International Journal of Inflammation http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Posttranscriptional Suppression of Lipopolysaccharide-Stimulated Inflammatory Responses by Macrophages in Middle-Aged Mice: A Possible Role for Eukaryotic Initiation Factor 2α Mon, 07 Apr 2014 13:38:44 +0000 http://www.hindawi.com/journals/iji/2014/292986/ The intensities of macrophage inflammatory responses to bacterial components gradually decrease with age. Given that a reduced rate of protein synthesis is a common age-related biochemical change, which is partially mediated by increased phosphorylation of eukaryotic initiation factor-2α (eIF-2α), we investigated the mechanism responsible for the deterioration of macrophage inflammatory responses, focusing specifically on the age-related biochemical changes in middle-aged mice. Peritoneal macrophages isolated from 2-month-old (young) and 12-month-old (middle-aged) male BALB/c mice were stimulated with lipopolysaccharide (LPS). Although LPS-stimulated secretion of tumor necrosis factor-α (TNF-α) by the macrophages from middle-aged mice was significantly lower than that from young mice, LPS caused marked increases in levels of TNF-α mRNA in macrophages from middle-aged as well as young mice. Moreover, LPS evoked similar levels of phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) in young and middle-aged mice. In contrast, the basal level of phosphorylated eIF-2α in macrophages from middle-aged mice was higher than that in macrophages from young mice. Salubrinal, an inhibitor of the phosphatase activity that dephosphorylates eIF-2α, suppressed the LPS-stimulated inflammatory responses in a murine macrophage cell line RAW264.7. These results suggest that posttranscriptional suppression of macrophage inflammatory responses during middle age requires phosphorylation of eIF-2α. Ken Shirato and Kazuhiko Imaizumi Copyright © 2014 Ken Shirato and Kazuhiko Imaizumi. All rights reserved. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling Sun, 06 Apr 2014 06:43:49 +0000 http://www.hindawi.com/journals/iji/2014/689360/ The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNF, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors. Maricica Pacurari, Ramzi Kafoury, Paul B. Tchounwou, and Kenneth Ndebele Copyright © 2014 Maricica Pacurari et al. All rights reserved. Interleukin-17A Exacerbates Ferric Chloride-Induced Arterial Thrombosis in Rat Carotid Artery Thu, 03 Apr 2014 15:49:45 +0000 http://www.hindawi.com/journals/iji/2014/247503/ Interleukin-17A (IL-17A), the most widely studied member of the IL-17 cytokine family, is a cytokine which emerged to be critical for host defense as well as in the pathogenesis of autoimmune disorders. Moreover, IL-17A is involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis and acute coronary syndrome and in the cardiovascular risk associated with systemic immunological disorders. Consistent with this, we have recently shown that IL-17A increases human and murine platelet response to ADP. In this study we expanded our previous observation and we describe for the first time an in vivo prothrombotic effect of the cytokine. Our results show that IL-17A is synergic with a low FeCl3 concentration in inducing carotid thrombus in rats and suggest that the effect is likely related to a downregulation of CD39 vascular expression and hydrolyzing activity. Our findings indicate that IL-17A might be an important molecule at the interface between hemostasis and inflammation. Francesco Maione, Antonio Parisi, Elisabetta Caiazzo, Silvana Morello, Fulvio D'Acquisto, Nicola Mascolo, and Carla Cicala Copyright © 2014 Francesco Maione et al. All rights reserved. Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA Tue, 01 Apr 2014 11:55:30 +0000 http://www.hindawi.com/journals/iji/2014/560790/ Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 106 to 107 CFU/mL inocula of community-acquired- (CA-) MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10–20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50–60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor) and Torin KU63794 (mTOR 1 and 2 inhibitors). Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages. Rebekah K. H. Shappley and Thomas Spentzas Copyright © 2014 Rebekah K. H. Shappley and Thomas Spentzas. All rights reserved. The Serum S100B Level as a Biomarker of Enteroglial Activation in Patients with Ulcerative Colitis Sun, 30 Mar 2014 12:08:08 +0000 http://www.hindawi.com/journals/iji/2014/986525/ Objective. Recent studies have demonstrated that enteric glial cells (EGC) participate in the homeostasis of the gastrointestinal tract. This study investigated whether enteroglial markers, including S100B protein and glial fibrillary acidic protein (GFAP), can serve as noninvasive indicators of EGC activation and disease activity in UC patients. Methods. This clinical prospective study included 35 patients with UC and 40 age- and sex-matched controls. The diagnosis of UC was based on standard clinical, radiological, endoscopic, and histological criteria. Clinical disease activity was evaluated using the Modified Truelove-Witts Severity Index. Serum samples were analyzed for human GFAP and S100B using commercial enzyme-linked immunosorbent assay kits. Results. GFAP was not detected in the serum of either UC patients or controls (). However, we found a significant () decrease in the serum S100B levels in the UC patients. No correlation between the serum S100B level and the disease activity or duration was observed (). The serum S100B levels did not differ between UC patients with active disease (24 patients, 68.6%) or in remission (11 patients, 31.4%) (). Conclusions. Ulcerative colitis patients had significantly lower serum S100B levels, while GFAP was of no diagnostic value in UC patients. Asuman Celikbilek, Mehmet Celikbilek, Seda Sabah, Nermin Tanık, Elif Borekci, Serkan Dogan, Yavuz Akin, Suleyman Baldane, Kemal Deniz, Neziha Yilmaz, Omer Ozbakir, and Mehmet Yucesoy Copyright © 2014 Asuman Celikbilek et al. All rights reserved. Carbon Black Particle Exhibits Size Dependent Toxicity in Human Monocytes Wed, 05 Feb 2014 11:44:24 +0000 http://www.hindawi.com/journals/iji/2014/827019/ Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicological researches suggest ultrafine particles (<100 nm) to be more harmful per unit mass than larger particles. In the present study, the effect of particle size (nano and micro) of carbon black (CB) particle on viability, phagocytosis, cytokine induction, and DNA damage in human monocytes, THP-1 cells, was analysed. The cells were incubated with nanosize (~50 nm) and micron (~500 nm) size of CB particles in a concentration range of 50–800 µg/mL. The parameters like MTT assay, phagocytosis assay, ELISA, gene expression, and DNA analysis were studied. Exposure to nano- and micron-sized CB particles showed size- and concentration dependent decrease in cell viability and significant increase in proinflammatory cytokines IL-1β, TNF-α and IL-6 as well as chemokine IL-8 release. Gene expression study showed upregulation of monocyte chemoattractant protein-1 gene while cyclooxygenase-2 gene remained unaffected. Nano CB particles altered the phagocytic capacity of monocytes although micron CB had no significant effect. CB particles did not show any significant effect on DNA of monocytes. The investigations indicate that CB particles in nanosize exhibit higher propensity of inducing cytotoxicity, inflammation, and altered phagocytosis in human monocytes than their micron size. Devashri Sahu, G. M. Kannan, and R. Vijayaraghavan Copyright © 2014 Devashri Sahu et al. All rights reserved. Clinical Feature of Intrahepatic B-Lymphocytes in Chronic Hepatitis B Tue, 21 Jan 2014 14:24:30 +0000 http://www.hindawi.com/journals/iji/2014/896864/ Humoral immunity constitutes major defense mechanism against viral infections. However, the association of hepatic injury and B-cells population in chronic hepatitis B virus (HBV) carriers has not been studied well. In this study, fifty seven hepatitis B surface antigen (HBsAg) positive and HBeAg negative patients were studied to determine the expression of CD20, a cell surface marker expressed on B-cells, in liver biopsy sections using immunohistochemistry. The patients’ clinical data at the time