Significant Reduction In Inflammatory Markers Research Articles

Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation

Unusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage. In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats. Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle. Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1β, IL-6, and IL-10). Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.

Omega3 Fatty Acids Intake Versus Diclofenac in Osteoarthritis Induced in Experimental rats

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by abnormal remodeling pattern of joints driven by inflammatory mediators within the affected joints. Its symptoms are many like pain, stiffness, and decreased function.Objective: The present study mainly focused on the anti-inflammatory effect of omega 3 fatty acids (F.As) versus diclofenac, non-steroidal anti-inflammatory drug in OA induced in ratsDesign: Intraarticular injection of monosodiumiodoacetate (MIA) 24.6 mg/kg in 0.6 ml saline was used to induce OA. Diclofenacand omega-3 F. These were administered orally, daily for 21 days and after 24 hours of OA induction.Results: Osteoarthritis induction resulted in an increase in serum levels of IL-6 (479.5%), TNF-a(545.5%), and CRP (754.2%) along with IL-10 level decrease (70.3%) as compared to normal group. Diclofenac intake demonstrated significant increase of IL-6 (24.9%), CRP (88.6%), and TNF-a (25.2%) compared to the OA control group. Omega 3 FAs intake showed significant reduction in inflammatory markers along with IL-10 increase, in comparison to OA group. Both treatment demonstrated a significant increase in TIMP2 along with decreased MMP2 and MPO in comparison with OA control. Positive correlation of IL-6 with MPO (r = 0.7, P=0.002), and negative one with IL-10 (r = 0.9, p<0.0001) and TIMP2 (r = -0.5, p<0.008) was observed. Interleukin-10 was negatively correlated with MMP2 (r = - 0.5, p<0.007) and MPO (r = -0.8, p<0.0001).Conclusion: Data derived from biochemical and histopathological results, indicated that omega3 FAs may be expressed as a natural anti-inflammatory agent of a significant potential in OA with evident remarkable effect.Keywords: OA; omega3FAs; diclofenac; MMP2; TIMP2; MPO

Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial

Objectives: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA).Method: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system.Results: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms.Conclusions: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.

The Comparative Effect of Pioglitazone and Metformin on Serum Osteoprotegerin, Adiponectin and Intercellular Adhesion Molecule Concentrations in Patients with Newly Diagnosed Type 2 Diabetes: a Randomized Clinical Trial

The etiologic role of inflammatory pathways in the development of diabetic complications, especially cardiovascular events, has been established. The anti-inflammatory role of metformin and pioglitazone has been described; however, no study to date has compared the efficacy of these common oral agents in this regard. In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin. In an open-label randomized clinical trial, 117 patients with newly diagnosed type 2 diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were randomly allocated to 2 arms receiving either 1,000 mg/d metformin or 30 mg/d pioglitazone, respectively. Biochemical assessments were made at baseline and the end of the 3 months trial. Significant reduction in FPG, insulin and HbA1c in women and men of both arms were observed. Log-hsCRP values significantly decreased in both arms. A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p=0.063). A greater reduction in log-ICAM levels was identifiable in men receiving pioglitazone compared to the other arm (p=0.008); in addition, the same trend was observed in log-OPG values (p=0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable between the 2 arms. A significant increase in adiponectin was observed in both men and women in the pioglitazone arm (p<0.001), whereas changes were non-significant in the metformin arm. Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers.

Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats.

BackgroundThe fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects.AimAbove mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats.MethodsTreated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests.Resultsd-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue.ConclusionOur findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and hyperglycemia with the preservation of β-cells in the progression of T2DM.

Vitamin D and inflammation

Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints.

The Effect of Green Tea on IL-6 and CRP level in Model of Polycystic Ovary Syndrome as an Inflammation State

Background: Having low-grade chronic inflammation state symptoms such as elevated C-reactive protein and interleukin-6 play a crucial role in polycystic ovary syndrome (PCOS). Green tea has anti-inflammatory properties. This research evaluates the effect of green tea on inflammatory indexes. Adult Wistar rats were exposed to subcutaneous administration of estradiol valerate for PCOS induction. PCOS rats were divided into control and experimental groups received intraperitoneal injection green tea extract daily. Animals were anesthesia with chloroform. Ovary and serum were taken to measure the inflammatory markes using ELISA kits and Histomorphometric studies. The data were analyzed using One-Way ANOVA with significance level P< 0.05. Results: The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. Disscoution: it can be concluded that having anti-inflammatory substances, green tea is effective in symptoms of this syndrome and metabolic syndrome.

