez

2011-01-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is an uncommon life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with infections, malignancy, drugs, and autoimmune diseases. We report a case of 19-year-old previously healthy female that presents with anemia and thrombocytopenia diagnosed with thrombotic thrombocytopenic purpura that was treated successfully with plasmapheresis and corticosteroids. Laboratory findings also revealed antinuclear antibodies and antibodies to double-stranded DNA. Two weeks after presentation developed inflammatory arthritis, fulfilling diagnostic criteria for systemic lupus erythematosus (SLE. Prompt diagnosis and treatment with plasma exchange and corticosteroids should be instituted as soon as the diagnosis of TTP is suspected, even if other diagnoses, including lupus, are possible. When present, the coexistence of these two etiologies can have a higher mortality than either disease alone. An underlying diagnosis of SLE should be considered in all patients presenting TTP and the study of this association may provide a better understanding of their immune-mediated pathophysiology.

A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

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Viner, Maya; Murakhovskaya, Irina

2017-07-01

: Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

[Fatal thrombotic microangiopathy in the mother and fetus].

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Udvardy, M; Telek, B; Kiss, A; Flóra Nagy, M; Mikó, T; Rák, K

1990-04-14

The appearance of thrombotic microangiopathy (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome) could have been documented in a 23 years old pregnant woman, who had been treated previously for immune-thrombocytolytic purpura. The disturbing anamnestic data caused significant delay in correct diagnosis and in starting of fresh-frozen plasma therapy, so the woman and her fetus (in utero) had been died. The specific histological microangiopathic lesions could have been well documented by the autopsy of the mother, however no such alterations could have been detected in the fetus and placenta. This latter intriguing observation might be remarkable in the evaluation of several concepts dealing with the aetiopathogenesis of thrombotic microangiopathy. The short review of literature of thrombotic microangiopathy in pregnancy and puerperial period is also given.

Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

Science.gov (United States)

Lamia, Rais; El Ati, Zohra; Ben Fatma, Lilia; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Ben Hmida, Fathi; Béji, Soumaya; Ben Moussa, Fatma

2016-01-01

Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication.

Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

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Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

2015-01-01

We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

Activation of Inflammatory and Pro-Thrombotic Pathways in Acute Stress Cardiomyopathy

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Timothy P. Fitzgibbons

2017-08-01

Full Text Available Stress cardiomyopathy (SCM is a unique cardiac disorder that more often occurs in women. SCM presents in a similar fashion as acute myocardial infarction (AMI, with chest pain, ECG changes, and congestive heart failure. The primary distinguishing feature is the absence of thrombotic coronary occlusion in SCM. How this reduction in cardiac function occurs in the absence of coronary occlusion remains unknown. Therefore, we tested the hypothesis that a targeted proteomic comparison of patients with acute SCM and AMI might identify relevant mechanistic differences. Blood was drawn in normal controls (n = 6, women with AMI (n = 12, or women with acute SCM (n = 15. Two-week follow-up samples were available in AMI (n = 4 and SCM patients (n = 11. Relative concentrations of 1,310 serum proteins were measured in each of the 48 samples using the SOMAscan assay. Women with AMI had greater myocyte necrosis, as reflected by a higher peak troponin I concentration (AMI 32.03 ± 29.46 vs. SCM 2.68 ± 2.6 ng/ml, p < 0.05. AMI and SCM patients had equivalent reductions in left ventricular ejection fraction [LVEF (% 39 ± 12 vs. 37 ± 12, p = 0.479]. In follow-up, women with SCM had a greater improvement in cardiac function [LVEF (% 60 ± 7 vs. 45 ± 13, p < 0.001]. No differentially expressed proteins were detected (absolute log2-fold change >1; q < 0.05 between AMI and SCM in the acute or recovery phase. However, when we compared normal controls to patients with AMI, there was differential expression of 35 proteins. When we compared normal controls to patients with SCM, 45 proteins were differentially expressed. In comparison to normal controls, biological processes such as complement, coagulation, and inflammation were activated in both AMI and SCM. There were four proteins that showed a non-significant trend to be increased in acute SCM vs. AMI (netrin-1, follistatin-like 3, kallikrein 7

Influenza-associated thrombotic microangiopathies.

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Bitzan, Martin; Zieg, Jakub

2017-09-07

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity rational treatment approaches.

Lipid profiles, inflammatory markers, and insulin therapy in youth with type 2 diabetes

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Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poo...

Ulcers and thrombotic neuropathy as first manifestations in a patient with antiphospholipid syndrome

International Nuclear Information System (INIS)

Bolivar G, Isabel; Cano L, Natalia; Carmona C, Daniela; Correa S Elizabeth, Guerra P Lina and other

2010-01-01

This following case report describes a 34 years-old man with chronic clinical skin ulcers and left lower monoparesis. Electromyography revealed sensory neuropathy of the left superficial fibular nerve; the echographic studies showed absence of artery or venous disorder. The patient showed no improvement of skin lesions with aggressive immunosuppression. The biopsy of the skin and the sural nerve reported thrombi and absence of inflammatory infiltrates; findings that support the diagnosis of thrombotic vasculopathy and neuropathy. The presence of lupus anticoagulant, prolonged PTT and positive anti-B2 glycoprotein antibodies were documented.

Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

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Yueniwati Y

2016-12-01

Full Text Available Yuyun Yueniwati,1 Ni Komang Darmiastini,1 Eko Arisetijono2 1Radiology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia; 2Neurology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia Background and objectives: Atherosclerosis causes reduction of the oxygen supply to structures in the far arterial wall, provoking the release of factors that drive angiogenesis of vasa vasorum, including VEGF. Other studies have revealed the inflammatory response in atherosclerosis and the role of platelet factor 4 (PF4 as an anti-angiogenic chemokine through the inhibition of VEGF. This cross-sectional study aims at measuring the effect of atherosclerosis assessed through carotid intima-media thickness (CIMT against plasma VEGF levels in patients with post-acute thrombotic stroke. Materials and methods: CIMT was assessed sonographically using GE Logiq S6 with 13 MHz frequency linear probe. VEGF-A plasma levels were measured using enzyme-linked immunosorbent assay (ELISA method. Differences among variables were compared statistically. The data were analyzed using Pearson correlation. Results: A total of 25 patients with post-acute thrombotic stroke were identified in days 7 to 90. CIMT thickening was indicated in 88% of patients (1.202 ± 0.312 mm, while an increase in plasma VEGF was identified in all patients (178.28 ± 93.96 ng/mL. There was no significant correlation between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke (p=0.741. A significant correlation was recognized between CIMT and total cholesterol (p=0.029 and low-density lipoprotein (p=0.018. Conclusion: There were no significant correlations between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke. However, plasma VEGF increased in patients with thrombotic stroke. CIMT measurement is a promising noninvasive modality to assess the vascular condition of patients with stroke and diabetes, while plasma VEGF

THE EFFECTS OF LONG-TERM REGULAR EXERCISE ON ENDOTHELIAL FUNCTIONS, INFLAMMATORY AND THROMBOTIC ACTIVITY IN MIDDLE-AGED, HEALTHY MEN

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Metin Ergün

2006-06-01

Full Text Available As studying with population carrying no classical cardiovascular risk factors seems to be an advantage in isolating effects of regular exercise on endothelial functions, inflammatory and thrombotic activity; the present study was designed to evaluate the clear effects of long-term regular exercise in middle-aged, healthy men. A total of 32 regularly exercising (three times per week, 12.8 ± 6.8 years men (Group I, mean age = 53.2 ± 6. 1 yrs and 32 sex- and age-matched sedentary subjects (Group II, mean age = 51.0 ± 7.7 yrs were involved in the study. All participants were non-smokers and with no history of hypertension and diabetes. During one day preceding tests, the subjects refrained from training and maintained their normal diet. In all subjects, body mass index (BMI, percentage of body fat (% BF and maximal oxygen uptake (VO2max were calculated. Serum uric acid, glucose, HbA1c, lipids, high-sensitive C-reactive protein (hs-CRP, fibrinogen levels, white blood cell (WBC and platelet count were measured. Resting heart rates and blood pressures were recorded and standard exercise stress test was applied using the modified Bruce protocol. Flow-mediated and nitrate-induced dilatation (FMD and NID of the brachial artery and carotid intima-media thickness (cIMT were evaluated as markers of endothelial functions and early atherosclerosis. Mean BMI, % BF, systolic and diastolic blood pressures, WBC and platelet count, HbA1c, total and LDL cholesterol, hs-CRP and fibrinogen levels were similar between the groups. Group I had significantly lower serum glucose, uric acid and triglyceride (p < 0.05, p < 0.005 and p < 0.05, respectively and higher HDL cholesterol levels (p < 0.0001 than in Group II. FMD values were significantly higher in Group I than in Group II (p < 0.005 while there were no significant differences in NID and cIMT measures between the groups. VO2max and cIMT showed a negative correlation in Group I (r = -0.463, p < 0.0001. Negative

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

Science.gov (United States)

Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

2010-03-18

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

Thrombotic microangiopathy associated with Valproic acid toxicity.

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Hebert, Sean A; Bohan, Timothy P; Erikson, Christian L; Swinford, Rita D

2017-08-03

Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.

Thrombotic stroke and myocardial infarction with hormonal contraception

DEFF Research Database (Denmark)

Lidegaard, Øjvind; Løkkegaard, Ellen; Jensen, Aksel Karl Georg

2012-01-01

Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting.......Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting....

Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report.

Science.gov (United States)

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Unlu, Serkan; Ertem, Kadir; Nizam, Ilknur

2014-08-01

Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. Copyright © 2014. Published by Elsevier Ltd.

MEAN PLATELET VOLUME AND RISK OF THROMBOTIC STROKE

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Prasantha Kumar Thankappan

2017-07-01

Full Text Available BACKGROUND Stroke is a major cause of long term morbidity and mortality. Several factors are known to increase the liability to stroke. Platelets play a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation. Platelet size (mean platelet volume, MPV is a marker and possible determinant of platelet function, large platelets being potentially more reactive. Hence an attempt has-been made to study the association if any between mean platelet volume and thrombotic stroke. The aim of this study was to determine whether an association exists between Mean Platelet Volume (MPV and thrombotic stroke. MATERIALS AND METHODS The study is a case control study and data was collected at Government Medical College Hospital, Kottayam, Kerala a tertiary care referral centre. The study was carried out among fifty patients diagnosed with thrombotic stroke and presenting to the hospital within forty eight hours of onset of symptoms. Fifty age group and sex matched controls were also recruited. Mean platelet volume was obtained using a SYSMEX automated analyser. RESULTS This study has shown a statistically significant relation between mean platelet volume and risk of thrombotic stroke but no statistically significant correlation between clinical severity of stroke and mean platelet volume. CONCLUSION This study has shown an elevation of MPV in acute phase of thrombotic stroke. Platelet mass was found to be more or less a constant. This study did not find a statistically significant correlation between clinical severity of stroke and mean platelet volume.

Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators.

Science.gov (United States)

Jin, Yiping; Arita, Makoto; Zhang, Qiang; Saban, Daniel R; Chauhan, Sunil K; Chiang, Nan; Serhan, Charles N; Dana, Reza

2009-10-01

Resolvins and lipoxins are lipid mediators generated from essential polyunsaturated fatty acids that are the first dual anti-inflammatory and pro-resolving signals identified in the resolution phase of inflammation. Here the authors investigated the potential of aspirin-triggered lipoxin (LX) A4 analog (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a murine model. ATLa and RvE1 receptor expression was tested in different corneal cell populations by RT-PCR. Corneal neovascularization (CNV) was induced by suture or micropellet (IL-1 beta, VEGF-A) placement. Mice were then treated with ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals. Infiltration of neutrophils and macrophages was quantified after immunofluorescence staining. The mRNA expression levels of inflammatory cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated intravitally and morphometrically. The receptors for LXA4, ALX/Fpr-rs-2 and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, ATLa-, RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating neutrophils and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 alpha, IL-1 beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these mediators had significantly suppressed suture-induced or IL-1 beta-induced hemangiogenesis (HA) but not lymphangiogenesis. Interestingly, only the application of ATLa significantly suppressed VEGF-A-induced HA. ATLa, RvE1, and RvD1 all reduce inflammatory corneal HA by early regulation of resolution mechanisms in innate immune responses. In addition, ATLa directly inhibits VEGF-A-mediated angiogenesis and is the most potent inhibitor of NV among this new genus of dual anti-inflammatory and pro-resolving lipid mediators.

GENDER-RELATED DIFFERENCES IN INFLAMMATORY AND LIPID PARAMETERS IN PATIENTS WITH DIABETES MELLITUS TYPE 2

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Boris Djindjic

2008-10-01

Full Text Available Diabetes mellitus type 2 (DM type 2 is one of the most common health problems worldwide. Diabetics have increased risk for development of wide spectrum of atherosclerotic complications, at the basis of which are inflammation and diabetic dyslipidemia. Increasing of relative risk for coronary artery disease development is higher in females with DM type 2.The aim of this study was determination of characteristic inflammatory and lipid disorders in type 2 diabetics and their association with patient gender.The study involved 35 patients with DM type 2 and stable angina pectoris. Besides anamnesis, all patients underwent clinical examinations (measure of blood pressure, body height and weight and calculation of body mass index. Inflammatory markers (sedimentation in I and II hour-SE I and SE II, C reactive protein - CRP, fibrinogen concentration and leukocyte count as well as lipid parameters (total cholesterol, LDL and HDL cholesterol concentration and triglycerides were determined in all the patients.Total cholesterol and triglycerides concentrations were higher in females with DM type 2 compared to males (p<0,05. There were not significant gender differences in HDL and LDL cholesterol concentration. All inflammatory markers (SE I and SE II, CRP, fibrinogen concentration and leukocyte count were higher in females with DM type 2 and CAD compared to men (p<0,05. In males, there was a strong positive correlation between SE I and SE II with total LDL (p<0,05 and HDL cholesterol concentrations (p<0,01. Concentration of CRP was only significantly connected with triglycerides concentration (p<0,05. There was a strong association between leukocyte count and increased triglycerides (p<0,05 and low HDL cholesterol concentration (p<0,01. In females, there was only a strong positive correlation between SE II (p<0,01 and CRP concentration (p<0,05 and triglycerides.Women with DM type 2 and clinically manifest CAD (stable angina pectoris are at higher risk for

Outcome of severe adult thrombotic microangiopathies in the intensive care unit.

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Pene, Frédéric; Vigneau, Cécile; Auburtin, Marc; Moreau, Delphine; Zahar, Jean-Ralph; Coste, Joël; Heshmati, Farhad; Mira, Jean-Paul

2005-01-01

Thrombotic microangiopathies, namely thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive diseases. Despite the dramatic improvement in the outcome by exogenous plasma supply, either through plasma infusion or through plasma exchange, patients frequently require support in the intensive care unit. In the present study, we evaluated the outcome of a large cohort of patients with severe thrombotic microangiopathies. A retrospective multicenter study from January 1998 to June 2001. Fourteen French university hospital medical intensive care units. Sixty three adult patients with severe thrombotic microangiopathies. Of the 63 patients, 19 had a clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic uremic syndrome and 26 had combined neurologic and renal failures. Infections were the main etiology associated with thrombotic microangiopathies. The mortality rate was 35%. Of the survivors, all achieved complete remission. Whereas neurologic failure assessed through the Glasgow coma scale was an independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002], renal impairment did not appear to be an adverse prognostic factor. The use of plasma exchange was independently associated with survival [HR=0.269 (CI 95%: 0.104-0.691), P=0.006]. Thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with high mortality. Neurologic impairment appears to be the main adverse prognostic factor correlated to mortality, and the study confirms the importance of plasma exchange in the treatment of high-risk patients.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism

NARCIS (Netherlands)

Biere-Rafi, Sara; Di Nisio, Marcello; Gerdes, Victor; Porreca, Ettore; Souverein, Patrick; de Boer, Anthonius; Büller, Harry; Kamphuisen, Pieter

2011-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of arterial thrombosis, but their effect on venous thrombotic events is less well established. The study aimed to assess the risk of symptomatic pulmonary embolism (PE) in patients using NSAIDs and to evaluate

Non-thrombotic Abnormalities on Lower Extremity Venous Duplex Ultrasound Examinations

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Adhikari, Srikar

2015-03-01

Full Text Available Introduction: Emergency physician-performed compression ultrasonography focuses primarily on the evaluation of the proximal veins of the lower extremity in patients with suspected deep venous thrombosis (DVT. A detailed sonographic evaluation of lower extremity is not performed. The objective of this study was to determine the prevalence of non-thrombotic findings on comprehensive lower extremity venous duplex ultrasound (US examinations performed on emergency department (ED patients. Methods: We performed a retrospective six-year review of an academic ED’s records of adult patients who underwent a comprehensive lower extremity duplex venous US examination for the evaluation of DVT. The entire US report was thoroughly reviewed for non-thrombotic findings. Results: We detected non-thrombotic findings in 263 (11%, 95% CI [9.5-11.9%] patients. Among the non-thrombotic findings, venous valvular incompetence (81, 30% was the most frequent, followed by cyst/mass (41, 15%, lymphadenopathy (33, 12%, phlebitis (12, 4.5%, hematoma (8, 3%, cellulitis (1, 0.3% and other (6, 2.2%. Conclusion: In our study, we detected a variety of non-thrombotic abnormalities on comprehensive lower extremity venous duplex US examinations performed on ED patients. Some of these abnormalities could be clinically significant and potentially be detected with point-of-care lower extremity US examinations if the symptomatic region is evaluated. In addition to assessment of the proximal veins for DVT, we recommend sonographic evaluation of the symptomatic area in the lower extremity when performing point-of-care ultrasound examinations to identify non-thrombotic abnormalities that may require immediate intervention or close follow up. [West J Emerg Med. 2015;16(2:250–254.

In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra Processing Waste

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Hafiz Ansar Rasul Suleria

2016-12-01

Full Text Available Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT, activated partial thromboplastin time (aPTT, and thromboelastography (TEG. All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.

In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste.

Science.gov (United States)

Suleria, Hafiz Ansar Rasul; Hines, Barney M; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A

2016-12-31

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone ( Haliotis rubra ) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.

Thrombotic manifestations in SAPHO syndrome. Review of the literature.

Science.gov (United States)

Carranco-Medina, Tatiana Elizabeth; Hidalgo-Calleja, Cristina; Calero-Paniagua, Ismael; Sánchez-González, María Dolores; Quesada-Moreno, Alba; Usategui-Martín, Ricardo; Pérez-Garrido, Laura; Gómez-Castro, Susana; Montilla-Morales, Carlos Alberto; Martínez-González, Olga; Del Pino-Montes, Javier

2015-01-01

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

NARCIS (Netherlands)

Kim, E.S.; Cha, Y.; Ham, M.; Jung, J.; Kim, S.G.; Hwang, S.; Kleemann, R.; Moon, A.

2014-01-01

A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for

Nonbacterial thrombotic endocarditis presenting as intracerebral hemorrhage.

Science.gov (United States)

Wigger, Olivier; Windecker, Stephan; Bloechlinger, Stefan

2016-12-01

Nonbacterial thrombotic endocarditis is a rare cause of valvular heart disease, most commonly associated with advanced malignancy. The morbidity of this kind of endocarditis lies in its tendency to embolize, while the valve function is usually preserved. The central nervous system is the most common site of embolization, leading to ischemic stroke. We report a case of nonbacterial thrombotic endocarditis complicated by intracerebral hemorrhage as the first manifestation of adenocarcinoma of the lung. The endocarditis led to severe aortic regurgitation. In view of the advanced stage of lung cancer, the patient refused further therapy. He passed away 3 weeks after first diagnosis of the adenocarcinoma.

Morphological signs of the intravital contraction (retraction of thrombotic emboli

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R R Khismatullin

2018-02-01

Full Text Available Aim. To establish whether contraction (retraction of thrombi and thrombotic emboli occurs in vivo using structural signs of blood clot compression, such as compressive deformation of erythrocytes and redistribution of fibrin on the surface of a clot. Methods. Three postmortem pulmonary thrombotic emboli were examined by scanning electron microscopy and light microscopy after staining with hematoxylin and eosin as well as with Mallory’s method. Results. In 2 studied pulmonary emboli, extracted 7 and 15 hours after patients’ death, polyhedral erythrocytes (polyhedrocytes were revealed that were formed as a result of mechanical deformation under the action of contractile forces generated by activated platelets. In addition, the uneven distribution of fibrin within the emboli was found with displacement of fibrin to the periphery of the emboli, which is characteristic for contracted blood clot. In the first and the «oldest» clot extracted 38 hours after the patient’s death, the described contraction signs were absent, which was likely related to the postmortem autolysis or intravital pathological impairment of contraction. Conclusion. Thrombotic emboli ex vivo have morphological signs of contraction, suggesting intravital compression of the primary thrombi and/or thrombotic emboli, which might be an important pathogenetic mechanism for modulation of impaired blood flow at the sites of thrombotic occlusion of a vessel; the presence or absence of compressed erythrocytes inside and predominant location of fibrin on the periphery of a thrombus or embolus can potentially serve as additional pathomorphological criteria of death coming prescription.

Anti-Inflammatory Activity and Mechanism of a Lipid Extract from Hard-Shelled Mussel (Mytilus Coruscus on Chronic Arthritis in Rats

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Guipu Li

2014-01-01

Full Text Available The present study was designed to investigate the anti-inflammatory activity and mechanism of a lipid extract from hard-shelled mussel (Mytilus coruscus on adjuvant-induced (AIA and collagen-induced arthritis (CIA in rats. AIA and CIA rats that received hard-shelled mussel lipid extract (HMLE group at a dose of 100 mg/kg demonstrated significantly lower paw swelling and arthritic index, but higher body weight gain than those which received olive oil (control group. Similar results were found in arthritic rats that received New Zealand green-lipped mussel lipid extract (GMLE at the same dosage. The levels of leukotriene B4 (LTB4, prostaglandin E2 (PGE2, thromboxane B2 (TXB2 in the serum, and interleukin-1β (IL-1β, IL-6, interferon-γ (INF-γ, tumor necrosis factor-α (TNF-α in the ankle joint synovial fluids of HMLE group rats were significantly lower than those of control group. However, the levels of IL-4 and IL-10 in HMLE group rats were significantly higher than those in the control group. Decreased mRNA expressions of matrix metalloproteinase 1 (MMP1 and MMP13, but increased tissue inhibitor of metalloproteinase 1 (TIMP1 were observed in the knee joint synovium tissues of HMLE group rats when compared with the control group. No hepatotoxicity was observed in both HMLE and GMLE group rats. The present results indicated that HMLE had a similarly strong anti-inflammatory activity as GMLE. Such a strong efficacy could result from the suppression of inflammatory mediators (LTB4, PGE2, TXB2, pro-inflammatory cytokines (IL-1β, IL-6, INF-γ, TNF-α and MMPs (MMP1, MMP13, and the promotion of anti-inflammatory cytokines (IL-4, IL-10 and TIMPs (TIMP1 productions.

Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura ...

African Journals Online (AJOL)

Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura. ... by features of microangiopathic hemolytic anemia and thrombocytopenia. ... Current knowledge in the etiopathogenesis, epidemiology, trends in the diagnosis and ...

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases

DEFF Research Database (Denmark)

Danesh, J; Erqou, S; Walker, M

2007-01-01

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person v......Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within....... This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular...

Genetic polymorphisms of T-1131C APOA5 and ALOX5AP ...

Indian Academy of Sciences (India)

Abstract. Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and ...

Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.

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Julio J Amaral

Full Text Available Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases.

The influence of regular walking at different times of day on blood lipids and inflammatory markers in sedentary patients with coronary artery disease.

Science.gov (United States)

Lian, Xiao-Qing; Zhao, Di; Zhu, Meng; Wang, Ze-Mu; Gao, Wei; Zhao, Huan; Zhang, Ding-Guo; Yang, Zhi-Jian; Wang, Lian-Sheng

2014-01-01

To examine the influence of walking at different times of day on lipids and inflammatory markers in sedentary patients with coronary artery disease (CAD). A total of 330 patients recruited from Nanjing between September 2011 and November 2012 were randomly assigned to a control group (n=110), morning (n=110) or evening walking group (n=110). Both the walking groups were asked to walk 30 min/day or more on at least 5 days/week either in the morning or evening for 12 weeks. Lipids and inflammatory markers were measured before and after exercise intervention. Compared with baseline, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were improved in all groups. Significances were shown in the changes of fibrinogen, high sensitivity C-reactive protein (hsCRP), white blood cell (WBC) count, TC, triglycerides, LDL-C, lipoprotein(a) between groups. The evening walking group had a larger decrease in fibrinogen (0.16 ± 0.19 g/L, Pwalking program successfully resulted in a favorable change in lipids and inflammatory markers. Patients in the evening walking group gained more benefits than those walking in the morning walking group. NCT01887093. © 2013.

The Effects of Body Acupuncture on Obesity: Anthropometric Parameters, Lipid Profile, and Inflammatory and Immunologic Markers

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Hamid Abdi

2012-01-01

Full Text Available A randomized controlled clinical trial in 196 obese subjects was performed to examine the effectiveness of body acupuncture on body weight loss, lipid profile and immunogenic and inflammatory markers. Subjects received authentic (cases or sham (controls acupuncture for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Subjects were assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps-27, 60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP levels were also assessed. A significant reduction in measures of adiposity and improvement in lipid profile were observed in both groups, but the levels of anti-Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid profile in cases were sustained in the second period, however, only changes in lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP levels continued to be reduced in cases but in controls only the reduction in hs-CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp-antibodies were more evident in cases. Body acupuncture in combination with diet restriction was effective in enhancing weight loss and improving dyslipidemia.

The Effects of Body Acupuncture on Obesity: Anthropometric Parameters, Lipid Profile, and Inflammatory and Immunologic Markers

Science.gov (United States)

Abdi, Hamid; Zhao, Baixiao; Darbandi, Mahsa; Ghayour-Mobarhan, Majid; Tavallaie, Shima; Rahsepar, Amir Ali; Parizadeh, Seyyed Mohammad Reza; Safariyan, Mohammad; Nemati, Mohsen; Mohammadi, Maryam; Abbasi-Parizad, Parisa; Darbandi, Sara; Akhlaghi, Saeed; Ferns, Gordon A. A.

2012-01-01

A randomized controlled clinical trial in 196 obese subjects was performed to examine the effectiveness of body acupuncture on body weight loss, lipid profile and immunogenic and inflammatory markers. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Subjects were assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps)-27, 60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP) levels were also assessed. A significant reduction in measures of adiposity and improvement in lipid profile were observed in both groups, but the levels of anti-Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid profile in cases were sustained in the second period, however, only changes in lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP levels continued to be reduced in cases but in controls only the reduction in hs-CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp-antibodies were more evident in cases. Body acupuncture in combination with diet restriction was effective in enhancing weight loss and improving dyslipidemia. PMID:22649299

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

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Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

2015-10-01

Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

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Sun, Yu-Yo; Morozov, Yury M; Yang, Dianer; Li, Yikun; Dunn, R Scott; Rakic, Pasko; Chan, Pak H; Abe, Koji; Lindquist, Diana M; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (pedaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

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Yu-Yo Sun

Full Text Available Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Thrombotic Management of Antiphospholipid Syndrome: Towards Novel Targeted Therapies.

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Islam, Md Asiful; Alam, Fahmida; Wong, Kah Keng; Kamal, Mohammad Amjad; Gan, Siew Hua

2017-01-01

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anti-inflammatory, anthropometric and lipomodulatory effects Dyglomera® (aqueous extract of Dichrostachys glomerata in obese patients with metabolic syndrome

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Dieudonne Kuate

2013-11-01

Full Text Available Background: Increased visceral fat, dyslipidemia and increased markers of inflammation and coagulation are cardiovascular risk factors commonly encountered in obese people with metabolic syndrome. Previous studies have shown that ground Dichrostachys glomerata (DG, a spice used in Western Cameroon, can have beneficial effects on inflammation and various other cardiovascular disease risk factors. The purpose of the present study was to evaluate the effects of Dyglomera®, an aqueous extract of DG (standardized to NLT 10% polyphenols on certain anthropometric, biochemical (including pro-inflammatory and pro-thrombotic states and hemodynamic parameters in obese patients with metabolic syndrome. Methods: The study was an 8-week randomized, double-blind, placebo-controlled trial involving 116 males and 202 females aged between 24 and 58 years. Participants were randomly divided into two groups: treatment and placebo. Capsules containing the active treatment (200 mg Dyglomera® or placebo (200 mg maize powder were administered 30–60 minutes before lunch and dinner throughout the study period. Various biochemical (namely, blood glucose, lipid profile, pro-inflammatory and pro-thrombotic markers, anthropometric and hemodynamic parameters were measured at baseline and after 4 and 8 weeks of treatment. Functional Foods in Health and Disease 2013; 3(11:416-427 Page 417 of 427 Results: At the end of the study, the Dyglomera® group showed statistically significant differences in all 16 parameters compared to baseline values. Changes in BMI and waist circumference were accompanied by changes in biochemical parameters, with the exception of adiponectin levels which were not correlated to waist circumference and PAI-1 values. The results confirm the hypothesis that Dyglomera®, the aqueous extract of DG, has antiinflammatory properties, and is effective in reducing cardiovascular disease risk factors associated with metabolic syndrome in obese human subjects.

Rivaroxaban vs Warfarin and Risk of Post-Thrombotic Syndrome among Patients with Venous Thromboembolism

DEFF Research Database (Denmark)

Søgaard, Mette; Nielsen, Peter Brønnum; Skjøth, Flemming

2018-01-01

BACKGROUND: The effectiveness of rivaroxaban to reduce post-thrombotic syndrome in patients with venous thromboembolism is largely unknown. We compared rates of post-thrombotic syndrome in patients given rivaroxaban versus warfarin in a cohort of routine clinical care patients with incident venous...... thromboembolism. METHODS: We linked Danish nationwide registries to identify all patients with incident venous thromboembolism who were new users of rivaroxaban or warfarin and compared rates of post-thrombotic syndrome using an inverse probability of treatment weighting approach to account for baseline...... confounding. RESULTS: We identified 19,939 oral anticoagulation naive patients with incident venous thromboembolism treated with warfarin or rivaroxaban (mean age 64 years, 48% females, 45.5% with pulmonary embolism). The propensity-weighted rate of post-thrombotic syndrome at 3 years follow-up was 0...

Comparison of percentage body fat and body mass index for the prediction of inflammatory and atherogenic lipid risk profiles in elderly women.

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Funghetto, Silvana Schwerz; Silva, Alessandro de Oliveira; de Sousa, Nuno Manuel Frade; Stival, Marina Morato; Tibana, Ramires Alsamir; Pereira, Leonardo Costa; Antunes, Marja Letícia Chaves; de Lima, Luciano Ramos; Prestes, Jonato; Oliveira, Ricardo Jacó; Dutra, Maurílio Tiradentes; Souza, Vinícius Carolino; Nascimento, Dahan da Cunha; Karnikowski, Margô Gomes de Oliveira

2015-01-01

To compare the clinical classification of the body mass index (BMI) and percentage body fat (PBF) for the prediction of inflammatory and atherogenic lipid profile risk in older women. Cross-sectional analytical study with 277 elderly women from a local community in the Federal District, Brazil. PBF and fat-free mass (FFM) were determined by dual energy X-ray absorptiometry. The investigated inflammatory parameters were interleukin 6 and C-reactive protein. Twenty-five percent of the elderly women were classified as normal weight, 50% overweight, and 25% obese by the BMI. The obese group had higher levels of triglycerides and very low-density lipoproteins than did the normal weight group (P≤0.05) and lower levels of high-density lipoproteins (HDL) than did the overweight group (P≤0.05). According to the PBF, 49% of the elderly women were classified as eutrophic, 28% overweight, and 23% obese. In the binomial logistic regression analyses including age, FFM, and lipid profile, only FFM (odds ratio [OR]=0.809, 95% confidence interval [CI]: 0.739-0.886; Pprofile is key to assessing the risk of cardiometabolic diseases. Classification based on dual energy X-ray absorptiometry measures, along with biochemical and inflammatory parameters, seems to have a great clinical importance, since it allows the lipid profile eutrophic distinction in elderly overweight women.

Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

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Otsui, Kazunori; Yamamoto, Junichiro; Inoue, Nobutaka

2018-02-01

Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

The Effects of Isoflavone Supplementation Plus Combined Exercise on Lipid Levels, and Inflammatory and Oxidative Stress Markers in Postmenopausal Women

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Jéssica S. Giolo

2018-03-01

Full Text Available This study tested the effect of isoflavone supplementation in addition to combined exercise training on plasma lipid levels, inflammatory markers and oxidative stress in postmenopausal women. Thirty-two healthy and non-obese postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (PLA; n = 15 or exercise + isoflavone supplementation (ISO; n = 17 groups. They performed 30 sessions of combined exercises (aerobic plus resistance over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Blood samples were collected after an overnight fast to analyze the lipid profile, interleukin-6 (IL-6, interleukin-8 (IL-8, superoxide dismutase (SOD, total antioxidant capacity (FRAP, and thiobarbituric acid reactive substances (TBARS, before and after ten weeks of the intervention. There were no differences in the changes (pre vs. post between groups for any of the inflammatory markers, oxidative stress markers or lipid profile variables. However, interleukin-8 was different between pre- and post-tests (p < 0.001 in both groups (Δ = 7.61 and 5.61 pg/mL as were cholesterol levels (p < 0.05, with no interaction between groups. The combination of isoflavone supplementation and exercise training did not alter oxidative stress markers in postmenopausal women, but exercise training alone may increase IL-8 and decrease total cholesterol levels.

Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component.

Science.gov (United States)

Tallberg, Thomas; Dabek, Jan; Hallamaa, Raija; Atroshi, Faik

2011-01-01

The central role performed by billions of vital central nervous system (CNS) lipids "lipidomics" in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.

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Cao, Wenjing; Pham, Huy P; Williams, Lance A; McDaniel, Jenny; Siniard, Rance C; Lorenz, Robin G; Marques, Marisa B; Zheng, X Long

2016-11-01

Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (Ppurpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. Copyright© Ferrata Storti Foundation.

Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.

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Bellante, Flavio; Redondo Saez, Patricia; Springael, Cecile; Dethy, Sophie

2014-07-01

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A systematic review of anti-thrombotic therapy in epistaxis.

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Musgrave, K M; Powell, J

2016-12-01

There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.

Science.gov (United States)

Detremerie, Celine; Timmermans, Frank; De Pauw, Michel; Gheeraert, Peter; Hemelsoet, Dimitri; Toeback, Jonas; Bové, Thierry; Vandecasteele, Els

2017-08-01

We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.

Lipidomics: The Function of Vital Lipids in Embryogenesis Preventing Autism Spectrum Disorders, Treating Sterile Inflammatory Diatheses with a Lymphopoietic Central Nervous System Component

Directory of Open Access Journals (Sweden)

Thomas Tallberg

2011-01-01

Full Text Available The central role performed by billions of vital central nervous system (CNS lipids “lipidomics” in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

Science.gov (United States)

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thrombotic thrombocytopenic purpura

International Nuclear Information System (INIS)

Heyns, A. du P.; Badenhorst, P.N.; Lotter, M.G.; Minnaar, P.C.; Vorster, B.J.; Retief, F.P.