of liver biopsy were acquired from their medical records. There was a significant association between log HBV DNA and both ALT (, ) and histologic activity index (HAI) total score (, ), respectively. The CD20 was expressed in all 57 liver biopsy samples with a submembranous and membranous staining pattern and its expression was significantly associated with HAI total score (, ) and stage of fibrosis (, ). The susceptible B lymphocytes to hepatitis B virus might be implicated in the development of immune mediated inflammation of HBV-induced hepatic injury. The present data also support that the liver is potentially one of the secondary lymphoid organs. Ashraf Mohamadkhani, Elnaz Naderi, Masoud Sotoudeh, Aezam Katoonizadeh, Ghodratollah Montazeri, and Hossein Poustchi Copyright © 2014 Ashraf Mohamadkhani et al. All rights reserved. Parecoxib Reduces Systemic Inflammation and Acute Lung Injury in Burned Animals with Delayed Fluid Resuscitation Tue, 21 Jan 2014 10:03:08 +0000 http://www.hindawi.com/journals/iji/2014/972645/ Burn injuries result in the release of proinflammatory mediators causing both local and systemic inflammation. Multiple organ dysfunctions secondary to systemic inflammation after severe burn contribute to adverse outcome, with the lungs being the first organ to fail. In this study, we evaluate the anti-inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were inflicted with 45% total body surface area full-thickness scald burns and subsequently subjected to delayed resuscitation with Hartmann’s solution. Parecoxib (0.1, 1.0, and 10 mg/kg) was delivered intramuscularly 20 min after injury followed by 12 h interval and the rats were sacrificed at 6 h, 24 h, and 48 h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and increased lung MPO levels. Animals treated with 1 mg/kg Parecoxib showed significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment of 1 mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without significantly affecting other organs. At present, no specific therapeutic agent is available to attenuate the systemic inflammatory response secondary to burn injury. The results suggest that Parecoxib may have the potential to be used both as an analgesic and ameliorate the effects of lung injury following burn. Si Jack Chong, Yong Chiat Wong, Jian Wu, Mui Hong Tan, Jia Lu, and Shabbir M. Moochhala Copyright © 2014 Si Jack Chong et al. All rights reserved. Necrotizing Soft Tissue Infections: Surgeon’s Prospective Tue, 24 Dec 2013 18:20:53 +0000 http://www.hindawi.com/journals/iji/2013/609628/ Necrotizing soft tissue infections (NSTIs) are fulminant infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Delay in diagnosing and treating these infections increases the risk of mortality. Early and aggressive surgical debridement with support for the failing organs significantly improves the survival. Although there are different forms of NSTIs like Fournier’s gangrene or clostridial myonecrosis, the most important fact is that they share common pathophysiology and principles of treatment. The current paper summarizes the pathophysiology, clinical features, the diagnostic workup required and the treatment principles to manage these cases. Shashi Prakash Mishra, Shivanshu Singh, and Sanjeev Kumar Gupta Copyright © 2013 Shashi Prakash Mishra et al. All rights reserved. Risk Factors for Chronic Mastitis in Morocco and Egypt Thu, 14 Nov 2013 09:38:52 +0000 http://www.hindawi.com/journals/iji/2013/184921/ Chronic mastitis is a prolonged inflammatory breast disease, and little is known about its etiology. We identified 85 cases and 112 controls from 5 hospitals in Morocco and Egypt. Cases were women with chronic mastitis (including periductal, lobular, granulomatous, lymphocytic, and duct ectasia with mastitis). Controls had benign breast disease, including fibroadenoma, benign phyllodes, and adenosis. Both groups were identified from histopathologically diagnosed patients from 2008 to 2011, frequency-matched on age. Patient interviews elicited demographic, reproductive, breastfeeding, and clinical histories. Cases had higher parity than controls (OR = 1.75, 1.62–1.90) and