P.01.2 ADALIMUMAB FOR THE TREATMENT OF POST-OPERATIVE RECURRENCE OF CROHN'S DISEASE. A SINGLE CENTRE EXPERIENCE

Background: Tumour necrosis factor alpha (TNF-a) plays an important role in malnutrition and growth retardation in paediatric inflammatory bowel disease (IBD) due to perpetuation of chronic inflammation. One of the objectives in the management of these patients should be to optimize their growth, which may be compromised due to uncontrolled disease and the effect of steroids. We aimed to study anti-TNF treatment effect on nutritional recovery in paediatric IBD, in relation to their efficacy in clinical response, both in shortand medium-term. Methods: Retrospective analysis of our paediatric IBD patients treated with anti-TNF between January 2002 and December 2010. We evaluated clinical response as defined by changes in activity scores (Paediatric Crohn’s Disease Activity Index [PCDAI] and Paediatric Ulcerative Colitis Activity Index [PUCAI]) at 2 and 8 weeks, 6 months and 1 year after its initiation. Changes in anthropometric measures (height and weight for age and body mass index [BMI]) and biochemical modifications (ESR, CRP, haemoglobin, platelets and albumin) were evaluated at 6 and 12 months. Results: 54 patients (34 boys) received anti-TNF (44 CD, 8 UC, 2 IBDU). Age at diagnosis: 11 years 5 months. Mean time from diagnosis to anti-TNF treatment: 17 months (range 0 121). Mean age at first infusion 13 years (1.1 17.3). Mean followup 35 months and mean number of infusions per patient 17. Forty-one patients received infliximab (IFX), 21 adalimumab (ADA) and 1 certolizumab pegol. Thirty-one patients (63%) had not previously received steroids. Mean basal PCDAI and PUCAI: 28.6 (2.5 62) and 39 (27 55) respectively. Clinical response was achieved in 47 cases (87%). Remission rate was 74.2% at 2 weeks, 87.7% at 8 weeks, 90% at 6 months, and 90.6% at 12 months. Seven patients experienced a relapse at some point of the follow-up. Median steroid-free time from the beginning of anti-TNF was 25.9 months (1 76). Mean BMI prior to treatment was 17, z-score 1.04 ( 4.2, +1.64). We observed improvement of anthropometry, with a mean BMI of 19.2 [z-score 0.27 ( 2.3, +1.78)] after 12 months. Biochemical parameters improvement was also observed at 6 and 12 months, with significant reduction of inflammatory markers and increase in haemoglobin and albumin levels. Conclusions: Anti-TNF treatment shows high efficacy in obtaining and maintaining clinical remission in paediatric IBD. Furthermore it has a positive impact on the nutritional status. This effect is parallel to the decrease in disease activity.

P603 Anti-TNF treatment is effective in inducing remission and restoring nutritional status in pediatric inflammatory bowel disease