1979-01-01

A 34-year-old woman presented with the clinical and laboratory features of thrombotic thrombocytopenic purpura (TTP). Studies with isologous platelets labelled with 111 In-oxine revealed a short half-life or circulating platelets (18,5 hours) and destruction of the transfused platelets in the spleen, liver and bone marrow. There was no scintigraphic evidence of deposition of labelled platelets in the vasculature. The patient was treated with daily fresh frozen plasma transfusions, but no improvement in platelet count or serum urea level was noted. Although there was no clinical evidence of a bleeding tendency at the time, the patient had a fatal cerebrovascular haemorrhage. The findings in this case suggest that an immune type destruction of platelets may occur in TTP

Ferulic Acid Supplementation Improves Lipid Profiles, Oxidative Stress, and Inflammatory Status in Hyperlipidemic Subjects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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Akkarach Bumrungpert

2018-06-01

Full Text Available Ferulic acid is the most abundant phenolic compound found in vegetables and cereal grains. In vitro and animal studies have shown ferulic acid has anti-hyperlipidemic, anti-oxidative, and anti-inflammatory effects. The objective of this study is to investigate the effects of ferulic acid supplementation on lipid profiles, oxidative stress, and inflammatory status in hyperlipidemia. The study design is a randomized, double-blind, placebo-controlled trial. Subjects with hyperlipidemia were randomly divided into two groups. The treatment group (n = 24 was given ferulic acid (1000 mg daily and the control group (n = 24 was provided with a placebo for six weeks. Lipid profiles, biomarkers of oxidative stress and inflammation were assessed before and after the intervention. Ferulic acid supplementation demonstrated a statistically significant decrease in total cholesterol (8.1%; p = 0.001, LDL-C (9.3%; p < 0.001, triglyceride (12.1%; p = 0.049, and increased HDL-C (4.3%; p = 0.045 compared with the placebo. Ferulic acid also significantly decreased the oxidative stress biomarker, MDA (24.5%; p < 0.001. Moreover, oxidized LDL-C was significantly decreased in the ferulic acid group (7.1%; p = 0.002 compared with the placebo group. In addition, ferulic acid supplementation demonstrated a statistically significant reduction in the inflammatory markers hs-CRP (32.66%; p < 0.001 and TNF-α (13.06%; p < 0.001. These data indicate ferulic acid supplementation can improve lipid profiles and oxidative stress, oxidized LDL-C, and inflammation in hyperlipidemic subjects. Therefore, ferulic acid has the potential to reduce cardiovascular disease risk factors.

Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

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Pallebage-Gamarallage Menuka

2012-09-01

Full Text Available Abstract Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA compromises blood–brain barrier (BBB integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG and amyloid-β enriched apolipoprotein (apo-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble. Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene

DEFF Research Database (Denmark)

Rank, Cecilie Utke; Kremer Hovinga, Johanna; Taleghani, Magnus Mansouri

2014-01-01

, causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26-year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity...

Nonbacterial thrombotic endocarditis in a Japanese autopsy sample. A review of eighty cases

Energy Technology Data Exchange (ETDEWEB)

Chino, F; Kodama, A; Otake, M; Dock, D S

1974-01-01

A study of nonbacterial thrombotic endocarditis was carried out in a series of 3404 autopsies performed upon A-bomb survivors in Hiroshima in the period 1953--70. The prevalence of the lesion was 2.4%, with a greater frequency among the elderly and among females, and with a significant relationship to malignant neoplasms. There was a great prevalence among cancers of the colon and rectum and female genitourinary tract. No relationship was noted between nonbacterial thrombotic endocarditis and radiation exposure. Histologic findings in the heart valve leaflets in close proximity to the verrucae suggest that in association with severe systemic disease, there appears a process consisting of degenerative changes in valve collagen and ground substance, with subsequent denudation of endothelium, localized almost entirely to the apposing leaflet surfaces of the left-heart valves. The verrucae of nonbacterial thrombotic endocarditis are then formed upon this abnormal leaflet surface. There is no doubt that this lesion represents a clinically important complication of severe systemic disease. It also seems likely that in some cases nonbacterial thrombotic endocarditis may complicate an illness which may otherwise be curable. Increasing awareness of this pathologic entity, coupled with echocardiographic techniques, will permit more frequent diagnosis in living

1,8-cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish

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Kyung-Hyun Cho1,2,*

2012-10-01

Full Text Available We recently reported that a water extract of laurel or turmeric,1,8-cineole enriched fractions, showed hypolipidemic activityin the zebrafish model. Therefore, the present study investigatedthe cineole’s anti-oxidant and anti-inflammatory activitiesin lipoprotein metabolism in vitro and in vivo. Cineolehad inhibitory effects on cupric ion-mediated oxidation of lipoproteinsin general, while simultaneously enhancing ferric ionremoval ability in high-density lipoprotein (HDL. Hypercholesterolemiawas induced in zebrafish using cholesterol-feedingtreatment, 4% cholesterol, for 3 weeks. After feeding with orwithout the addition of cineole, the results revealed that cineolepossessed lipid-lowering and anti-inflammatory activitiesin hypercholesterolemic zebrafish. In addition, serum amyloidA and interleukin-6 levels were lowered and lipid accumulationwas decreased in the liver. Conclusively, 1,8-cineole wasfound to have anti-oxidant activities in lipoprotein metabolismboth in vitro and in vivo with simultaneous reduction of lipidaccumulation in the liver of zebrafish.

Splenectomy for the treatment of thrombotic thrombocytopenic purpura

NARCIS (Netherlands)

Kappers-Klunne, MC; Wijermans, P; Fijnheer, R; Croockewit, AJ; van der Holt, B; de Wolf, JTM; Lowenberg, B; Brand, A

Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these

Thrombotic thrombocytopenic purpura possibly triggered by Graves’ disease

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Chitnis, Saurabh D; Mene-Afejuku, Tuoyo O; Aujla, Amandeep; Shady, Ahmed; Gil, Gaby S; Cativo, Eder Hans; Popescu-Martinez, Andrea

2017-01-01

Abstract Thrombotic thrombocytopenic purpura (TTP) is a part of a spectrum of thrombotic microangiopathy syndromes which are mainly characterized by platelet aggregation causing microangiopathic hemolytic anemia, thrombocytopenia and microvascular occlusion. In literature, very few cases expressing a direct association between pre-existing Grave’s disease and TTP have been described. A 37-year-old African–American woman with past medical history of Grave’s disease and polysubstance abuse who presented with complaints of dyspnoea at rest and chest pain was diagnosed to have TTP on further evaluation. Patient also showed severely elevated thyroid hormones and suppressed thyroid stimulating hormone levels indicating severe thyrotoxicosis. Initiation of prompt management of TTP and thyrotoxicosis led to a favorable patient outcome. In conclusion, patients presenting with thyrotoxicosis, thrombocytopenia and microangioapthic hemolytic anemia without an alternative cause should be treated and screened for TTP due to the high fatality associated with untreated or untimely detection of this disease. PMID:29744115

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

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Luther, Natascha; Shahneh, Fatemeh; Brähler, Melanie; Krebs, Franziska; Jäckel, Sven; Subramaniam, Saravanan; Stanger, Christian; Schönfelder, Tanja; Kleis-Fischer, Bettina; Reinhardt, Christoph; Probst, Hans Christian; Wenzel, Philip; Schäfer, Katrin; Becker, Christian

2016-12-09

Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution. © 2016 American Heart Association, Inc.

Anti-jugular vein thrombotic effect of Morinda citrifolia L. [noni] in male SD rats

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Mian-Ying Wang

2011-09-01

Full Text Available Background: Venous thromboembolism (VTE is a common and serious medical condition, which is estimably responsible for more than 300,000 hospital admissions annually in the USA. Pulmonary embolism (PE is a major complication of VTE, which contributes to 12% death of hospitalized patients. Heparin is the most common anti-coagulant, but severe allergic reactions, bleeding, and thrombocytopenia limit its use. Thus, seeking a botanical, nontoxic antithrombotic alternative is an interesting area. Morinda citrifolia L. [noni] is a medicinal plant used in folk remedies by Polynesians for over 2,000 years. It has been reported to have a broad range of therapeutic and preventive effects. The bioactivities of NJ have been continuously discovered with antioxidative, anti-inflammatory, analgesic, and immune modifying activities. Our novel hypothesis is whether NJ has an anti-venous thrombotic effect in rodents. To examine our hypothesis, this study was designed to examine the anti-thrombotic effect of NJ on the jugular vein thrombosis model induced by ferric chloride in SD rats.Material and Methods: NJ and placebo used in this study were donated by Morinda Holding Inc. NJ was formulated with grape juice and blue berry juice. Placebo was prepared by using the same procedure of NJ preparation, but without NJ in it. Thirty-six male SD rats were divided into six groups. Anti-venous thrombotic activities of 5% NJ, 10% NJ, heparin, and 10% NJ plus heparin were examined and compared with the positive and blank controls. Thrombosis was induced by application of a filter paper soaked in 50% ferric chloride on the right jugular vein. AFunctional Foods in Health and Disease 2011; 9:297-3092-cm fragment of the occluded vein (thrombus was removed and weighed after 1-hour maturation. Blood samples were collected for platelet count, aPTT, and PT tests.Results: The weight of a 2-cm fragment of normal jugular vein was 9.9 ± 2.1 mg, while the weight of the occluded vein in

A case of refractory thrombotic thrombocytopenic purpura treated ...

African Journals Online (AJOL)

Background. Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threaten- ing disorder that occurs due to deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member. 13), which is a von Willebrand factor (VWF) cleaving protein.[1]. The absent or severely reduced activity ...

The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus.

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Arablou, Tahereh; Aryaeian, Naheed; Valizadeh, Majid; Sharifi, Faranak; Hosseini, AghaFatemeh; Djalali, Mahmoud

2014-06-01

To assess the effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. In a double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients were enrolled. They allocated randomly into ginger group and control group. They consumed 1600 mg ginger versus 1600 mg wheat flour placebo daily for 12 weeks. Serum sugar, lipids, CRP, PGE2 and TNFα were measured before and after intervention. Ginger reduced fasting plasma glucose, HbA1C, insulin, HOMA, triglyceride, total cholesterol, CRP and PGE₂ significantly compared with placebo group (p  0.05). Ginger improved insulin sensitivity and some fractions of lipid profile, and reduced CRP and PGE₂ in type 2 diabetic patients. Therefore ginger can be considered as an effective treatment for prevention of diabetes complications.

Synthesis of quinoline attached-furan-2(3H-ones having anti-inflammatory and antibacterial properties with reduced gastro-intestinal toxicity and lipid peroxidation

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Akhter Mymoona

2011-01-01

Full Text Available A series of 3-[2-chloroquinolin-3-ylmethylene]-5-aryl-furan-2(3H-ones {3(a-p} were synthesized. The required 3-(substitutedbenzoyl propionic acids {2(a-d} were prepared under Friedal Craft acylation reaction conditions. The substituted 2-chloroquinoline-3-carbaldehydes {1(a-d} were synthesized by reaction of substitutedphenylethanone-oxime with phosphorus oxychloride in presence of dimethyl formamide using the Vilsmeir Haack reaction method. These compounds were screened for their anti-inflammatory and antibacterial activities along with their ulcerogenic and lipid peroxidation potentials. The compounds that showed significant anti-inflammatory activity were further screened for their analgesic activity. The compounds were less toxic in terms of ulcerogenicity as compared to a standard, which was also supported by lipid peroxidation studies. The antibacterial activities were performed against Staphylococcus aureus and Escherichia coli. Compounds 3f, 3n and 3o showed significant activity against both S. aureus and E. coli having an MIC value of 6.25μg mL-1.

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers.

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Madani, Fatima Zohra; Hafida, Merzouk; Merzouk, Sid Ahmed; Loukidi, Bouchra; Taouli, Katia; Narce, Michel

2016-01-01

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

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İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome

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Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-01-01

Abstract Rationale: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. Patient concerns: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Diagnoses: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. Intervetions: The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Outcomes: Clinical improvement ensued. At follow-up the patient is well. Lessons: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities. PMID:29642153

Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

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Praveen Kumar Gaur

2013-01-01

Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

The effects of pilates exercise on lipid metabolism and inflammatory cytokines mRNA expression in female undergraduates.

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Kim, Hyo-Jin; Kim, Jiyeon; Kim, Chang-Sun

2014-09-01

The purpose of the study was to verify the effects of Pilates exercise by observing the impact of 8 weeks of Pilates exercise on lipid metabolism and inflammatory cytokine mRNA expression in female undergraduates in their 20s who had no prior experience in Pilates exercise and had not exercised in the previous 6 months. There were 18 subjects with no prior experience in Pilates exercise. The subjects were separated into the Pilates exercise group (n = 9) and the non-exercise control group (n = 9). The former performed Pilates exercise for 60-70 minutes over 8 weeks with a gradual strength increase of 9-16 in the Rating of Perceived Exercise (RPE). The body composition, creatine kinase in the bloodstream and lipid metabolism (TC, LDL-C, HDL-C, TG) were measured before and after the experiment and Real-Time PCR was used to investigate the mRNA expression of the inflammatory cytokines IL-6 and TNF-⍺. The creatine kinase (CK) in the blood had significant differences between the groups. The test group showed significant increase compared to the control group after 8 weeks of Pilates exercise (p = 0.007). Lipid analysis showed that the level of high-density lipoprotein cholesterol (HDL-C) was significantly different in the two groups (p = 0.049), with the Pilates exercise group exhibiting significantly higher levels compared to the control group. No significant differences were observed in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). IL-6 mRNA expression did not show significant differences between the groups either. Timing and TNF-α mRNA expression showed significant effect in both the exercise and the control groups (p = 0.013) but no correlation. It was found from the study that Pilates exercise for 8 weeks affected CK expression (the muscle damage marker) and induced positive changes in the levels of high-density lipoprotein.

Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

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Manteiga, Sara; Lee, Kyongbum

2017-04-01

A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant.

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Posch, Florian; Gebhart, Johanna; Rand, Jacob H; Koder, Silvia; Quehenberger, Peter; Pengo, Vittorio; Ay, Cihan; Pabinger, Ingrid

2017-03-10

Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.

Limitations of ADAMTS-13 activity level in diagnosing thrombotic thrombocytopenic purpura in pregnancy.

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Ehsanipoor, Robert M; Rajan, Priya; Holcombe, Randall F; Wing, Deborah A

2009-10-01

In pregnancy, it may be difficult to differentiate the syndrome of hemolysis, elevated liver enzymes, and low platelets from thrombotic thrombocytopenia purpura. Severely depressed (present a case of a patient that presented at 20 weeks gestation with elevated liver enzymes and thrombocytopenia. The diagnosis was unclear at the time of presentation. She underwent induction of labor, and during the postpartum course, she was eventually diagnosed with thrombotic thrombocytopenia purpura; however, her activity level of a disintegrin and metalloproteinase with thrombospondin motifs-13 was only moderately depressed at 15% (normal pregnancy value 41%-105%).

Thrombotic Microangiopathy with Skin Localization Secondary to Cytarabine-Daunorubicin Association: Report of a Case

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S. Regragui

2012-01-01

Full Text Available The thrombotic microangiopathy is a syndrome characterized by the combination of mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In addition to the idiopathic form, several cases are identified as secondary to pregnancy, infections, disease systems, organ transplants, and cancer. Other forms are secondary to drugs including antimitotics. We report the case of a patient followed for acute myelogenous leukemia. She received induction chemotherapy combining daunorubicin and cytarabine, complicated by thrombotic thrombocytopenic purpura.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

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Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic

Emerging Evidence for Platelets as Immune and Inflammatory Effector Cells

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Matthew Thomas Rondina

2014-12-01

Full Text Available While traditionally recognized for their roles in hemostatic pathways, emerging evidence demonstrates that platelets have previously unrecognized, dynamic roles that span the immune continuum. These newly-recognized platelet functions, including the secretion of immune mediators, interactions with endothelial cells, monocytes, and neutrophils, toll-like receptor (TLR mediated responses, and induction of neutrophil extracellular trap (NET formation, bridge thrombotic and inflammatory pathways and contribute to host defense mechanisms against invading pathogens. In this focused review, we highlight several of these emerging aspects of platelet biology and their implications in clinical infectious syndromes.

The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

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Nemmar A

2017-04-01

Full Text Available Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Al-Khod, Sultanate of Oman Abstract: Cerium oxide nanoparticles (CeO2 NPs, used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours effect of intratracheal (IT instillation of either CeO2 NPs (0.1 or 0.5 mg/kg or saline (control on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice. CeO2 NPs induced a significant increase of neutrophils into the bronchoalveolar lavage (BAL fluid with an elevation of tumor necrosis factor α (TNFα and a decrease in the activity of the antioxidant catalase. Lung sections of mice exposed to CeO2 NPs showed a dose-dependent infiltration of inflammatory cells consisting of macrophages and neutrophils. Similarly, the plasma levels of C-reactive protein and TNFα were significantly increased, whereas the activities of catalase and total antioxidant were significantly decreased. Interestingly, CeO2 NPs significantly and dose dependently induced a shortening of the thrombotic occlusion time in pial arterioles and venules. Moreover, the plasma concentrations of fibrinogen and plasminogen activator inhibitor-1 were significantly elevated by CeO2 NPs. The direct addition of CeO2 NPs (1, 5, or 25 µg/mL to mouse whole blood, collected from the inferior vena cava, in vitro neither caused significant platelet aggregation nor affected prothrombin time or partial

Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity

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Elisabete da Costa

2017-03-01

Full Text Available The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS. One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG, digalactosyl diacylglyceride (DGDG, sulfoquinovosyl monoacylglyceride (SQMG, sulfoquinovosyl diacylglyceride (SQDG, the phospholipids phosphatidylcholine (PC, lyso-PC, phosphatidylglycerol (PG, lyso-PG, phosphatidylinositol (PI, phosphatidylethanolamine (PE, phosphatic acid (PA, inositolphosphoceramide (IPC, and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS. Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50 of 12.2 μg/mL and 12.9 μg/mL, respectively and inhibited the production of nitric oxide (NO evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL. These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems.

Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice

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Patties, I.; Glasow, A. [University of Leipzig, Department of Radiation Therapy, Leipzig (Germany); Haagen, J. [University of Technology, Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); Doerr, W. [University of Technology, Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); CCC, Medical University/AKH, Department of Radiation Oncology and Christian Doppler Laboratory for Medical Radiation Research for Radiooncology, Vienna (Austria); Hildebrandt, G. [University of Rostock, Department of Radiotherapy and Radiation Oncology, Rostock (Germany)

2014-09-09

Radiation-induced heart disease represents a late complication of thoracic radiotherapy. We investigated the inflammatory and thrombotic response after local heart irradiation in wild-type and atherosclerosis-prone mice. Atherosclerosis-prone ApoE{sup -/-} and C57BL/6 wild-type mice were sacrificed 20, 40, and 60 weeks after irradiation with 0.2, 2, 8, or 16 Gy. The expression of CD31, vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM), and CD45 were quantified by immunofluorescence staining of heart tissue sections. Microvascular density decreased at 40 weeks after 16 Gy in C57BL/6 but not in ApoE{sup -/-} mice. CD31 expression declined in C57BL/6 mice at 40 weeks (8 Gy), but increased in ApoE{sup -/-} mice at 20 (2/8/16 Gy) and 60 weeks (16 Gy). Capillary area decreased in C57BL/6 at 40 weeks (8/16 Gy) but increased in ApoE{sup -/-} mice at 20 weeks (16 Gy). Endocardial VCAM-1 expression remained unchanged. TM-positive capillaries decreased at 40 weeks (8/16 Gy) in C57BL/6 and at 60 weeks (2/16 Gy) in ApoE{sup -/-} mice. Leukocyte infiltration transiently rose 40 weeks after 8 Gy (only ApoE{sup -/-}) and 16 Gy. After receiving a low irradiation dose of 0.2 Gy, no significant changes were observed in any of the mouse models. This study demonstrated that local heart irradiation affects microvascular structure and induces inflammatory/thrombotic responses in mice in a dose- and time-dependent manner. Thereby, significant prothrombotic changes were found in both strains, although they were progressive in ApoE{sup -/-} mice only. Proinflammatory responses, like the increase of adhesion molecules and leukocyte infiltration, were more pronounced and occurred at lower doses in ApoE{sup -/-} vs. C57BL/6 mice. These findings indicate that metabolic risk factors, such as decreased ApoE lipoproteins, may lead to an enhanced proinflammatory and prothrombotic late response in locally irradiated hearts. (orig.) [German] Strahlungsinduzierte kardiovaskulaere

Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

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Feng, Zhi-Gang; Cortina, Miguel; Chesnutt, Jennifer KW; Han, Hai-Chao

2017-01-01

Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. PMID:29327739

Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

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Ji Wang

2016-06-01

Full Text Available Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

Bone tissue, blood lipids and inflammatory profiles in adolescent male athletes from sports contrasting in mechanical load.

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Agostinete, Ricardo R; Duarte, João P; Valente-Dos-Santos, João; Coelho-E-Silva, Manuel J; Tavares, Oscar M; Conde, Jorge M; Fontes-Ribeiro, Carlos A; Condello, Giancarlo; Capranica, Laura; Caires, Suziane U; Fernandes, Rômulo A

2017-01-01

Exploring the effect of non-impact and impact sports is particular relevant to understand the interaction between skeletal muscle and bone health during growth. The current study aimed to compare total and regional bone and soft-tissue composition, in parallel to measurements of blood lipid and inflammatory profiles between adolescent athletes and non-athletes. Anthropometry, biological maturity, dual energy X-ray absorptiometry (DXA) scans, training load and lipid and inflammatory profiles were assessed in a cross-sectional sample of 53 male adolescents (20 non-athletes, 15 swimmers and 18 basketball players) aged 12-19 years. Multiple comparisons between groups were performed using analysis of variance, covariance and magnitude effects (ES-r and Cohen's d). The comparisons of controls with other groups were very large for high-sensitivity C-reactive protein (d range: 2.17-2.92). The differences between sports disciplines, regarding tissue outputs obtained from DXA scan were moderate for all variables except fat tissue (d = 0.4). It was possible to determine small differences (ES-r = 0.17) between controls and swimmers for bone area at the lower limbs (13.0%). In parallel, between swimmers and basketball players, the gradient of the differences was small (ES-r range: 0.15-0.23) for bone mineral content (24.6%), bone area (11.3%) and bone mineral density (11.1%) at the lower limbs, favoring the basketball players. These observations highlight that youth male athletes presented better blood and soft tissues profiles with respect to controls. Furthermore, sport-specific differences emerged for the lower limbs, with basketball players presenting higher bone mineral content, area and density than swimmers.

Thrombotic complications in children with cancer.

LENUS (Irish Health Repository)

Smith, O P

2012-02-01

The last decade has seen advances in treatment of life-threatening disease in children--especially cancer where the overall cure rate is now in the region of 80%. Similar to adults, children with cancer are at a substantial risk of developing thromboembolism (TE). One of the costs of achieving this has been more children developing thrombotic disease, the majority of which are related to indwelling vascular catheters and as a resultTE is being diagnosed with increasing frequency in these younger patients. In the Canadian Paediatric Thrombophilia Registry, 20% of the patients with TE had cancer. This figure is in contrast to only 2.3 cases of malignancy\\/1000 children and an estimated incidence of thrombosis of 0.7\\/100,000 in the general paediatric population. However, the true prevalence of TE in children with cancer is unknown as rates can vary from 1% to as high as 44% [5] and this reflects the heterogeneity of such studies in terms of; (i) type of cancer, (ii) was the TE, symptomatic or asymptomatic and (iii) were the studies prospective or retrospective. Happening alongside these advances have been an explosion in our knowledge of the understanding at the molecular level of blood coagulation in particular how the natural anticoagulant and fibrinolytic pathways work and how they differ in children and adults. Stemming from these discoveries new anticoagulant therapeutics have become available to the paediatrian and over the next decade their true place in the treatment of childhood thrombotic disease will be established.

Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers.

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de Oliveira, Wilson Pascoalino Camargo; Tavoni, Thauany Martins; Freitas, Fatima Rodrigues; Silva, Bruna Miranda Oliveira; Maranhão, Raul Cavalcante

2017-08-01

Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1β, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.

[Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis].

Science.gov (United States)

Aceves-Velázquez, Eduardo; Vieyra-Herrera, Gerardo; Rodríguez-Chávez, Laura; Herrera-Alarcón, Valentín

2017-07-16

According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Bioactive Lipids and Chronic Inflammation: Managing the Fire Within

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Valerio Chiurchiù

2018-01-01

Full Text Available Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes. They are secreted by basically all cells involved in inflammatory processes and constitute the crucial infrastructure that triggers, coordinates and confines inflammatory mechanisms. However, these molecules are also deeply involved in the detrimental transition from acute to chronic inflammation, be it for persistent or excessive action of pro-inflammatory lipids or for the impairment of the functions carried out by resolving ones. As a matter of fact, bioactive lipids have been linked, to date, to several chronic diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis. This review summarizes current knowledge on the involvement of the main classes of endogenous bioactive lipids—namely classical eicosanoids, pro-resolving lipid mediators, lysoglycerophospholipids/sphingolipids, and endocannabinoids—in the cellular and molecular mechanisms that lead to the pathogenesis of chronic disorders.

Thrombotic Thrombocytopenic Purpura Associated with Pneumococcal Sepsis

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Jeffrey R Schriber

1993-01-01

Full Text Available The first documented case of thrombotic thrombocytopenic purpura (TTP associated with pneumococcal septicemia is reported. This association has been previously demonstrated with hemolytic uremic syndrome. The patient presented with recurrent seizures, oliguric renal failure, fever, thrombocytopenia and microangiopathic hemolytic anemia; coagulation studies were normal. Blood and sputum cultures were positive for Streptococcus pneumoniae. The patient responded to therapy with plasmapheresis and antiplatelet agents as well as antibiotics. Coincident infection should be searched for in all cases of TTP.

A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses.

Science.gov (United States)

Köberlin, Marielle S; Snijder, Berend; Heinz, Leonhard X; Baumann, Christoph L; Fauster, Astrid; Vladimer, Gregory I; Gavin, Anne-Claude; Superti-Furga, Giulio

2015-07-02

Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cytoplasmic lipid bodies of human neutrophilic leukocytes

International Nuclear Information System (INIS)

Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

1989-01-01

The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

Decreased inducibility of TNF expression in lipid-loaded macrophages

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Kallin Bengt

2002-10-01

Full Text Available Abstract Background Inflammation and immune responses are considered to be very important in the pathogenesis of atherosclerosis. Lipid accumulation in macrophages of the arterial intima is a characteristic feature of atherosclerosis which can influence the inflammatory potential of macrophages. We studied the effects of lipid loading on the regulation of TNF expression in human monocyte-derived macrophages. Results In macrophages incubated with acetylated low density lipoprotein (ac-LDL for 2 days, mRNA expression of TNF in cells stimulated with TNF decreased by 75%. In cell cultures stimulated over night with IL-1β, lipid loading decreased secretion of TNF into culture medium by 48%. These results suggest that lipid accumulation in macrophages makes them less responsive to inflammatory stimuli. Decreased basal activity and inducibility of transcription factor AP-1 was observed in lipid-loaded cells, suggesting a mechanism for the suppression of cytokine expression. NF-κB binding activity and inducibility were only marginally affected by ac-LDL. LDL and ac-LDL did not activate PPARγ. In contrast, oxidized LDL stimulated AP-1 and PPARγ but inhibited NF-κB, indicating that the effects of lipid loading with ac-LDL were not due to oxidation of lipids. Conclusions Accumulation of lipid, mainly cholesterol, results in down-regulation of TNF expression in macrophages. Since monocytes are known to be activated by cell adhesion, these results suggest that foam cells in atherosclerotic plaques may contribute less potently to an inflammatory reaction than newly arrived monocytes/macrophages.

Comparison of percentage body fat and body mass index for the prediction of inflammatory and atherogenic lipid risk profiles in elderly women

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Funghetto SS

2015-01-01

Full Text Available Silvana Schwerz Funghetto,1 Alessandro de Oliveira Silva,2 Nuno Manuel Frade de Sousa,3 Marina Morato Stival,1 Ramires Alsamir Tibana,4 Leonardo Costa Pereira,1 Marja Letícia Chaves Antunes,1 Luciano Ramos de Lima,1 Jonato Prestes,4 Ricardo Jacó Oliveira,1 Maurílio Tiradentes Dutra,2 Vinícius Carolino Souza,1,4 Dahan da Cunha Nascimento,4 Margô Gomes de Oliveira Karnikowski1 1University of Brasília (UnB, Brasília, DF, Brazil; 2Center University of Brasilia (UNICEUB, Brasilia, DF, Brazil; 3Laboratory of Exercise Physiology, Faculty Estácio de Sá of Vitória, ES, Brazil; 4Catholic University of Brasília, Brasília, DF, Brazil Objective: To compare the clinical classification of the body mass index (BMI and percentage body fat (PBF for the prediction of inflammatory and atherogenic lipid profile risk in older women.Method: Cross-sectional analytical study with 277 elderly women from a local community in the Federal District, Brazil. PBF and fat-free mass (FFM were determined by dual energy X-ray absorptiometry. The investigated inflammatory parameters were interleukin 6 and C-reactive protein.Results: Twenty-five percent of the elderly women were classified as normal weight, 50% overweight, and 25% obese by the BMI. The obese group had higher levels of triglycerides and very low-density lipoproteins than did the normal weight group (P≤0.05 and lower levels of high-density lipoproteins (HDL than did the overweight group (P≤0.05. According to the PBF, 49% of the elderly women were classified as eutrophic, 28% overweight, and 23% obese. In the binomial logistic regression analyses including age, FFM, and lipid profile, only FFM (odds ratio [OR]=0.809, 95% confidence interval [CI]: 0.739–0.886; P<0.0005 proved to be a predictor of reaching the eutrophic state by the BMI. When the cutoff points of PBF were used for the classification, FFM (OR=0.903, CI=0.884–0.965; P=0.003 and the total cholesterol/HDL ratio (OR=0.113, CI=0.023–0

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case report.

Science.gov (United States)

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-04-01

The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Clinical improvement ensued. At follow-up the patient is well. The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.

Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

Science.gov (United States)

Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

2013-06-01

In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed. Copyright © 2012 Elsevier B.V. All rights reserved.

Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

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Shahida A. Khan

2014-01-01

Full Text Available Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs and G protein coupled receptors (GPCRs. In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

KAUST Repository

Tirinato, Luca; Pagliari, Francesca; Limongi, Tania; Marini, Monica; Falqui, Andrea; Seco, J.; Candeloro, Patrizio; Liberale, Carlo; Di Fabrizio, Enzo M.

2017-01-01

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

KAUST Repository

Tirinato, Luca

2017-08-13

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

Prothrombin G20210A gene mutation in pregnant females with thrombotic obstetric complications

International Nuclear Information System (INIS)

Alam, M.A.; Ali, N.; Ayyub, M.

2018-01-01

To determine the frequency of prothrombin G20210A gene mutation in pregnant females with adverse thrombotic obstetric complication and to compare it with prothrombin G20210A gene's frequency in control population. Study Design: Case control study. Place and Duration of Study: Department of Haematology, Army Medical College Rawalpindi and Military Hospital Rawalpindi, from Nov 2013 to Oct 2014. Material and Methods: Sixty pregnant females were included in the study; 30 were cases with adverse thrombotic obstetric complication, while 30 were controls. Detailed history was obtained and 3 ml blood in EDTA tube was collected. DNA was extracted from whole blood and through RT-PCR, presence of prothrombin G20210A gene mutation was looked for in patients and controls. Data was analyzed using SPSS 21. Results: A total of 60 women-30 cases with thrombotic obstetric complications as 'cases' and 30 as 'controls'- were included in the study. Mean age of 'cases' was 28.70 +- 4.23 years while that of 'controls' was 27.33 +- 4.49 years. There was no statistically significant difference among the two groups (p=0.54). In case group only one of 30 (3.3%) patients had heterozygous F2 G20210A mutation while 29 (96.7%) patients had wild type allele. In control group, all the 30 (100%) subjects had wild type allele. The odds of finding the mutation in cases was 1:29 i.e. 0.03 as compared to zero in the control group. The difference was statistically insignificant (p=0.5). Conclusion: Our study shows that the frequency of F2 G20210A gene mutation in pregnant females having adverse thrombotic obstetric complications was not significantly different from its frequency in control population. (author)

ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura.

Science.gov (United States)

Doll, Jacob A; Kelly, Jacob P

2014-07-01

Acute myocardial infarction is a common complication of thrombotic thrombocytopenic purpura (TTP), but rarely the presenting manifestation. Anti-thrombotic therapy for myocardial infarction is rarely utilized in the setting of TTP because of elevated bleeding risk. We report a case of TTP presenting with ST-segment elevation myocardial infarction and treated with thrombolytic therapy. The resultant cardiac and neurological complications highlight the challenges of using evidence-based therapy for myocardial infarction in the setting of TTP.

Post-thrombotic syndrome of the lower extremities

International Nuclear Information System (INIS)

Bosnjakovic, S.; Gerhard, U.; Buck, J.

1980-01-01

The postthrombotic syndrome with chronic venous insufficiency develops either gradually over a number of years or after a latent period of varying length. The clinical manifestations correlate with morphological and functional phlebographic findings of the superficial and deep veins. The conservative therapy of the post-thrombotic syndrome, consisting of anti-coagulant therapy, compression dressing or active physical exercise, must be consistently enforced. Indication of vascular surgical intervention should be carefully noted. Optimal examination of the patho-anatomical findings in the phlebogram is imperative as an important aid in decision-making. (orig.) [de

Post-thrombotic syndrome of the lower extremities

Energy Technology Data Exchange (ETDEWEB)

Bosnjakovic, S; Gerhard, U; Buck, J

1980-09-01

The postthrombotic syndrome with chronic venous insufficiency develops either gradually over a number of years or after a latent period of varying length. The clinical manifestations correlate with morphological and functional phlebographic findings of the superficial and deep veins. The conservative therapy of the post-thrombotic syndrome, consisting of anti-coagulant therapy, compression dressing or active physical exercise, must be consistently enforced. Indication of vascular surgical intervention should be carefully noted. Optimal examination of the patho-anatomical findings in the phlebogram is imperative as an important aid in decision-making.

Effects of blood products on inflammatory response in endothelial cells in vitro.

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Martin Urner

Full Text Available BACKGROUND: Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. METHODS: The inflammatory response from pre-activated (endotoxin-stimulated and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC, platelet concentrates (PC and fresh frozen plasma (FFP was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. RESULTS: Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. CONCLUSION: Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.

[Thrombosis and post-thrombotic syndrome as a consequence of an accident].

Science.gov (United States)

Wahl, U; Hirsch, T

2015-10-01

Phlebothromboses represent alarming complications in accident victims since they can cause fatal pulmonary embolisms. More than half of those affected also develop post-thrombotic syndrome in the course of the illness. In addition to making clinical assessments, the traumatologist should also have fundamental knowledge about diagnostic methods and be familiar with interpreting internal findings. Colour-coded duplex sonography plays a central role in diagnosing thrombosis and in assessing functional limitations. Further information can be gathered from various phlebological procedures. The expert evaluation of the immediate, as well as the long-term consequences of an accident frequently require leg swelling to be classified. It is not uncommon for post-thrombotic syndrome to be diagnosed for the first time during this process. An additional vascular appraisal is often required. An appreciation of social-medical and insurance-related aspects means a high degree of responsibility is placed on the expert.

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

Science.gov (United States)

Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

2018-01-01

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

Directory of Open Access Journals (Sweden)

Giovanna Trinchese

2018-01-01

Full Text Available Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM and donkey milk (DM are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM, DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA, a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of

Bioactivities of Milk Polar Lipids in Influencing Intestinal Barrier Integrity, Systemic Inflammation, and Lipid Metabolism

OpenAIRE

Zhou, Albert Lihong

2013-01-01

The purpose of lactation is for nutrient provision and also importantly for protection from various environmental stressors. Milk polar lipids reduce cholesterol, protect against bacterial infection, reduce inflammation and help maintain gut integrity. Dynamic interactions within dietary fat, lipid metabolism, gut permeability and inflammatory cytokines remain unclear in the context of obesity and systemic inflammation. A rat model and three mouse models were developed to test the hypotheses ...