more reported history of contraception use (OR = 2.73, 2.07–3.61). Cases were less likely to report wearing a bra (OR = 0.56, 0.47–0.67) and less often used both breasts for breastfeeding (OR = 4.40, 3.39–5.72). Chronic mastitis cases were significantly less likely to be employed outside home (OR = 0.71, 0.60–0.84) and more likely to report mice in their households (OR = 1.63, 1.36–1.97). This is the largest case-control study reported to date on risk factors for chronic mastitis. Our study highlights distinct reproductive risk factors for the disease. Future studies should further explore these factors and the possible immunological and susceptibility predisposing conditions. Hanna N. Oltean, Amr S. Soliman, Omar S. Omar, Tamer F. Youssef, Mehdi Karkouri, Azza Abdel-Aziz, Ahmad Hablas, Taylor Blachley, Ali Tahri, and Sofia D. Merajver Copyright © 2013 Hanna N. Oltean et al. All rights reserved. Cost Effectiveness of TNF- Inhibitors in Rheumatoid Arthritis Wed, 13 Nov 2013 16:36:05 +0000 http://www.hindawi.com/journals/iji/2013/581409/ Background. TNF- inhibitors have shown to be effective in reducing disease activity and improving the quality of life. Due to the high costs associated with acquisition of this treatment, this study was undertaken to evaluate the ICER of TNF- antagonists (etanercept, adalimumab, and infliximab) in improving the quality of life. Methods. The HAQ and SF-36 were administered at phases 1, 2, and 3, in order to assess the improvement in the QOL. Suppression of disease activity was assessed through the DAS-28. Results. Statistically significant improvements () were noted for the SF-36 and HAQ after 3 months and for the DAS-28 after 6 months of TNF- inhibitor therapy. The mean ICER per 10% improvement in the HAQ, DAS-28, and SF-6D were €1976.5, €2086.5, and €2316.4, respectively, following 6 months of TNF- intervention. Most favorable ICERs were reported from a patient who had to undergo surgical intervention whilst on DMARD therapy. Conclusion. Significant improvement was observed in patients’ quality of life, after a short timeframe of 6 months. Such data is useful information in the light of convincing policy makers, in terms of providing access to the medications to individual patients on national health service schemes. Cynthia Said, Bernard Coleiro, Maurice Zarb Adami, Lilian M. Azzopardi, and Anthony Serracino Inglott Copyright © 2013 Cynthia Said et al. All rights reserved. Prostaglandin E2 Does Not Modulate CCR7 Expression and Functionality after Differentiation of Blood Monocytes into Macrophages Tue, 05 Nov 2013 13:11:24 +0000 http://www.hindawi.com/journals/iji/2013/918016/ Previously, we demonstrated that prostaglandin E2 (PGE2) induces C-C chemokine receptor type 7 (CCR7) expression on human monocytes, which stimulates their subsequent migration in response to the CCR7 natural ligands CCL19 and CCL21. In this study, we determined whether PGE2 affects CCR7 expression on macrophages. Flow cytometric analysis and chemotaxis assays were performed on Mono Mac-1-derived macrophage (MDMM-1) as well as unpolarized monocyte-derived macrophages (MDMs) to determine the CCR7 expression and functionality in the presence of PGE2. Data revealed that a MDMM-1 exhibited markedly downregulated CCR7 expression and functionality that were partially restored by treatment with PGE2. In MDMs, we observed a drastic downregulation of CCR7 expression and functionality that were unaffected following PGE2 treatment. Our data indicate that monocyte differentiation induces the loss of CCR7 expression and that PGE2 is unable to modulate CCR7 expression and functionality as shown previously in monocytes. Marc-André Allaire, Bérengère Tanné, Sandra C. Côté, and Nancy Dumais Copyright © 2013 Marc-André Allaire et al. All rights reserved. Circulating Anti-Beta2-Glycoprotein I Antibodies Are Associated with Endothelial Dysfunction, Inflammation, and High Nitrite Plasma Levels in Patients with Intermittent Claudication Thu, 10 Oct 2013 14:34:12 +0000 http://www.hindawi.com/journals/iji/2013/268079/ Our aim is to investigate a possible association of circulating anti-beta2-glycoprotein I