Background: Tumour necrosis factor alpha (TNF-a) plays an important role in malnutrition and growth retardation in paediatric inflammatory bowel disease (IBD) due to perpetuation of chronic inflammation. One of the objectives in the management of these patients should be to optimize their growth, which may be compromised due to uncontrolled disease and the effect of steroids. We aimed to study anti-TNF treatment effect on nutritional recovery in paediatric IBD, in relation to their efficacy in clinical response, both in shortand medium-term. Methods: Retrospective analysis of our paediatric IBD patients treated with anti-TNF between January 2002 and December 2010. We evaluated clinical response as defined by changes in activity scores (Paediatric Crohn’s Disease Activity Index [PCDAI] and Paediatric Ulcerative Colitis Activity Index [PUCAI]) at 2 and 8 weeks, 6 months and 1 year after its initiation. Changes in anthropometric measures (height and weight for age and body mass index [BMI]) and biochemical modifications (ESR, CRP, haemoglobin, platelets and albumin) were evaluated at 6 and 12 months. Results: 54 patients (34 boys) received anti-TNF (44 CD, 8 UC, 2 IBDU). Age at diagnosis: 11 years 5 months. Mean time from diagnosis to anti-TNF treatment: 17 months (range 0 121). Mean age at first infusion 13 years (1.1 17.3). Mean followup 35 months and mean number of infusions per patient 17. Forty-one patients received infliximab (IFX), 21 adalimumab (ADA) and 1 certolizumab pegol. Thirty-one patients (63%) had not previously received steroids. Mean basal PCDAI and PUCAI: 28.6 (2.5 62) and 39 (27 55) respectively. Clinical response was achieved in 47 cases (87%). Remission rate was 74.2% at 2 weeks, 87.7% at 8 weeks, 90% at 6 months, and 90.6% at 12 months. Seven patients experienced a relapse at some point of the follow-up. Median steroid-free time from the beginning of anti-TNF was 25.9 months (1 76). Mean BMI prior to treatment was 17, z-score 1.04 ( 4.2, +1.64). We observed improvement of anthropometry, with a mean BMI of 19.2 [z-score 0.27 ( 2.3, +1.78)] after 12 months. Biochemical parameters improvement was also observed at 6 and 12 months, with significant reduction of inflammatory markers and increase in haemoglobin and albumin levels. Conclusions: Anti-TNF treatment shows high efficacy in obtaining and maintaining clinical remission in paediatric IBD. Furthermore it has a positive impact on the nutritional status. This effect is parallel to the decrease in disease activity.

Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmuno-burst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial.

e13098 Background: TSPP is a poly-epitope peptide anticancer vaccine able to generate a thymidylate syntase (TS) specific T cell response with antitumor activity in preclinical models, expecially when used in sequential combination with 5-FU. TS is in fact involved in DNA replication and is the major pharmacological target of fluoropyrimidines whose activity leads in turn to TS upregulation. On these basis we designed a phase Ib trial where we investigated the safety and the immunobiological activity of TSPP + GOLFIG (Gemcitabine + FOLFOX-4 + GM-CSF + IL-2) regimen. Methods: TSPP/VAC-1 (Eudract 2009-016897-33) is a monocentric dose finding Phase Ib trial. 12 pretreated metastatic colon cancer patients were enrolled between April and November 2011. All of them received biochemotherapy according to the GOLFIG regimen biweekly and TSPP (on day 7) diluted in motanide ISA720 (1:1) at the dosage of 100 (3 patients), 200 (3 patients) and 300 ug (6 patients). Results: No life-threatening adverse events were observed. Grade 3 leucopenia (2 cases), thrombocitopenia (3 cases), anemia (3 cases), nausea/vomiting (2 cases), and dyarrhea (4 cases) along with 3 cases of oxaliplatin reaction were recorded. Fever and flu-like symptoms were common along cytokine administration. An IFN-gamma ELISPOT assay recorded an increase in TS specific CTL precursors in 3/6 evaluable patients; it was also observed an increase in lymphocytes, eosinophils, terminal effector memory and central memory T cells and in both c-ANCA and p-ANCA (P= 0.02) in the peripheral blood and a significant reduction in inflammatory markers (LDH, CRP and ESR). Quality of life analysis revealed a general improvement in patients’health state along the treatment. 1 partial response, 6 disease stabilizations and 2 progessions of disease were recorded. TSPP Maximal Tolerated Dose was not reached, while the Optimal Biological Dose was identified at 300 ug. Conclusions: Our results suggest that the GOLFIG + TSPP vaccine combination is safe and immunologically active and deserves to be evaluated in a further phase II trial.