Assessment of serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease after telmisartan combined with lipid-lowering drug treatment

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Xin Wang

2017-07-01

Full Text Available Objective: To study the effect of telmisartan combined with lipid-lowering drug therapy on serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease. Methods: A total of 106 patients with type 2 diabetes mellitus complicated by coronary heart disease who were treated in our hospital between September 2013 and October 2016 were collected and then divided into the control group (n=55 who received conventional treatment + lipid-lowering drug treatment and the observation group (n=51 who received conventional treatment + lipid-lowering drug + telmisartan treatment after the therapies were reviewed. Before and after treatment, serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were compared between two groups of patients. Results: Before treatment, the differences in serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between two groups of patients. After treatment, serum TG and LDL-C levels in observation group were lower than those in control group while HDL-C level was higher than that in control group; serum inflammatory mediators IL-6, IL-8, HMGB1 and TNF-α levels were lower than those in control group; serum oxidative stress indexes MDA and ROS levels were lower than those in control group while GSH-Px level was higher than that in control group. Conclusion: Telmisartan combined with lipid-lowering drug therapy can effectively optimize the lipid metabolism and reduce the systemic inflammatory response and oxidative stress response in patients with type 2 diabetes mellitus complicated by coronary heart disease.

[Secondary thrombotic microangiopathies].

Science.gov (United States)

Coppo, P

2017-11-01

Thrombotic microangiopathies (TMA) are termed secondary when associated to a specific context favouring their occurrence. They encompass mainly TMA associated with pregnancy, allogeneic hematopoietic stem cell transplantation, cancer, drugs, or HIV infection. Secondary TMA represent a heterogeneous group of diseases which clinical presentation largely depends on the associated context. It is therefore mandatory to recognize these conditions since they have a significant impact in TMA management and prognosis. A successful management still represents a challenge in secondary TMA. Significant progresses have been made in the understanding of pregnancy-associated TMA, allowing an improvement of prognosis; on the opposite, other forms of secondary TMA such as hematopoietic stem cell transplantation-associated TMA or TMA associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of TMA, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Pneumococcal Induced T-activation with Resultant Thrombotic Microangiopathy

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J.W. Oliver

2010-01-01

Full Text Available Thrombotic microangiopathies are disorders resulting from platelet thromboses forming in the microvasculature with resultant schistocyte forms. Hemolytic uremic syndrome (HUS is a microangiopathic hemolytic anemia often complicated by acute renal failure in children. HUS is typically caused by bacterial infection, most commonly enterohemorrhagic Escherichia coli. Neuraminidase-producing organisms, such as Streptococcus pneumoniae have also been reported as potential etiologies. The pathogenesis in these cases involves cleavage of sialic acid residues from the surfaces of erythrocytes, platelets, and glomerular capillary endothelial cells, exposing the Thomsen-Friedenreich antigen, a process known as T-activation. We describe a 2-year-old girl who presented with pneumococcal pneumonia and sepsis ultimately resulting in a thrombotic microangiopathy with acute renal failure, most consistent with HUS. The patient's direct antiglobulin test was positive. Polyagglutination was observed with human adult serum, but not with umbilical cord serum. Her red blood cells (RBCs were reactive against peanut and soybean lectins, but not Salvia sclarea or Salvia horminum lectins. These findings are consistent with T-activation. Clinicians should be cognizant of the possibility of T-activation with resultant HUS in patients infected with neuraminidase-producing bacteria. Such patients may be difficult to identify using monoclonal typing antisera, as these typically do not have anti-T antibodies. Whether such patients are at risk for transfusion-associated hemolysis is debatable.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

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Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β+-thalassemia patient: a rare and challenging condition.

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Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

2014-10-01

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Waist-to-Height Ratio in Indian Women: Comparison With Traditional Indices of Obesity, Association With Inflammatory Biomarkers and Lipid Profile.

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Dilip Malshe, Sharvari; Anand Udipi, Shobha

2017-07-01

We compared waist-to-height ratio (WHtR) with traditional anthropometric indices in healthy women aged 21 to 45 years from urban slums of Mumbai city, India. Lipid profile and inflammatory markers were measured in a subsample of 200 women, and their relationship with WHtR was examined. Mean WHtR was 0.50 ± 0.1, but a little more than half (51.9%) of the women had WHtR ≥0.50. WHtR could correctly identify centrally obese adult women, even when they were categorized as healthy or normal according to body mass index, waist circumference, waist to hip ratio, and percentage body fat. Also, in centrally obese women, inflammatory markers-namely, high-sensitivity C-reactive protein, interleukin-6, and interleukin-10-were significantly and positively correlated with WHtR. Thus, results of this study indicate that WHtR is a simple and effective anthropometric variable that has the potential to identify central obesity and the associated inflammation even in women with normal BMI.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

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Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

The role of lipids in psoriasis

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Anna Baran

2017-12-01

Full Text Available Psoriasis, affecting 2–4% of the world’s population, is a chronic recurrent inflammatory skin disease. Its multifactorial aetiopathogenesis consists of, for example, abnormal epidermal proliferation, immune disturbances, and genetic, psychosomatic, environmental and hormonal factors. Psoriasis is also considered to be a systemic disorder closely associated with cardiovascular diseases, atherosclerosis, diabetes mellitus, obesity or metabolic syndrome. Lipids have a variety of biological functions. They participate not only in energy storage and expenditure or the formation of cell membranes, but also in inflammatory and metabolic signalling pathways. Disturbances in their homeostasis lead to the development of immunometabolic disorders, including psoriasis. Based on the available literature, this article presents selected molecular and clinical aspects involved in the multidirectional effect of lipids on psoriasis.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

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Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research

Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

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Nieto-Ríos, John Fredy; Álvarez Barreneche, María Fernanda; Penagos, Sara Catalina; Bello Márquez, Diana Carolina; Serna-Higuita, Lina Maria; Ramírez Sánchez, Isabel Cristina

2018-02-01

Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura.

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Peyvandi, F; Scully, M; Kremer Hovinga, J A; Knöbl, P; Cataland, S; De Beuf, K; Callewaert, F; De Winter, H; Zeldin, R K

2017-07-01

Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody ® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for 'embolic and thrombotic events' was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab

The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action.

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Yong Zhou

2010-01-01

Full Text Available The nonsteroidal anti-inflammatory drug (NSAID, indomethacin (Indo, has a large number of divergent biological effects, the molecular mechanism(s for which have yet to be fully elucidated. Interestingly, Indo is highly amphiphilic and associates strongly with lipid membranes, which influence localization, structure and function of membrane-associating proteins and actively regulate cell signaling events. Thus, it is possible that Indo regulates diverse cell functions by altering micro-environments within the membrane. Here we explored the effect of Indo on the nature of the segregated domains in a mixed model membrane composed of dipalmitoyl phosphatidyl-choline (di16:0 PC, or DPPC and dioleoyl phosphatidyl-choline (di18:1 PC or DOPC and cholesterol that mimics biomembranes.Using a series of fluorescent probes in a fluorescence resonance energy transfer (FRET study, we found that Indo induced separation between gel domains and fluid domains in the mixed model membrane, possibly by enhancing the formation of gel-phase domains. This effect originated from the ability of Indo to specifically target the ordered domains in the mixed membrane. These findings were further confirmed by measuring the ability of Indo to affect the fluidity-dependent fluorescence quenching and the level of detergent resistance of membranes.Because the tested lipids are the main lipid constituents in cell membranes, the observed formation of gel phase domains induced by Indo potentially occurs in biomembranes. This marked Indo-induced change in phase behavior potentially alters membrane protein functions, which contribute to the wide variety of biological activities of Indo and other NSAIDs.

The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

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Iung, Bernard; Rodés-Cabau, Josep

2014-11-07

Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Incorporation of n-3 PUFA and γ-linolenic acid in blood lipids and red blood cell lipids together with their influence on disease activity in patients with chronic inflammatory arthritis - a randomized controlled human intervention trial

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Springer Monika

2011-08-01

Full Text Available Abstract Background and aim Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial. Design Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study. Patients received the respective capsules (1: 3.0 g n-3 LC-PUFA/d; 2: 3.2 g γ-linolenic acid/d; 3: 1.6 g n-3 LC-PUFA + 1.8 g γ-linolenic acid/d; 4: 3.0 g olive oil for a twelve week period. Clinical status was evaluated and blood samples were taken at the beginning and at the end of the period. Differences before and after intervention were tested with paired t-test or with Wilcoxon test for non-normal data distribution. Results 60 patients (54 rheumatoid arthritis, 6 psoriatic arthritis were randomised, 47 finished per protocol. In group 1, the ratio of arachidonic acid (AA/eicosapentaenoic acid (EPA decreased from 6.5 ± 3.7 to 2.7 ± 2.1 in plasma lipids and from 25.1 ± 10.1 to 7.2 ± 4.7 in erythrocyte membranes (p ≤ 0.001. There was no significant influence on AA/EPA ratio due to interventions in group 2-4. In group 2, the intake of γ-linolenic acid resulted in a strong rise of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte membranes. The combination of n-3 LC-PUFA and γ-linolenic acid (group 3 led to an increase of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte mem-branes. This increase was only half of that in group 2. Conclusions Incorporation of eicosanoid precursor FAs was influenced by an intake of n-3 LC-PUFA and γ-linolenic acid suggesting a possible benefit for therapy of chronic inflammatory diseases. Trial Registration ClinicalTrials NCT01179971

Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats.

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Xue, Mei; Jiang, Zhen-zhou; Wu, Tao; Li, Ji; Zhang, Liang; Zhao, Yan; Li, Xue-jun; Zhang, Lu-Yong; Yang, Shu-yu

2012-08-15

Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30 mg/kg) and TWHF group (120, 60, 30 mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60 mg/kg (psystem can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF

[Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and treatment?

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Charmetant, Xavier; Jolivot, Anne; Fournier, Thomas; Puthet, Jean-Charles; Cassier, Philippe; Lemoine, Sandrine; Juillard, Laurent

2017-06-01

Thrombotic microangiopathy is a rare but severe complication of treatment with gemcitabine. Its prevalence increases because gemcitabine's indications are growing. We report four cases, which presented with common clinical and biological manifestations, i.e. high blood pressure, proteinuria and increasing plasmatic creatinine level. However, severity was not similar, hemodialysis was inconstant. There is no consensus on treatment for this condition. Stopping gemcitabine is essential. Treatment was dispensed considering the severity of the presentation: plasma exchange therapy of variable outcome, and eculizumab, which was efficient when used. It's important to note that this syndrome includes common and frequent signs in patients receiving chemotherapies. But they must encourage the research of most specific signs, such as hypertension, mechanic hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic microangiopathy as early as possible to treat it precociously, and to prevent additional gemcitabine injections. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Mango Supplementation Has No Effects on Inflammatory Mediators in Obese Adults

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Evans, Shirley F; Beebe, Maureen; Mahmood, Maryam; Janthachotikun, Sawanya; Eldoumi, Heba; Peterson, Sandra; Payton, Mark; Perkins-Veazie, Penelope; Smith, Brenda J; Lucas, Edralin A

2017-01-01

This pilot study examined the effects of freeze-dried mango (Mangifera indica L.) supplementation on anthropometric measurements, lipid parameters, and inflammatory mediators in obese individuals. A total of 20 obese (body mass index [BMI]: 30-35 kg/m2) adults (11 men and 9 women), aged 20 to 50 years, received 10 g/d of ground freeze-dried mango pulp for 12 weeks. Anthropometrics, lipids, and inflammatory mediators were assessed at baseline and after 12 weeks of mango supplementation. There were no differences between baseline and final visits in inflammatory mediators, lipids, diet, physical activity, and anthropometrics. Relationships were present at baseline and final visits between adiponectin and high-density lipoprotein cholesterol and between leptin and fat mass. Correlations were found after 12 weeks of mango supplementation between leptin and the following variables: waist-to-height ratio, BMI, percent fat, and fat mass. Our findings demonstrate that 12-week consumption of freeze-dried mango by obese individuals has no impact on obesity-related inflammation. PMID:28983188

Valsartan Decreases Platelet Activity and Arterial Thrombotic Events in Elderly Patients with Hypertension

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Fang Wu

2015-01-01

Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events.

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Ho, K T; Ahn, C W; Alarcón, G S; Baethge, B A; Tan, F K; Roseman, J; Bastian, H M; Fessler, B J; McGwin, G; Vilá, L M; Calvo-Alén, J; Reveille, J D

2005-10-01

To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive

Antiplatelet therapy and vascular disease: an update.

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Buch, Mamta H; Prendergast, Bernard D; Storey, Robert F

2010-08-01

Atherosclerosis is a diffuse, systemic disorder of the large and medium-sized arterial vessels, affecting the coronary, cerebral and peripheral circulation. Chronic inflammatory processes are the central pathophysiological mechanism largely driven by lipid accumulation, and provide the substrate for occlusive thrombus formation. The clinical sequelae of acute arterial thrombosis, heart attack and stroke, are the most common causes of morbidity and mortality in the industrialized world. Such acute events are characterized by rupture or erosion of the atherosclerotic plaque leading to acute thrombosis. The atherosclerotic process and associated thrombotic complications are collectively termed atherothrombosis. The platelet is a pivotal mediator of various endothelial, immune, thrombotic and inflammatory responses and therefore a key player in the initiation and progression of atherothrombosis. A robust evidence base supports the clear clinical benefits of antiplatelet agents in the primary and secondary therapy of atherothrombotic disorders. Percutaneous coronary and peripheral interventions have an established central role in the management of atherothrombotic disease and demand a greater understanding of platelet biology. In this article, we provide a clinically orientated overview of the pathophysiology of arterial thrombosis and the evidence supporting the use of the various established antiplatelet therapies, and discuss new and future agents.

Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

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Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

2017-07-01

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease.

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Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark; Nielsen, Ole Haagen; Reed, Michelle Ac; Atkins, Karen; Günther, Ulrich Leonhard; Hao, Fuhua; Wang, Yulan

2017-10-16

One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors. Successive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1 H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB. Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting. 1 H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially

A report of three cases with thrombotic thrombocytopenic purpura (TTP) secondary to an occult gastric adenocarcinoma

International Nuclear Information System (INIS)

Forat, Y.M.; Hashemian, Z.; Nazmieh, H.; Ghadimi, H.R.

2009-01-01

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic microangiopathy with clinical findings consisting of fever, microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fluctuating neurologic impairment and renal dysfunction. However, Microangiopathic hemolytic anemia has been described in association with disseminated malignancies, most commonly adenocarcinoma of the breast or stomach. We present three patients with microangiopathic anemia in whom metastatic cancer was finally diagnosed; however, they died of refractory hemolytic anemia in the end. The occurrence of microangiopathic hemolytic anemia and thrombocytopenia in patients with disseminated malignant in gastric adenocarsinoma is well documented. Therefore, the diagnosis of tumor-associated TTP should be considered in unresponsive TTP patient treated with plasmapheresis. (author)

Effect of anti-gut inflammatory agent on insulin resistance and lipid ...

African Journals Online (AJOL)

The level of fasting blood glucose, fasting plasma insulin and the curve of glucose tolerance test (GTT) in mice fed LFD, HFD or HFC diet were not affected by 5-ASA treatment. Although plasma lipid levels were similar between 5-ASA consuming and non-5-ASA groups in mice fed LFD and HFD, improved lipid profile was ...

Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding.

Science.gov (United States)

Kim, Seung Young; Hyun, Jong Jin; Suh, Sang Jun; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Park, Jong Jae; Chun, Hoon Jai; Lee, Sang Woo

2016-04-01

To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.

Improved endothelial function and lipid profile compensate for impaired hemostatic and inflammatory status in iatrogenic chronic subclinical hyperthyroidism of thyroid cancer patients on L-t4 therapy.

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Gazdag, A; Nagy, E V; Burman, K D; Paragh, G; Jenei, Z

2010-06-01

We aimed to compare the changes of endothelial function and haemostatic, inflammatory and metabolic parameters of short-term iatrogenic hypothyroidism to the characteristics of subclinical hyperthyroidism in patients with differentiated thyroid cancer. Twenty four women (mean age 42.4+/-8.1 years) had undergone total thyroidectomy and radioiodine ablation in treatment for differentiated thyroid cancer. We measured serum thyroglobulin, thyroid function, plasma levels of lipid parameters, homocystine, C-reactive protein, fibrinogen, von Willebrandt factor activity (vWF), nitric oxide, as well as flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation of the brachial artery during iatrogenic hypothyroidism (TSH 89.82+/-29.36 mU/L) and again in the same patients during subclinical hyperthyroidism secondary to exogenous levothyroxine administration (TSH 0.24+/-0.11 mU/L). In hypothyroidism, FMD was markedly lower than in subclinical hyperthyroidism (6.79+/-4.44 vs. 14.37+/-8.33%, phyperthyroidism was associated with improved endothelial function and lipid profile, while haemostatic and inflammatory parameters were impaired. The two opposite mechanisms may well compensate for each other at the level of the vessel wall. (c) J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

Atypical presentation of post infectious glomerulonephritis as malignant hypertension and thrombotic microangiopathy

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M Vankalakunti

2014-01-01

Full Text Available Infection-related glomerulonephritis presents commonly as acute nephritic illness, hypertension, hypocomplementinemia following an episode of pharyngitis or pyoderma. Atypical features like thrombotic microangiopathy (TMA, produced by neuraminidase antigen targeting endothelium have been described rarely. We report a case of TMA secondary to malignant hypertension, coexisting with post infectious glomerulonephritis.

Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations

OpenAIRE

Nahar, Pragati P.; Slitt, Angela L.; Seeram, Navindra P.

2015-01-01

Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low ...

Novel platelet-agglutinating protein from a thrombotic thrombocytopenic purpura plasma.

OpenAIRE

Siddiqui, F A; Lian, E C

1985-01-01

A novel platelet-agglutinating protein (PAP) was purified approximately 2,000-fold from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) by ammonium sulfate fractionation, DEAE-Sephacel and concanavalin A-Sepharose chromatographies. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with and without reduction, this preparation revealed a major protein band with a molecular weight of 37,000, and a minor band with a molecular weight of 32,000-34,000. After eluti...

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis

DEFF Research Database (Denmark)

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R

2017-01-01

BACKGROUND: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. OBJECTIVE: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional ...

Evaluation of Some Inflammatory and Biochemical Markers in Acute Coronary Syndrome

International Nuclear Information System (INIS)

Abdel-Messeih, PH.L.; Nossier, N.M.; Mansour, H.H.

2012-01-01

The term acute coronary syndrome (ACS) encompasses a range of thrombotic coronary artery diseases, including unstable angina (UA) and both ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Bio markers play an important role in the diagnosis of non-ST-elevation ACS (NSTE-ACS) including unstable angina and non-STEMI. Among these, cardiac troponin and creatine phosphokinase myocardial band appeared to be the most sensitive and specific markers of myocardial injury. The important role of inflammatory processes in the development and progression of atherosclerosis has been clearly established. Different circulating inflammatory bio markers indicating the instability of atherosclerotic plaque have been identified and serve as diagnostic tools for the identification of patients with unstable angina or acute myocardial infarction and to identify risk patients. The present study was carried out on twenty patients with (NSTE-ACS). The level of serum troponin I (cTnI), creatine phosphokinase-total (CPK-T), myocardial band of creatine phosphokinase (CPK-MB), pregnancy associated plasma protein-A (PAPP-A) and highly sensitive C-reactive protein (hsCRP) were determined. The results showed increase in the level of cardiac bio markers (cTnI, CPK-MB, CPK-T) and inflammatory markers (PAPP-A, hsCRP). It could be concluded that the increase in inflammatory markers correlate especially PAPP-A in NSTE-ACS with the increase of cardiac bio markers

Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli.

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Rodriguez, Jose A; Orbe, Josune; Martinez de Lizarrondo, Sara; Calvayrac, Olivier; Rodriguez, Cristina; Martinez-Gonzalez, Jose; Paramo, Jose A

2008-01-01

Atherosclerosis is the common pathophysiological substrate of ischemic vascular diseases and their thrombotic complications. The unbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) has been hypothesized to be involved in the growth, destabilization, and eventual rupture of atherosclerotic lesions. Different MMPs have been assigned relevant roles in the pathology of vascular diseases and MMP-10 (stromelysin-2) has been involved in vascular development and atherogenesis. This article examines the pathophysiological role of MMPs, particularly MMP-10, in the onset and progression of vascular diseases and their regulation by pro-inflammatory stimuli. MMP-10 over-expression has been shown to compromise vascular integrity and it has been associated with aortic aneurysms. MMP-10 is induced by C-reactive protein in endothelial cells, and it is over-expressed in atherosclerotic lesions. Additionally, higher MMP-10 serum levels are associated with inflammatory markers, increased carotid intima-media thickness and the presence of atherosclerotic plaques. We have cloned the promoter region of the MMP-10 gene and studied the effect of inflammatory stimuli on MMP-10 transcriptional regulation, providing evidences further supporting the involvement of MMP-10 in the pathophysiology of atherothrombosis.

The modified pulse-spray method using Urokinase in subacute and chronic thrombotic arterial occlusion

International Nuclear Information System (INIS)

Kim, Youn Kil; Hahn, Seong Tae; Baek, Jee Hee; Kim, Choon Yul; Shinn, Kyung Sub

1996-01-01

To evaluate the effectiveness and safety of the modified pulse-spray method using Urokinase(UK) in subacute and chronic thrombotic arterial occlusion. Modified pulse-spray methods using UK were performed in seven patients with subacute (1 week-1month) to chronic (1month-5years) occlusive symptoms such as limb pain, claudication and impotence. Angiographic examination revealed thrombotic occlusion of the aorta, common iliac arteries, brachial arterio-venous hemodialysis graft and femoro-popliteal bypass graft. The patients underwent thrombolysis using modified pulse-spray and additional constant infusion of UK. In the presence of underlying stenosis or organized clots, balloon angioplasty or stent placement was performed. Complete lysis was obtained in five of seven patients. For initial lysis, the mean dose of UK was 420,000 units, and the mean modified pulse-spray time was 50 minutes. Mean total dose of UK and mean total time for complete lysis were 800,000 units and 161 minutes, respectively. Thrombolysis of the femoro-popliteal bypass graft failed due to severe occlusion of the distal anastomosis. Partial lysis was achieved in one patient with aorto-illac occlusion, but further thrombolysis was stopped due to bleeding at the puncture site. The modified pulse-spray method using UK is effective in treating subacute and chronic arterial thrombotic occlusion. It augments the speed, safety and efficacy of thrombolysis. When underlying stenosis or organized clots remain after thrombolysis, ballon angioplasty or stent placement would be helpful

Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid β-protein precursor abolishes its anti-thrombotic properties in vivo.

Science.gov (United States)

Xu, Feng; Davis, Judianne; Hoos, Michael; Van Nostrand, William E

2017-07-01

Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid β-protein precursor (AβPP) inhibit cerebral thrombosis. KPI domain-lacking forms of AβPP are abundant in brain. Regions of AβPP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of AβPP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo. To determine the extent of KPI function of AβPP in regulating cerebral thrombosis we generated a recombinant reactive center KPI R13I mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti-coagulant properties of wild-type and R13I mutant KPI were investigated in vitro. Cerebral thrombosis of wild-type, AβPP knock out and AβPP/KPI R13I mutant mice was evaluated in experimental models of carotid artery thrombosis and intracerebral hemorrhage. Recombinant mutant KPI R13I domain was ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit the clotting of plasma in vitro. AβPP/KPI R13I mutant mice were similarly deficient as AβPP knock out mice in regulating cerebral thrombosis in experimental models of carotid artery thrombosis and intracerebral hemorrhage. We demonstrate that the anti-thrombotic function of AβPP primarily resides in the KPI activity of the protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Complete resolution of transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease by defibrotide and plasma exchange.

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Beşişik, Sevgi Kalayoğlu; Oztürk, Gülistan Bahat; Calişkan, Yaşar; Sargin, Deniz

2005-03-01

Transplantation-associated thrombotic microangiopathy has been associated with significantly reduced survival following allogeneic bone marrow transplantation. We describe here the course of Transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease, and response to plasma exchange therapy. A 19-year-old male patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched brother for lymphoblastic lymphoma in the first complete remission. Transplantation-associated thrombotic microangiopathy was diagnosed 17 days after transplantation. At that time, neurological abnormalities were not present. Cyclosporin A (CsA) was discontinued. Hematological stabilization was recorded. On day +20, abdominal distention, painful hepatomegaly and ascites complicated the clinical picture. With a high hepatic venous pressure gradient (18mmH20), veno-occlusive disease of the liver was diagnosed and defibrotide was started, which resulted in a dramatic cessation of pain and increase in urinary output. However, transplantation-associated thrombotic microangiopathy-related symptoms progressed and plasma exchange was instituted, which resulted in worsening of veno-occlusive disease symptoms. He was referred to the Intensive Care Unit due to respiratory compromise and was intubated. Plasma exchange was continued in order after hemofiltration. In three days, fever resolved, hemofiltration could be stopped, and ventilator dependence ended. After 19 aphereses, serum LDH level returned to normal and schistocytes were minimal on microscopic examination of the blood film. Platelet count increase was more gradual. Plasma exchange was discontinued. On the 40th day of defibrotide, all symptoms related with veno-occlusive disease were resolved and defibrotide was stopped. We think that our case is important to establish the relation and management strategy of these two small vessel complications of HSCT.

Thrombocytosis distinguishes POEMS syndrome from chronic inflammatory demyelinating polyneuropathy.

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Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2015-10-01

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome may be mistaken for chronic inflammatory demyelinating polyneuropathy (CIDP). Differentiating the 2 entities is crucial, as there are major treatment implications. We compared platelet counts in 136 POEMS patients and 67 CIDP controls. Of the patients with POEMS, 53.7% had thrombocytosis, compared with 1.5% of those with CIDP (P < 0.0001). The median platelet count in patients with POEMS was 467,000/μl compared with 275,000/μl in those with CIDP (P < 0.0001). Thrombocytosis is a helpful indicator to prompt clinicians to consider the diagnosis of POEMS syndrome in patients who are thought to have CIDP, and is an important reminder of the increased risk of thrombotic events in POEMS syndrome. © 2015 Wiley Periodicals, Inc.

Diagnostic accuracy of guys Hospital stroke score (allen score) in acute supratentorial thrombotic/haemorrhagic stroke

International Nuclear Information System (INIS)

Zulfiqar, A.; Toori, K. U.; Khan, S. S.; Hamza, M. I. M.; Zaman, S. U.

2006-01-01

A consecutive series of 103 patients, 58% male with mean age of 62 year (range 40-75 years), admitted with supratentorial stroke in our teaching hospital were studied. All patients had Computer Tomography scan brain done after clinical evaluation and application of Allen stroke score. Computer Tomography Scan confirmed thrombotic stroke in 55 (53%) patients and haemorrhagic stroke in 48 (47%) patients. Out of the 55 patients with definitive thrombotic stroke on Computer Tomography Scan, Allen stroke score suggested infarction in 67%, haemorrhage in 6% and remained inconclusive in 27% of cases. In 48 patients with definitive haemorrhagic stroke on Computer Tomography Scan, Allen stroke score suggested haemorrhage in 60%, infarction in 11% and remained inconclusive in 29% of cases. The overall accuracy of Allen stroke score was 66%. (author)

Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis

DEFF Research Database (Denmark)

Bang, Casper N; Greve, Anders; Boman, Kurt

2012-01-01

Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS).......Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS)....

A case report: Cavitary infarction caused by pulmonary tumor thrombotic microangiopathy in a patient with pancreatic intraductal papillary mucinous neoplasm

Energy Technology Data Exchange (ETDEWEB)

Bae, Kyoung Kyg; Kwon, Woon Jung; Choi, Seong Hoon; Lee, Jong Hwa; Cha, Hee Jeong [Ulsan University Hospital, University of Ulsan School of Medicine, Ulsan (Korea, Republic of)

2015-08-15

Pulmonary tumor embolism is commonly discovered at autopsy, but is rarely suspected ante-mortem. Microangiopathy is an uncommon and distinct form of simple tumor pulmonary embolism. Here, we present a 52-year-old male with tumor thrombotic microangiopathy and pulmonary infarction, which might have originated from intraductal papillary mucinous tumor of the pancreas. Multiple wedge-shaped consolidations were found initially and aggravated with cavitation. These CT features of pulmonary infarction were pathologically confirmed to result from pulmonary tumor thrombotic microangiopathy.

Thyroid Dysfunction and Fibrin Network Structure: A Mechanism for Increased Thrombotic Risk in Hyperthyroid Individuals

NARCIS (Netherlands)

Hooper, J. M. W.; Stuijver, D. J. F.; Orme, S. M.; van Zaane, B.; Hess, K.; Gerdes, V. E.; Phoenix, F.; Rice, P.; Smith, K. A.; Alzahrani, S. H.; Standeven, K. F.; Ajjan, R. A.

2012-01-01

Context: Hyperthyroidism is associated with increased thrombosis risk, and fibrin clot structure determines susceptibility to vascular thrombotic events. Objective: Our objective was to investigate clot formation and lysis in hyperthyroidism using observational and interventional studies. Design: Ex

Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis

NARCIS (Netherlands)

Tick, L. W.; Kramer, M. H. H.; Rosendaal, F. R.; Faber, W. R.; Doggen, C. J. M.

2008-01-01

BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). OBJECTIVES: To determine the risk of PTS after DVT and to assess risk factors for PTS. METHODS: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk

Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

Science.gov (United States)

Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

2005-05-01

The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response.

A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

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Risa Yamada

2011-01-01

Full Text Available Thrombotic thrombocytopenia purpura (TTP caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA. Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE. In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

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Connie Slocum

2014-07-01

Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

Science.gov (United States)

Wu, Fang; Wang, Hong-Yan; Cai, Fan; Wang, Ling-Jie; Zhang, Feng-Ru; Chen, Xiao-Nan; Yang, Qian; Jiang, Meng-Hui; Wang, Xue-Feng; Shen, Wei-Feng

2015-01-20

Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

[Embolic stroke by thrombotic non bacterial endocarditis in an Antiphospholipid Syndrome patient].

Science.gov (United States)

Graña, D; Ponce, C; Goñi, M; Danza, A

2016-01-01

The antiphospholipid syndrome (APS) is an acquired thrombophilia, considered a systemic autoimmune disorder. We report a patient with APS who presented multiple cerebral infarcts (stroke) as a complication of a thrombotic non bacterial endocarditis. We review the literature focused on the physiological mechanism that produce this disease and its complications. Clinical features and their prognostic value and the different therapeutic options were also studied.

Emerging roles of eosinophils and eosinophil-derived lipid mediators in the resolution of inflammation

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Yosuke eIsobe

2012-08-01

Full Text Available Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programs that enable inflamed tissues to return to homeostasis. The mechanisms by which acute inflammation is resolved are of interest, and research in recent years has uncovered new endogenous anti-inflammatory and pro-resolving lipid mediators (i.e. lipoxins, resolvins, protectin, and maresin generated from polyunsaturated fatty acids (PUFAs. This review presents new insights into the cellular and molecular mechanisms of inflammatory resolution, especially the roles of eosinophils, and a series of omega-3 PUFA derived anti-inflammatory lipid mediators that they generate.

Is There a Role for Bioactive Lipids in the Pathobiology of Diabetes Mellitus?

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Undurti N. Das

2017-08-01

Full Text Available Inflammation, decreased levels of circulating endothelial nitric oxide (eNO and brain-derived neurotrophic factor (BDNF, altered activity of hypothalamic neurotransmitters (including serotonin and vagal tone and gut hormones, increased concentrations of free radicals, and imbalance in the levels of bioactive lipids and their pro- and anti-inflammatory metabolites have been suggested to play a role in diabetes mellitus (DM. Type 1 diabetes mellitus (type 1 DM is due to autoimmune destruction of pancreatic β cells because of enhanced production of IL-6 and tumor necrosis factor-α (TNF-α and other pro-inflammatory cytokines released by immunocytes infiltrating the pancreas in response to unknown exogenous and endogenous toxin(s. On the other hand, type 2 DM is due to increased peripheral insulin resistance secondary to enhanced production of IL-6 and TNF-α in response to high-fat and/or calorie-rich diet (rich in saturated and trans fats. Type 2 DM is also associated with significant alterations in the production and action of hypothalamic neurotransmitters, eNO, BDNF, free radicals, gut hormones, and vagus nerve activity. Thus, type 1 DM is because of excess production of pro-inflammatory cytokines close to β cells, whereas type 2 DM is due to excess of pro-inflammatory cytokines in the systemic circulation. Hence, methods designed to suppress excess production of pro-inflammatory cytokines may form a new approach to prevent both type 1 and type 2 DM. Roux-en-Y gastric bypass and similar surgeries ameliorate type 2 DM, partly by restoring to normal: gut hormones, hypothalamic neurotransmitters, eNO, vagal activity, gut microbiota, bioactive lipids, BDNF production in the gut and hypothalamus, concentrations of cytokines and free radicals that results in resetting glucose-stimulated insulin production by pancreatic β cells. Our recent studies suggested that bioactive lipids, such as arachidonic acid, eicosapentaneoic acid, and docosahexaenoic

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis

OpenAIRE

Sakthirajan, R.; Dhanapriya, J.; Dineshkumar, T.; Gopalakrishnan, N.; Murugan, S.; Balasubramaniyan, T.

2017-01-01

Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and ...

Deciphering the acylation pattern of Yersinia enterocolitica lipid A.

Science.gov (United States)

Reinés, Mar; Llobet, Enrique; Dahlström, Käthe M; Pérez-Gutiérrez, Camino; Llompart, Catalina M; Torrecabota, Nuria; Salminen, Tiina A; Bengoechea, José A

2012-01-01

Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS) lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2)-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the reduced activation of

Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis

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Carlos A. M. Silva

2018-02-01

Full Text Available The spectrum of clinical forms observed in leprosy and its pathogenesis are dictated by the host’s immune response against Mycobacterium leprae, the etiological agent of leprosy. Previous results, based on metabolomics studies, demonstrated a strong relationship between clinical manifestations of leprosy and alterations in the metabolism of ω3 and ω6 polyunsaturated fatty acids (PUFAs, and the diverse set of lipid mediators derived from PUFAs. PUFA-derived lipid mediators provide multiple functions during acute inflammation, and some lipid mediators are able to induce both pro- and anti-inflammatory responses as determined by the cell surface receptors being expressed, as well as the cell type expressing the receptors. However, little is known about how these compounds influence cellular immune activities during chronic granulomatous infectious diseases, such as leprosy. Current evidence suggests that specialized pro-resolving lipid mediators (SPMs are involved in the down-modulation of the innate and adaptive immune response against M. leprae and that alteration in the homeostasis of pro-inflammatory lipid mediators versus SPMs is associated with dramatic shifts in the pathogenesis of leprosy. In this review, we discuss the possible consequences and present new hypotheses for the involvement of ω3 and ω6 PUFA metabolism in the pathogenesis of leprosy. A specific emphasis is placed on developing models of lipid mediator interactions with the innate and adaptive immune responses and the influence of these interactions on the outcome of leprosy.

[Association between venous thrombosis and dyslipidemia].

Science.gov (United States)

García Raso, Aránzazu; Ene, Gabriela; Miranda, Carolina; Vidal, Rosa; Mata, Raquel; Llamas Sillero, M Pilar

2014-07-07

Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome. Copyright © 2013 Elsevier España, S.L. All rights reserved.