antibodies (ABGPI) with the endothelial dysfunction, nitric oxide bioactivity dysregulation, and the inflammatory status that surrounds peripheral arterial disease. We carried out an observational translational study, including 50 male patients with intermittent claudication and a healthy control group of 10 male subjects, age and sex matched with the cases. Flow-mediated arterial dilatation (FMAD) was assessed as a surrogate of endothelial dysfunction, and C-reactive protein (hsCRP) was determined as a marker of inflammation. Nitrite plasma levels were measured by colorimetric analysis. Circulating ABGPI titer was detected with indirect immunofluorescence. Titers <1 : 10 represented the reference range and the lower detection limit of the test. Circulating ABGPI titer ≥1 : 10 was detected in 21 (42%) patients and in none of the control subjects (). Patients with ABGPI titer ≥1 : 10 had a lower FMAD (). The CRP levels were higher in patients with ABGPI titer ≥1 : 10 (). The nitrite plasma levels were higher in patients with ABGPI titer ≥1 : 10 (). These data suggest that these circulating ABGPI may collaborate in the development of atherosclerosis; however, further prospective studies are required to establish a causal relationship. Cesar Varela, Joaquin de Haro, Silvia Bleda, Leticia Esparza, Ignacio Lopez de Maturana, and Francisco Acin Copyright © 2013 Cesar Varela et al. All rights reserved. Curbing Inflammation Tue, 01 Oct 2013 11:22:21 +0000 http://www.hindawi.com/journals/iji/2013/468287/ R. Clive Landis, Christopher D. Buckley, Paulo Roberto B. Evora, and David A. Hart Copyright © 2013 R. Clive Landis et al. All rights reserved. Effects of Flavonoids from French Marigold (Florets of Tagetes patula L.) on Acute Inflammation Model Sun, 22 Sep 2013 12:09:35 +0000 http://www.hindawi.com/journals/iji/2013/309493/ The major components patuletin and patulitrin were isolated from French marigold (florets of Tagetes patula). Patuletin and patulitrin were found to inhibit acute inflammation in mice. Oral administration of patuletin and patulitrin significantly suppressed hind-paw edema induced by carrageenin and histamine, while topical application of patuletin and patulitrin significantly inhibited ear edema induced by 12-O-tetradecanoylphorbol-13-acetate and arachidonic acid. Thus, oral and topical administration of patuletin and patulitrin inhibited acute inflammation in mice. These results suggest the anti-inflammatory efficacy of French marigold. Ken Yasukawa and Yoshimasa Kasahara Copyright © 2013 Ken Yasukawa and Yoshimasa Kasahara. All rights reserved. Statin Modulation of Human T-Cell Proliferation, IL-1 and IL-17 Production, and IFN- T Cell Expression: Synergy with Conventional Immunosuppressive Agents Wed, 18 Sep 2013 08:23:22 +0000 http://www.hindawi.com/journals/iji/2013/434586/ HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (), simvastatin significantly decreased intracellular CD4+ T-cell expression of IFN- () to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN- expression, although to a lesser degree (). All three statins reduced levels of IL-17 production (). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1 production (). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells. Ashmal Jameel, Kenneth G.-J. Ooi, Natasha R. Jeffs, Grazyna Galatowicz, Susan L. Lightman, and Virginia L. Calder Copyright © 2013 Ashmal Jameel et al. All rights reserved. Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases Wed, 11 Sep 2013 15:00:51 +0000 http://www.hindawi.com/journals/iji/2013/403460/ The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-B as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions. Yaw Kuang Chuah, Rusliza Basir, Herni Talib, Tung Hing Tie, and Norshariza Nordin Copyright © 2013 Yaw Kuang Chuah et al. All rights reserved. Thromboangiitis Obliterans (Buerger’s Disease)—Current Practices Wed, 11 Sep 2013 14:47:42 +0000 http://www.hindawi.com/journals/iji/2013/156905/ Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental inflammatory disease that most commonly affects the small and medium-sized arteries and veins in the upper and lower extremities. Cigarette