Decrease In CRP Research Articles

Efficacy of tocilizumab treatment in COVID-19 patients with cytokine release syndrome

Background/Aim: Cytokine release syndrome, a potentially life-threatening condition in SARS‐CoV‐2 (COVID-19) patients, plays a critical role that may lead to the prioritization of tocilizumab (TCZ) in the treatment of this disease. We aimed to present our TCZ-treated SARS‐CoV‐2 patients’ data that might help and guide clinicians in dealing with this infectious disease in their daily practice and research. Methods: This is a retrospective multicenter cohort study from two Turkish pandemic centers. A total of 5165 patients’ data who were hospitalized due to SARS‐CoV‐2 pneumonia from March 16 to May 20, 2020 were screened and 72 patients treated with TCZ were included in the study. We evaluated patients' demographic data, laboratory and imaging studies, and clinical outcomes and the effect of TCZ treatment on patients' laboratory and clinical results. Results: O2 saturation levels significantly increased, and fever significantly decreased on the 5th day after TCZ therapy compared to before its initiation (P=0.001, P=0.010, respectively). The decrease in troponin-I, creatinine, LDH, fibrinogen, CRP, procalcitonin, CK, and ferritin levels after TCZ therapy were significant (P0.05 for all). Importantly, we found a significant increase in mortality rates in patients who received azithromycin, oseltamivir, and ascorbic acid treatments compared to those who did not receive those treatments (P

PAINFUL SUBACUTE THYROIDITIS TREATMENT APPROACH

The aim: The study was aimed to compare the efficiency of intrathyroid steroid injection to oral steroid intake in patients with subacute thyroiditis. Materials and methods: 32 patients with subacute thyroiditis with insufficient result from NSAIDs treatment were randomly divided into two groups. The 1st group received two intrathyroid steroid injections, the 2nd group received oral prednisone. The results of the treatment were evaluated via ultrasound and evaluation of ESR and CRP at 0, 2, 4, 8 and 16 weeks of treatment. Results: Patients of the 1st group showed much faster result at the ultrasound compared to the 2nd group: mean decrease in hypoechogenity area 44,42% vs 16,35% at week 2, p < 0,001; 93,29% vs 75,98% at week 4, p < 0,001; 97,8% vs 95,24% at week 8, p = 0,4; mean decrease in ESR 66,34% vs 51,92% at week 2, p = 0,023; 84,43% vs 74,94% at week 4, p = 0,023; mean decrease in CRP 26,53% vs 20,77% at week 2, p = 0,024, 33,77% vs 29,98%, at week 4, p = 0,026. No side effects were noted during the treatment of patients of the 1st group. Conclusions: Compared to oral steroid intake intrathyroid steroid injection is faster, safer and generally better tolerated by patients.

A comparative analysis of high-flux and low-flux dialysis in cervical cancer patients with obstructive renal failure showing no significantly improved renal function after catheterisation.

Objective:This study aims to compare the clinical application value of high-flux dialysis with low-flux dialysis in patients without significantly improved renal function after cervical cancer and obstructive renal failure catheterisation.Methods:This prospective randomised study was conducted from January 2018 to December 2019. Eighty cervical cancer patients with obstructive renal failure who showed no significant renal function improvement after catheterisation were randomised into two groups (n = 40 in each group) in the Second People’s Hospital of Yibin City. High-flux and low-flux dialysis were employed in the experimental group and the control group, respectively. Treatments in both groups were provided every other day, with the whole course lasting one week. Data were recorded before and after dialysis included inflammatory factors such as IL-6, CRP and TNF-a, large and moderate molecular toxins (e.g., β2 micro-globulin, parathyrin (PTH) and cysteine protease inhibitor). Renal function changes during the dialysis were also recorded. Afterwards, the two groups were compared regarding the overall efficacy.Results:Both the experimental group and the control group experienced a significant decrease in IL-6, CRP, TNF-a, β2 micro-globulin, PTH and cysteine protease inhibitor, with the decrease in the experimental group being more evident (p < 0.05). After dialysis was completed, the experimental group restored renal function indicators such as Cre, CysC and serum K+ levels more quickly than the control group (p < 0.05). The effective rate was 100% for the experimental group and 87.5% for the control group. The intragroup difference in the efficacy.was significant.Conclusions:High-flux dialysis appears to be more beneficial for cervical cancer patients with obstructive renal failure, showing no significant improvement in renal function after catheterisation. It restored renal function more quickly, had more radical draining of inflammatory factors and large and moderate molecular toxins, and had a higher overall effective rate.

Evaluation of bowel wall thickness by ultrasound as early diagnostic tool for therapeutic response in Crohn's disease patients treated with ustekinumab.