IgA Nephropathy and Thrombotic Microangiopathy

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Graciela De Rosa

2017-06-01

Full Text Available Introduction: Although the association between thrombotic microangiopathy (TMA and IgA nephropathy (IgAN is a known fact, its prevalence, pathogenesis and progression are not clear yet. Methods: A descriptive, retrospective study involving 12 patients with IgAN and TMA (IgAN-TMA was carried out; patients were diagnosed by a renal biopsy performed in our hospital in order to analyze clinicopathologic features. All the biopsy samples were processed for light microscopy and immunofluorescence. Results: The prevalence of patients with IgAN-TMA was 4.4% (12/274. The mean age was 33 and 58.3% of the subjects were men, showing, during diagnosis, mean systolic and diastolic blood pressure values of 171.3±53 mmHg and 97.5±19.8 mmHg, respectively. The average amount of protein in urine was 5.3 ± 3.7g/24 h and 8 patients had nephrotic- range proteinuria. Impairment of renal function was found in 11 patients, with a mean serum creatinine level of 7.2±4.7 mg/dL. No clinical or laboratory findings suggested thrombotic microangiopathy in any of the patients. The renal biopsy showed acute TMA with arteriolar fibrin thrombi in 75% of the subjects and ‘onion-skin-like’ chronic lesions with concentric intimal hyperplasia in 83.3% of them, which were associated with a high percentage of global glomerulosclerosis (72%, moderate tubular atrophy (38.6% and/or interstitial fibrosis (31.3%. In 91.7% of the cases, TMA was related to histological grade 5. Conclusions: The prevalence and significance of the relationship between IgAN and TMA pose the question of whether TMA is the cause or consequence of advanced stage IgAN. Several clinicopathologic studies have proved that TMA plays a major role in IgAN progression. The connection of TMA with creatinine serum and proteinuria levels seems to support this conclusion. While systemic TMA usually affects multiple organs, in these cases, the kidney was the only one compromised. Endothelial injury and the

Thrombotic thrombocytopenic purpura and deep vein thrombosis as the presenting manifestations of systemic lupus erythematosus: A case report and review of literature

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Mohammad AH Mashhadi

2011-01-01

Full Text Available Systemic lupus erythematosus (SLE, is sometimes complicated by the rare fatal syndrome, Thrombotic thrombocyto-penic purpura (TTP, but the occurrence of TTP as the initial manifestation of SLE is very rare. Since they have similar-ities in some features, the differentiation of TTP from SLE may be missed. SLE patients are also more prone to throm-botic events. Here we report a case with TTP and deep vein thrombosis as the presenting symptoms of SLE.

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

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Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Chong, Yee-Song; Yu, Lian; Gao, Jian-Qing

2017-01-01

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE 2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

The association of JAK2V617F mutation and leukocytosis with thrombotic events in essential thrombocythemia.

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Hsiao, Hui-Hua; Yang, Ming-Yu; Liu, Yi-Chang; Lee, Ching-Ping; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Lin, Sheng-Fung

2007-11-01

The Janus kinase 2 mutation, JAK2 (V617F), and megakaryocytic mutations, MPL (W515L/K), have been identified and correlated with a subtype of essential thrombocythemia (ET) patients. We investigated the frequency of mutations in ET patients and analyzed the relationship with their clinical features. Fifty-three ET patients were enrolled in the study. The amplification refractory mutation system was applied for the mutation survey of the JAK2V617F, while the polymerase chain reaction with sequencing was used for the mutation survey of MPLW515L/K. Thirty-five (66%) patients harboring the JAK2 (V617F) mutation, including 3 homozygous and 32 heterozygous changes, but no MPLW515L/K mutation, were found. During follow-up, 17 (32.1%) patients suffered from documented thrombotic events, with 15 having JAK2V617F mutations. Statistical analysis showed that patients with the JAK2 mutation had significantly higher leukocytes, hemoglobin level, and thrombotic event (p = 0.043, p = 0.001, and p = 0.029, respectively). Thrombotic events were also significantly correlated with leukocytosis and older age. The JAK2V617F mutation was noted in a certain population of ET patients and correlated with leukocytosis, high hemoglobin level, and thrombosis. Therefore, detection of the JAK2V617F mutation can affect not only the diagnosis, but also the management of ET patients.

Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease

DEFF Research Database (Denmark)

Lidegaard, O

1995-01-01

OBJECTIVE: To assess the risk of developing cerebral thromboembolism among pregnant women and among fertile women with hypertension, migraine, diabetes, and previous thrombotic disease, and to investigate the interaction of these risk factors with the use of oral contraceptives. DESIGN...... multivariate analysis, pregnancy implied an odds ratio (OR) for a cerebral thromboembolic attack of 1.3 (nonsignificant), diabetes an OR of 5.4 (P hypertension an OR of 3.1 (P ... thromboembolism whereas diabetes, hypertension, migraine and past thromboembolic events increased the risk of cerebral thromboembolism significantly. Women with these increased thrombotic risks should use oestrogen-containing oral contraceptives only after careful considerations of the risks, if at all....

Exogenous lipid pneumonia

International Nuclear Information System (INIS)

Bernasconi, A.; Gavelli, G.; Zompatori, M.; Galleri, C.; Zanasi, A.; Fabbri, M.; Bazzocchi, F.

1988-01-01

Exogenous lipid pneumonia (ELP) is caused by the aspiration of animal, vegetal or, more often, mineral oils. Even though it may also be acute, ELP is most frequently a chronic disease, affecting people with predisposing factors, such as neuromuscular disorders, structural abnormalities and so on; very often exogenous lipid pneumonia is found in tracheotomized patients. The pathology of lipid pneumonia is a chronic inflammatory process evolving in foreign-body-like reaction, and eventually in ''end-stage lung'' condition. Clinically, most patients are asymptomatic; few cases only present with cough, dyspnea and chest pain. Eight cases of ELP, studied over the past 3 years, are described in this paper. All the patients were examined by chest radiographs and standard tomograms; 3 patients underwent CT. X-ray features were mono/bilateral consolidation of the lower zones, with air bronchogram and variable reduction in volume. CT density was not specific for fat tissue. In all cases the diagnosis was confirmed at biopsy. In 5 patients, followed for at least one year, clinical-radiological features showed no change. Thus, complications of ELP (especially malignant evolution) could be excluded. The authors conclude that lipid pneumonia must be considered in differential diagnosis of patients with history of usage of oils and compatible X-ray findings. The usefulness of an accurate follow-up is stressed

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

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Mahe J

2013-08-01

Full Text Available Julien Mahe,1 Aurélie Meurette,2 Anne Moreau,3 Caroline Vercel,2 Pascale Jolliet1,4 1Clinical Pharmacology Department, Institute of Biology, University Hospital, Nantes, France; 2Clinical Nephrology and Immunology Department, University Hospital, Nantes, France; 3Laboratory of Pathology, University Hospital, Nantes, France; 4EA 4275 Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France Abstract: Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. Keywords: thrombotic microangiopathy, interferon beta, hemolytic-uremic syndrome, antiangiogenic activity

A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis

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Arimoto M

2012-03-01

Full Text Available Miyoko Arimoto1, Yutaka Komiyama2, Fumiko Okamae1, Akemi Ichibe1, Setsuko Teranishi1, Hirohiko Tokunaga1, Keiko Nakaya3, Michie Fujiwara3, Manabu Yamaoka4, Shuji Onishi4, Rie Miyamoto5, Naoto Nakamichi5, Shosaku Nomura51Blood Transfusion Unit, Kansai Medical University Takii Hospital, 2Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 3Clinical Medical Technology Unit, Kansai Medical University Takii Hospital, 4Blood Transfusion Unit, Kansai Medical University Hirakata Hospital, 5First Department of Internal Medicine, Kansai Medical University, Moriguchi, JapanAbstract: Thrombotic thrombocytopenic purpura (TTP is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, acute pancreatitis, plasma exchange

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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Wen Liang

Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

A Case of Systemic Lupus Erythematosus developing Two years after Remission of Thrombotic Thrombocytopenic Purpura

Science.gov (United States)

Myung, Seung-Jae; Yoo, Bin; Lee, Kyoo-Hyung; Yoo, Mi-Ran; Choi, Seung-Won; Yoo, Eun-Sil; Chi, Hyun-Sook; Moon, Hee-Bom

1996-01-01

We describe a 17-year-old male who presented with thrombotic thrombocytopenic purpura (TTP) and 2 years thereafter developed central nervous system lupus and nephritis. The association of TTP and systemic lupus erythematosus has been described, but the unusual sequence and chronological separation is very rare. PMID:8854658

Ambient particulate air pollution from vehicles promotes lipid peroxidation and inflammatory responses in rat lung.

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Pereira, C E L; Heck, T G; Saldiva, P H N; Rhoden, C R

2007-10-01

Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 +/- 0.51;P-20: 5.01 x 105 +/- 0.81; P air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

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Chase W Kessinger

Full Text Available Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT will develop the post-thrombotic syndrome (PTS. Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice. Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1, tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs, and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

Science.gov (United States)

Kessinger, Chase W; Kim, Jin Won; Henke, Peter K; Thompson, Brian; McCarthy, Jason R; Hara, Tetsuya; Sillesen, Martin; Margey, Ronan J P; Libby, Peter; Weissleder, Ralph; Lin, Charles P; Jaffer, Farouc A

2015-01-01

Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

Thrombotic thrombocytopenic purpura (TTP or Moschowitz syndrome: a true hematologic emergency

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Deborah Melis

2012-01-01

Full Text Available Introduction: Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy caused by congenital or inherited disorders involving the processing of the ultra-large forms of von Willebrand factor. As a result, platelet-rich microthrombi form in the small arterial vessels of various organs, particularly those of the brain, heart, and kidneys. The idiopathic autoimmune form of TTP is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, various disseminated malignancies, and drugs. If not promptly treated, TTP is associated with high mortality, making it a true medical emergency. Materials and methods: The article is based on a review of the literature published between January and October of 2009. Its aim is to clarify the diagnosis, treatment, and follow-up of TTP. Results: Diagnostic criteria include the presence of microangiopathic hemolytic anemia associated with thrombocytopenia in the absence of other obvious causes. Assays of ADAMTS13 activity and titration of acquired antibodies against this enzyme are indicated in the follow-up of disease and as prognostic indicators. Treatment centers around daily plasma exchange associated with immunosuppressant drug therapy, particularly steroids and more recently the monoclonal anti-CD20 antibody rituximab. Discussion: Despite improved treatment, TTP is still associated with significant mortality (10—20%, particularly when plasma exchange is initiated late. Relapse also occurs in a substantial proportion of patients (10—40% although the frequency of this outcome may be reduced by rituximab therapy.

Deciphering the acylation pattern of Yersinia enterocolitica lipid A.

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Mar Reinés

Full Text Available Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis.

Science.gov (United States)

Sakthirajan, R; Dhanapriya, J; Dineshkumar, T; Gopalakrishnan, N; Murugan, S; Balasubramaniyan, T

2017-01-01

Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis

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R Sakthirajan

2017-01-01

Full Text Available Rheumatoid arthritis (RA is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.

Acute Thrombotic Coronary Occlusion in a Patient with Coronary Artery Anomaly

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Beganu Elena

2017-09-01

Full Text Available Patients with coronary artery anomalies are more susceptible to develop acute thrombotic coronary occlusions due to the abnormal anatomy of these arteries and the disturbance of the pathophysiological mechanisms that lead to an accelerated atherosclerosis development. The following article presents the case of a 64-year-old female patient diagnosed with anterior ST-segment elevation myocardial infarction. The patient underwent primary percutaneous coronary intervention, which revealed the absence of the right coronary artery and separated origins of the left anterior descending artery and the left circumflex artery from the aorta.

Evaluation of anti-inflammatory effect of statins in chronic periodontitis

OpenAIRE

Snophia Suresh; Satya Narayana; P Jayakumar; Uma Sudhakar; V Pramod

2013-01-01

Objectives: Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Materials and Methods: Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of De...

Cholesterylbutyrate Solid Lipid Nanoparticles as a Butyric Acid Prodrug

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Alessandro Mauro

2008-02-01

Full Text Available Cholesterylbutyrate (Chol-but was chosen as a prodrug of butyric acid.Butyrate is not often used in vivo because its half-life is very short and therefore too largeamounts of the drug would be necessary for its efficacy. In the last few years butyric acid'santi-inflammatory properties and its inhibitory activity towards histone deacetylases havebeen widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs, whose lipid matrixis Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and totest its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsionmethod; their average diameter is on the order of 100-150 nm and their shape is spherical.The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer celllines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity wasevaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In thereview we will present data on Chol-but SLNs in vitro and in vivo experiments, discussingthe possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic andchronic inflammatory diseases.

Correlation of oxidative stress and inflammatory markers with the ...

African Journals Online (AJOL)

Background: Reactive oxygen species have been shown to mediate inflammatory process and may be involved in lipid peroxidation. Methods:This study evaluates superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, C- reactive protein and fibrinogen in the serum of patients with sickle cell disease ...

Biologic activity of porphyromonas endodontalis complex lipids.

Science.gov (United States)

Mirucki, Christopher S; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E; Clark, Robert B; Nichols, Frank C

2014-09-01

Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis and evaluate their capacity to promote proinflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Constituent lipids of both organisms were fractionated by high-performance liquid chromatography and were structurally characterized using electrospray mass spectrometry or electrospray-mass spectrometry/mass spectrometry. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. P. endodontalis total lipids were shown to promote tumor necrosis factor alpha secretion from RAW 264.7 cells, and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells, but osteoblast differentiation in culture was inhibited and appeared to be dependent on Toll-like receptor 2 expression. These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate

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Kabagambe Edmond K

2009-10-01

Full Text Available Abstract Background Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2 gene polymorphisms (rs12255372 and rs7903146, consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate. Methods Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 ± 16 y were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes. Results Under the additive or dominant model, there were no significant differences (P > 0.05 in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-α and MCP-1 across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (P Conclusion Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

Science.gov (United States)

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

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Michael J. Haley

2017-10-01

Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study.

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Heiko Rühl

Full Text Available The increased thrombotic risk of oral contraceptives (OC has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC. To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use.Blood samples were collected prospectively from healthy women (n = 21 before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA technology. Thrombin generation markers and other hemostasis parameters were measured additionally.All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003. Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur.In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk.

The association between inflammatory markers and obesity-related factors in Tehranian adults: Tehran lipid and glucose study.

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Faam, Bita; Zarkesh, Maryam; Daneshpour, Maryam Sadat; Azizi, Fereidoun; Hedayati, Mehdi

2014-08-01

Obesity considered being a low-grade inflammatory disease. The objective of this study was to examine the association between inflammatory markers (IM) including C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and homocystein (Hcy) and obesity-related factors (e.g. BMI, waist, hip) in adult participants of Tehran lipid and glucose study (TLGS). In this cross-sectional study, 352 individuals (132 men and 220 women), age ≥19 years, were randomly recruited from participants of TLGS population. The serum levels of hs-CRP, IL-6, Hcy were determined using the enzyme linked immunosorbent assay (ELISA) method. Variables were compared by sample t-test. Bivariate linear correlation was estimated using Pearson's correlation coefficient. Linear regression analysis was applied to investigate the association between IMs and anthropometric and biochemical variables. The mean age of participants was 46.1±16.1 years. abdominal obesity was present in 199(56.5%) individuals. levels of hs-CRP and IL-6 increased in the abdominally obese group (1507±3.3 vs. 577.8±4.3 ng/ml P<0.001) (3.6±3.3 vs. 1.9±3.8 pg/ml P< 0.001), and in the same group, the best predictors for hs-CRP, IL-6 and Hcy were waist (WC), waist to height ratio (WHtR) and wrist respectively; hip and WHtR were the best predictors for Hcy and hs-CRP in the normal group. A linear augmentation in hs-CRP and IL-6 levels was observed in association with obesity categorizes. This study provides evidence that abdominally obese individuals had higher levels of IMs. Wrist, waist and WHtR were the best predictors for Hcy, hs-CRP and IL-6 respectively in this group.

Convergent synthesis of a deuterium-labeled serine dipeptide lipid for analysis of biological samples.

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Dietz, Christopher; Clark, Robert B; Nichols, Frank C; Smith, Michael B

2017-05-30

Bacterial serine dipeptide lipids are known to promote inflammatory processes and are detected in human tissues associated with periodontal disease or atherosclerosis. Accurate quantification of bacterial serine lipid, specifically lipid 654 [((S)-15-methyl-3-((13-methyltetradecanoyl)oxy)hexadecanoyl)glycyl-l-serine, (3S)-l-serine] isolated from Porphyromonas gingivalis, in biological samples requires the preparation of a stable isotope internal standard for sample supplementation and subsequent mass spectrometric analysis. This report describes the convergent synthesis of a deuterium-substituted serine dipeptide lipid, which is an isotopically labeled homologue that represents a dominant form of serine dipeptide lipid recovered in bacteria. Copyright © 2017 John Wiley & Sons, Ltd.

Exudative Retinal Detachment Treatment in a Patient with Thrombotic Thrombocytopenic Purpura

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Magali Sampo

2016-02-01

Full Text Available Purpose: We report a case of unilateral exudative retinal detachment in a patient with thrombotic thrombocytopenic purpura (TTP, without associated hypertension, successfully treated with plasmapheresis. Case Report: A 46-year-old woman with a medical history of TTP presented with unilateral exudative retinal detachment. Biological and radiological assessment eliminated other causes of exudative retinal detachment, including hypertension. Plasma exchange was performed, followed by a rapid improvement in visual acuity and total disappearance of serous detachment. Conclusion: Exudative unilateral retinal detachment is a rare complication of TTP and can be successfully treated by plasma exchange.

Effects of short-term consumption of bread obtained by an old Italian grain variety on lipid, inflammatory, and hemorheological variables: an intervention study.

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Sofi, Francesco; Ghiselli, Lisetta; Cesari, Francesca; Gori, Anna Maria; Mannini, Lucia; Casini, Alessandro; Vazzana, Concetta; Vecchio, Vincenzo; Gensini, Gian Franco; Abbate, Rosanna; Benedettelli, Stefano

2010-06-01

The aim of this study was to evaluate the influence of short-term dietary intake of bread obtained by a selected variety of old grain grown in Tuscany, Italy on some parameters related to the atherosclerotic process. Twenty healthy subjects (median age, 39.5 years) followed for 10 weeks a diet containing bread (150 g/day) made from the test grain (test period) and for the same period a diet containing commercially available bread of the same quantity (control period). Lipid, inflammatory, and hemorheological profiles before and after dietary intervention were evaluated. The test period showed a significant (P bread obtained from an old grain variety seems to impose a favorable status with regard to lower circulating levels of markers of atherosclerosis.

Effects of atorvastatin and rosuvastatin on blood lipids, platelet ...

African Journals Online (AJOL)

Blood lipids, PAR, inflammatory factors and carotid atherosclerotic plaque were recorded and compared. Results: Following treatment, total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower (p < 0.05) than in the control group, while high ...

Apolipoprotein M in lipid metabolism and cardiometabolic diseases

DEFF Research Database (Denmark)

Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

2015-01-01

: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

Drinking orange juice increases total antioxidant status and decreases lipid peroxidation in adults.

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Foroudi, Shahrzad; Potter, Andrew S; Stamatikos, Alexis; Patil, Bhimanagouda S; Deyhim, Farzad

2014-05-01

Cardiovascular disease (CVD) is the leading cause of death in the world and is the primary cause of mortality among Americans. One of the many reasons for the pathogenesis of CVD is attributed to eating diets high in saturated fat and refined carbohydrates and low in fruits and vegetables. Epidemiological evidence has supported a strong association between eating diets rich in fruits and vegetables and cardiovascular health. An experiment was conducted utilizing 24 adults with hypercholesterolemia and hypertriglyceridemia to evaluate the impact of drinking 20 fl oz of freshly squeezed orange juice daily for 90 days on blood pressure, lipid panels, plasma antioxidant capacity, metabolic hormones, lipid peroxidation, and inflammatory markers. Except for addition of drinking orange juice, subjects did not modify their eating habits. The findings suggested that drinking orange juice does not affect (P>.1) blood pressure, lipid panels, metabolic hormones, body fat percentage, or inflammatory markers. However, total plasma antioxidant capacity was significantly increased (Pjuice consumption. Drinking orange juice may protect the cardiovascular system by increasing total plasma antioxidant status and by lowering lipid peroxidation independent of other cardiovascular risk markers evaluated in this study.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

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Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

Young Ischemic Stroke as Presentation of Thrombotic Thrombocytopenic Purpura: A Case Report

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Ahmad Najib Azmi

2017-12-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a rare disorder with an estimated incidence of 3 - 7/1,000,000. It is an autoimmune disorder characterized by fever, neurological signs, microangiopathic hemolytic anemia, thrombocytopenia and renal failure. This case report will describe a young lady who presented with acute middle cerebral artery infarct and was subsequently diagnosed to have TTP. Therapeutic plasma exchange (TPE did not improve the neurological deficit. This case highlights the importance of recognizing TTP as a possible differential diagnosis in young onset stroke.

Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

International Nuclear Information System (INIS)

Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

2011-01-01

Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

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Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

Trichinella Nativa Outbreak With Rare Thrombotic Complications Associated With Meat From a Black Bear Hunted in Northern Ontario.

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Dalcin, Daniel; Zarlenga, Dante S; Larter, Nicholas C; Hoberg, Eric; Boucher, Daniel A; Merrifield, Samuel; Lau, Rachel; Ralevski, Filip; Cheema, Karamjit; Schwartz, Kevin L; Boggild, Andrea K

2017-05-15

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have not been previously associated with Trichinella nativa infection. Patient interviews and medical chart reviews were conducted on 10 men who became ill following consumption of a common source of black bear meat. Trichinella serology on patient sera as well as polymerase chain reaction (PCR) and larval identification of the meat samples was conducted. All 10 exposed individuals developed an acute illness clinically compatible with trichinellosis, characterized by fever, abdominal pain, and diarrhea, along with eosinophilia ranging from 0.9 × 109/L to 6.1 × 109/L. Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-elevation myocardial infarction and sinus venous tract thrombosis occurred as a complication of trichinellosis in 2 patients. Acute serology was nonreactive in all patients, though convalescent serology was reactive in 6 of 8 (75%) patients for whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and was corroborated by microscopic larval identification. We report a 100% attack rate of T. nativa from bear meat among those who were exposed, and demonstrate that this species can cause serious thrombotic complications of trichinellosis in humans. Education of hunters and the public regarding the importance of proper preparation of wild game prior to ingestion is warranted. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

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Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

2016-12-01

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo.

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Kramkowski, K; Leszczynska, A; Przyborowski, K; Kaminski, T; Rykaczewska, U; Sitek, B; Zakrzewska, A; Proniewski, B; Smolenski, R T; Chabielska, E; Buczko, W; Chlopicki, S

2016-01-01

The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery. Sodium nitrite (NaNO2, 0.17 mmol/kg twice daily for 3 days, p.o) was administered with or without one of the XOR-inhibitors: allopurinol (ALLO) and febuxostat (FEB) (100 and 5 mg/kg, p.o., for 3 days). Nitrite treatment (0.17 mmol/kg), which was associated with a significant increase in NOHb, nitrite/nitrate plasma concentration, resulted in a substantial decrease in thrombus weight (TW) (0.48 ± 0.03 mg vs. vehicle [VEH] 0.88 ± 0.08 mg, p < 0.001) without a significant hypotensive effect. The anti-thrombotic effect of nitrite was partially reversed by FEB (TW = 0.63 ± 0.06 mg, p < 0.05 vs. nitrites), but not by ALLO (TW = 0.43 ± 0.02 mg). In turn, profound anti-platelet effect of nitrite measured ex vivo using collagen-induced whole-blood platelet aggregation (70.5 ± 7.1% vs. VEH 100 ± 4.5%, p < 0.05) and dynamic thromboxaneB2 generation was fully reversed by both XOR-inhibitors. In addition, nitrite decreased plasminogen activator inhibitor-1 concentration (0.47 ± 0.13 ng/ml vs. VEH 0.62 ± 0.04 ng/ml, p < 0.05) and FEB/ALLO reversed this effect. In vitro the anti-platelet effect of nitrite (1 mM) was reversed by FEB (0.1 mM) under hypoxia (0.5%O2) and normoxia (20%O2). Nitrite treatment had no effect on coagulation parameters. In conclusion, the nitrite-induced anti-platelet effect in rats in vivo is mediated by XOR, but XOR does not fully account for the anti-thrombotic effects of nitrite.

Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

OpenAIRE

Shoeb, Mohammad; Ramana, Kota V

2011-01-01

Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of...

Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

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Soronen Jarkko

2012-04-01

Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

Plasma exchange in Immunoglobulin A nephropathy with thrombotic microangiopathy and acute cortical necrosis

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P Doddi

2016-01-01

Full Text Available A 25-year-old female presented with decreased urine output, deranged renal function, thrombocytopenia, and hemolytic anemia. Kidney biopsy was consistent with thrombotic microangiopathy with acute cortical necrosis and Immunoglobulin A nephropathy (IgAN. Hemolytic anemia, thrombocytopenia and urine output improved after five sessions of plasma exchange. Renal function showed a delayed recovery and serum creatinine normalized by 3 months. This is first case of successful use of plasma exchange in hemolytic uremic syndrome with cortical necrosis associated with IgAN.

Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase

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Hugo C Castro Faria Neto

2005-03-01

Full Text Available Platelet-activating factor (PAF is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH, a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation.

Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis

DEFF Research Database (Denmark)

Ma, Liqun; Zhong, Jian; Zhao, Zhigang

2011-01-01

Activation of transient receptor potential vanilloid type-1 (TRPV1) channels may affect lipid storage and the cellular inflammatory response. Now, we tested the hypothesis that activation of TRPV1 channels attenuates atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) but not Apo...

Effect of anti-gut inflammatory agent on insulin resistance and lipid ...

African Journals Online (AJOL)

Purpose: To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different ... insulin and the curve of glucose tolerance test (GTT) in mice fed LFD, HFD or HFC diet were not affected by ... diabetes, the extent to which gut inflammation .... and homeostasis of glucose in diet-induced.

Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

Science.gov (United States)

Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

2015-02-01

De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

Awareness of antiplatelet resistance in patient with repeated episodes of thrombotic events

Science.gov (United States)

Dalimunthe, N. N.; Hamonangan, R.; Antono, D.; Prasetya, I.; Rusdi, L.

2018-03-01

Antiplatelet has been the cornerstones management of acute coronary syndrome. However, numbers of patients on these agents had episodes of adverse cardiovascular events. A 65-year-old woman post cardiac coronary bypass surgery on dual antiplatelet therapy, Aspirin, and Clopidogrel underwent several episodes of thrombotic events despite good adhered to thedailyantiplatelet regimen.These recurrent events had led to clinical suspicious of antiplatelet resistance. Platelet function test was performed which indicates a poor platelet response to Clopidogrel. Clopidogrelwas discontinued and Ticagrelor was prescribed together with Aspirin. During two months of follow up, there is no episode of chest discomfort.

Production of vegetable oil blends and structured lipids and their effect on wound healing

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Juliana Neves Rodrigues Ract

2015-06-01

Full Text Available Two oil blends (sunflower/canola oils 85/15 (BL1 and canola/linseed oils 70/30 (BL2, were prepared and enzymatically interesterified to be applied to surgically-induced wounds in rats. Following surgery, the animals were submitted to the Treatment with Physiological Saline (TPS (control group, Blends (TBL, and Structured Lipids (TSL. The control group (TPS received physiological saline solution for 15 days. In TBL, BL1 was administered during the inflammation phase (days 0-3 and BL2 in the tissue formation and remodeling phase (days 4-15. In TSL, Structured Lipid 1 (SL1 and Structured Lipid 2 (SL2 were used instead of BL1 and BL2, respectively. The aim of this study was to compare wound closure evolution among rats treated with the blends or structured lipids versus control rats treated with physiological saline. The wound healing process was evaluated by measuring the wound areas along the treatments and the concentrations of cytokines. An increase in the areas of wounds treated with the blends and structured lipids in the inflammatory phase was observed, followed by a steeper closure curve compared to wounds treated with physiological saline. The changes observed during the inflammatory phase suggest a potential therapeutic application in cutaneous wound healing which should be further investigated.

A 3-year follow-up of a patient with acute renal failure caused by thrombotic microangiopathy related to antiphospholipid syndrome: case report.

Science.gov (United States)

Zhou, X-J; Chen, M; Wang, S-X; Zhou, F-D; Zhao, M-H

2017-06-01

Background Microvascular manifestations of antiphospholipid antibody syndrome in the kidneys include acute renal failure, thrombotic microangiopathy and hypertension. Therapy has been largely empiric. Case report A 49-year-old Chinese man presented with anuric acute renal failure without abundant proteinuria and heavy haematuria, but markedly low levels of urinary sodium, potassium and chlorine upon admission. On day 1 of hospitalization, his thrombocytopenia, anaemia and renal failure showed rapid progression. The presence of lupus anticoagulant and vascular ischaemia of the small vessels in renal arteriography were also observed. Anticoagulants, continuous renal replacement therapy, glucocorticoids and six sessions of plasma exchange were started. After the fourth plasma exchange (on day 20), his urine output increased and began to normalize. On day 25, haemodialysis was stopped and his general condition gradually improved. A renal biopsy was subsequently performed, and the histopathological diagnosis was thrombotic microangiopathy due to antiphospholipid antibody syndrome. A further 3-year follow-up showed that his haemoglobin level, platelet count and serum creatinine were within the normal range, with stable blood pressure. Conclusion Treatment modalities such as anticoagulation, immunosuppression and plasma exchange are likely to be necessary when severe acute renal failure combined with thrombotic microangiopathy present in nephropathy of antiphospholipid antibody syndrome.

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease

DEFF Research Database (Denmark)

Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark

2017-01-01

and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially...... changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD....

Preparation and biodistribution of 99Tcm-lomefloxacin in inflammatory model mice

International Nuclear Information System (INIS)

Liu Jianfeng; Han Jiankui; Zhang Chao; Hou Guihua

2009-01-01

Objective: The study of 99 TC m -ciprofloxacin, a fluoroquinolones antibiotic, as a tracer for infection and inflammation imaging has been reported. The aim of this study was to investigate the radio-labeling and biodistribution of lomefloxacin (fluoroquinolones analogue) as an inflammatory imaging agent. Methods: 99 TC m -lomefloxacin was prepared and it underwent quality control with thin layer chromatography (TLC). The different labeling conditions were compared. The radiochemical purity, labeling efficiency, stability and lipid/water partition coefficient of 99 TC m -lomefloxacin were measured. The binding activities of 99 TC m -lomefloxacin with Staphylococci aureus (S. aureus)in vitro were tested. 99 TC m -lomefloxacin was in-ieeted through tail vein in the S. aureus-induced inflammatory model mice. The mice were sacrificed and their blood. inflammatory muscles. major organs were taken out at different time after tracer inieetion. Then the radioactivity count of these samples was measured to observe biodistribution. Whole-body radioauto-graphic images were obtained with storage phosphor screen system. Variance analysis using Concise Statis-tics 10.3 software was performed. Results: 99 TC m -lomefloxacin was lipid-soluble with labeling efficiency of 97.5%. The radiochemieal purity was more than 95% at 6 h after storing in room temperature. In vitro test 99 TC m -lomefloxacin showed good binding characteristic with S. auaresu and was positively correlated with the colony number of S. aureus. The highest binding appeared at 1 h. In vivo 99 TC 5 m-lomefloxacin apparently accumulated in inflammatory tissues at 2 h after tracer injection with the uptake ratio of 4.07 ± 1.05 in inflammatory muscles to control muscles. Whole-body autoradiography showed that all inflammation foci were visualized. Conclusion: 99 TC m -lomefloxacin may be a novel potential agent for inflammatory imaging. (authors)

The predictive effect of inflammatory markers and lipid accumulation product index on clinical symptoms associated with polycystic ovary syndrome in nonobese adolescents and younger aged women.

Science.gov (United States)

Tola, Esra Nur; Yalcin, Serenat Eris; Dugan, Nadiye

2017-07-01

The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. A total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMIpredictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular mechanism of intracellular lipid accumulation: Suppressive effect of PycnogenolR in liver cells

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Shoichiro Ikuyama

2013-09-01

Full Text Available ABSTRACTCells are physiologically ready to accumulate lipids such as triacylglycerides in the cytoplasm.Five classes of perilipin (PLIN family proteins are known to be involved in the process of intracellular lipid accumulation. PLIN2 is expressed ubiquitously including adipocytes, hepatocytes and macrophages. Over-expression of PLIN2 is demonstrated in the lesions of fatty liver diseases and atherosclerosis. Suppression of PLIN2 expression prevents from developing these pathological conditions in animal models, suggesting that PLIN2 could be a therapeutic target molecule for excessive intracellular lipid accumulation which leads to various metabolic derangements. The PLIN2 gene promoter has two important cis-acting elements in close proximity:AP-1 element which mediates inflammatory signals and PPRE which mediates free fatty acid effect. In NMuLi mouse liver cells, FFA such as oleic acid requires both functional AP-1 and PPRE simultaneously to stimulate the promoter activity, indicating the presence of intimate interaction of inflammatory and metabolic signals on this gene. PycnogenolR, French maritime pine bark extracts, suppressed the oleic acid-induced PLIN2 expression and lipid accumulation in NMuLi cells. We found that PycnogenolR did not suppress the PLIN2 promoter activity or AP-1 binding to DNA. Instead, PycnogenolRfacilitates the PLIN2 mRNA degradation, leading to suppression of lipid accumulation. This effect seems to be independent of antioxidant effect of PycnogenolR.We raise the idea that PLIN2 is a putative target molecule for prevention of pathological condition induced by excessive lipid accumulation, and this class of natural compounds could be putative therapeutic modalities.Key words: PycnogenolR, lipid droplet, perilipin, fatty liver disease

Excellent long-term results with iliac stenting in local anesthesia for post-thrombotic syndrome

DEFF Research Database (Denmark)

Klitfod, Lotte; Just, Sven; Foegh, Pia

2015-01-01

BACKGROUND: Only 20% of iliac veins will recanalize on anticoagulation (AC) treatment alone and may, therefore, develop venous obstruction after iliofemoral deep venous thrombosis (DVT). A considerable number of these patients will suffer from post-thrombotic syndrome (PTS) leading to impaired qu...... stent was 89% (17/19) and 16 patients (84 %) had almost or total symptom relief at follow-up. CONCLUSION: Endovascular stenting of iliac obstruction in local anesthesia is minimally invasive and shows excellent long-term outcomes for patients suffering from PTS....

Clinical trial: marine lipid suppositories as laxatives.

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Ormarsson, Orri Thor; Geirsson, Thormodur; Bjornsson, Einar Stefan; Jonsson, Tomas; Moller, Pall; Loftsson, Thorsteinn; Stefansson, Einar

2012-09-01

Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials.

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

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Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Inflammatory Markers and Clustered Cardiovascular Disease Risk Factors in Danish Adolescents

DEFF Research Database (Denmark)

Bugge, Anna; El-Naaman, Bianca; McMurray, Robert G

2012-01-01

Aims: To evaluate the associations between inflammatory markers and clustering of cardiovascular disease (CVD) risk factors, and to examine how inflammatory markers and CVD risk are related to fatness and cardiorespiratory fitness (VO(2peak)) in adolescents. Methods: Body mass and height, skinfolds...... and blood pressure of 413 adolescents (mean age 13.4 ± 0.3 years) were measured. Circulating fasting levels of glucose, insulin, lipids, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)α, soluble TNF receptor-1 (sTNFR1), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1Ra) were...

Nutraceuticals in lipid-lowering treatment: a narrative review on the role of chitosan.

Science.gov (United States)

Patti, Angelo Maria; Katsiki, Niki; Nikolic, Dragana; Al-Rasadi, Khalid; Rizzo, Manfredi

2015-05-01

Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids, lipoproteins, blood pressure, glucose, and insulin levels and their anti-inflammatory and anti-oxidant effects are documented. However, larger, prospective clinical trials are required to confirm such benefits. Such treatments may be recommended when lipid-lowering drugs are neither indicated nor tolerated as well as in order to achieve therapeutic targets and/or overcome residual CV risk. © The Author(s) 2014.