Abstract P77: Reduced Inflammatory Response with a Novel Cardiopulmonary Bypass Circuit: A Prospective Randomized Evaluation

BACKGROUND: The detrimental effects of inflammation following cardiopulmonary bypass (CPB) result in poor postoperative outcomes in patients undergoing heart surgery. A novel CPB circuit (Admiral, Eurosets, Italy) with its inner surface coated with a proprietary phosphorylcholine coating was hypothesized to elicit a reduced inflammatory response compared to a conventional CPB circuit. METHODS: Patients undergoing isolated aortic valve surgery were enrolled in a prospective study and either assigned to Admiral group (Admiral, n=15) or the conventional CPB group (Dideco, n=15). The Admiral oxygenator reduces priming volumes, decreases membrane surface area and incorporates a cell-saver selectively filtering the blood collected through mediastinal cavity before re-transfusion into the patient. The conventional CPB circuit used was a Dideco D903 Avant with an open cardiotomy reservoir. Clinical data and biochemical parameters were measured postoperatively, during CPB and at 1, 18, 36, 48 and 72 hours, respectively. RESULTS: Preoperative demographics such as age (68.2±10.4 vs. 70.9±10), Euroscore (6.8±2.3 vs. 6.2±1.1) as well as others did not differ between Admiral and Dideco groups, respectively. The CPB time (Admiral=104±30 vs. Dideco=99±17 minutes, p=NS), aortic cross clamp time (Admiral=73.2±17.5 vs. Dideco=73.8±19 minutes, p=NS) and the incidence of perioperative complications were also comparable. There was a significant decrease in the Admiral group with respect to inflammatory response, assessed by means of D-dimer (Admiral=1332.3±953.9 vs. Dideco=2791.9±1740.7, p=0.02), CRP (Admiral=169.1±164.8 vs. Dideco=57.1±39.3, p=0.04), IL-6 (Admiral=11.8±12.5 vs. Dideco=26.5±24.9, p=0.02) and TNF-a (Admiral=29±28.7 vs. Dideco=45.5±23.6, p=0.03). CONCLUSIONS: Although no considerable difference was detected in terms of peri-operative outcomes, the Admiral oxygenator did result in a significant reduction of inflammatory markers in immediately postoperative course primarily due to its enhanced biocompatibility. More powerful studies may yield potentially incremental benefits with Admiral oxygenator in future.

Impact of selective cyclooxygenase-2 inhibition on the pathophysiology of atherosclerosis and unstable angina

Background: Selective COX-2 inhibitors (celecoxib) are effective anti-inflammatory drugs, though they may increase cardiovascular risk. Objectives: To verify the possible pathophysiological role of COX-2 inhibitors on experimental atherosclerosis and its clinical outcomes in patients with unstable angina (UA). Methods: Atherosclerosis was induced in twenty four Boscat rabbits and celecoxib was administered as a prophylactic and therapeutic agent. At the end of experiment, the animals were killed and their serum and aortic tissues were evaluated for lipid profile and histopathological examination. In the human study, forty UA patients (group I: received the usual regimen of UA and aspirin for 30 days and group II: additionally received celecoxib and ten controls were incorporated into the study. Estimation of CRP, IL-6 and lipid profiles was carried out at the baseline and 30 days after. Results: Celecoxib administration attenuated the progression of atherosclerosis. Also, after 30-days, group II of UA patients showed a significant reduction of inflammatory markers, risky lipids and CV events with a raise in HDL levels when compared to group I. Conclusion: Celecoxib has beneficial lowering effect on the levels of inflammatory markers, risky lipids and on the size of atheromatous patches. This may explain its potential role in decreasing CV events in UA patients.

Characterization of the Corneal Surface in Limbal Stem Cell Deficiency and after Transplantation of Cultivated Limbal Epithelium