smoking has been implicated as the main etiology of the disease. In eastern parts of the world TAO forms 40–60% of peripheral vascular diseases. Clinical features and angiographic finding are the basis of early diagnosis of TAO. Abstinence from smoking is the only definitive treatment to prevent disease progression. Medical management in form of aspirin, pentoxyfylline, cilostazol, and verapamil increase pain-free walking distance in intermittent claudication, but long term usage fails to prevent disease progression in patients who continue to smoke. Surgical treatment in form of revascularization, lumbar sympathectomy, omentopexy, and Ilizarov techniques help reduce pain and promote healing of trophic changes. Newer treatment modalities like spinal cord stimulation, prostacyclin, bosentan, VEGF, and stem cell therapy have shown promising results. Latest treatment options include peripheral mononuclear stem cell, and adipose tissue derived mononuclear stem cells have been shown to be effective in preventing disease progression, decrease major amputation rates, and improving quality of life. Abhishek Vijayakumar, Rahul Tiwari, and Vinod Kumar Prabhuswamy Copyright © 2013 Abhishek Vijayakumar et al. All rights reserved. Inflammation in Retinal Disease Tue, 10 Sep 2013 14:31:32 +0000 http://www.hindawi.com/journals/iji/2013/724648/ Scott M. Whitcup, Robert B. Nussenblatt, Susan L. Lightman, and David A. Hollander Copyright © 2013 Scott M. Whitcup et al. All rights reserved. The Evolving Treatment Options for Diabetic Macular Edema Mon, 09 Sep 2013 12:18:53 +0000 http://www.hindawi.com/journals/iji/2013/689276/ Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, and diabetic macular edema (DME) is the most common cause of visual impairment in individuals with DR. This review focuses on the pathophysiology, previous treatment paradigms, and emerging treatment options in the management of DME. Atul Jain, Neeta Varshney, and Colin Smith Copyright © 2013 Atul Jain et al. All rights reserved. Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold Tue, 27 Aug 2013 08:38:19 +0000 http://www.hindawi.com/journals/iji/2013/151028/ Palmitoylethanolamide (PEA) is a food component known since 1957. PEA is synthesized and metabolized in animal cells via a number of enzymes and exerts a multitude of physiological functions related to metabolic homeostasis. Research on PEA has been conducted for more than 50 years, and over 350 papers are referenced in PubMed describing the physiological properties of this endogenous modulator and its pharmacological and therapeutical profile. The major focus of PEA research, since the work of the Nobel laureate Levi-Montalcini in 1993, has been neuropathic pain states and mast cell related disorders. However, it is less known that 6 clinical trials in a total of nearly 4000 people were performed and published last century, specifically studying PEA as a therapy for influenza and the common cold. This was done before Levi-Montalcini’s clarification of PEA’s mechanism of action, analyzing the role of PEA as an anti-inflammatory agent. We will review in depth these studies, as the results support the effectiveness and safety of PEA in flu and respiratory infections. J. M. Keppel Hesselink, Tineke de Boer, and Renger F. Witkamp Copyright © 2013 J. M. Keppel Hesselink et al. All rights reserved. Ankylosing Spondylitis: From Cells to Genes Sun, 21 Jul 2013 12:00:08 +0000 http://www.hindawi.com/journals/iji/2013/501653/ Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology, though it is considered an autoimmune disease. HLA-B27 is the risk factor most often associated with AS, and although the mechanism of involvement is unclear, the subtypes and other features of the relationship between HLA-B27 and AS have been studied for years. Additionally, the key role of IL-17 and Th17 cells in autoimmunity and inflammation suggests that the latter and the cytokines involved in their generation could play a role in the pathogenesis of this disease. Recent studies have described the sources of IL-17 and IL-23, as well as the characterization of Th17 cells in autoimmune diseases. Other