The role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids

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Gijs eKooij

2012-04-01

Full Text Available ATP-binding cassette (ABC transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB. These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS. Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within the brain. Importantly, recent data indicate that endogenous substrates for ABC transporters may include inflammatory mediators, such as prostaglandins, leukotrienes, cytokines, chemokines and bioactive lipids, suggesting a potential role for ABC transporters in immunological responses, and more specifically in inflammatory brain disorders, such as multiple sclerosis (MS. In this review, we will give a comprehensive overview of recent findings that illustrate this novel role for ABC transporters in neuro-inflammatory processes. Moreover, we will provide first insights into underlying mechanisms and focus on the importance for bioactive lipids, in particular platelet-activating factor (PAF, herein. A thorough understanding of these events may form the basis for the development for selective treatment modalities to dampen the neuro-inflammatory attack in MS and thereby reducing tissue damage.

Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

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Fomenko Iryna

2015-03-01

Full Text Available The use of nonsteroidal anti-inflammatory drugs (NSAIDs in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS, arginase, cyclooxygenase (COX and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX inhibitor, darbufelone were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS. WRS brought about an increase of inducible NOS (iNOS activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

A case of progressive hypertension preceding gemcitabine-associated thrombotic microangiopathy complicated by acute kidney injury and stroke.

LENUS (Irish Health Repository)

Phelan, Paul J

2009-01-01

Gemcitabine-associated thrombotic microangiopathy is being increasingly recognized as a serious complication of treatment. We report a normotensive patient who developed progressive hypertension after commencing gemcitabine therapy. She also developed subtle changes in her platelet count and serum creatinine months before her emergent presentation. Clinicians should be aware of new onset or worsening hypertension and \\'mild\\' biochemical changes in gemcitabine-treated patients.

An Uncommon Cause of Stroke: Non-bacterial Thrombotic Endocarditis.

Science.gov (United States)

Gundersen, Hilde; Moynihan, Barry

2016-10-01

Our objective is to present the case of an uncommon but probably under-recognized cause of stroke: Non-bacterial thrombotic endocarditis (NBTE). A 59-year-old man presented to our hospital with multiple bihemispheric infarcts despite taking rivaroxaban for pulmonary emboli diagnosed 2 weeks earlier. The patient's symptoms progressed quickly and he died within a week of his initial presentation despite attempts at neuroradiologically guided clot retrieval and early recognition and treatment of disseminated intravascular coagulation. On postmortem examination it was discovered that he had an undiagnosed squamous cell adenocarcinoma of the lung and NBTE. NBTE is difficult to diagnose and difficult to treat. It is associated with a mortality rate and is often not diagnosed until autopsy. However there are case reports in the literature where NBTE has been successfully treated. Early recognition and prompt treatment of the underlying disease process is the essential first step. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages.

Science.gov (United States)

Giannotti, Karina Cristina; Leiguez, Elbio; Carvalho, Ana Eduarda Zulim de; Nascimento, Neide Galvão; Matsubara, Márcio Hideki; Fortes-Dias, Consuelo Latorre; Moreira, Vanessa; Teixeira, Catarina

2017-06-22

Crotoxin B (CB) is a catalytically active group IIA sPLA 2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA 2 s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ 2 (15-Deoxy-Delta-12,14-prostaglandin J 2 ) production and involvement of LDs in 15-d-PGJ 2 biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ 2 . LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA 2 and PLD. Both 15-d-PGJ 2 and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ 2 , a pro-resolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA 2 can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes.

Anti-inflammatory and antispasmodic activity of Ipomoea imperati (Vahl Griseb (Convolvulaceae

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A.C.B. Paula

2003-01-01

Full Text Available Ipomoea imperati (Convolvulaceae lives on the sandy shores of the Brazilian coast and in other areas of the world. The anti-inflammatory activity of a methanol-water extract of the leaves of I. imperati was investigated in experimental models of acute and subchronic inflammation. Topical application of the extract (10 mg/ear inhibited mouse ear edema induced by croton oil (89.0 ± 1.3% by the lipid fraction with an IC50 of 3.97 mg/ear and 57.0 ± 1.3% by the aqueous fraction with an IC50 of 3.5 mg/ear and arachidonic acid (42.0 ± 2.0% with an IC50 of 4.98 mg/ear and 31.0 ± 2.0% with an IC50 of 4.72 mg/ear. Phospholipase A2, purified from Apis mellifera bee venom, was also inhibited by the extract (5.0 mg/ml lipid and aqueous fraction in vitro in a dose-dependent manner (85% by the lipid fraction with an IC50 of 3.22 mg/ml and 25% by the aqueous fraction with an IC50 of 3.43 mg/ml. The methanol-water extract of I. imperati (1000 mg/kg administered by the oral route also inhibited the formation of cotton pellet-induced granulomas (73.2 ± 1.2% by the lipid fraction and 56.14 ± 2.7% by the aqueous fraction and did not cause gastric mucosal lesions. I. imperati extracts (10 mg/ml also inhibited in a dose-dependent manner the muscle contractions of guinea pig ileum induced by acetylcholine and histamine (IC50 of 1.60 mg/ml for the lipid fraction and 4.12 mg/ml for the aqueous fraction. These results suggest the use of I. imperati as an anti-inflammatory and antispasmodic agent in traditional medicine.

Tacrolimus-induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients.

Science.gov (United States)

Nwaba, A; MacQuillan, G; Adams, L A; Garas, G; Delriviere, L; Augustson, B; DeBoer, B; Moody, H; Jeffrey, G P

2013-03-01

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 ± 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 ± 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival

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Duncan Howie

2018-01-01

Full Text Available The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.

Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?

Science.gov (United States)

Campello, Elena; Radu, Claudia M; Spiezia, Luca; Simioni, Paolo

2017-06-27

Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) in patients with inherited and acquired thrombophilia [mainly antiphospholipid antibody syndrome (APS)]. However, a number of questions remain unanswered. Prognostic markers capable of estimating the individual VTE risk would be of great use. Microparticles (MPs) are sub-micron membrane vesicles constitutively released from the surface of cells after cellular activation and apoptosis. The effects of MPs on thrombogenesis include the exposure of phopshatidylserine and the expression of tissue factor and MPs have been described in clinical studies as possible diagnostic and prognostic biomarkers for VTE. This review will provide a novel perspective on the current knowledge and research trends on the possible role of MPs in hereditary thrombophilia and APS. Basically, the published data show that circulating MPs may contribute to the development of VTE in thrombophilic carriers, both in mild and severe states. Moreover, the presence of endothelial-MPs and platelet-MPs has been described in antiphospholipid syndrome and seems to be directly linked to antiphospholipid antibodies and not to other underlying autoimmune disorders or the thrombotic event itself. In conclusion, circulating MPs may constitute an epiphenomenon of thrombophilia itself and could be up-regulated in acute particular conditions, promoting a global prothrombotic state up to the threshold of the clinical relevant thrombotic event.

Microangiopatia trombótica en adultos Thrombotic microangiopathy in adults

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Gonzalo J. Barrientos

2006-08-01

Full Text Available Las microangiopatías trombóticas (MAT incluyen la púrpura trombótica trombocitopénica (PTT, el síndrome urémico hemolítico (SUH y las microangiopatías del embarazo. Se describen ocho pacientes adultos con cuadros de microangiopatía trombótica, que fueron atendidos en el Hospital Italiano de Buenos Aires entre 2003 y 2004. El promedio de edad fue de 40 años, con igual proporción de hombres y mujeres. En cuatro de los ocho pacientes descriptos el diagnóstico se realizó al ingreso. Cuatro pacientes evolucionaron con características de SUH, tres como PTT y uno como MAT del embarazo. Todos los pacientes presentaron trombocitopenia y anemia hemolítica microangiopática. La insuficiencia renal fue la tercera característica más frecuente. Aquellos con diagnóstico de PTT presentaron los cuadros de mayor gravedad. Todos los pacientes fueron tratados con plasmaféresis. El tratamiento inmunosupresor también fue utilizado. Cuatro pacientes se recuperaron completamente, 2 fallecieron, 1 permanece con insuficiencia renal crónica con requerimiento de hemodiálisis y 1 fue colectomizado. Las MAT son desórdenes oclusivos de la microcirculación, con repercusión sistémica y/o renal. Existe superposición de los cuadros de PTT/SUH, y éstos pueden ser idiopáticos o secundarios. La importancia de un diagnóstico y tratamiento precoz radica en su elevada morbimortalidad. Entre los diagnósticos diferenciales figuran la sepsis, las enfermedades oncológicas, las vasculitis sistémicas, la eclampsia y otros. La infusión del plasma y principalmente la plasmaféresis son los tratamientos fundamentales. Aún se requiere mejorar el manejo y la evolución de estos síndromes, dada la elevada morbimortalidad que conllevan.Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP, hemolytic uremic syndrome (HUS and pregnancy associated thrombotic microangiopathy (TMA. Eight adult patients (four males and four

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

OpenAIRE

Lara Primo; Harvey Danielle; Levandovsky Mark; Wun Ted

2008-01-01

Abstract Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for imp...

LipidPedia: a comprehensive lipid knowledgebase.

Science.gov (United States)

Kuo, Tien-Chueh; Tseng, Yufeng Jane

2018-04-10

Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

Pregnancy shortly after an acute episode of severe acquired thrombotic thrombocytopenic purpura.

Science.gov (United States)

Panaitescu, Anca M; Stoia, Razvan; Ciobanu, Anca M; Demetrian, Mihaela; Peltecu, Gheorghe

2016-12-01

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal condition. In women with a previous history of TTP there is increased risk of recurrence during pregnancy and the puerperium. There is some evidence that the risk of relapse during pregnancy is increased if the interval between the event and conception is short. We present a case in which pregnancy was achieved a few days after full recovery from an acute episode of severe acquired TTP (ADAMTS13 activity <0.1%) which was successfully treated with four courses of plasma exchange. There was no relapse of TTP during pregnancy and a healthy baby was delivered at term; the puerperium was uneventful. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thrombotic thrombocytopenic purpura with decreased level of ADAMTS-13 activity and increased level of ADAMTS-13 inhibitor in an adolescent

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Eun Mi Yang

2010-03-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

Ecklonia cava Extract and Dieckol Attenuate Cellular Lipid Peroxidation in Keratinocytes Exposed to PM10.

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Lee, Jeong-Won; Seok, Jin Kyung; Boo, Yong Chool

2018-01-01

Airborne particulate matter can cause oxidative stress, inflammation, and premature skin aging. Marine plants such as Ecklonia cava Kjellman contain high amounts of polyphenolic antioxidants. The purpose of this study was to examine the antioxidative effects of E. cava extract in cultured keratinocytes exposed to airborne particulate matter with a diameter of <10  μ m (PM10). After the exposure of cultured HaCaT keratinocytes to PM10 in the absence and presence of E. cava extract and its constituents, cell viability and cellular lipid peroxidation were assessed. The effects of eckol and dieckol on cellular lipid peroxidation and cytokine expression were examined in human epidermal keratinocytes exposed to PM10. The total phenolic content of E. cava extract was the highest among the 50 marine plant extracts examined. The exposure of HaCaT cells to PM10 decreased cell viability and increased lipid peroxidation. The PM10-induced cellular lipid peroxidation was attenuated by E. cava extract and its ethyl acetate fraction. Dieckol more effectively attenuated cellular lipid peroxidation than eckol in both HaCaT cells and human epidermal keratinocytes. Dieckol and eckol attenuated the expression of inflammatory cytokines such as tumor necrosis factor- (TNF-) α , interleukin- (IL-) 1 β , IL-6, and IL-8 in human epidermal keratinocytes stimulated with PM10. This study suggested that the polyphenolic constituents of E. cava , such as dieckol, attenuated the oxidative and inflammatory reactions in skin cells exposed to airborne particulate matter.

Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats.

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Yeh, S; Chao, C; Lin, M; Chen, W

2000-04-01

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.

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Li, Xinwei; Huang, Weikun; Gu, Jingmin; Du, Xiliang; Lei, Lin; Yuan, Xue; Sun, Guoquan; Wang, Zhe; Li, Xiaobing; Liu, Guowen

2015-10-01

Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver. Copyright © 2015. Published by Elsevier Inc.

Contribution of coagulation factor VII R353Q polymorphism to the risk of thrombotic disorders development (venous and arterial: A case-control study

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Hanan Azzam

2017-07-01

Conclusion: FVII R353Q polymorphism did not contribute to an increased risk of thrombosis (arterial and venous; also carrying the Q allele (of R353Q did not confer protection against acute thrombotic events.

Depression Following Thrombotic Cardiovascular Events in Elderly Medicare Beneficiaries: Risk of Morbidity and Mortality

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Christopher M. Blanchette

2009-01-01

Full Text Available Purpose. Depression and antidepressant use may independently increase the risk of acute myocardial infarction and mortality in adults. However, no studies have looked at the effect of depression on a broader thrombotic event outcome, assessed antidepressant use, or evaluated elderly adults. Methods. A cohort of 7,051 community-dwelling elderly beneficiaries who experienced a thrombotic cardiovascular event (TCE were pooled from the 1997 to 2002 Medicare Current Beneficiary Survey and followed for 12 months. Baseline characteristics, antidepressant utilization, and death were ascertained from the survey, while indexed TCE, recurrent TCE, and depression (within 6 months of indexed TCE were taken from ICD-9 codes on Medicare claims. Time to death and first recurrent TCE were assessed using descriptive and multivariate statistics. Results. Of the elders with a depression claim, 71.6% had a recurrent TCE and 4.7% died within 12 months of their indexed TCE, compared to 67.6% and 3.9% of those elders without a depression claim. Of the antidepressant users, 72.6% experienced a recurrent TCE and 3.9% died, compared to 73.7% and 4.6% in the subset of selective serotonin reuptake inhibitor (SSRI users. Depression was associated with a shorter time to death (P=.008 in the unadjusted analysis. However, all adjusted comparisons revealed no effect by depression, antidepressant use, or SSRI use. Conclusions. Depression was not associated with time to death or recurrent TCEs in this study. Antidepressant use, including measures of any antidepressant use and SSRI use, was not associated with shorter time to death or recurrent TCE.

Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

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Patschan Daniel

2011-12-01

Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

Thrombophilic Risk Factors in Patients With Inflammatory Bowel Disease.

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Yazici, Ayten; Senturk, Omer; Aygun, Cem; Celebi, Altay; Caglayan, Cigdem; Hulagu, Sadettin

2010-06-01

Inflammatory bowel disease (IBD) patients have an increased risk for thromboembolism. The aim of this study was to assess the presence of thrombophilic risk factors in IBD patients and to assess the associations of these factors with disease activity. Forty-eight patients with IBD (24 ulcerative colitis, 24 Crohn's disease) and 40 matched healthy control individuals were enrolled. In addition to routine biochemical analysis, fasting blood samples were studied for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, protein-C, protein-S, antithrombin III, factor VII, factor VIII, D-dimer, vitamin B 12 , folic acid and homocysteine. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer and the number of platelets were significantly higher in patients with IBD. When compared to control group, in patients with Crohn's disease serum homocystein levels were significantly higher (p = 0.025) while serum folic acid levels were significantly lower (p homocystein and the number of platelets were found to be significantly higher in Crohn's disease patients who were in active period of the disease. Thrombophilic defects are multifactorial and might be frequently seen in IBD patients. They might contribute to thrombotic complications of this disease.

Anticoagulant and anti-thrombotic treatments in the management of hematological malignancies in a home care program

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Andrea Tendas

2011-01-01

Full Text Available Aim: Anticoagulants (AC and anti-platelet (AP agents are widely administered to patients with hematological malignancies (HM. However, HM patients may be at high risk of bleeding and hemorrhagic complications, because of different form of coagulopathies and several degrees of thrombocytopenia. Materials and Methods: A prospective evaluation of the use of anticoagulant and anti-thrombotic agents as well as of bleeding and thrombotic complications in a consecutive cohort of patients, which were followed during the first semester of 2010 by our home care service, was performed. In this regard, three pharmacological class of agents, such as oral anticoagulants (warfarin and acenocumarine, low molecular weight heparin (LMWH and anti-platelet (AP drugs were considered. Results: Out of 129 patients, 26 (20% were treated with AC/AP drugs. Warfarin, acenocumarine, LMWH as well as AP were used in 7, 11 and 12 patients, respectively. Adverse events (bleeding were observed in 3 patients (11.5%, 2 cases being on warfarin (replaced by LMWH and 1 being AP (suspension without replacement; out of the 3 patients with bleeding, none presented thrombocytopenia. Conclusions: Despite the frequent findings of hemostatic disorders in a population of frail patients managed in a home care setting, our experience demonstrated that the use of AC/AP drugs has been very rarely responsible for significant complications.

Selective identification of specialized pro-resolving lipid mediators from their biosynthetic double di-oxygenation isomers.

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Hansen, Trond V; Dalli, Jesmond; Serhan, Charles N

The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions. Most often the different families among these mediators are chemically characterized by two or three chiral, secondary alcohols, separated by either an E,E,Z -triene or an E,Z,E,E -tetraenemoiety. The lipoxygenases also form other oxygenated polyunsaturated natural products, coined double di-oxygenation products, that are constitutional isomers of the protectin and maresin families of specialized pro-resolving lipid mediators. Very often these products exhibit similar chromatographic properties and mass spectrometrical fragment ions as the pro-resolving mediators. In addition, the double di-oxygenation products are sometimes formed in larger amounts than the specialized pro-resolving lipid mediators. Thus, it is not always possible to distinguish between the specialized pro-resolving mediators and their double di-oxygenation isomers in biological systems, using LC/MS-based techniques. Herein, a convenient and easy-to-use protocol to meet this challenge is presented.

Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

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Fabrizio Vianello

2011-01-01

Full Text Available Polycythemia vera (PV and essential thrombocythemia (ET are two Philadelphia-negative myeloproliferative neoplasms (MPN associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis.

Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are associated with Raynaud phenomenon and migraine in primary thrombotic antiphospholipid syndrome.

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Kopytek, M; Natorska, J; Undas, A

2018-04-01

Objectives Antibodies to phosphatidylserine/prothrombin complex (aPS/PT) detectable in sera of some patients with antiphospholipid syndrome (APS) have been shown to correlate with thrombosis. However, associations of aPS/PT antibodies with APS related disorders remain unclear. Aim To evaluate whether there are any associations between aPS/PT antibodies and Raynaud phenomenon, migraine and/or valvular lesions in primary thrombotic APS (PAPS). Methods We enrolled 67 consecutive patients (56 women) with thrombotic PAPS (VTE in 80.6%), aged 46.2 ± 13.5 years. The exclusion criteria were: acute coronary syndromes or stroke within preceding 6 months, cancer, severe comorbidities and pregnancy. The IgG and IgM aPS/PT antibodies were determined by ELISA with the cut-off of 30 units. We recorded Raynaud phenomenon, migraine and valvular lesions. Results Positive IgM or/and IgG aPS/PT antibodies were observed in 29 patients (43.3%), with a higher prevalence of IgM antibodies ( n = 27, 40.3%) compared with IgG isotype ( n = 12, 17.9%, p = 0.014). aPS/PT antibodies were observed most commonly in patients with triple aPL ( n = 12, 85.7%) compared with those with double ( n = 5, 35.7%) or single aPL antibodies (n = 12, 30.8%, p = 0.03), with no association with demographics, the ANA titre, the type of thrombotic events or medications. Raynaud phenomenon, migraine and valvular lesions were observed in 15% ( n = 10), 30% ( n = 20) and 18% ( n = 12) of the patients, respectively. Raynaud phenomenon and migraine, but not valvular lesions, were markedly more frequent in PAPS patients presenting with positive aPS/PT antibodies ( n = 10, 34.5% vs. n = 0, 0%; p = 0.0001). Conclusions In PAPS patients aPS/PT antibodies are related to the occurrence of both Raynaud phenomenon and migraine.

Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

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Shoeb, Mohammad; Ramana, Kota V

2011-01-01

Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

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Mojgan Masoodi

Full Text Available Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

The Role of Lipids in Human Milk and Infant Formulae

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Alessandra Mazzocchi

2018-05-01

Full Text Available The quantity and quality of dietary lipids in infant formulae have a significant impact on health outcomes, especially when fat storing and/or absorption are limited (e.g., preterm birth and short bowel disease or when fat byproducts may help to prevent some pathologies (e.g., atopy. The lipid composition of infant formulae varies according to the different fat sources used, and the potential biological effects are related to the variety of saturated and unsaturated fatty acids. For example, since lipids are the main source of energy when the normal absorptive capacity of the digestive tract is compromised, medium-chain saturated fatty acids might cover this requirement. Instead, ruminant-derived trans fatty acids and metabolites of n-3 long-chain polyunsaturated fatty acids with their anti-inflammatory properties can modulate immune function. Furthermore, dietary fats may influence the nutrient profile of formulae, improving the acceptance of these products and the compliance with dietary schedules.

Serum lipid profile and inflammatory markers in the aorta of cholesterol-fed rats supplemented with extra virgin olive oil, sunflower oils and oil-products.

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Katsarou, Ageliki I; Kaliora, Andriana C; Papalois, Apostolos; Chiou, Antonia; Kalogeropoulos, Nick; Agrogiannis, George; Andrikopoulos, Nikolaos K

2015-01-01

Extra virgin olive oil (EVOO) major and minor component anti-inflammatory effect on aorta was evaluated; Wistar rats were fed (9 weeks) on either a high-cholesterol diet (HCD) or a HCD supplemented with oils, i.e. EVOO, sunflower oil (SO), high-oleic sunflower oil (HOSO), or oil-products modified to their phenolic content, i.e. phenolics deprived-EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], HOSO enriched with the EVOO phenolics [HOSO(+)]. HCD induced dyslipidemia and resulted in higher aorta adhesion molecules levels at euthanasia. Groups receiving EVOO, EVOO(-), HOSO, HOSO(+) presented higher serum TC and LDL-c levels compared to cholesterol-fed rats; attenuation of aorta E-selectin levels was also observed. In EVOO/EVOO(-) groups, aorta vascular endothelial adhesion molecule-1 (VCAM-1) was lower compared to HCD animals. SO/SO(+) diets had no effect on endothelial dysfunction amelioration. Overall, our results suggest that major and/or minor EVOO constituents improve aorta E-selectin and VCAM-1, while serum lipids do not benefit.

Sleep deprivation affects inflammatory marker expression in adipose tissue

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Santos Ronaldo VT

2010-10-01

Full Text Available Abstract Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C group and a paradoxical sleep deprivation by 96 h (PSD group. Ten rats were randomly assigned to either the control group (C or the PSD. Mesenteric (MEAT and retroperitoneal (RPAT adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL-6, interleukin (IL-10 and tumour necrosis factor (TNF-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG, VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

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Mörtzell, M; Berlin, G; Nilsson, T; Axelsson, C G; Efvergren, M; Audzijoni, J; Griskevicius, A; Ptak, J; Blaha, M; Tomsova, H; Liumbruno, G M; Centoni, P; Newman, E; Eloot, S; Dhondt, A; Tomaz, J; Witt, V; Rock, G; Stegmayr, B

2011-10-01

Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact

Associations of amylin with inflammatory markers and metabolic syndrome in apparently healthy Chinese.

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Xinwei Hou

Full Text Available BACKGROUND: Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese. METHODS: A population-based sample of 1,011 Chinese men and women aged 35-54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6], insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001 without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001. After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46 comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR. CONCLUSIONS: Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively.

Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study

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Cheung, Y. Whitney; Bouman, Annemieke C.; Castoldi, Elisabetta; Wielders, Simone J.; Spronk, Henri M. H.; ten Cate, Hugo; ten Cate-Hoek, Arina J.; ten Wolde, Marije

2016-01-01

Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence.

Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

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Liang, W.; Verschuren, L.; Mulder, P.; Hoorn, J.W.A. van der; Verheij, J.; Dam, A.D. van; Boon, M.R.; Princen, H.M.G.; Havekes, L.M.; Kleemann, R.; Hoek, A.M. van den

2015-01-01

BACKGROUND AND PURPOSE: Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes

Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

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Liang, Wen; Verschuren, Lars; Mulder, Petra; van der Hoorn, José W. A.; Verheij, Joanne; van Dam, Andrea D.; Boon, Mariette R.; Princen, Hans M. G.; Havekes, Louis M.; Kleemann, Robert; van den Hoek, Anita M.

2015-01-01

Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes and metabolic syndrome

Accumulation of Oxidized Low-Density Lipoprotein in Psoriatic Skin and Changes of Plasma Lipid Levels in Psoriatic Patients

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Nilgun Solak Tekin

2007-01-01

Full Text Available Background. Psoriasis is a chronic inflammatory skin disease characterized by an accelerated turnover of epidermal cells and an incomplete differentiation in epidermis with lesion. However, the exact etiology of psoriasis is unknown. Abnormalities in essential fatty acid metabolism, free radical generation, lipid peroxidation, and release of lymphokines have been proposed. Objective. Our purpose was to evaluate the plasma lipids and oxidized low-density lipoprotein accumulation in psoriatic skin lesion in order to ascertain the possible participation of oxidative stress and oxidative modification of lipids in pathogenesis of psoriasis. Methods. The study group included 84 patients with psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid profile was determined. Psoriatic and nonlesional skin samples of psoriatic patients were evaluated for the presence of oxidized low-density lipoprotein by using an immune-fluorescent staining method. Results. The mean levels of lipids (total cholesterol, triglyceride, and LDL cholesterol in patients with psoriasis were found to be significantly higher than those of healthy subjects. Psoriatic skins were shown positive oxidized low-density lipoprotein staining. There was no staining in nonlesional skin samples of the same individuals. Conclusion. Lipid peroxidation mediated by free radicals is believed to be one of the important causes of cell membrane destruction and cell damage. This study shows for the first time the accumulation of oxidized low-density lipoprotein in psoriatic skin lesion. We believe that accumulation of ox-LDL in psoriatic skin may have an important role in the immune-inflammatory events that result in progressive skin damage.

Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

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Angela Maria Rizzo

Full Text Available Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

Lipid management among individuals with inflammatory arthritis in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

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Navarro-Millán, Iris; Gamboa, Christopher M; Curtis, Jeffrey R; Safford, Monika M

2018-01-01

Objective Hyperlipidemia guidelines do not currently identify inflammatory arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared hyperlipidemia treatment of individuals with and without IA (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national cohort. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were classified as having IA (without diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or IA); or no IA, diabetes, or hypertension. Multivariable logistic regression models examined the odds of medical treatment among those with hyperlipidemia. Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted odds of treatment were similar between participants with IA and those without IA, hypertension, or diabetes. Participants with diabetes and no IA and participants with hypertension and no IA were twice as likely to be treated for hyperlipidemia as those without IA, diabetes, or hypertension. Conclusion Despite their higher CVD risk, patients with IA were as likely to be treated for hyperlipidemia as those without diabetes, hypertension, or IA. Lipid guidelines should identify IA as a CVD risk factor to improve CVD risk optimization in IA.

Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome

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Carla Lubrano

2015-01-01

Full Text Available The pathogenesis of obesity (OB and metabolic syndrome (MetS implies free radical-, oxidized lipid- (LOOH-, and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA. Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2 hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues.

Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling

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Caesar, Robert; Tremaroli, Valentina; Kovatcheva-Datchary, Petia

2015-01-01

Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased...... Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif(-/-) and Myd88(-/-) mice are protected against lard......-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation...

Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus droebachiensis

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Alexander N. Shikov

2017-11-01

Full Text Available The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW lipids. Ethanol extract (55 °C contained about equal amounts of saturated (SaFA and monounsaturated fatty acids (MUFA representing 60% of total fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and MUFAs, respectively. Non-methylene-interrupted dienes (13% were composed of eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC-PUFA included two main components, n6 arachidonic and n3 eicosapentaenoic acids, even with equal concentrations (15 μg/mg and a balanced n6/n3 PUFA ratio (0.86. The UPLC-ELSD analysis showed that a great majority of the lipids (80% in the ethanolic extract were phosphatidylcholine (60 μg/mg and phosphatidylethanolamine (40 μg/mg, while the proportion of neutral lipids remained lower than 20%. In addition, alkoxyglycerol derivatives—chimyl, selachyl, and batyl alcohols—were quantified. We have assumed that the mechanism of action of body wall lipids in the present study is via the inhibition of MAPK p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid fraction as a source for the development of drugs with anti-inflammatory activity.

Detailed Distribution of Lipids in Greenshell™ Mussel (Perna canaliculus

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Matthew R. Miller

2014-04-01

Full Text Available Greenshell™ mussels (GSM–Perna canaliculus are a source of omega-3 (n-3 long-chain polyunsaturated fatty acids (LC-PUFA. Farmed GSM are considered to be a sustainable source of LC-PUFA as they require no dietary inputs, gaining all of their oil by filter-feeding microorganisms from sea water. GSM oil is a high-value product, with a value as much as 1000 times that of fish oils. GSM oil has important health benefits, for example, anti-inflammatory activity. It also contains several minor lipid components that are not present in most fish oil products, and that have their own beneficial effects on human health. We have shown the lipid content of the female GSM (1.9 g/100 g ww was significantly greater than that of the male (1.4 g/100 g ww. Compared with male GSM, female GSM contained more n-3 LC-PUFA, and stored a greater proportion of total lipid in the gonad and mantle. The higher lipid content in the female than the male GSM is most likely related to gamete production. This information will be useful to optimize extraction of oils from GSM, a local and sustainable source of n-3 LC-PUFA.

Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.

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Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

2013-09-01

Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

Exploring lipids with nonlinear optical microscopy in multiple biological systems

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Alfonso-Garcia, Alba

Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by

Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

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Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

2016-07-01

Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even

Gender Differences in Associations Between Intraprocedural Thrombotic Events During Percutaneous Coronary Intervention and Adverse Outcomes

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Schoos, Mikkel; Mehran, Roxana; Dangas, George D

2016-01-01

quantitative coronary angiography (QCA) analysis, from the ACUITY and HORIZONS-AMI trials. We compared major adverse cardiac events (MACE) at in-hospital, 30-day, and 1-year follow-up and major bleeding at 30 days according to gender and the presence or absence of IPTE. IPTE was identified in 507 patients (7....... Intraprocedural Thrombotic Events (IPTEs) are defined as new or increasing thrombus, abrupt vessel closure, no reflow or slow reflow, or distal embolization at any time during percutaneous coronary intervention. IPTEs were evaluated in this pooled analysis of 6,591 patients with stent implantation and blinded...

Predictors of the post-thrombotic syndrome with non-invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis

NARCIS (Netherlands)

Tick, L.W.; Doggen, Catharina Jacoba Maria; Rosendaal, F.R.; Faber, W.R.; Bousema, M.T.; Mackaay, A.J.C.; van Balen, P.; Kramer, H.H.

2010-01-01

Background: Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors

Antimicrobial aspects of inflammatory resolution in the mucosa: A role for pro-resolving mediators1

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Campbell, Eric L.; Serhan, Charles N.; Colgan, Sean P.

2011-01-01

Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial antigens, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier, in recent years numerous findings implicate an active role of the epithelium with pro-resolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and pro-resolution lipid mediators. These autacoids, derived from ω-6 and ω-3 polyunsaturated fatty acids, are implicated in the initiation, progression and resolution of acute inflammation and display specific, epithelial-directed actions focused on mucosalhomeostasis. We also summarize present knowledge of mechanisms for resolution via regulation of epithelial-derived antimicrobial peptides in response to pro-resolving lipid mediators. PMID:21934099

Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.

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Petronilho, Fabricia; Michels, Monique; Danielski, Lucinéia G; Goldim, Mariana Pereira; Florentino, Drielly; Vieira, Andriele; Mendonça, Mariana G; Tournier, Moema; Piacentini, Bárbara; Giustina, Amanda Della; Leffa, Daniela D; Pereira, Gregório W; Pereira, Volnei D; Rocha, João Batista Teixeira Da

2016-09-01

The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB. Copyright © 2016 Elsevier GmbH. All rights reserved.

Lipids Derived from Virulent Francisella tularensis Broadly Inhibit Pulmonary Inflammation via Toll-Like Receptor 2 and Peroxisome Proliferator-Activated Receptor α

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Crane, Deborah D.; Ireland, Robin; Alinger, Joshua B.; Small, Pamela

2013-01-01

Francisella tularensis is a Gram-negative facultative intracellular pathogen that causes an acute lethal respiratory disease in humans. The heightened virulence of the pathogen is linked to its unique ability to inhibit Toll-like receptor (TLR)-mediated inflammatory responses. The bacterial component and mechanism of this inhibition are unknown. Here we show that lipids isolated from virulent but not attenuated strains of F. tularensis are not detected by host cells, inhibit production of proinflammatory cytokines by primary macrophages in response to known TLR ligands, and suppress neutrophil recruitment in vivo. We further show that lipid-mediated inhibition of inflammation is dependent on TLR2, MyD88, and the nuclear hormone and fatty acid receptor peroxisome proliferator-activated receptor α (PPARα). Pathogen lipid-mediated interference with inflammatory responses through the engagement of TLR2 and PPARα represents a novel manipulation of host signaling pathways consistent with the ability of highly virulent F. tularensis to efficiently evade host immune responses. PMID:23925884

Polyene-lipids: a new tool to image lipids

DEFF Research Database (Denmark)

Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

2005-01-01

conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated......Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases

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Yongchun Shen

2012-01-01

Full Text Available Airway mucus hypersecretion (AMH is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis

NARCIS (Netherlands)

Ramcharan, A.S.; van Stralen, K.J.; Snoep, J.D.; Mantel-Teeuwisse, A.K.; Doggen, Catharina Jacoba Maria

2009-01-01

Background: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets.

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Lecomte, Manon; Couëdelo, Leslie; Meugnier, Emmanuelle; Loizon, Emmanuelle; Plaisancié, Pascale; Durand, Annie; Géloën, Alain; Joffre, Florent; Vaysse, Carole; Michalski, Marie-Caroline; Laugerette, Fabienne

2017-05-01

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods. Copyright © 2017 Elsevier Inc. All rights reserved.

[Treatment and prevention of erosive and ulcerative lesions in the stomach and duodenum caused by intake of non-steroidalanti-inflammatory drugs].

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Luzina, E V

2014-01-01

Therapy with non-steroidal anti-inflammatory drugs (NSAIDs) is a diffcult task. Good anti-inflammatory effect increases the risk of gastrointestinal complications with a frequency of 10-50%. The risk further increases with age (above 60-70 yr), the history of ulcer disease concomitant intake of acetylsalicylic acid, anticoagulants, and glucocorticosteroids. Long-term antisecretory therapy with proton pump inhibitors, e.g., esomeprazole, was shown to be an effective prophylactic tool. This drug maintains the intragastric pH value above 4 for 15 hr on the average. The risk of erosive and ulceraive lesions in the stomach and duodenum significantly decreases by selective cyclooxygenase-2 inhibitors, e.g., coxibs, that however increase the risk of thrombotic cardiovascular complications. The author proposes recommendations on the use of NSAIDs in the patients at risk of serious gastrointestinal and cardiovascular pathology. Naproxen in combination with proton pitmp inhibitors is the drug of choice among NSAIDs. Vimovo is a fixed combination of naproxen and esomeprazole. Results of comparative studies on the efficacy of vimovo and celecoxib are presented along with the data on the safety of this. combination compared with that of naproxen monotherapy

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

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Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

2016-01-01

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

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Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

2016-03-31

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.