Transplantation of in vitro-cultivated limbal epithelium (TCLE) recently was developed to treat limbal stem cell deficiency (LSCD). The objective of this study was to characterize changes in the cornea during LSCD and on the corneal surface after TCLE. Experimental study. The pannus tissue excised from the corneas of 17 LSCD patients was analyzed to characterize the changes in the cornea during LSCD. Five corneal buttons obtained during perforating keratoplasty (pKP) from patients who had undergone TCLE at least 6 months before pKP were examined to assess the effect of TCLE. Six samples of healthy central cornea and 6 of bulbar conjunctiva served as control tissue. The expression of epithelial lineage markers (keratin [K] 3, K12, K19, and mucin 5AC) and inflammatory markers (interleukin-1alpha [IL-1alpha], IL-1beta, intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1], and vascular endothelial growth factor [VEGF]) were analyzed using real-time polymerase chain reaction, Western blotting, and immunofluorescence in the tissue samples. Comparison of the markers' expression patterns. The expression of all markers differed in healthy cornea and conjunctiva. Expression of lineage markers was similar in pannus to conjunctiva, but not to cornea. Interleukin-1beta, ICAM-1, VCAM-1, and VEGF were increased significantly in pannus compared with the levels in healthy cornea. Interleukin-1alpha, IL-1beta, and ICAM-1 were increased compared with healthy conjunctiva. The TCLE improved vision and reduced inflammation, vascularization, and discomfort. After TCLE, the lineage markers in the excised corneal buttons showed a corneal phenotype and a significant reduction in inflammatory markers in 4 of 5 cases. Limbal stem cell deficiency is characterized by ingrowth of abnormal inflamed tissue with a conjunctival phenotype. Transplantation of limbal epithelium cultivated in vitro on intact amniotic membrane restored a noninflamed ocular surface and a corneal phenotype. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and α1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI < 1). After the pharmacological treatment, high significant ( P < 0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI > 1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5+/-5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2+/-4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0+/-1.0 compared with 6.0+/-2.0 days respectively; P=0.022), ST segment normalization (3.5+/-1.0 compared with 4.5+/-1.0 days respectively; P=0.001), pericardial effusion (4.5+/-1.0 compared with 5.5+/-1.0 days respectively; P=0.001) and ESR (5.0+/-1 compared with 6.0+/-2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5+/-2.0 compared with 6.5+/-2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.

Relation of Inflammatory Status to Major Adverse Cardiac Events and Reverse Remodeling in Patients Undergoing Cardiac Resynchronization Therapy

Inflammatory markers are involved in heart failure (HF) pathophysiology. However, the link between these markers and reverse remodeling as well as major adverse cardiac events (HF death, sudden death, and unplanned cardiac rehospitalizations) in patients who undergo cardiac resynchronization therapy (CRT) has not been evaluated. We recorded major adverse cardiac events of 140 patients (on optimized medical therapy, left ventricular ejection fraction 29.9 +/- 9.6%, New York Heart Association Class III-IV, with intraventricular dyssynchrony) who underwent CRT (enrolled since April 2004). Moreover, we evaluated before and after 6 months of CRT: interleukin-6, high-sensitivity C-reactive protein, New York Heart Association class, quality of life (score on Minnesota Living with Heart Failure questionnaire), 6-minute walking test, left ventricular end-diastolic and end-systolic volumes (nonindexed and indexed by body surface area), and left ventricular ejection fraction. Adverse cardiac events were observed in 40 patients (28.6%): 22 deaths and 18 cardiac unplanned rehospitalizations. Only patients without adverse events during follow-up showed a significant reduction of inflammatory markers and left ventricular volumes (reverse remodeling), despite a significant improvement of clinical status observed in both groups of patients. The reduction of inflammatory status seems to be linked to reverse remodeling as well as to a better clinical prognosis in patients with HF who underwent CRT.

In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients

The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. A significant reduction in total cholesterol from 221+/-44 mg/dl to 184+/-41 mg/dl (3 months) and to 186+/-39 mg/dl (6 months) (P<0.02) and low-density lipoprotein cholesterol from 139+/-40 mg/dl to 104+/-29 mg/dl (3 months) and to 100+/-31 mg/dl (6 months) (P<0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P = 0.03) at 6 months (P<0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5 pg/ml (IQR 3.1) (P = 0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4 mg/l (IQR 1.3) (P = NS) at 6 months] or plasma lipids [LDL-cholesterol from 127+/-32 mg/dl to 131+/-21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155+/-95 pg/ml monocytes for IL-6 and 722+/-921 pg/ml monocytes for IL-8) vs HS (137+/-87 pg/ml monocytes and 186+/-125 pg/ml monocytes) (P<0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954+/-321 pg/ml monocytes for CKD and 1451+/-237 pg/ml monocytes for HS; P<0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.