cells, such as NK and regulatory T cells, have been implicated in autoimmunity and have been evaluated to ascertain their possible role in AS. Moreover, several polymorphisms, mutations and deletions in the regulatory proteins, protein-coding regions, and promoter regions of different genes involved in immune responses have been discovered and evaluated for possible genetic linkages to AS. In this review, we analyze the features of HLA-B27 and the suggested mechanisms of its involvement in AS while also focusing on the characterization of the immune response and the identification of genes associated with AS. José Francisco Zambrano-Zaragoza, Juan Manuel Agraz-Cibrian, Christian González-Reyes, Ma. de Jesús Durán-Avelar, and Norberto Vibanco-Pérez Copyright © 2013 José Francisco Zambrano-Zaragoza et al. All rights reserved. Preoperative White Blood Cell Count and Risk of 30-Day Readmission after Cardiac Surgery Thu, 18 Jul 2013 12:10:13 +0000 http://www.hindawi.com/journals/iji/2013/781024/ Approximately 1 in 5 patients undergoing cardiac surgery are readmitted within 30 days of discharge. Among the primary causes of readmission are infection and disease states susceptible to the inflammatory cascade, such as diabetes, chronic obstructive pulmonary disease, and gastrointestinal complications. Currently, it is not known if a patient’s baseline inflammatory state measured by crude white blood cell (WBC) counts could predict 30-day readmission. We collected data from 2,176 consecutive patients who underwent cardiac surgery at seven hospitals. Patient readmission data was abstracted from each hospital. The independent association with preoperative WBC count was determined using logistic regression. There were 259 patients readmitted within 30 days, with a median time of readmission of 9 days (IQR 4–16). Patients with elevated WBC count at baseline (10,000–12,000 and >12,000 mm3) had higher 30-day readmission than those with lower levels of WBC count prior to surgery (15% and 18% compared to 10%–12%, ). Adjusted odds ratios were 1.42 (0.86, 2.34) for WBC counts 10,000–12,000 and 1.81 (1.03, 3.17) for WBC count > 12,000. We conclude that WBC count measured prior to cardiac surgery as a measure of the patient’s inflammatory state could aid clinicians and continuity of care management teams in identifying patients at heightened risk of 30-day readmission after discharge from cardiac surgery. Jeremiah R. Brown, R. Clive Landis, Kristine Chaisson, Cathy S. Ross, Lawrence J. Dacey, Richard A. Boss Jr., Robert E. Helm, Susan R. Horton, Patricia Hofmaster, Cheryl Jones, Helen Desaulniers, Benjamin M. Westbrook, Dennis Duquette, Kelly LeBlond, Reed D. Quinn, Patrick C. Magnus, David J. Malenka, and Anthony W. DiScipio Copyright © 2013 Jeremiah R. Brown et al. All rights reserved. The Effects of Insufflation Conditions on Rat Mesothelium Mon, 24 Jun 2013 11:27:02 +0000 http://www.hindawi.com/journals/iji/2013/816283/ Aim. The aim of this investigation was to examine the alterations in the peritoneum after cold dry CO2, heated dry CO2, and humidified heated CO2 at pressures equivalent to intraperitoneal pressures used in human laparoscopy. Methods. Eighteen rats were divided into 4 treatment groups—group 1: untreated control; group 2: insufflation with cold dry CO2; group 3: insufflation with heated, dry CO2; group 4: insufflation with heated and humidified CO2. The abdomen was insufflated to 5 mm/Hg (flow rate 50 mL/min) for 2 h. Twelve hours later, tissue samples were collected for analysis by light microscopy (LM) and scanning electron microscopy (SEM). Results. Group 1: no abnormalities were detected. Group 2: specimens revealed an inflammatory response with loss of mesothelium and mesothelial cell nuclei showing lytic change. Cells were rounded with some areas of cell flattening and separation. Group 3: some animals showed little or no alteration, while others had a mild inflammatory response. Mesothelial cells were rounded and showed crenation on the exposed surface. Group 4: specimens showed little change from the control group. Conclusions. The LM results indicate that insufflations with heated, humidified CO2 are the least likely to induce mesothelial damage. Andrew K. Davey, Jessica Hayward, Jean K. Marshall, and Anthony E. Woods Copyright © 2013 Andrew K. Davey et al. All rights reserved. Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation Thu, 06 Jun 2013 11:21:12 +0000 http://www.hindawi.com/journals/iji/2013/601424/ Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these subjects are limited justifying this paper. Tales Rubens de Nadai, Mariane Nunes de Nadai, Agnes Afrodite Sumarelli Albuquerque, Marco Tulio Menezes de Carvalho, Andrea Carla Celotto, and Paulo Roberto Barbosa Evora Copyright © 2013 Tales Rubens de Nadai et al. All rights reserved. Curbing Inflammation in the Ischemic Heart Disease Thu, 30 May 2013 13:52:37 +0000 http://www.hindawi.com/journals/iji/2013/183061/ A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement. It is surprising to note, based on a wide literature overview including the following 30 years (decades of 1960, 1970, and 1980), that the inflammatory acute myocardium infarction lost its focus, virtually disappearing from the literature reports. The reversal of this historical process occurs in the 1990s with the explosion of studies involving cytokines. Considering the importance of inflammation in the pathophysiology of ischemic heart disease, the aim of this paper is to present a conceptual overview in order to explore the possibility of curbing this inflammatory process. Paulo Roberto B. Evora, Julio Nather, Paulo Victor Tubino, Agnes Afrodite S. Albuquerque, Andrea Carla Celotto, and Alfredo J. Rodrigues Copyright © 2013 Paulo Roberto B. Evora et al. All rights reserved. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System Wed, 29 May 2013 14:12:33 +0000 http://www.hindawi.com/journals/iji/2013/578480/ Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. Kate Marie Lewis, Renée Jade Turner, and Robert Vink Copyright © 2013 Kate Marie Lewis et al. All rights reserved. Platelet Parameters in Hepatic Hydatid Cysts Mon, 27 May 2013 18:51:47 +0000 http://www.hindawi.com/journals/iji/2013/593273/ Background. Hepatic hydatid cyst infection is caused by microorganisms named Echinococcus which belong to family Taeniidae. Platelets are considered as a mediator in inflammation and infectious diseases because of the various proinflammatory substances that they contain. Design and Methods. Thirty-three patients who were admitted to Doğubayazıt State Hospital’s General Surgery Clinic with a diagnosis of hepatic cyst hydatid were enrolled in this retrospective study. Laboratory data of the patients in pre- and postoperative periods were obtained from computerized medical records database of the hospital. Results. Preoperative mean platelet volume (MPV) of the patients was significantly increased compared to postoperative MPV values. Conclusion. We claim that MPV is a useful follow-up marker after surgery in patients with hydatid cyst. Mustafa Sit, Gülali Aktaş, Edip Erdal Yilmaz, İsmail Necati Hakyemez, Aytekin Alçelik, and Abdülkadir Küçükbayrak Copyright © 2013 Mustafa Sit et al. All rights reserved. The Role of the Immune Response in Age-Related Macular Degeneration Thu, 23 May 2013 11:20:03 +0000 http://www.hindawi.com/journals/iji/2013/348092/ Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD. Scott M. Whitcup, Akrit Sodhi, John P. Atkinson, V. Michael Holers, Debasish Sinha, Bärbel Rohrer, and Andrew D. Dick Copyright © 2013 Scott M. Whitcup et al. All rights reserved. Curbing Inflammation in Burn Patients Mon, 20 May 2013 17:02:22 +0000 http://www.hindawi.com/journals/iji/2013/715645/ Patients who suffer from severe burns develop metabolic imbalances and systemic inflammatory response syndrome (SIRS) which can result in multiple organ failure and death. Research aimed at reducing the inflammatory process has yielded new insight into burn injury therapies. In this review, we discuss strategies used to curb inflammation in burn injuries and note that further studies with high quality evidence are necessary. Jayme A. Farina Jr., Marina Junqueira Rosique, and Rodrigo G. Rosique Copyright © 2013 Jayme A. Farina Jr. et al. All rights reserved.