Thrombotic microangiopathy purpura in a patient with metastatic colorectal carcinoma

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Tea Nizič-Kos

2015-09-01

Full Text Available  AbstractBackground: Thrombotic microangiopathy (TMA is a rare syndrome that leads to excessive formation of blood clots, microthrombosis and is accompanied by non-autoimune haemolytic anemia and thrombocytopenia. Only few cases describing TMA caused by cancer are being reported in the literature.Patient: A 42-year old male patient with metastatic carcinoma of sigma and several accompanying diagnoses (pulmonary embolism, deep vein thrombosis, cerebrovascular insult had later developed clinical and laboratory signs of TMA. TMA was unresponsive to plasmapheresis, which was discontinued and first cycle of chemotherapy was applied. The patient died soon after. The autopsy did not provide any additional information about the disease, there were no signs of malignant bone marrow infiltration.Conclusion: The diagnosis of secondary TMA remains a diagnostic and therapeutic challenge. It appears as a rare complication in patients with cancer. Treatment is difficult because the cause of TMA (malignancy is hard to remove. Patients with cancer do not respond to plasmapheresis, which often delays the application of chemotherapy, the only effective treatment for TMA. Consequently this condition has poor prognosis.

Thrombotic Microangiopathic Hemolytic Anemia without Evidence of Hemolytic Uremic Syndrome

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Şinasi Özsoylu

2016-03-01

Full Text Available In a recent issue of this journal Dr. Oymak and her colleagues presented a clinically and genetically well-studied 5-year-old boy who was seen with severe microangiopathic hemolytic anemia without laboratory findings of renal involvement despite complement factor H gene mutations [1]. Because of Yeneral’s extensive review [2] on atypical hemolytic uremic syndrome (aHUS published recently in the Turkish Journal of Hematology, I brought it to readers’ attention that more recently some authors do not use ‘aHUS’, which was historically used to distinguish heterogeneous uncharacterized syndromes from Shiga toxin-related HUS, since the term lacks both specificity and suggested causes [3]. Though in our patient with thrombotic thrombocytopenic purpura renal involvement was documented at the beginning but not in the last two recurrences, neither serum nor urinary findings indicated kidney involvement [4]. Although the discussions of Dr. Oymak et al. are well taken, the term ‘microangiopathic hemolytic anemia’ is covering the syndrome to a large extent as suggested by George and Nester

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

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Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

2018-05-17

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable

Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

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Cataland, S R; Wu, H M

2015-06-01

Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

Bee venom processes human skin lipids for presentation by CD1a.

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Bourgeois, Elvire A; Subramaniam, Sumithra; Cheng, Tan-Yun; De Jong, Annemieke; Layre, Emilie; Ly, Dalam; Salimi, Maryam; Legaspi, Annaliza; Modlin, Robert L; Salio, Mariolina; Cerundolo, Vincenzo; Moody, D Branch; Ogg, Graham

2015-02-09

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom-derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease. © 2015 Bourgeois et al.

Experimental acute thrombotic stroke in baboons

International Nuclear Information System (INIS)

Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.; Waltz, T.A.; Zyroff, J.; Hanson, S.R.; Battenberg, E.

1986-01-01

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9 cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8

Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.

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Shoeb, Mohammad; Ramana, Kota V

2012-01-01

Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. Copyright © 2011 Elsevier Inc. All rights reserved.

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation: an Update

Science.gov (United States)

Stavrou, Evi; Lazarus, Hillard M.

2010-01-01

Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended. PMID:21776339

THROMBOTIC MICROANGIOPATHY IN HAEMATOPOIETIC CELL TRANSPLANTATION:AN UPDATE

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Evi Stavrou

2010-10-01

Full Text Available Allogeneic hematopoietic cell transplantation (HCT represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA. In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases, patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents.  Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages.

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Min Mao

Full Text Available The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol. The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

Metabolic reprogramming through fatty acid transport protein 1 (FATP1 regulates macrophage inflammatory potential and adipose inflammation

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Amy R. Johnson

2016-07-01

Full Text Available Objective: A novel approach to regulate obesity-associated adipose inflammation may be through metabolic reprogramming of macrophages (MΦs. Broadly speaking, MΦs dependent on glucose are pro-inflammatory, classically activated MΦs (CAM, which contribute to adipose inflammation and insulin resistance. In contrast, MΦs that primarily metabolize fatty acids are alternatively activated MΦs (AAM and maintain tissue insulin sensitivity. In actuality, there is much flexibility and overlap in the CAM-AAM spectrum in vivo dependent upon various stimuli in the microenvironment. We hypothesized that specific lipid trafficking proteins, e.g. fatty acid transport protein 1 (FATP1, would direct MΦ fatty acid transport and metabolism to limit inflammation and contribute to the maintenance of adipose tissue homeostasis. Methods: Bone marrow derived MΦs (BMDMs from Fatp1−/− and Fatp1+/+ mice were used to investigate FATP1-dependent substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. We also generated C57BL/6J chimeric mice by bone marrow transplant specifically lacking hematopoetic FATP1 (Fatp1B−/− and controls Fatp1B+/+. Mice were challenged by high fat diet (HFD or low fat diet (LFD and analyses including MRI, glucose and insulin tolerance tests, flow cytometric, histologic, and protein quantification assays were conducted. Finally, an FATP1-overexpressing RAW 264.7 MΦ cell line (FATP1-OE and empty vector control (FATP1-EV were developed as a gain of function model to test effects on substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. Results: Fatp1 is downregulated with pro-inflammatory stimulation of MΦs. Fatp1−/− BMDMs and FATP1-OE RAW 264.7 MΦs demonstrated that FATP1 reciprocally controled metabolic flexibility, i.e. lipid and glucose metabolism, which was associated with inflammatory response. Supporting our previous work demonstrating the positive relationship between glucose

Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

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Jung-Woo Kang

2014-01-01

Full Text Available Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101 on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-κB, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-κB translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators.

Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

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Analia E Garcia

Full Text Available The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS-induced arthritis model with four groups of rats: 1 untreated, 2 clopidogrel-treated, 3 PG-PS-induced, and 4 PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN gamma, and IL-6, an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4 were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

Science.gov (United States)

Garcia, Analia E; Mada, Sripal R; Rico, Mario C; Dela Cadena, Raul A; Kunapuli, Satya P

2011-01-01

The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4) were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

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Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

2013-01-01

Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response

OpenAIRE

Greineisen, William E.; Maaetoft-Udsen, Kristina; Speck, Mark; Balajadia, Januaria; Shimoda, Lori M. N.; Sung, Carl; Turner, Helen

2015-01-01

Lipid bodies (LB) are reservoirs of precursors to inflammatory lipid mediators in immunocytes, including mast cells. LB numbers are dynamic, increasing dramatically under conditions of immunological challenge. We have previously shown in vitro that insulin-influenced lipogenic pathways induce LB biogenesis in mast cells, with their numbers attaining steatosis-like levels. Here, we demonstrate that in vivo hyperinsulinemia resulting from high fat diet is associated with LB accumulation in muri...

The effect of different beverage consumption (dough, non-alcoholic beer, carbohydrated replacement drink) on performance, lipids profile, inflammatory biomarkers after running-based anaerobic sprint test in taekwondo players.

Science.gov (United States)

Shiranian, Afshin; Darvishi, Leila; Askari, Gholamreza; Ghiasvand, Reza; Feyzi, Awat; Hariri, Mitra; Mashhadi, Nafiseh Shokri; Mehrabani, Sanaz

2013-04-01

After exercise, recovery is very essential in professional sport. Athletes use sport beverages to enhance endurance and physical performance. The purpose of this study was to examine the effects of Dough versus non-alcoholic beer and carbohydrate (CHO) fluid on performance, lipids profile, inflammatory biomarkers after Running-based Anaerobic Sprint Test (R.A.S.T) in Taekwondo players. This study was conducted as repeated measures crossover design with 22 men Taekwondo player. Subjects completed standard protocol R.A.S.T so that immediately and 1 h posterior R.A.S.T protocol received number 1 beverage. Subjects spend 2 h recovery periods. Second and third sessions trial were similar to prior trial, separated by at least 4 days, instead of number 1 beverage, participants received number 2 and number 3 beverage. Data showed that average pre- and post-recovery in C-reactive protein (CRP) or Dough significantly decreased (P 0.05). About mean pre- and post-recovery in low density lipoprotein (LDL) and high density lipoprotein (HDL) there were no significant differences in all three beverages. Besides, amount of CRP was significant between three beverages (P 0.05) in dietary intake were observed between three treatment periods. Dough was effective in reducing LDL and reducing inflammatory biomarkers including CRP with little effect on performance in subjects.

The C50T polymorphism of the cyclooxygenase-I gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

NARCIS (Netherlands)

Clappers, Nick; van Oijen, Martijn G. H.; Sundaresan, Santosh; Brouwer, Marc A.; te Morsche, Rene H. M.; Keuper, Wessel; Peters, Wilbert H. M.; Drenth, Joost P. H.; Verheugt, Freek W. A.

2008-01-01

prevents thrombotic events by inhibiting platelet cyclooxygenase-I (COX-1), thus reducing thromboxane A2 formation and platelet aggregation.The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin.We studied

Gender difference in hipolipemic and anti-inflammatory effects of statins in diabetics with coronary artery disease

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Đinđić Boris

2009-01-01

Full Text Available Background/Aim. Statins produce hipolipemic and pleotropic effects on markers of inflammation with stabilization of atheromatous plaque. The aim of this paper was to examine gender difference in hipolipemic and antiinflammatory effects of statins in patients with diabetes mellitus (DM type 2 with coronary artery disease (CAD. Methods. Sixty dyslipidemic patients with DM type 2 were analyzed. Lifestyle modification and hipolipemic diet were applied in all patients divided into two groups: 30 patients with statins therapy (20 mg of simvastatin or equivalent dose of some other statins, during 3 months and 30 patients without statins therapy. Estimation of obesity, quality of glicoregulation, and determination of inflammatory parameters: Creactive protein (CRP, fibrinogen, total and differential leukocyte count, intracellular adhesive molecules (ICAM-1, vascular adhesive molecule-(VCAM-1 and lipid profile (total cholesterol - TC, LDL-C, HDL-C, triglicerides - TG were done. Results. Women with DM type 2 were more obese and had significant disturbances in lipid profiles, glicoregulation and inflammatory markers compared to men. Statins therapy significantly improved all lipid parameters and quality of glicoregulation in women, while there were only significant reduction of LDL-C and nonHDL-C in males. There were more significant reductions of inflammatory markers in women as compared to men with statins therapy. In the group without statins there was not such significant reduction. Concentration of ICAM-1 was the lowest in men on statins therapy, while there were no significant variability of VCAM-1 values between groups and genders. Conclusion. Women with DM type 2 and CAD have more prominent lipoprotein disorders and impaired glicoregulation with expression of enhanced proinflamatory state which could not be seen in men. Statins therapy exerts more favorable effects in women leading to stabilization of lipoprotein profiles, improvement of

Association between chronic periodontitis and serum lipid levels

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Pejčić Ana

2012-01-01

Full Text Available Background/Aim. Periodontitis is a local inflammatory process mediating destruction of periodontal tissues triggered by bacterial insult. However, this disease is also characterized by systemic inflammatory host responses that may contrbute, in part, to the recently reported increased risk for systemic diseases, including an altered lipid metabolism. On the other hand, many people in the world are affected by hyperlipidemia, which is a known risk faktor for atherosclerosis. The aim of this study was to determine the relationship between periodontal disease and blood lipid levels. Methods. A total of 50 patients with periodontitis included in this study had no documented history of recent acute coronary events. The healthy, non-periodontal subjects (comparison group comprised 25 subjects. All the patients were periodontology examined and completed a medical history. Dental plaque index, probing depth, gingival index bleeding on probing and clinical attechment levels were recorded. Blood samples were taken on admission for measurements of serum total cholesterol, triglycerides, hight density lipoprotein cholesterol (HDL-cholesterol, and low density lipoprotein cholesterol (LDL-cholesterol. Results. The obtained results showed that mean levels of cholesterol (6.09 ± 1.61 mmol/L, triglycerdes (2.19+1.67mmol/l and LDL cholesterol (4.09 ± 1.40 mmol/L in individuals with periodontitis were higer, and levels od HDL (1.43 ± 0.51 mmol/L was lower than those of individuals without periodontitis (4.86 ± 1.37; 1.14 ± 0.71; 3.18 ± 0.64; 1.53 ± 0.32 mmol/L, respectively. Conclusion. This study confirms a significant relationship between periodontal disease, regardless its intensity, and blood lipid levels in the studied population. The results imply that periodontitis may be a risk factor and may contribute to the pathogenesis of atherosclerosis and cardiovascular diseases (CVD. However, future prospective randomized studies have to determine whether

Omega-3 fatty acids and inflammatory processes: from molecules to man.

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Calder, Philip C

2017-10-15

Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance. © 2017 The Author

Anti-Inflammatory Prostanoids: Focus on the Interactions between Electrophile Signaling and Resolution of Inflammation

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Beatriz Díez-Dacal

2010-01-01

Full Text Available Prostanoids are products of cyclooxygenase biosynthetic pathways and constitute a family of lipidic mediators of widely diverse structures and biological actions. Besides their known proinflammatory role, numerous works have revealed the anti-inflammatory effects of various prostanoids and established their role in the resolution of inflammation. Among these, prostaglandins with cyclopentenone structure (cyPG are electrophilic lipids that may act through various mechanisms, including the activation of nuclear and membrane receptors and, importantly, direct addition to protein cysteine residues and modification of protein function. Due to their ability to influence cysteine modification–mediated signaling, cyPG may play a critical role in the interplay between redox and inflammatory signaling pathways. Moreover, cellular redox status modulates cyPG addition to proteins; thus, a reciprocal regulation exists between these two factors. After initial controversy, it is becoming clear that endogenous cyPG are generated at concentrations sufficient to promote inflammatory resolution. As for other prostanoids, cyPG effects are highly dependent on context factors and they may exert pro- or anti-inflammatory actions in a cell type–dependent manner, or even biphasic or dual actions in a given cell type or tissue. In light of the growing number of cyPG protein targets identified, cyPG resemble other pleiotropic mediators acting through protein modification. However, their complex structure results in an inter- and intramolecular selectivity of the residues being modified, thus opening the way for structure-activity and drug discovery studies. Detailed characterization of cyPG interactions with cellular proteins will help us to understand their mechanism of action fully and establish their therapeutic potential in inflammation.

Weight cycling enhances adipose tissue inflammatory responses in male mice.

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Sandra Barbosa-da-Silva

Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

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Griffiths Gareth

2009-07-01

Full Text Available Abstract Background Phosphatidylcholine (PC is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. Methods PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs. Results The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs. Conclusion PC

Meta-analysis of studies on the effect of vitamin D supplementation on blood glucose, lipid profile and inflammatory markers in patients with diabetes

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H Fallahzadeh

2016-01-01

Full Text Available Introduction: Vitamin D deficiency and type 2 diabetes are both common diseases. Numerous studies have examined the relationship between the two. The purpose of this study was to investigate the effect of vitamin D supplementation on glycemic status, lipid profile and inflammatory markers in patients with diabetes. Method: Type of systematic review and meta-analysis, which is actually a review on the studies available. Beginning a search extensively on electronic resources English, including EMBASE, Web of science, Medline Scopus and Who and electronic resources Persian including SID and Google scholar for diabetes-related research papers do. Result: The test of heterogeneity, studies with significant heterogeneity in vitamin D, HOMA-IR and insulin sensitivity were the random effects model was used and the mean difference and 95% confidence intervals between the two groups in the vitamin D , 1.87 and (-5.49,9.23, HOMA-IR 0.09 and (-.023,0.05 and insulin sensitivity, 0.24 and (-0.75,0.26, respectively. Discussion: The overall results of this study showed that the meta-analysis, vitamin D and insulin sensitivity in diabetic patients is effective and HOMA-IR is not effective on patients with diabetes.

Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways

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Md Rashedunnabi Akanda

2018-02-01

Full Text Available Globally, gastric ulcer is a vital health hazard for a human. Rabdosia inflexa (RI has been used in traditional medicine for inflammatory diseases. The present study aimed to investigate the protective effect and related molecular mechanism of RI using lipopolysaccharide (LPS-induced inflammation in RAW 246.7 cells and HCl/EtOH-induced gastric ulcer in mice. We applied 3-(4,5-dimethyl-thiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, nitric oxide (NO, reactive oxygen species (ROS, histopathology, malondialdehyde (MDA, quantitative real-time polymerase chain reaction (qPCR, immunohistochemistry (IHC, and Western blot analyses to evaluate the protective role of RI. Study revealed that RI effectively attenuated LPS-promoted NO and ROS production in RAW 246.7 cells. In addition, RI mitigated gastric oxidative stress by inhibiting lipid peroxidation, elevating NO, and decreasing gastric inflammation. RI significantly halted elevated gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, inducible nitric oxide synthetase (iNOS, and cyclooxygenase-2 (COX-2 in gastric tissue. Likewise, RI markedly attenuated the mitogen-activated protein kinases (MAPKs phosphorylation, COX-2 expression, phosphorylation and degradation of inhibitor kappa B (IκBα and activation of nuclear factor kappa B (NF-κB. Thus, experimental findings suggested that the anti-inflammatory and gastroprotective activities of RI might contribute to regulating pro-inflammatory cytokines and MAPK/NF-κB signaling pathways.

Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects.

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Camargo-Ramos, Claudia Marcela; Correa-Bautista, Jorge Enrique; Correa-Rodríguez, María; Ramírez-Vélez, Robinson

2017-10-06

Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogotá, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow-mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and blood pressure were measured and a cardiometabolic risk score (MetScore) was calculated. A lower DII score (anti-inflammatory diet) was significantly associated with higher high-density lipoprotein-cholesterol (HDL-C) and FMD, and lower Hb1Ac and MetScore ( p diet) showed a positive relationship with MetScore ( r = 0.410, p diet was inversely associated with an improved cardiometabolic profile, suggesting the importance of promoting anti-inflammatory diets as an effective strategy for preventing CVD.

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

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Perry, Rachel J; Samuel, Varman T.; Petersen, Kitt Mia Falck

2014-01-01

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding...... of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol...... activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes....

Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women?

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Luciana Debortoli de Carvalho

2015-12-01

Full Text Available Abstract INTRODUCTION : The human T-lymphotropic virus-1 (HTLV-1 is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS : Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS : Elevated levels of triglyceride and very low-density lipoproteins (VLDL were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02. CONCLUSIONS : Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

Avanti lipid tools: connecting lipids, technology, and cell biology.

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Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

2014-08-01

Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions. Copyright © 2014. Published by Elsevier B.V.

Anti-protein C antibodies are associated with resistance to endogenous protein C activation and a severe thrombotic phenotype in antiphospholipid syndrome.

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Arachchillage, D R J; Efthymiou, M; Mackie, I J; Lawrie, A S; Machin, S J; Cohen, H

2014-11-01

Antiphospholipid antibodies may interfere with the anticoagulant activity of activated protein C (APC) to induce acquired APC resistance (APCr). To investigate the frequency and characteristics of APCr by using recombinant human APC (rhAPC) and endogenous protein C activation in antiphospholipid syndrome (APS). APCr was assessed in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls with rhAPC or Protac by thrombin generation. IgG anti-protein C and anti-protein S antibodies and avidity were assessed by ELISA. APS patients showed greater resistance to both rhAPC and Protac than non-APS patients and normal controls (median normalized endogenous thrombin potential inhibition): APS patients with rhAPC, 81.3% (95% confidence interval [CI] 75.2-88.3%; non-APS patients with rhAPC, 97.7% (95% CI 93.6-101.8%; APS patients with Protac, 66.0% (95% CI 59.5-72.6%); and non-APS patients with Protac, 80.7 (95% CI 74.2-87.2%). APS patients also had a higher frequency and higher levels of anti-protein C antibodies, with 60% (15/25) high-avidity antibodies. High-avidity anti-protein C antibodies were associated with greater APCr and with a severe thrombotic phenotype (defined as the development of recurrent VTE while patients were receiving therapeutic anticoagulation or both venous and arterial thrombosis). Twelve of 15 (80%) patients with high-avidity anti-protein C antibodies were classified as APS category I. Thrombotic APS patients showed greater APCr to both rhAPC and activation of endogenous protein C by Protac. High-avidity anti-protein C antibodies, associated with greater APCr, may provide a marker for a severe thrombotic phenotype in APS. However, in patients with category I APS, it remains to be established whether anti-protein C or anti-β2 -glycoprotein I antibodies are responsible for APCr. © 2014 International Society on Thrombosis and Haemostasis.

JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.

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Pósfai, Éva; Marton, Imelda; Király, Péter Attila; Kotosz, Balázs; Kiss-László, Zsuzsanna; Széll, Márta; Borbényi, Zita

2015-07-01

Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

iNKT Cells and Their potential Lipid Ligands during Viral Infection

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Anunya eOpasawatchai

2015-07-01

Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms

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Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2008-01-01

Atherosclerosis is a key factor in vascular disease, and cigarette smoking is a well-known risk factor that may induce an inflammatory response and enhance plaque formation in arteries. Thromboxane (Tx) is one key inflammatory mediator involved in the pathogenesis of cardiovascular disease....... The present study was designed to test if lipid soluble smoking particles (DSP) enhance TxA(2) receptor (TP) expression in rat mesenteric arteries, and if intracellular mitogen-activated protein kinase (MAPK) pathways play a role. Organ culture of rat mesenteric arteries in the presence of DSP (0.2 microl...

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

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Nicoletta Riva

2015-01-01

Full Text Available It is generally recommended that patients with splanchnic vein thrombosis (SVT should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y. The recurrence rate was highest in the first year after VKA discontinuation (8.2/100’pt-y and in patients with permanent risk factors (10.2/100’pt-y. Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups.

Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: A randomized, double-blind, placebo-controlled trial.

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Hernández-Velázquez, B; Camara-Lemarroy, C R; González-González, J A; García-Compean, D; Monreal-Robles, R; Cordero-Pérez, P; Muñoz-Espinosa, L E

2016-01-01

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an acute inflammatory response and melatonin has a variety of immunomodulatory and antioxidant effects studied experimentally in pancreatobiliary pathology. The aim of our study was to evaluate the effects of peri-procedural administration of melatonin on the inflammatory response and lipid peroxidation associated with ERCP. In this proof-of-concept clinical trial, 37 patients with a high probability of choledocholithiasis were randomized to receive peri-procedure (ERCP) melatonin or placebo. We measured the serum concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), lipid peroxidation, amylase, and liver function tests 24h before and after the procedure. We found no pre-procedure or post-procedure differences between the melatonin group or the placebo group (P>.05) in the serum concentrations of TNF-alpha (melatonin: 153.8 vs. 149.4ng/m; placebo: 103.5 vs. 107.3ng/ml), IL-6 (melatonin: 131.8 vs. 133.3ng/ml; placebo: 177.8 vs. 197.8ng/ml), or VEGF (melatonin: 157.3 vs. 157.8pg/ml; placebo: 97.3 vs. 97.8pg/ml), or in relation to lipid peroxidation (melatonin: 39.2 vs. 72.3μg/ml; placebo: 66.4 vs. 90.5μg/ml). After ERCP, a significant decrease in the AST, ALT, and total bilirubin levels was found only in the melatonin group (P<.05). The administration of melatonin was safe and tolerable. Melatonin is safe and tolerable in patients undergoing ERCP, but it does not appear to affect inflammatory cytokine concentrations or lipid peroxidation. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins.

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Florens, Nans; Calzada, Catherine; Lyasko, Egor; Juillard, Laurent; Soulage, Christophe O

2016-12-16

Chronic kidney disease (CKD) is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.

Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder.

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Zhao, Xiao-Juan; Yang, Yan-Zi; Zheng, Yan-Jing; Wang, Shan-Chun; Gu, Hong-Mei; Pan, Ying; Wang, Shui-Juan; Xu, Hong-Jiang; Kong, Ling-Dong

2017-08-15

Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels. Furthermore, magnesium isoglycyrrhizinate modulated lipid metabolism-related genes characterized by up-regulating peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1), and down-regulating sensor for fatty acids to control-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of fructose-fed rats, resulting in the reduction of triglyceride and total cholesterol levels. These effective actions were further confirmed in fructose-exposed BRL-3A and HepG2 cells. The molecular mechanisms underpinning these observations suggest that magnesium isoglycyrrhizinate may inhibit NF-κB/NLRP3 inflammasome activation to reduce immunological-inflammatory response, which in turn may prevent liver lipid metabolic disorder and accumulation under high fructose condition. Thus, blockade of NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury with

Spontaneous charged lipid transfer between lipid vesicles.

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Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

2017-10-03

An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

Myocardial contrast defect associated with thrombotic coronary occlusion: Pre-autopsy diagnosis of a cardiac death with post-mortem CT angiography

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Lee, Heon; Cha, Jang Gyu [Dept. of Radiology, Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Park, Hye Jin; Lee, Soo Kyoung; Yang, Kyung Moo [Dept. of Forensic Medicine, National Forensic Service, Wonju (Korea, Republic of)

2015-10-15

We report the case of a female who died of suspected acute myocardial infarction. Post-mortem CT angiography (PMCTA) was performed with intravascular contrast infusion before the standard autopsy, and it successfully demonstrated the complete thrombotic occlusion of a coronary artery and also a corresponding perfusion defect on myocardium. We herein describe the PMCTA findings of a cardiac death with special emphasis on the potential benefits of this novel CT technique in forensic practice.

Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy.

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Vesely, S K

2015-06-01

Patients who have recovered from their acute episode of acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery. © 2015 International Society on Thrombosis and Haemostasis.

Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

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Niaz Faraz

2010-01-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.

Mitochondrial dysfunction in human skeletal muscle biopsies of lipid storage disorder.

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Debashree, Bandopadhyay; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Natarajan, Archana; Christopher, Rita; Nalini, Atchayaram; Bindu, Parayil Sankaran; Gayathri, Narayanappa; Srinivas Bharath, Muchukunte Mukunda

2018-02-09

Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling, contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle. We carried out morphological and biochemical analysis of mitochondrial function in muscle biopsies of human subjects with LSDs (n = 7), compared to controls (n = 10). Routine histology, enzyme histochemistry and ultrastructural analysis indicated altered muscle cell morphology and mitochondrial structure. Protein profiling of the muscle mitochondria from LSD samples (n = 5) (vs. control, n = 5) by high-throughput mass spectrometric analysis revealed that impaired metabolic processes could contribute to mitochondrial dysfunction and ensuing myopathy in LSDs. We propose that impaired fatty acid and respiratory metabolism along with increased membrane permeability, elevated lipolysis and altered cristae entail mitochondrial dysfunction in LSDs. Some of these mechanisms were unique to LSD apart from others that were common to dystrophic and inflammatory muscle pathologies. Many differentially regulated mitochondrial proteins in LSD are linked with other human diseases, indicating that mitochondrial protection via targeted drugs could be a treatment modality in LSD and related metabolic diseases. © 2018 International Society for Neurochemistry.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

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Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects

OpenAIRE

Camargo-Ramos, Claudia Marcela; Correa-Bautista, Jorge Enrique; Correa-Rodríguez, María; Ramírez-Vélez, Robinson

2017-01-01

Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogotá, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow-mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and...

Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

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Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

2016-08-10

There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

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Ole A Andreassen

Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

Effects of curcumin on HDL functionality.

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Ganjali, Shiva; Blesso, Christopher N; Banach, Maciej; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

2017-05-01

Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

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Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Obesity-driven gut microbiota inflammatory pathways to metabolic syndrome

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Luiz Henrique Agra eCavalcante-Silva

2015-11-01

Full Text Available The intimate interplay between immune system, metabolism and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signalling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome.

Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal macrophages of rats.

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Rao, Y Poorna Chandra; Sugasini, D; Lokesh, B R

2016-10-28

Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to maintain serum lipids at desirable levels. Inflammation also plays an important role on cardiovascular health. The role of minor constituents present in unsaponifiable fraction (UF) of RBO on inflammatory markers is not well understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol (γ-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a period of 60 days. Groundnut oil with UF (GNO-N), UF removed GNO (GNO-MCR) and GNO-MCR supplemented with UF from RBO or γ-ORY was also used for comparison. The peritoneal macrophages from the rats were activated and pro-inflammatory mediators such as Reactive Oxygen Species (ROS), eicosanoids, cytokines, hydrolytic enzymes of lysosomal origin were monitored. The results indicated that UF of RBO and γ-ORY supplemented in the dietary oils play a significant role in reducing the secretion of pro-inflammatory mediators by macrophages. Hence γ-ORY in RBO significantly contributed to the anti-inflammatory properties of RBO. Copyright © 2016 Elsevier Inc. All rights reserved.

Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory effects.

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Briançon-Marjollet, Anne; Monneret, Denis; Henri, Marion; Joyeux-Faure, Marie; Totoson, Perle; Cachot, Sandrine; Faure, Patrice; Godin-Ribuot, Diane

2016-11-01

What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and

Anti-inflammatory properties of blended edible oil with synergistic antioxidants.

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Upadya, Haridas; Devaraju, C J; Joshi, Shashank R

2015-01-01

Blending of oil combines the potency of two edible oils and offers a balance of fatty acids. Various cooking preparations existing across different ethnicities and regions subject oil to different cooking temperatures thereby causing deterioration of the oil due to oxidative stress. In order to prevent the oxidative damage of unsaturated fatty acid, a blend of rice bran oil (RBO) and safflower oil (SO) (70:30) with an antioxidant technology was designed. A controlled trial was carried out to assess the efficacy of the blend on different biomarkers including lipid parameters and some important inflammatory markers that have the potency to lead to various lifestyle diseases. A prospective, double-blind, randomized, parallel group study (on 80 adult hyperlipidemic patients) was conducted for 3 months. During the study, all the subjects were recommended lifestyle modifications, which included, exercise regime and diet counseling; oil quantity consumed was 1 L/person/month for both the groups. The subjects were divided into two groups; one group, continued with their regularly consumed oil whereas, the other was given the test oil. Biomarkers assessed were lipid profile and seven other inflammatory markers were assessed. Low-density lipoprotein cholesterol (LDL-C) the primary marker for cardiovascular diseases showed a decrease of 56.07 ± 04.31 mg/dL and 31.98 ± 03.81 mg/dL (P < 0.001 by analysis of variance [ANOVA]) from baseline in test and control group, respectively, during 3 months. Similar reduction trends were observed for total cholesterol where -52.31 ± 13.04 mg/dL and 31.98 ± 04.12 mg/dL (P < 0.001 by ANOVA, between the groups) were seen in test and control group, respectively. Oxidized LDL and high sensitivity C-reactive protein showed a reduction of 2.23 ± 1.3 units/dL and 0.87 ± 2.85 mg/L in test group whereas; an increase of 1.04 ± 1.73 units/dL and 0.44 ± 2.37 mg/L was seen in the control group, respectively (P < 0.05 by Student's t-test, between

Anti-inflammatory properties of blended edible oil with synergistic antioxidants

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Haridas Upadya

2015-01-01

Full Text Available Background: Blending of oil combines the potency of two edible oils and offers a balance of fatty acids. Various cooking preparations existing across different ethnicities and regions subject oil to different cooking temperatures thereby causing deterioration of the oil due to oxidative stress. In order to prevent the oxidative damage of unsaturated fatty acid, a blend of rice bran oil (RBO and safflower oil (SO (70:30 with an antioxidant technology was designed. A controlled trial was carried out to assess the efficacy of the blend on different biomarkers including lipid parameters and some important inflammatory markers that have the potency to lead to various lifestyle diseases. Study Design: A prospective, double-blind, randomized, parallel group study (on 80 adult hyperlipidemic patients was conducted for 3 months. During the study, all the subjects were recommended lifestyle modifications, which included, exercise regime and diet counseling; oil quantity consumed was 1 L/person/month for both the groups. The subjects were divided into two groups; one group, continued with their regularly consumed oil whereas, the other was given the test oil. Biomarkers assessed were lipid profile and seven other inflammatory markers were assessed. Results: Low-density lipoprotein cholesterol (LDL-C the primary marker for cardiovascular diseases showed a decrease of 56.07 ± 04.31 mg/dL and 31.98 ± 03.81 mg/dL (P < 0.001 by analysis of variance [ANOVA] from baseline in test and control group, respectively, during 3 months. Similar reduction trends were observed for total cholesterol where −52.31 ± 13.04 mg/dL and 31.98 ± 04.12 mg/dL (P < 0.001 by ANOVA, between the groups were seen in test and control group, respectively. Oxidized LDL and high sensitivity C-reactive protein showed a reduction of 2.23 ± 1.3 units/dL and 0.87 ± 2.85 mg/L in test group whereas; an increase of 1.04 ± 1.73 units/dL and 0.44 ± 2.37 mg/L was seen in the control group

Serum lipids and lipoproteins in patients with psoriasis.

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Taheri Sarvtin, Mehdi; Hedayati, Mohammad Taghi; Shokohi, Tahereh; HajHeydari, Zohreh

2014-05-01

Psoriasis is a common chronic and recurrent inflammatory skin disorder characterized by hyperproliferation of keratinocytes and infiltration of T cells, monocytes/macrophages and neutrophils into dermal and epidermal layers of the skin. The prevalence of cardiovascular disorders in these patients is remarkably higher compared to normal individuals, which seems to be associated with the hyperlipidemia. This study was designed and conducted to investigate the serum lipid profile in psoriatic patients and its association with the severity of disease. This case-control study was performed on 50 plaque-type psoriasis patients and 50 healthy individuals as control, matched for age and sex. Blood samples were collected after 14 h fasting. Serum triglyceride, cholesterol and lipoproteins were assayed using the standard kit (made by Pars Azmon Co. Iran). Certain parameters, including serum triglyceride, cholesterol, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), were significantly higher in the case group compared to the controls (P lipoprotein (HDL) was significantly lower in the former (P < 0.001). In addition, there was a significant relationship between severity of psoriasis and serum lipid profile. The results have revealed the higher plasma level of lipids in psoriatic patients. This may elevate the risk of atherosclerosis, particularly cardiovascular disorders. Therefore, from the epidemiological point of view, screening psoriatic patients, particularly those with severe psoriasis, is recommended.

The adaptor protein alpha-syntrophin regulates adipocyte lipid droplet growth

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Eisinger, Kristina; Rein-Fischboeck, Lisa; Pohl, Rebekka; Meier, Elisabeth M.; Krautbauer, Sabrina; Buechler, Christa, E-mail: christa.buechler@klinik.uni-regensburg.de

2016-07-01

The scaffold protein alpha-syntrophin (SNTA) regulates lipolysis indicating a role in lipid homeostasis. Adipocytes are the main lipid storage cells in the body, and here, the function of SNTA has been analyzed in 3T3-L1 cells. SNTA is expressed in preadipocytes and is induced early during adipogenesis. Knock-down of SNTA in preadipocytes increases their proliferation. Proteins which are induced during adipogenesis like adiponectin and caveolin-1, and the inflammatory cytokine IL-6 are at normal levels in the mature cells differentiated from preadipocytes with low SNTA. This suggests that SNTA does neither affect differentiation nor inflammation. Expression of proteins with a role in cholesterol and triglyceride homeostasis is unchanged. Consequently, basal and epinephrine induced lipolysis as well as insulin stimulated phosphorylation of Akt and ERK1/2 are normal. Importantly, adipocytes with low SNTA form smaller lipid droplets and store less triglycerides. Stearoyl-CoA reductase and MnSOD are reduced upon SNTA knock-down but do not contribute to lower lipid levels. Oleate uptake is even increased in cells with SNTA knock-down. In summary, current data show that SNTA is involved in the expansion of lipid droplets independent of adipogenesis. Enhanced preadipocyte proliferation and capacity to store surplus fatty acids may protect adipocytes with low SNTA from lipotoxicity in obesity. - Highlights: • Alpha-syntrophin (SNTA) is expressed in 3T3-L1adipocytes. • SNTA knock-down in preadipocytes has no effect on adipogenesis. • Mature 3T3-L1 differentiated from cells with low SNTA form small lipid droplets. • SCD1 and MnSOD are reduced in adipocytes with low SNTA. • SCD1 knock-down does not alter triglyceride levels.

Endocarditis trombótica no bacteriana bivalvular asociada a cáncer y ecocardiograma transesofágico Bivalvular non bacterial thrombotic endocarditis associated with cancer and transesophageal echocardiography

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Marcelo Zylberman

2006-06-01

Full Text Available La endocarditis trombótica no bacteriana es la causa más frecuente de accidente cerebrovascular isquémico en pacientes con cáncer. En estos pacientes se hallaron vegetaciones valvulares hasta en el 9% de las autopsias. Sin embargo, la afección bivalvular es poco frecuente, observándose en el 9% de las endocarditis trombóticas. Se presenta una paciente con cáncer de ovario que presentó afasia e imágenes compatibles con isquemia cerebral. El ecocardiograma transtorácico fue normal. El ecocardiograma transesofágico evidenció vegetaciones en las válvulas aórtica y mitral. Se enfatiza la importancia de sospechar endocarditis trombótica no bacteriana en enfermos con cáncer y embolismo sistémico y en la escasa frecuencia de afección bivalvular.Non bacterial thrombotic endocarditis is the most frequent cause of ischemic stroke in cancer patients. Up to 9% of autopsies of cancer patients show non infectious valvular masses. However, bivalvular involvement is not frequently occurring in 9% of non bacterial thrombotic endocarditis. We report a patient with ovarian cancer who presented aphasia. The MRI was compatible with cerebral ischemia. The transthoracic echocardiogram was normal and a transesophageal echocardiogram showed vegetations in aortic and mitral valves. We emphasize the importance of suspecting non bacterial thrombotic endocarditis in patients with cancer and systemic embolism and the low frequency of bivalvular involvement.

Synthesis of new piroxicam derivatives and their influence on lipid bilayers.

Science.gov (United States)

Szczęśniak-Sięga, Berenika; Maniewska, Jadwiga; Poła, Andrzej; Środa-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

2014-01-01

A novel series of potentially biologically active 1,2-benzothiazine 1,1-dioxides--analogs of piroxicam (a recognized non-steroidal anti-inflammatory drug) were synthesized from commercially available saccharin. All of the synthesized compounds were subjected to preliminary evaluation for their ability to interact with lipid bilayers. The influence of the new derivatives of piroxicam on liposomes made of EYPC was investigated by fluorescence spectroscopy with two fluorescent probes--Laurdan and Prodan. All the studied compounds showed an interaction with model membranes.

Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

International Nuclear Information System (INIS)

Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke

1995-01-01

A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author)

Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke [Okayama Univ. (Japan). School of Medicine

1995-01-01

A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author).

Hyperhomocysteinemia - an additional risk factor of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome

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I. E. Shirokova

2003-01-01

Full Text Available Objective. To assess homocystein (HC level in systemic lupus erythematosus (SLE with antiphospholipid syndrome (APS and its relation to thrombosis development and blood lipide spectrum disturbances. Material and methods. 32 pts (12 male and 20 female with mean age 36 12 years and mean disease duration 13 11 years were included. 8 pts had SLE without APS, 13 - SLE with APS and 11 - primary APS (PAPS. All pts were divided into 2 groups depending on blood HC level. 26 pts with HC level more than 12 mcg/d! were included In group 1 and 6 pts with HC level less than 12 mcg/dl - in group 2. HC level was measured with high efficacious liquid chromatography (HELC. Lipid-protein blood spectrum was assessed in all pts. Results. Elevated HC level was revealed in 26 from 32 pts: in 16 with SLE (including 12 pts with APS and in 10 with PAPS. HC concentration did not depend on APS presence, but frequence of hyperhomocysteinemia (HHC significantly associated with APS and thrombotic complications. 20 from 26 (76,9% pts with HHC had thrombosis history. Only I from 6 (16,7% pts with normal HC level had thrombosis history (exact Fisher test p=0,02. HC level did not depend on age and sex. Changes of blood lipid-protein indices were revealed in most pts. Lipid spectrum disturbances were confined largely to cholesterol elevation due to increase of atherogenic lipoproteins cholesterol. Only 22% of pts showed decrease of antiatherogenic lipoproteins concentration. Bblood lipid-protein spectrum indices did not depend on HC level. Conclusion. HHC is present in 84,6% of pts with APS (primary and secondary. In pts with APS HHC is more frequent than in pts without APS. HHC is associated with thrombotic complications. HHC and lipid-protein spectrum disturbances are independent risk factors of thrombotic complications in pts with SLE and APS.

Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

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Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

2014-09-01

Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Anti-Inflammatory Effects of Interleukin-19 in Vascular Disease

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Ross N. England

2012-01-01

Full Text Available Despite aggressive dietary modification, lipid-lowering medications, and other interventional medical therapy, vascular disease continues to be a leading cause of mortality in the western world. It is a significant medical and socioeconomic problem contributing to mortality of multiple diseases including myocardial infarction, stroke, renal failure, and peripheral vascular disease. Morbidity and mortality of vascular disease are expected to worsen with the increasing number of patients with comorbid conditions such as obesity, metabolic syndrome, and diabetes mellitus type 2. Vascular diseases such as atherosclerosis, restenosis, and allograft vasculopathy are recognized to be driven by inflammation, and as such, cytokines which mediate inflammation not only represent important targets of rational therapy, but also can be considered as possible therapeutic modalities themselves. In this paper, we will examine the role of inflammatory cytokines and lymphocyte Th1/Th2 polarity in vascular inflammation, with a focus on atherosclerotic vascular disease. We will then introduce a recently described Th2 interleukin, interleukin-19 (IL-19, as a previously unrecognized mediator of vascular inflammatory disorders. We will review our current understanding of this interleukin in health and disease and present the possibility that IL-19 could represent a potential therapeutic to combat vascular inflammatory disease.

Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro

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Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhi, Wenbing; Liu, Fang; He, Zehong; Wang, Xiuei; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn

2017-04-01

Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I. - Highlights: • AO-I inhibited Ox-LDL-induced VSMCs proliferation and migration. • AO-I alleviated inflammatory response via inhibiting TNF-α, IL-6 and NO production. • AO-I restored HO-1 expression and down-regulated PCNA expression. • MCP-1 overexpression is potentially regulated by NF-κB and p38 MAPK pathway. • AO-I possesses strong anti-lipid peroxidation effect.

The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura

KAUST Repository

Lancellotti, S.

2015-08-13

Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli – An Anti-thrombotic Mechanism in the Kidney

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Ramesh Tati

2017-02-01

Full Text Available Adequate cleavage of von Willebrand factor (VWF prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3, cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura

KAUST Repository

Lancellotti, S.; Peyvandi, F.; Pagliari, M.; Cairo, A.; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, I.; Mastrangelo, S.; Cavallo, Luigi; Oliva, R.; De Cristofaro, R.

2015-01-01

Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

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Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

2013-01-01

Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

NETosis before and after Hyperglycemic Control in Type 2 Diabetes Mellitus Patients.

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Agostina Carestia

Full Text Available Diabetes is characterized by chronic inflammation, endothelial dysfunction, increased risk of infections and early cardiovascular disease. By releasing neutrophil extracellular traps (NETs, neutrophils kill bacteria and exert pro-inflammatory and pro-thrombotic activities. Increased NETosis has been found in cross-sectional studies including treated type 2 diabetes mellitus (T2DM patients. In this study, we determined whether the ability of neutrophils to form NETs differs in diabetic patients pre- and post-hyperglycemic control versus healthy donors (HD, and the relationship between NETosis with pro-thrombotic, pro-inflammatory biomarkers and thrombotic clinical events.Diabetic patients recently diagnosed and after 6 and 12 months of treatment (N = 25 and HD (N = 25 were included. NET formation was studied by microscopy and fluorometry. Nucleosomes, HNE-DNA complexes, von Willebrand factor (vWF, IL6 and TNFα plasma levels were measured by ELISA and P-selectin on the platelet surface was assessed by cytometry.Basal levels of NETs in recently diagnosed T2DM patients were higher compared to HD. While TNFα stimulation of control neutrophils resulted in DNA release, patient neutrophils were not responsive. Although glycemia decreased after 6 months of metformin treatment, basal and TNFα and PMA-stimulated NETs reached normal values after 12 months. Compared to controls, nucleosomes, HNE-DNA complexes, IL-6 and TNFα levels were increased in recently diagnosed patients and decreased after 12 months of treatment. P-selectin and vWF levels were similar in both populations.Our data suggest that NETs could represent a biomarker for T2DM. Increased NETosis in T2DM patients does not appear to be the consequence of impaired glycemic control but rather due to pro-inflammatory cytokines and is not related to thrombotic events.

Acquired Thrombotic Thrombocytopenic Purpura in a Patient with Pernicious Anemia

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Ramesh Kumar Pandey

2017-01-01

Full Text Available Introduction. Acquired thrombotic thrombocytopenic purpura (TTP has been associated with different autoimmune disorders. However, its association with pernicious anemia is rarely reported. Case Report. A 46-year-old male presented with blood in sputum and urine for one day. The vitals were stable. The physical examination was significant for icterus. Lab tests’ results revealed leukocytosis, macrocytic anemia, severe thrombocytopenia, renal dysfunction, and unconjugated hyperbilirubinemia. He had an elevated LDH, low haptoglobin levels with many schistocytes, nucleated RBCs, and reticulocytes on peripheral smear. Low ADAMTS13 activity (<10% with elevated ADAMTS13 antibody clinched the diagnosis of severe acquired TTP, and plasmapheresis was started. There was an initial improvement in his hematological markers, which were however not sustained on discontinuation of plasmapheresis. For his refractory TTP, he was resumed on daily plasmapheresis and Rituximab was started. Furthermore, the initial serum Vitamin B12 and reticulocyte index were low in the presence of anti-intrinsic factor antibody. So with the concomitant diagnosis of pernicious anemia, Vitamin B12 was supplemented. The rest of the immunological workups were negative. Subsequently, his symptoms resolved and his hematological parameters improved. Discussion. While pernicious anemia can masquerade as TTP, an actual association between the two can also occur and needs further evaluation and characterization.

Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

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Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

2015-01-01

Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

Lipids, lipid bilayers and vesicles as seen by neutrons

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Seto, Hideki

2011-01-01

Lipid molecules self-assemble into bilayers in water with their hydrocarbon chains facing inward due to their amphiphilic nature. The structural and dynamical properties of lipids and lipid bilayers have been studied by neutron scattering intensively. In this article, 3 topics are shown as typical examples. 1) a time-resolved small-angle neutron scattering on uni-lamellar vesicles composed of deuterated and protonated lipids to determine lipid kinetics, 2) small-angle neutron scattering to investigate spontaneous formation of nanopores on uni-lamellar vesicles, and 3) neutron spin echo study to determine bending modulus of lipid bilayers. (author)

Effect of piroxicam on lipid membranes: Drug encapsulation and gastric toxicity aspects.

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Wilkosz, Natalia; Rissanen, Sami; Cyza, Małgorzata; Szybka, Renata; Nowakowska, Maria; Bunker, Alex; Róg, Tomasz; Kepczynski, Mariusz

2017-03-30

Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. Copyright © 2017 Elsevier B.V. All rights reserved.

Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

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Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

2015-01-01

Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins

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Nans Florens

2016-12-01

Full Text Available Chronic kidney disease (CKD is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.

Association between tetrodotoxin resistant channels and lipid rafts regulates sensory neuron excitability.

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Alessandro Pristerà

Full Text Available Voltage-gated sodium channels (VGSCs play a key role in the initiation and propagation of action potentials in neurons. Na(V1.8 is a tetrodotoxin (TTX resistant VGSC expressed in nociceptors, peripheral small-diameter neurons able to detect noxious stimuli. Na(V1.8 underlies the vast majority of sodium currents during action potentials. Many studies have highlighted a key role for Na(V1.8 in inflammatory and chronic pain models. Lipid rafts are microdomains of the plasma membrane highly enriched in cholesterol and sphingolipids. Lipid rafts tune the spatial and temporal organisation of proteins and lipids on the plasma membrane. They are thought to act as platforms on the membrane where proteins and lipids can be trafficked, compartmentalised and functionally clustered. In the present study we investigated Na(V1.8 sub-cellular localisation and explored the idea that it is associated with lipid rafts in nociceptors. We found that Na(V1.8 is distributed in clusters along the axons of DRG neurons in vitro and ex vivo. We also demonstrated, by biochemical and imaging studies, that Na(V1.8 is associated with lipid rafts along the sciatic nerve ex vivo and in DRG neurons in vitro. Moreover, treatments with methyl-β-cyclodextrin (MβCD and 7-ketocholesterol (7KC led to the dissociation between rafts and Na(V1.8. By calcium imaging we demonstrated that the lack of association between rafts and Na(V1.8 correlated with impaired neuronal excitability, highlighted by a reduction in the number of neurons able to conduct mechanically- and chemically-evoked depolarisations. These findings reveal the sub-cellular localisation of Na(V1.8 in nociceptors and highlight the importance of the association between Na(V1.8 and lipid rafts in the control of nociceptor excitability.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice.

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Carlson, Sarah J; Nandivada, Prathima; Chang, Melissa I; Mitchell, Paul D; O'Loughlin, Alison; Cowan, Eileen; Gura, Kathleen M; Nose, Vania; Bistrian, Bruce R; Puder, Mark

2015-02-01

Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome

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Erkan, Doruk; Salmon, Jane E.

2016-01-01

Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous, small vessel) and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe form of the disease, characterized by multiple organ thromboses occurring in a short period and commonly associated with thrombotic microangiopathy (TMA). Similar to patients with complement regulatory gene mutations developing TMA, increased complement activation on endothelial cells plays a role in hypercoagulability in aPL-positive patients. In mouse models of APS, activation of the complement is required and interaction of complement (C) 5a with its receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated pregnancy loss and thrombosis in these experimental models. Clinical studies of anti-C5 monoclonal antibody in aPL-positive patients are limited to a small number of case reports. Ongoing and future clinical studies of complement inhibitors will help determine the role of complement inhibition in the management of aPL-positive patients. PMID:27020721

Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

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Aimee L. Dordevic

2015-07-01

Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

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Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine

2014-01-01

ABSTRACT Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. PMID:25139899

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway

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Wang Jun

2012-10-01

Full Text Available Abstract Background Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS to imitate inflammatory conditions. Results In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4 antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB, which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1, compared with transforming growth factor-β1 (TGF-β1. Conclusions Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway.

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Wang, Jun; Si, Yanfang; Wu, Chen; Sun, Lu; Ma, Yudong; Ge, Aili; Li, Baomin

2012-10-17

Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1). Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of

Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

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João Tadeu Damian Souto Filho

2011-01-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

An increase in epicardial fat in women is associated with thrombotic risk.

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Basurto Acevedo, Lourdes; Barrera Hernández, Susana; Fernández Muñoz, María de Jesús; Saucedo García, Renata Patricia; Rodríguez Luna, Ana Karen; Martínez Murillo, Carlos

2018-01-29

A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of Lipid Peroxidation-Derived α, β-Unsaturated Aldehydes in Vascular Dysfunction

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Seung Eun Lee

2013-01-01

Full Text Available Vascular diseases are the most prominent cause of death, and inflammation and vascular dysfunction are key initiators of the pathophysiology of vascular disease. Lipid peroxidation products, such as acrolein and other α, β-unsaturated aldehydes, have been implicated as mediators of inflammation and vascular dysfunction. α, β-Unsaturated aldehydes are toxic because of their high reactivity with nucleophiles and their ability to form protein and DNA adducts without prior metabolic activation. This strong reactivity leads to electrophilic stress that disrupts normal cellular function. Furthermore, α, β-unsaturated aldehydes are reported to cause endothelial dysfunction by induction of oxidative stress, redox-sensitive mechanisms, and inflammatory changes such as induction of cyclooxygenase-2 and cytokines. This review provides an overview of the effects of lipid peroxidation products, α, β-unsaturated aldehydes, on inflammation and vascular dysfunction.

Antioxidant and Anti-Inflammatory Activities in Extracts from Minke Whale (Balaenoptera acutorostrata Blubber

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Mari Johannessen Walquist

2017-01-01

Full Text Available Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-PUFA is commonly recognized to reduce cardiovascular disease (CVD. In previous studies, cold-pressed whale oil (CWO and cod liver oil (CLO were given as a dietary supplement to healthy volunteers. Even though CWO contains less than half the amount of LC-n3-PUFA of CLO, CWO supplement resulted in beneficial effects on anti-inflammatory and CVD risk markers compared to CLO. In the present study, we prepared virtually lipid-free extracts from CWO and CLO and evaluated the antioxidative capacity (AOC and anti-inflammatory effects. Oxygen radical absorbance capacity (ORAC and ferric reducing antioxidant power (FRAP assays were used to test the AOC, and the results indicated high levels of antioxidants present in all extracts. The anti-inflammatory effects of the extracts were tested with lipopolysaccharide- (LPS- treated THP-1 cells, measuring its ability to reduce cytokine and chemokine secretion. Several CWO extracts displayed anti-inflammatory activity, and a butyl alcohol extract of CWO most effectively reduced TNF-α (50%, p<0.05 and MCP-1 (85%, p<0.001 secretion. This extract maintained a stable effect of reducing MCP-1 secretion (60%, p<0.05 even after long-term storage. In conclusion, CWO has antioxidant and anti-inflammatory activities that may act in addition to its well-known LC-n3-PUFA effects.

Level of inflammatory factors in chronic hemodialysis patients with and without cardiovascular disease

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Shahram Taheri

2017-01-01

Full Text Available Background: Considering the existence of controversies about the predictive value of inflammatory markers for cardiovascular disease (CVD, we aimed to compare the level of high-sensitivity C-reactive protein (hs-CRP and interlukin-6 (IL-6 level in chronic hemodialysis (HD patients with and without CVD. Materials and Methods: In this historical cohort study, HD patients with and without CVD disease were enrolled. The presence of CVD risk factors, level of inflammatory factors including IL-6 and hs-CRP as well as lipid levels, fasting blood sugar, and other biochemical factors were compared in two studied groups. Results: During the study, eighty HD patients with (n = 40 and without (n = 40 CVD were enrolled. Diabetes was more prevalent among HD patients with CVD than those without CVD (P 0.05. Univariate analysis of variance test indicated that there was not any significant relationship between hs-CRP and CVD (P > 0.05. Conclusion: The findings indicated that the level of inflammatory factors including hs-CRP and IL-6 are not significantly different in HD patients with and without CVD. However, for obtaining more definite conclusion in this field and evaluation their predicting role in this field, it is recommended to study other novel inflammatory markers as well as the additive effect of the inflammatory factors with traditional ones in larger sample size and longer follow-up.

Lipid Cell Biology: A Focus on Lipids in Cell Division.

Science.gov (United States)

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Lipidomic Approaches towards Deciphering Glycolipids from Microalgae as a Reservoir of Bioactive Lipids

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Elisabete da Costa

2016-05-01

Full Text Available In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs are quite abundant in microalgae and are considered an important source of fatty acids (FAs. GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids and often contain polyunsaturated fatty acids (PUFAs like n-3 α-linolenic (ALA 18:3, eicosapentaenoic (EPA, 20:5 and docosahexaenoic (DHA, 22:6. GLs comprise three major classes: monogalactosyldiacyl glycerolipids (MGDGs, digalactosyl diacylglycerolipids (DGDGs and sulfoquinovosyl diacylglycerolipids (SQDGs, whose composition in FA directly depends on the growth conditions. Some of these lipids are high value-added compounds with antitumoral, antimicrobial and anti-inflammatory activities and also with important nutritional significance. To fully explore GLs’ bioactive properties it is necessary to fully characterize their structure and to understand the relation between the structure and their biological properties, which can be addressed using modern mass spectrometry (MS-based lipidomic approaches. This review will focus on the up-to-date FA composition of GLs identified by MS-based lipidomics and their potential as phytochemicals.

Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin.

Science.gov (United States)

Bergheim, Ina; Weber, Synia; Vos, Miriam; Krämer, Sigrid; Volynets, Valentina; Kaserouni, Seline; McClain, Craig J; Bischoff, Stephan C

2008-06-01

Consumption of refined carbohydrates in soft drinks has been postulated to be a key factor in the development of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to test the effects of ad libitum access to different sugars consumed in drinking water on hepatic fat accumulation. For 8 weeks, C57BL/J6 mice had free access to solutions containing 30% glucose, fructose, sucrose, or water sweetened with artificial sweetener (AS) or plain water. Body weight, caloric intake, hepatic steatosis and lipid peroxidation were assessed. Total caloric intake and weight gain were highest in mice exposed to glucose. In contrast, hepatic lipid accumulation was significantly higher in mice consuming fructose compared to all other groups. Moreover, endotoxin levels in portal blood and lipid peroxidation as well as TNFalpha expression were significantly higher in fructose fed mice than in all other groups. Concomitant treatment of fructose fed mice with antibiotics (e.g., polymyxin B and neomycin) markedly reduced hepatic lipid accumulation in fructose fed mice. These data support the hypothesis that high fructose consumption may not only lead to liver damage through overfeeding but also may be directly pro-inflammatory by increasing intestinal translocation of endotoxin.

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease

OpenAIRE

Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark; Nielsen, Ole Haagen; Reed, Michelle A.C.; Atkins, Karen; Günther, Ulrich Leonhard; Hao, Fuhua; Wang, Yulan

2017-01-01

Background One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnos...

The clinical expression of hereditary protein C and protein S deficiency: : a relation to clinical thrombotic risk-factors and to levels of protein C and protein S

NARCIS (Netherlands)

Henkens, C. M. A.; van der Meer, J.; Hillege, J. L.; Bom, V. J. J.; Halie, M. R.; van der Schaaf, W.

We investigated 103 first-degree relatives of 13 unrelated protein C or protein S deficient patients to assess the role of additional thrombotic risk factors and of protein C and protein S levels in the clinical expression of hereditary protein C and protein S deficiency. Fifty-seven relatives were

Immune response to Lactobacillus plantarum expressing Borrelia burgdorferi OspA is modulated by the lipid modification of the antigen.

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Beatriz del Rio

2010-06-01

Full Text Available Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response.We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively.Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

Science.gov (United States)

Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

2015-02-01

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency ( 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

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Bendapudi, Pavan K; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S

2015-12-01

The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P 10% varied significantly across the institutions in our consortium (13·2-63·8%, P 10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE. © 2015 John Wiley & Sons Ltd.

Late endovascular removal of Günther-Tulip inferior vena cava filter and stent reconstruction of chronic post-thrombotic iliocaval obstruction after 4753 days of filter dwell time: a case report with review of literature.

Science.gov (United States)

Doshi, Mehul Harshad; Narayanan, Govindarajan

2016-12-01

Chronic post-thrombotic obstruction of the inferior vena cava (IVC) or iliocaval junction is an uncommon complication of long indwelling IVC filter. When such an obstruction is symptomatic, endovascular treatment options include stent placement with or without filter retrieval. Filter retrieval becomes increasingly difficult with longer dwell times. We present a case of symptomatic post-thrombotic obstruction of the iliocaval junction related to Günther-Tulip IVC filter (Cook Medical Inc, Bloomington, IN) with dwell time of 4753 days, treated successfully with endovascular filter removal and stent reconstruction. Filter retrieval and stent reconstruction may be a treatment option in symptomatic patients with filter-related chronic IVC or iliocaval junction obstruction, even after prolonged dwell time.

Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies.

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von Baeyer, Hans

2002-08-01

Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence-based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)-associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy-associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post-bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA-associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX/FFP) over plasma transfusion in the management of TTP/HUS. The results prove the greater clinical success of the latter type of plasma administration. Standard PEX/FFP has reduced the

Lipid Structure in Triolein Lipid Droplets

DEFF Research Database (Denmark)

Chaban, Vitaly V; Khandelia, Himanshu

2014-01-01

of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations......Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...

Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

OpenAIRE

Francesco Caso; Luisa Costa; Donato Rigante; Orso Maria Lucherini; Paolo Caso; Vittoria Bascherini; Bruno Frediani; Rolando Cimaz; Edoardo Marrani; Laura Nieves-Martín; Mariangela Atteno; Carmela G. L. Raffaele; Giusyda Tarantino; Mauro Galeazzi; Leonardo Punzi

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molec...

Bioactive lipids as radioprotectors and potentiators of radiotherapy

International Nuclear Information System (INIS)

Das, Undurti N.

2016-01-01

Selective elimination of tumor cells with little or no effects on normal cells is desirable for the treatment of cancer. Radiotherapy, a well accepted form of cancer therapy, is associated with significant side effects that need to be eliminated or dampened. Our studies revealed that radiation can produce significant changes in the metabolism of essential fatty acids that could be related to its actions and side effects. It was noted that UVB exposed skin produced PGE2, PGF2a and PGE3 that accompany the erythema in the first 24-48 h, associated with increased COX-2 expression at 24 h. Leukocyte chemoattractants 11-, 12- and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3"+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. On the other hand, anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Thus, skin lesions are characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution. The enhanced expression of 15-HETE at 72 h is interesting since it forms the precursor to antiinflammatory bioactive lipids. We and others also showed that the anti-cancer action of radiation and chemotherapeutic drugs can be augmented by certain polyunsaturated fatty acids with little or no action on normal cells. Even tumor cell drug resistance could be reversed by these bioactive lipids. Our recent studies revealed that these bioactive lipids also prevent genetic damage induced by radiation and other drugs. These studies imply that employing certain bioactive lipids may be exploited as radiation protective molecules and as enhancers of the anti-cancer action of radiation in the therapy of cancer. (author)

The efficacy of Isotretinoin-loaded solid lipid nanoparticles in comparison to Isotrex® on acne treatment

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Shiva Golmohammadzadeh

2013-01-01

Full Text Available Abstract: Topical retinoids are considered as the first line therapy in the treatment of acne vulgaris, but they are associated with cutaneous irritation. In this study, isotretinoin-loaded solid lipid nanoparticles(IT-SLN were prepared to treat the mild to moderate acne. Also using IT-SLN would minimize IT adverse effects in comparison to commercial product, Isotrex®. This study was conducted to prepare and characterize IT-SLN and assessing the efficiency of IT-SLN comparing to Isotrex® acne. IT-SLN was prepared using hot high pressure homogenization method.  IT-SLN contained 0.05% IT in 5% of lipid phase (Glyceryl monostearate- GMS and tween 80 (2.5 % w/v was used as surfactant in the aqueous phase. IT-SLN was characterized by particle size analyzing, differential scanning calorimetry and transmission electron microscopy. Encapsulation efficacy was also obtained using spectrophotometry. The efficacy of IT-SLN was evaluated in a randomized, single-blind, parallel-group study and compared with Isotrex®. Forty patients encountered in the study and divided in two groups. Treatment regimen was once-nightly topical administration accompanied with topical administration of clindamycin 2% solution twice a day for 8 weeks. The particle size of IT-SLN was around 60 nm with PDI of 0.4 and zeta potential was about -40 mV. Encapsulation efficacy of IT in SLN in crystalline form was 84±0.21%. IT-SLN produced significantly better treatment than Isotrex® in both non-inflammatory and inflammatory lesions according to its recovery percent after 8 weeks. Also IT-SLN gained better global assessment scores. Our results showed that IT-SLN had higher efficacy than Isotrex® to clear non-inflammatory and inflammatory lesions.

Analysis of lipid profile in lipid storage myopathy.

Science.gov (United States)

Aguennouz, M'hammed; Beccaria, Marco; Purcaro, Giorgia; Oteri, Marianna; Micalizzi, Giuseppe; Musumesci, Olimpia; Ciranni, Annmaria; Di Giorgio, Rosa Maria; Toscano, Antonio; Dugo, Paola; Mondello, Luigi

2016-09-01

Lipid dysmetabolism disease is a condition in which lipids are stored abnormally in organs and tissues throughout the body, causing muscle weakness (myopathy). Usually, the diagnosis of this disease and its characterization goes through dosage of Acyl CoA in plasma accompanied with evidence of droplets of intra-fibrils lipids in the patient muscle biopsy. However, to understand the pathophysiological mechanisms of lipid storage diseases, it is useful to identify the nature of lipids deposited in muscle fiber. In this work fatty acids and triglycerides profile of lipid accumulated in the muscle of people suffering from myopathies syndromes was characterized. In particular, the analyses were carried out on the muscle biopsy of people afflicted by lipid storage myopathy, such as multiple acyl-coenzyme A dehydrogenase deficiency, and neutral lipid storage disease with myopathy, and by the intramitochondrial lipid storage dysfunctions, such as deficiencies of carnitine palmitoyltransferase II enzyme. A single step extraction and derivatization procedure was applied to analyze fatty acids from muscle tissues by gas chromatography with a flame ionization detector and with an electronic impact mass spectrometer. Triglycerides, extracted by using n-hexane, were analyzed by high performance liquid chromatography coupled to mass spectrometer equipped with an atmospheric pressure chemical ionization interface. The most representative fatty acids in all samples were: C16:0 in the 13-24% range, C18:1n9 in the 20-52% range, and C18:2n6 in the 10-25% range. These fatty acids were part of the most representative triglycerides in all samples. The data obtained was statistically elaborated performing a principal component analysis. A satisfactory discrimination was obtained among the different diseases. Using component 1 vs component 3 a 43.3% of total variance was explained. Such results suggest the important role that lipid profile characterization can have in supporting a correct

Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response.

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William E Greineisen

Full Text Available Lipid bodies (LB are reservoirs of precursors to inflammatory lipid mediators in immunocytes, including mast cells. LB numbers are dynamic, increasing dramatically under conditions of immunological challenge. We have previously shown in vitro that insulin-influenced lipogenic pathways induce LB biogenesis in mast cells, with their numbers attaining steatosis-like levels. Here, we demonstrate that in vivo hyperinsulinemia resulting from high fat diet is associated with LB accumulation in murine mast cells and basophils. We characterize the lipidome of purified insulin-induced LB, and the shifts in the whole cell lipid landscape in LB that are associated with their accumulation, in both model (RBL2H3 and primary mast cells. Lipidomic analysis suggests a gain of function associated with LB accumulation, in terms of elevated levels of eicosanoid precursors that translate to enhanced antigen-induced LTC4 release. Loss-of-function in terms of a suppressed degranulation response was also associated with LB accumulation, as were ER reprogramming and ER stress, analogous to observations in the obese hepatocyte and adipocyte. Taken together, these data suggest that chronic insulin elevation drives mast cell LB enrichment in vitro and in vivo, with associated effects on the cellular lipidome, ER status and pro-inflammatory responses.

Chlamydia trachomatis Is Responsible for Lipid Vacuolation in the Amniotic Epithelium of Fetal Gastroschisis.

Science.gov (United States)

Feldkamp, Marcia L; Ward, Diane M; Pysher, Theodore J; Chambers, Christina T

2017-07-17

Vacuolated amniotic epithelium with lipid droplets in gastroschisis placentas is an unusual finding. Mass spectrometry of lipid droplets identified triglycerides, ester-linked to an unusual pattern of fatty acids. We hypothesize that these findings result from a Chlamydia trachomatis infection during the periconceptional period. The rising incidence of chlamydia infections has paralleled the increasing prevalence of gastroschisis among women less than 25 years of age. Histologically, young women are at greatest risk for a chlamydia infection due to their immature columnar epithelium, the preferential site for attachment of Chlamydia trachomatis infectious particle (elementary body). Chlamydia trachomatis survive in an inclusion, relying on its host to acquire essential nutrients, amino acids, and nucleotides for survival and replication. If essential nutrients are not available, the bacteria cannot replicate and may be trafficked to the lysosome for degradation or remain quiescent, within the inclusion, subverting innate immunologic clearance. Chlamydiae synthesize several lipids (phosphatidylethanolamine, phosphatidylserine, and phosphoatidylglycerol); however, their lipid content reveal eukaryotic lipids (sphingomyelin, cholesterol, phosphatidylcholine, and phosphatidylinositol), evidence that chlamydiae "hijack" host lipids for expansion and replication. The abnormal amniotic epithelial findings are supported by experimental evidence of the trafficking of host lipids into the chlamydiae inclusion. If not lethal, what harm will elementary bodies inflict to the developing embryo? Do these women have a greater pro-inflammatory response to an environmental exposure, whether cigarette smoking, change in partner, or a pathogen? Testing the hypothesis that Chlamydia trachomatis is responsible for amniotic epithelium vacuoles will be a critical first step. Birth Defects Research 109:1003-1010, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Alterations in lipid metabolism and antioxidant status in lichen planus

Directory of Open Access Journals (Sweden)

Falguni H Panchal

2015-01-01

Full Text Available Background: Lichen planus (LP, a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis. Aim and Objective: The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients. Materials and Methods: The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP, malondialdehyde (MDA, and catalase (CAT activity. Results: Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC, triglycerides, and low-density lipoprotein cholesterol (LDL-C along with decreased levels of high-density lipoprotein cholesterol (HDL-C in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96 was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76 was seen between CAT activity and LP duration. Conclusion: Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in

The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

International Nuclear Information System (INIS)

Xian, Wenjing; Wu, Yan; Xiong, Wei; Li, Longyan; Li, Tong; Pan, Shangwen; Song, Limin; Hu, Lisha; Pei, Lei; Yao, Shanglong

2016-01-01

Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

Energy Technology Data Exchange (ETDEWEB)

Xian, Wenjing [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wu, Yan [Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiong, Wei [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Longyan [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Tong [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pan, Shangwen [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Song, Limin [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Hu, Lisha [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pei, Lei [Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yao, Shanglong, E-mail: ysltian@163.com [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); and others

2016-03-25

Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

MR imaging of abscess by use of lipid-coated iron oxide particles

International Nuclear Information System (INIS)

Chan, T.W.; Eley, C.G.S.; Kressel, H.Y.

1990-01-01

The authors of this paper investigate the potential application of lipid-coated iron oxide particles as an MR contrast agent for imaging inflammatory process by using a rat subcutaneous abscess model induced by turpentine. Ten male Sprague-Dawley rats received subcutaneous injections of 0.1 mL of turpentine in the flank. At 24-36 hours later, the rats developed a subcutaneous abscess of 1-1.8 cm. An intravenous injection of lipid-coated iron oxide particles, Ferrosome (Vestar) at doses of 25, 40, 100, 200 μg/kg was administered. The animals were imaged at 12-24 hours later on a 1.5-T magnet using a 3-inch (7.62-cm) surface coil. Two animals were also imaged 5 days later. T1-weighted, T2-weighted, and multiplanar gradient-recalled (MPGR) sequences were obtained. The abscess was then excised and examined with routine H-E and iron staining

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

Science.gov (United States)

Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

2010-03-01

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

International Nuclear Information System (INIS)

Anantachaisilp, Suranan; Smith, Siwaporn Meejoo; Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong; Pratontep, Sirapat; Puttipipatkhachorn, Satit

2010-01-01

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ( 1 H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1 H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1 H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

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Lau, Y C; Xiong, Q; Ranjit, P; Lip, G Y H; Blann, A D

2016-08-01

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

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Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

2010-01-01

Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats.

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Longhi, Rafael; Almeida, Roberto Farina; Machado, Letiane; Duarte, Maria Marta Medeiros Frescura; Souza, Débora Guerini; Machado, Priscila; de Assis, Adriano Martimbianco; Quincozes-Santos, André; Souza, Diogo Onofre

2017-04-01

Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats. Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed. Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.

High content cell-based assay for the inflammatory pathway

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Mukherjee, Abhishek; Song, Joon Myong

2015-07-01

Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and molecular mechanisms underlying the inflammatory pathways may be effective in targeting and modulating their outcome. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that effectively combines the pro-inflammatory features with the pro-apoptotic potential. Increased levels of TNF-α observed during acute and chronic inflammatory conditions are believed to induce adverse phenotypes like glucose intolerance and abnormal lipid profile. Natural products e. g., amygdalin, cinnamic acid, jasmonic acid and aspirin have proven efficacy in minimizing the TNF-α induced inflammation in vitro and in vivo. Cell lysis-free quantum dot (QDot) imaging is an emerging technique to identify the cellular mediators of a signaling cascade with a single assay in one run. In comparison to organic fluorophores, the inorganic QDots are bright, resistant to photobleaching and possess tunable optical properties that make them suitable for long term and multicolor imaging of various components in a cellular crosstalk. Hence we tested some components of the mitogen activated protein kinase (MAPK) pathway during TNF-α induced inflammation and the effects of aspirin in HepG2 cells by QDot multicolor imaging technique. Results demonstrated that aspirin showed significant protective effects against TNF-α induced cellular inflammation. The developed cell based assay paves the platform for the analysis of cellular components in a smooth and reliable way.

Impact of cooked functional meat enriched with omega-3 fatty acids and rosemary extract on inflammatory and oxidative status; a randomised, double-blind, crossover study.

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Bermejo, L M; López-Plaza, B; Weber, T K; Palma-Milla, S; Iglesias, C; Reglero, G; Gómez-Candela, C

2014-11-01

n-3 fatty acid intake has been associated with inflammatory benefits in cardiovascular disease (CVD). Functionalising meat may be of great interest. The aim of the present study was to assess the effect of functional meat containing n-3 and rosemary extract on inflammatory and oxidative status markers in subjects with risk for CVD. A randomised, double-blind, cross-over study was undertaken to compare the effects on the above markers of consuming functional or control meat products. 43 volunteers with at least two lipid profile variables showing risk for CVD were randomly assigned to receive functional meat (FM) or control meat (CM) over 12-weeks with a 4-week wash-out interval before crossover. Functional effects were assessed by examining lipid profile, CRP, PAI-1, TNF-alpha, IL-6, fibrinogen (inflammatory markers), and TBARS, FRAP and 8-iso-PGF2 (oxidative status markers). 33 subjects (24 women) aged 50.7±8.8 years completed the study. In FM treatment, PAI-1, fibrinogen and 8-iso-PGF2 decreased significantly after 12 weeks, while FRAP significantly increased. In contrast, in CM treatment, a significant increase was seen in PAI-1, while FRAP significantly declined. Significant differences were also seen between the FM and CM treatments after 12 weeks in terms of the change observed in PAI-1, FRAP and 8-iso-PGF2 values. No significant differences were seen in anthropometric variables nor were adverse effects reported. The consumption of FM containing n-3 and rosemary extract improved oxidative and inflammatory status of people with at least two lipid profile variables showing risk for CVD. The inclusion of such functional meat in a balanced diet might be a healthy lifestyle option. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

THROMBOTIC MICROANGIOPATHY IN HAEMATOPOIETIC CELL TRANSPLANTATION:AN UPDATE

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Hillard Michael Lazarus

2010-08-01

Full Text Available Allogeneic hematopoietic cell transplantation (HCT represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA. In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases, patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents.  Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

Energy Technology Data Exchange (ETDEWEB)

Anantachaisilp, Suranan; Smith, Siwaporn Meejoo [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong [National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Pratontep, Sirapat [College of KMITL Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Bangkok (Thailand); Puttipipatkhachorn, Satit, E-mail: uracha@nanotec.or.th [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand)

2010-03-26

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of {gamma}-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the {gamma}-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ({sup 1}H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the {sup 1}H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of {gamma}-oryzanol inside the lipid nanoparticles, the {sup 1}H-NMR revealed that the chemical shifts of the liquid lipid in {gamma}-oryzanol loaded systems were found at rather higher field than those in {gamma}-oryzanol free systems, suggesting incorporation of {gamma}-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of {gamma}-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models

Anti-inflammatory effects of tetradecylthioacetic acid (TTA in macrophage-like cells from Atlantic salmon (Salmo salar L.

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Grammes Fabian

2011-07-01

Full Text Available Abstract Background Commercial Atlantic salmon is fed diets with high fat levels to promote fast and cost-effective growth. To avoid negative impact of obesity, food additives that stimulate fat metabolism and immune function are of high interest. TTA, tetradecylthioacetic acid, is a synthetic fatty acid that stimulates mitochondrial β-oxidation most likely by activation of peroxysome proliferator-activated receptors (PPARs. PPARs are important transcription factors regulating multiple functions including fat metabolism and immune responses. Atlantic salmon experiments have shown that TTA supplemented diets significantly reduce mortality during natural outbreaks of viral diseases, suggesting a modulatory role of the immune system. Results To gain new insights into TTA effects on the Atlantic salmon immune system, a factorial, high-throughput microarray experiment was conducted using a 44K oligo nucleotide salmon microarray SIQ2.0 and the Atlantic salmon macrophage-like cell line ASK. The experiment was used to determine the transcriptional effects of TTA, the effects of TTA in poly(I:C elicited cells and the effects of pretreating the cells with TTA. The expression patterns revealed that a large proportion of genes regulated by TTA were related to lipid metabolism and increased mitochondrial β-oxidation. In addition we found that for a subset of genes TTA antagonized the transcriptional effects of poly(I:C. This, together with the results from qRT-PCR showing an increased transcription of anti-inflammatory IL10 by TTA, indicates anti-inflammatory effects. Conclusions We demonstrate that TTA has significant effects on macrophage-like salmon cells that are challenged by the artificial dsRNA poly(I:C. The immune stimulatory effect of TTA in macrophages involves increased lipid metabolism and suppressed inflammatory status. Thus, suggesting that TTA directs the macrophage-like cells towards alternative, anti-inflammatory, activation. This has

Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae.

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Backhouse, N; Rosales, L; Apablaza, C; Goïty, L; Erazo, S; Negrete, R; Theodoluz, C; Rodríguez, J; Delporte, C

2008-03-05

Buddleja globosa, known as "matico", is employed in Chile for wound healing. To validate the traditional use of the crude drug through in vivo and in vitro evaluation of the anti-inflammatory, analgesic and antioxidant properties of its extracts. Sequential hexane, dichloromethane, methanol and total methanol extracts were studied using bioguided fractionation. The following activities were investigated: analgesic (writhing test), oral and topic anti-inflammatory (paw- and ear-induced edema), free radical scavenging and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl, DPPH, superoxide anion, lipid peroxidation and xanthine oxidase inhibition). Sodium naproxen, nimesulide, indomethacin were used as reference drugs for in vivo, quercetin and allopurinol for in vitro assays. A mixture of alpha- and beta-amyrins was isolated from the hexane extract that showed 41.2% of analgesic effect at 600 mg/kg, inhibited by 47.7 and 79.0% the arachidonic acid (AA) and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation at 3mg/20 microL/ear, respectively. A mixture of beta-sitosterol, stigmasterol, stigmastenol, stigmastanol and campesterol was isolated from the fraction CD4-N and beta-sitosterol-glycoside from the fraction CD5-N, reducing TPA-induced inflammation by 78.2 and 83.7% at 1mg/20 microL/ear, respectively. The fraction CD4-N at 300 mg/kg also showed analgesic activity (38.7%). The methanol extract at 600mg/kg per os showed anti-inflammatory effect (61.4%), topic anti-inflammatory (56.7% on TPA) and analgesic activity (38.5%). Verbascoside and luteolin-7-O-glucoside were the major components of the methanol extract; apigenin 7-O-glucoside was also detected. Inhibition of superoxide anion, lipoperoxidation, and DPPH bleaching effect was found in the methanol serial and global extracts. The present report demonstrate the analgesic and anti-inflammatory properties of Buddleja globosa and validate its use in Chilean traditional medicine.

Associations between lipid metabolism and fertility in the dairy cow.

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Wathes, D Claire; Clempson, Andrew M; Pollott, Geoff E

2012-01-01

Dairy cows mobilise body tissues to support milk production and, because glucose supplies are limited, lipids are used preferentially for energy production. Lipogenic activity is switched off and lipolytic mechanisms in adipose tissue increase through changes in the expression of several key enzymes. This results in a loss of body condition, together with high circulating concentrations of non-esterified fatty acids. Changes in the synthesis, secretion and signalling pathways of somatotrophic hormones (insulin, growth hormone, insulin-like growth factor 1) and adipokines (e.g. leptin) are central to the regulation of these processes. A high reliance on fatty acids as an energy source in the peripartum period causes oxidative damage to mitochondria in metabolically active tissues, including the liver and reproductive tract. The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway. Polymorphisms in TFAM and UCP2, two autosomal mitochondrial genes, have been associated with longevity in dairy cows. Polymorphisms in many other genes that affect lipid metabolism also show some associations with fertility traits. These include DGAT1, SCD1, DECR1, CRH, CBFA2T1, GH, LEP and NPY. Excess lipid accumulation in oocytes and the regenerating endometrium reduces fertility via reductions in embryo survival and increased inflammatory changes, respectively.

The effect of consuming Palmaria palmata-enriched bread on inflammatory markers, antioxidant status, lipid profile and thyroid function in a randomised placebo-controlled intervention trial in healthy adults.

Science.gov (United States)

Allsopp, Philip; Crowe, William; Bahar, Bojlul; Harnedy, Pádraigín A; Brown, Emma S; Taylor, Sonja S; Smyth, Thomas J; Soler-Vila, Anna; Magee, Pamela J; Gill, Chris I R; Strain, Conall R; Hegan, Vicky; Devaney, Martin; Wallace, Julie M W; Cherry, Paul; FitzGerald, Richard J; Strain, J J; O'Doherty, John V; McSorley, Emeir M

2016-08-01

Palmaria palmata (P. Palmata) is reported to contain anti-inflammatory and antioxidant compounds albeit no study has investigated these effects in humans. A randomised parallel placebo-controlled human intervention study was carried out to investigate the effect of consuming P. Palmata (5 g/day) incorporated into a bread on serum markers of inflammation [C-reactive protein (CRP); cytokine analysis] with secondary analysis investigating changes in lipids (cholesterol, triglycerides), thyroid function [thyroid-stimulating hormone (TSH)] and antioxidant status ferric reducing antioxidant power. ANCOVA with baseline values as covariates, controlling for age, BMI, sex and smoking status, was used to compare differences between treatment groups over time . In vitro studies investigated the inflammatory activity of P. Palmata extracts (hot water, cold water and ethanol extract), protein extracts and associated protein hydrolysates using a Caco-2 inflammation cell model. Consumption of P. Palmata-enriched bread significantly increased serum CRP (+16.1 %, P = 0.011), triglycerides (+31.9 %, P = 0.001) and TSH (+17.2 %, P = 0.017) when compared to the control group. In vitro evaluation of P. palmata extracts and protein hydrolysates identified a significant induction of IL-8 secretion by Caco-2 cells, and the hot water P. palmata extract was shown to increase adipocyte glycerol release (P < 0.05). Evidence from this human study suggests that P. palmata stimulates inflammation, increases serum triglycerides and alters thyroid function; however, these changes are not likely to impact health as changes remained within the normal clinical range. The data from the in vitro study provided indications that IL-8 may contribute to the apparent immunostimulation noted in the human study.

Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system.

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Xin Sun

2010-02-01

Full Text Available Inflammatory response following central nervous system (CNS injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS and its animal model, experimental autoimmune encephalomyelitis (EAE, there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI, i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-kappaB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-kappaB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin and myelin basic protein (MBP, one of the major proteins of myelin are not able to activate NF-kappaB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI.

Effect of the microfiltration process on antioxidant activity and lipid peroxidation protection capacity of blackberry juice

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Gabriela Azofeifa

2011-08-01

Full Text Available Phytochemicals are highly concentrated in berries, especially polyphenols as anthocyanins and ellagitannins. These compounds have been associated with antioxidant capacity, lipid peroxidation protection, anti-inflammatory activity, anti-carcinogenic activity, obesity prevention and others. Blackberries are commonly grown and consumed as juice in Latin-American countries. However, blackberry juice is easily fermented and different industrial techniques are being applied to enable the juice to be stored for longer periods. One important issue required for these techniques is to preserve the health-promoting capacities of blackberries. This study compared the antioxidant activity and the lipid peroxidation protector effect between a fresh blackberry juice (FJ and a microfiltrated blackberry juice (MJ. Chemical analysis of both juices show less polyphenols concentration in the MJ. Despite this difference, values for biological activities, such as protection of lipid peroxidation, was not significantly different between FJ and MJ. These results suggest that the compounds responsible for the antioxidant activity are maintained even after microfiltration and the free radical scavenging capacity of these compounds could protect the initiation of lipid peroxidation. Microfiltration could be used as an industrial technique to produce blackberry juice that maintains biological activities of polyphenols.

[Changes of monocyte and monocyte-platelet aggregates in different subgroups of thrombotic events in patients with acute myocardial infarction during PCI].

Science.gov (United States)

Wang, Sheng; Sun, Cuifang; Liao, Wang; Wu, Zhongwei; Wang, Yudai; Huang, Xiuxian; Lu, Sijia; Dong, Xiaoli; Shuai, Fujie; Li, Bin

2017-07-01

Objective To investigate the impact of thrombotic events on the alterations of monocyte and monocyte-platelet aggregates (MPAs) in patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI). Methods Blood was collected before PCI for flow cytometry. Monocyte subsets and MPAs were detected by four-color platform (CDl4-APC, CDl6-PE-Cy7, CD86-PE and CD41-Alexa Fluor R 488). According to the expression of the platelet surface marker CD41, the number of monocyte subsets and MPAs was analyzed using the fluorescent microspheres of absolute counting tube. The Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis were performed. Results CD14 + CD16 ++ monocytes in intraprocedural thrombotic events (IPTE) group were significantly fewer than those in non-IPTE group, and the percentage in total mononuclear cells decreased. Compared with non-IPTE group, MPA binding ratio and monocyte subset MPA binding ratio were significantly higher in IPTE group. ROC analysis showed that MPA binding ratio and subgroup MPA binding ratio had a better predictive value for IPTE in patients with AMI. Conclusion The CD14 + CD16 ++ monocytes in IPTE group were significantly fewer than those in the non-IPTE group. MPA binding ratio and MPA binding ratio of monocyte subsets were significantly higher in the IPTE group than in the non-IPTE group, so they have a good predictive value for IPTE in patients with AMI.

Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

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2006-12-01

clinically silent , advanced lesions are the critical stage of human atherosclerosis. They are the precursor to plaque rupture and acute thrombotic...present), 1-2 students and 1 fellow Attending in Combined Endocrine/Diabetes, Thyroid , and Lipid Clinics (1987-present), 1-2 students and 1-2 clinical

Understanding the NSAID related risk of vascular events

NARCIS (Netherlands)

Vonkeman, Harald Erwin; Brouwers, Jacobus R.B.J.; van de Laar, Mart A F J

2006-01-01

Concern is growing about an increased risk of thrombotic events (including myocardial infarction and stroke) during the use of non-steroidal anti-inflammatory drugs (NSAIDs), in particular the so called selective cyclo-oxygenase-2 (COX 2) inhibitors. Although clinical trials give conflicting results

The Role Of Protective Heat Shock Protein 70 And Proinflammatory Heat Shock Protein 60 Toward The Functional Status Of Acute Thrombotic Ischemic Stroke

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Bertha Jean Que

2015-08-01

Full Text Available Abstract Clinical experience suggests that the functional status of stroke patients is not directly proportional to the number of risk factors this means that there are other factors that influence the status of functional role. The aim of this study is to explain the changes in levels of HSP70 and HSP60 associated with changes the functional status of stroke which measured with National Institutes of Health Stroke Scale NIHSS in acute thrombotic ischemic stroke. This research is quantitative research is an observational analytic with a longitudinal observational design prospective cohort study and case control. Data was collected by consecutive sampling. Examination of serum levels of HSP 70 HSP60 and assessment of NIHSS done in three times at the same time they are the first day amp8804 48 hours the third day 72 hours and fifth day 120 hours. There is a significant difference P 0.05 levels of HSP 60 and HSP 70 between patients with acute ischemic stroke cases with normal people control. Change dynamic level of HSP70 HSP60 and NIHSS according time of examination there is a significant difference. The first day of HSP 70 levels the third and fifth shaped the decline curve according to the NIHSS improvement while the levels of HSP60 formed a pattern opposite to the NIHSS. Curve levels of HSP70 and HSP60 levels to get to the point value of HSP 60 and HSP70 normal control. In general there was no effect of risk factors on extensive infarction NIHSS HSP70 and HSP60 except the variable age to HSP70 which in the elderly 70-75 years levels of HSP70 is higher than other age groups. Changes in levels of HSP70 and HSP60 follow the pattern of change in NIHSS towards improvement. Therefore HSP70 and HSP60 can serve as a prediction for degree of functional the acute thrombotic ischemic stroke. Risk factors are the cause of stroke but do not affect the NIHSS. Age affects levels of HSP 70. In general HSP60 and HSP70 can be used as a diagnostic and prognostic

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

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Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

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Alejandro Macchia

Full Text Available The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG among patients with type II diabetes mellitus and no previous cardiovascular events.Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks, assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018. On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716. The effects of treatments on measurements of TG using other agonists were consistent.While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.ClinicalTrials.gov NCT00793754.

Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

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González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

2011-01-01

Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

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Chuan Wang

Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura.

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Nagai, Yoshiko; Itabashi, Mitsuyo; Mizutani, Mayuko; Ogawa, Tetsuya; Yumura, Wako; Tsuchiya, Ken; Nitta, Kosaku

2008-02-01

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.

Lipid somersaults

DEFF Research Database (Denmark)

Günther-Pomorski, Thomas; Menon, Anant K.

2016-01-01

Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

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Ganka Bekyarova

2017-04-01

Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

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Jaleh Varshosaz

2011-01-01

Full Text Available Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs. The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs. LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model.

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

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Pablo Esteban Morales

2017-01-01

Full Text Available Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR. In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome.

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Montalvão, Silmara; Elídio, Priscila Soares; da Silva Saraiva, Sabrina; de Moraes Mazetto, Bruna; Colella, Marina Pereira; de Paula, Erich Vinícius; Appenzeller, Simone; Annichino-Bizzacchi, Joyce; Orsi, Fernanda Andrade

2016-12-01

Antibodies directed against domain 1 of β2 glycoprotein 1 (aβ2GP1-Dm1) have been involved in the immunopathogenesis of antiphospholipid syndrome (APS). However, the clinical relevance of aβ2GP1-Dm1 in thrombotic APS has not yet been fully explored. To determine the frequency of aβ2GP1-Dm1 in a cohort of patients with thrombotic APS, and to evaluate whether testing for aβ2GP1-Dm1 could have a clinical impact upon the risk assessment of the disease. Patients were tested for aβ2GP1-Dm1 antibodies by chemiluminescence (BioFlash/AcuStar®, ES). The presence of aβ2GP1-Dm1 was evaluated in different clinical presentations of the disease. Eight-four patients with a history of venous or arterial thrombosis were included. Forty-five (54%) patients had aβ2GP1 antibodies and 40% of them were positive for aβ2GP1-Dm1. Levels of aβ2GP1-Dm1 were higher in patients with systemic autoimmune disease (AUC=0.665; 95% CI=0.544-0.786; P=0.01), positive antinuclear antibody (AUC=0.654; 95% CI=0.535-0.772; P=0.01), triple antiphospholipid antibody (aPL) positivity (AUC=0.680; 95% CI=0.534-0.825; P=0.02) and positive lupus anticoagulant (AUC=0.639; 95% CI=0.502-0.776; P=0.07). In this cohort, aβ2GP1-Dm1 antibodies were not associated with the site of the first thrombosis (OR=0,62, 95% CI=0.20-1.94, P=0.42), thrombosis recurrence (OR=1.0, 95% CI=0.37-2.71, P=1.0) or pregnancy morbidity (OR=1.5, 95% CI=0.33-7.34, P=0.58). In multivariate analysis, positivity for aβ2GP1-Dm1 antibodies was associated with the diagnosis of systemic autoimmune disease (OR=4.01, 95% CI=1.14-14.2; P=0.03) and triple aPL positivity (OR=3.59, 95% CI=0.87-14.85; P=0.07). In the present cohort of thrombotic-APS patients, aβ2GP1-Dm1 antibodies were related to the diagnosis of systemic autoimmunity and complex serological profile of the disease, as triple aPL positivity and positive antinuclear antibody. Thus, our results suggest that testing for aβ2GP1-Dm1 antibodies may be useful for improving APS risk

Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases.

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Nakayama, Hiroyuki; Otsu, Kinya

2018-03-06

Mitochondria play a central role in multiple cellular functions, including energy production, calcium homeostasis, and cell death. Currently, growing evidence indicates the vital roles of mitochondria in triggering and maintaining inflammation. Chronic inflammation without microbial infection - termed sterile inflammation - is strongly involved in the development of heart failure. Sterile inflammation is triggered by the activation of pattern recognition receptors (PRRs) that sense endogenous ligands called damage-associated molecular patterns (DAMPs). Mitochondria release multiple DAMPs including mitochondrial DNA, peptides, and lipids, which induce inflammation via the stimulation of multiple PRRs. Among the mitochondrial DAMPs, mitochondrial DNA (mtDNA) is currently highlighted as the DAMP that mediates the activation of multiple PRRs, including Toll-like receptor 9, Nod-like receptors, and cyclic GMP-AMP synthetase/stimulator of interferon gene pathways. These PRR signalling pathways, in turn, lead to the activation of nuclear factor-κB and interferon regulatory factor, which enhances the transcriptional activity of inflammatory cytokines and interferons, and induces the recruitment of inflammatory cells. As the heart is an organ comprising abundant mitochondria for its ATP consumption (needed to maintain constant cyclic contraction and relaxation), the generation of massive amounts of mitochondrial radical oxygen species and mitochondrial DAMPs are predicted to occur and promote cardiac inflammation. Here, we will focus on the role of mtDNA in cardiac inflammation and review the mechanism and pathological significance of mtDNA-induced inflammatory responses in cardiac diseases. © 2018 The Author(s).

The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning

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Arik Eisenkraft

Full Text Available Organophosphates (OPs are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, without proper and early antidotal treatment, death. Most of these compounds are highly lipophilic. Sulfur mustard is a toxic lipophilic alkylating agent, exerting its damage through alkylation of cellular macromolecules (e.g., DNA, proteins and intense activation of pro-inflammatory pathways. Currently approved antidotes against OPs include the peripheral anticholinergic drug atropine and an oxime that reactivates the inhibited cholinesterase. Benzodiazepines are used to stop organophosphate-induced seizures. Despite these approved drugs, efforts have been made to introduce other medical countermeasures in order to attenuate both the short-term and long-term clinical effects following exposure. Currently, there is no antidote against sulfur mustard poisoning. Intravenous lipid emulsions are used as a source of calories in parenteral nutrition. In recent years, efficacy of lipid emulsions has been shown in the treatment of poisoning by fat-soluble compounds in animal models as well as clinically in humans. In this review we discuss the usefulness of intravenous lipid emulsions as an adjunct to the in-hospital treatment of chemical warfare agent poisoning. Keywords: Intravenous lipid emulsion, Organophosphates, Sulfur mustard, Antidotes, Poisoning, Chemical Warfare agents

Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

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Cruz-Garcia, Lourdes; Schlegel, Amnon

2014-09-01

Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

OpenAIRE

Corey A. Carter; Robert Browning; Bryan T. Oronsky; Jan J. Scicinski; Christina Brzezniak

2016-01-01

A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance ...

Targeting GPR120 and other fatty acid sensing GPCRs ameliorates insulin resistance and inflammatory diseases

Science.gov (United States)

Talukdar, Saswata; Olefsky, Jerrold M; Osborn, Olivia

2011-01-01

The last decade has seen great progress in the understanding of the molecular pharmacology, physiological function and therapeutic potential of the G protein-coupled receptors. Free Fatty acids (FFAs) have been demonstrated to act as ligands of several GPCRs including GPR40, GPR43, GPR84, GPR119 and GPR120. We have recently shown that GPR120 acts as a physiological receptor of ω3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects. The important role GPR120 plays in the control of inflammation raises the possibility that targeting this receptor could have therapeutic potential in many inflammatory diseases including obesity and type 2 diabetes. In this review, we discuss lipid-sensing GPCRs and highlight potential outcomes of targeting such receptors in ameliorating disease. PMID:21663979

Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

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Takahiro Ueno

2008-11-01

Full Text Available Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%–0.2%, w/v. Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01, supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM, suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

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Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Lipid Mediators Are Critical in Resolving Inflammation: A Review of the Emerging Roles of Eicosanoids in Diabetes Mellitus

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Fernando H. G. Tessaro

2015-01-01

Full Text Available The biosynthesis pathway of eicosanoids derived from arachidonic acid, such as prostaglandins and leukotrienes, relates to the pathophysiology of diabetes mellitus (DM. A better understanding of how lipid mediators modulate the inflammatory process may help recognize key factors underlying the progression of diabetes complications. Our review presents recent knowledge about eicosanoid synthesis and signaling in DM-related complications, and discusses eicosanoid-related target therapeutics.

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

NARCIS (Netherlands)

Neumann, S.

2008-01-01

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

MANAGEMENT OF CHRONIC IDIOPATHIC THROMBOTIC THROMBOCYTOPENIC PURPURA WITH SPLENECTOMY

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Mojca Modic

2002-07-01

Full Text Available Background. Treatment of thrombotic thrombocytopenic purpura (TTP with plasma exchange (PE has reduced mortality rates from 90% in untreated patients to less than 20%. Despite primary effective PE, relapses occur in up to 40% of patients. Beside PE, second line treatment options are corticosteroids, vincristine, defibrotide, prostacycline. We describe two patients with relapsing TTP treated successfully with splenectomy.Patients and methods. Case 1. A 20–year female was diagnosed in October 2000 with idiopathic chronic relapsing TTP. First episode of PE plus methylprednisolone treatment led to complet remission. Subsequent relapses occured 3, 6 and 8 months after first TTP episode. Every relaps was effectivelly treated with PE and methylprednisolone. Because of more and more frequent TTP relapses laparoscopic splenectomy was performed. Currently, 7 months after splenectomy she is in complet TTP remission.Case 2. A 18–year female, was diagnosed in January 1997 with idiopathic TTP. After PE and methylprednisolone complete remission was established. Relaps occured after nearly three years. Later on, TTP got chronic course with neurological clinical symptoms and plateled drops as soon as PE treatment was withdrawn. Besides PE and methylprednisolone she received also defibrotide. Because of chronic, PE dependant TTP, laparoscopic splenectomy was performed. Today, 15 months after splenectomy she is in complete TTP remission.Conclusions. In idiopathic relapsing and chronic TTP, PE treatment only is usually not sufficient for durable remission. Second line TTP treatment drugs have limited efficacy. Based on our experience in patients with relapsing and/or chronic TTP, laparoscopic splenectomy should be considered as a first treatment option, especialy in junger patients.

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

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Silva, Paula Simplício da; Mediano, Mauro Felippe Felix; Silva, Gilberto Marcelo Sperandio da; Brito, Patricia Dias de; Cardoso, Claudia Santos de Aguiar; Almeida, Cristiane Fonseca de; Sangenis, Luiz Henrique Conde; Pinheiro, Roberta Olmo; Hasslocher-Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andrea Silvestre de

2017-06-09

Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. NCT01863576.

Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

Science.gov (United States)

Nauman, Mohd; Kale, R K; Singh, Rana P

2018-03-07

Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and

Cell-based lipid flippase assay employing fluorescent lipid derivatives

DEFF Research Database (Denmark)

Jensen, Maria Stumph; Costa, Sara; Günther-Pomorski, Thomas

2016-01-01

P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases, s...... flippase activities in the plasma membrane of cells, using yeast as an example.......P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases......, studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates. Here, we describe an assay based on fluorescent lipid derivatives to monitor and characterize lipid...

Effect of anti-gut inflammatory agent on insulin resistance and lipid profile of mice fed different diets

NARCIS (Netherlands)

Wang, Zheng; Bao, Zhijun

Purpose: To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different diets. Methods: Groups of 9 - 10 mice each were randomly assigned to 6 different diets, low-fat diet (LFD) with or without 5-ASA, high-fat diet (HFD) with or without 5-ASA, and

Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

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Brante P Sampey

Full Text Available Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD to "Cafeteria diets" (CAF consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

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Maes Michael

2012-06-01

Full Text Available Abstract It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia, physio-somatic (fatigue, hyperalgesia, malaise, anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuroinflammation and (neurodegenerative processes following less well defined triggers.

Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies

International Nuclear Information System (INIS)

Zhang, Zongyao; Zhang, Xu-Xiang; Wu, Bing; Yin, Jinbao; Yu, Yunjiang; Yang, Liuyan

2016-01-01

Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2 mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies

Energy Technology Data Exchange (ETDEWEB)

Zhang, Zongyao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Zhang, Xu-Xiang, E-mail: zhangxx@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Wu, Bing; Yin, Jinbao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Yu, Yunjiang [Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Yang, Liuyan, E-mail: yangly@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

2016-09-05

Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2 mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

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Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

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Tamez, Hector; Généreux, Philip; Yeh, Robert W; Amin, Amit P; Fan, Weihong; White, Harvey D; Kirtane, Ajay J; Stone, Gregg W; Gibson, C Michael; Harrington, Robert A; Bhatt, Deepak L; Pinto, Duane S

2018-05-04

Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI. © 2018 Wiley Periodicals, Inc.

Two divergent paths: compression vs. non-compression in deep venous thrombosis and post thrombotic syndrome

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Eduardo Simões Da Matta

Full Text Available Abstract Use of compression therapy to reduce the incidence of postthrombotic syndrome among patients with deep venous thrombosis is a controversial subject and there is no consensus on use of elastic versus inelastic compression, or on the levels and duration of compression. Inelastic devices with a higher static stiffness index, combine relatively small and comfortable pressure at rest with pressure while standing strong enough to restore the “valve mechanism” generated by plantar flexion and dorsiflexion of the foot. Since the static stiffness index is dependent on the rigidity of the compression system and the muscle strength within the bandaged area, improvement of muscle mass with muscle-strengthening programs and endurance training should be encouraged. Therefore, in the acute phase of deep venous thrombosis events, anticoagulation combined with inelastic compression therapy can reduce the extension of the thrombus. Notwithstanding, prospective studies evaluating the effectiveness of inelastic therapy in deep venous thrombosis and post-thrombotic syndrome are needed.

Prevention and treatment of the post-thrombotic syndrome and of the chronic thromboembolic pulmonary hypertension.

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Pesavento, Raffaele; Prandoni, Paolo

2015-02-01

Post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are late complications of venous thromboembolism. The purpose of this review is to present and discuss recently published studies that have improved our knowledge of PTS and CTEPH. The current understanding of the pathophysiology of PTS and CTEPH is discussed as well as the importance of chronic residual venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and the current concept of misguided thrombus resolution. The surprising finding that elastic compression stockings may not be effective in preventing PTS and the novel medical treatment in CTEPH are discussed in detail. Novel direct oral anticoagulants show potential for prevention of PTS. No firm conclusions can be drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for inoperable patients and those with persistent pulmonary hypertension after surgery have become available and further research on wider indication for their use is urgently needed.

Core hydrophobicity tuning of a self-assembled particle results in efficient lipid reduction and favorable organ distribution.

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Banik, Bhabatosh; Wen, Ru; Marrache, Sean; Kumar, Anil; Kolishetti, Nagesh; Howerth, Elizabeth W; Dhar, Shanta

2017-12-21

Atherosclerosis, the deadliest disease in the United States, arises due to the build up of plaques in the arteries as a result of excessive cholesterol deposition and an impaired cholesterol removal process. High density lipoproteins (HDL), popularly known as "good cholesterol", are naturally occurring nano-sized particles that, along with apolipoproteins, are deployed to maintain cholesterol homeostasis in the body. Both cholesterol efflux, from the fat-laden macrophages in the arteries, and intracellular lipid transport, to deliver cholesterol to the mitochondria of liver cells for metabolism, hold key responsibilities to maintain healthy lipid levels inside the body. We designed a library of nine mitochondria targeted polymer-lipid hybrid nanoparticles (NPs), comprised of completely synthetic yet biodegradable components, that are capable of performing HDL-like functions. Using this library, we optimized a superior mitochondria targeted NP candidate, which can show favourable organ distribution, therapeutic potential, and non-toxic properties. Two targeted NP formulations with optimum NP size, zeta potential, and cholesterol binding and release properties were identified. Lipid reduction and anti-oxidative properties of these two NPs demonstrated cholesterol removal ability. In vivo therapeutic evaluation of the targeted-NP formulations in apolipoprotein E knockout (apoE - / - ) mice indicated lipid reduction and anti-inflammatory properties compared to non-targeted NPs. This synthetic targeted NP with potential abilities to participate in both extra- and intracellular cholesterol transport might potentiate therapeutic interventions for heart diseases.

Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.

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López-Moreno, Javier; García-Carpintero, Sonia; Jimenez-Lucena, Rosa; Haro, Carmen; Rangel-Zúñiga, Oriol A; Blanco-Rojo, Ruth; Yubero-Serrano, Elena M; Tinahones, Francisco J; Delgado-Lista, Javier; Pérez-Martínez, Pablo; Roche, Helen M; López-Miranda, José; Camargo, Antonio

2017-09-06

Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.

Inflammatory myofibroblastic tumor

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Sangeeta Palaskar

2011-01-01

Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

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Mahaveer Golechha

2014-01-01

Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance.

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Claeson, Anna-Sara; Gouveia-Figueira, Sandra; Häggström, Jenny; Fowler, Christopher J; Nording, Malin L

2017-06-01

Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: Experimental animal study

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Sirajudeen KNS

2011-10-01

Full Text Available Abstract Background Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. Methods A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data. Results There was no statistically significant difference in clinical inflammatory features (p > 0.05 between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade. There was also no significant difference in the level of total antioxidant status as well as lipid

Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study.

Science.gov (United States)

Bashkaran, Karuppannan; Zunaina, Embong; Bakiah, Shaharuddin; Sulaiman, Siti Amrah; Sirajudeen, Kns; Naik, Venkatesh

2011-10-09

Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data. There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous humour (p = 0.117, p = 0

Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: Experimental animal study

Science.gov (United States)

2011-01-01

Background Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. Methods A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data. Results There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous

Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Cells.

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Choi, Hyeon-Son; Im, Suji; Park, Yooheon; Hong, Ki-Bae; Suh, Hyung Joo

2016-01-01

The aim of this study was to investigate the effect of deer bone oil extract (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions: methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had relatively more hydrophilic lipid complexes, including unsaturated fatty acids, than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, α-linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38, and 32%, respectively, compared with DBOE. The concentration of sugar moieties was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose-dependent manner. This DBO-M-mediated decrease in NO production was due to downregulation of mRNA and protein levels of inducible nitric oxide synthase (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as cyclooxygenase (COX-2), interleukin (IL)-1β, and IL-12β, was suppressed by DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than DBOE and DBO-H, could play an important role in suppressing inflammatory responses by controlling pro-inflammatory cytokines and mediators.

Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages.

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Rombaldova, Martina; Janovska, Petra; Kopecky, Jan; Kuda, Ondrej

2017-08-26

It is becoming increasingly apparent that mutual interactions between adipocytes and immune cells are key to the integrated control of adipose tissue inflammation and lipid metabolism in obesity, but little is known about the non-inflammatory functions of adipose tissue macrophages (ATMs) and how they might be impacted by neighboring adipocytes. In the current study we used metabolipidomic analysis to examine the adaptations to lipid overload of M1 or M2 polarized macrophages co-incubated with adipocytes and explored potential benefits of omega-3 polyunsaturated fatty acids (PUFA). Macrophages adjust their metabolism to process excess lipids and M2 macrophages in turn modulate lipolysis and fatty acids (FA) re-esterification of adipocytes. While M1 macrophages tend to store surplus FA as triacylglycerols and cholesteryl esters in lipid droplets, M2 macrophages channel FA toward re-esterification and β-oxidation. Dietary omega-3 PUFA enhance β-oxidation in both M1 and M2. Our data document that ATMs contribute to lipid trafficking in adipose tissue and that omega-3 PUFA could modulate FA metabolism of ATMs. Copyright © 2017 Elsevier Inc. All rights reserved.