Ustekinumab was approved for the treatment of patients with moderate to severe CD 2. Development of predictors for selecting patients responding to ustekinumab has to be the next step. US offers a noninvasive method with great sensitivity in detecting CD activity 11. To evaluate BWT by BS as early diagnostic tool for treatment response in CD patients treated with ustekinumab at week 8. This is a prospective monocentric study. Twenty-three CD patients had BS at the time of first and second application. BS was performed by one of 2 experienced DEGUM certificated sonographers, with evaluation by both independently and blindly. Primary endpoint was substantial sonographic response defined as decrease of BWT ≥ 1 mm. Secondary endpoint was concordance between sonographic and clinical response, defined as decrease of CDAI ≥ 70 points and sonographic and biochemical response defined as decrease of CRP ≥ 0.5 mg/dl. At week 8, BS detected in 10 of 23 patients a substantial decrease of BWT ≥ 1 mm; in 7, a decrease < 1 mm. Compared to baseline, all 17 patients showed generally improved blood data and 16/17 generally improved clinical data. Of those with a decrease of BWT ≥ 1 mm, we observed a substantial decrease of CDAI ≥ 70 points in 9/10 patients and a substantial decrease of CRP ≥ 0.5 mg/dl in 8/10 patients. Our study suggests that sonographic measurement of BWT can be a helpful parameter for selecting patients responding early to ustekinumab and for providing assistance in terms of further treatment interval at week 8.

Rituximab in patients with acute ST-elevation myocardial infarction (RITA-MI)

Abstract Background In pre-clinical models of acute myocardial infarction (MI), mature B cells selectively mobilise inflammatory monocytes into the heart, leading to increased infarct size and deterioration of myocardial function. Anti-CD20 antibody-mediated depletion of B cells limited infarct size and improved cardiac function. Rituximab is a monoclonal antibody targeted against human B cells and has been used in the treatment of autoimmune diseases and cancers. However, its use in cardiovascular disease is untested and is currently contraindicated. Purpose We assessed the safety, feasibility and pharmacodynamic effect of rituximab given acutely to patients with ST-elevation MI (STEMI). Method RITA-MI was a prospective, open-label, dose-escalation, single-arm, phase 1/2a clinical trial, which tested rituximab administered as a single intravenous dose in patients with STEMI within 48 hours of symptom onset. Four escalating doses (200, 500, 700 and 1000mg) were used with 6 patients in each group. Follow-up was performed during initial inpatient stay; on days 6 and 14; and at 3 and 6 months. The primary endpoint was safety, whilst secondary endpoints were changes in B cells and their subsets, immune cell subsets, and cardiac and inflammatory biomarkers. [NCT:03072199] Results Overall, rituximab was well tolerated across all doses with the most common adverse event being gastrointestinal disturbance. This was due to the concomitant oral secondary prevention medication started after a STEMI. Five severe adverse events were reported, none of which were assessed as being related. Rituximab caused a mean 96.3% (95% CI 93.8–98.8%) depletion of B cell within 30 mins of the infusion starting across all dose groups. At 6 hours a rebound in B cells was seen in the 200, 500 and 700mg doses, likely related to the emigration of B cells from secondary lymphoid tissues. Maximal B cell depletion was seen at day 6, which was lower than baseline for all doses (p&amp;lt;0.001) (figure 1). B cell repopulation at 6months was dose-dependent. In addition, there was modulation of returning B cell subsets characterised by increased transitional B cells (figure 1C). Immunoglobulin (IgG, IgM and IgA) levels were not affected during follow-up. Rituximab also caused an acute and transient decrease in lymphocytes (both CD4+ and CD8+ T cells) and monocytes, whilst transiently increasing neutrophils at the 6-hour timepoint. Cardiac biomarkers showed a decrease in CRP and BNP. Clinical echocardiogram showed an increase in ejection fraction at follow up (mean increase in EF of 7.8% (95% CI 3.11–12.6)). Conclusion Rituximab appears safe and feasible when given in acute STEMIs. We have shown for the first time that depletion of B cells within 30mins of starting rituximab which demonstrates the biological plausibility of our treatment paradigm. Additional new insight into the mechanism of action of rituximab was found. This has led directly to the setting up of a phase 2b trial. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Union Research Council

An Unexpected Cause of Low Back Pain - A Case Report

Introduction: Low back pain is rarely the first manifestation of malignancy. The symptoms may be exacerbated by coexisting inflammation and subside after antibiotic therapy. Such a clinical course may lead to a delay in the diagnosis of cancer. Case Description: 65-year-old smoking man was admitted to the Neurology Department with severe low back pain and increased serum levels of inflammatory markers. The chest X-ray was normal. Due to repeated complaints, a wide range of diagnostics of the lesion was performed. An isolated irregular infiltration penetrating the intervertebral foramina and involving the L5 spinous process and the right dorsal extensor muscle along the vertebral arch, in a total size up to 3.5 cm, in addition to the degenerative disc changes, was visualized in magnetic resonance imaging (MRI). Prolonged antibiotic therapy resulted in a significant decrease in CRP and clinical improvement. During the second exacerbation of the refractory back pain in the L-S and Th regions after 15 months, the pathological structures initially diagnosed as inflammatory infiltrations were finally recognized as a metastatic infiltration of squamous cell carcinoma (SCC) of the lung. The CT examination to the chest demonstrated a large irregular tumor in the right lung. Conclusion: The reported rare case of SCC non-small cell lung cancer metastasis to the lumbar and presacral spinal region shows limited usefulness of MRI to give a specific diagnosis of such infiltration. Despite the rarity of tumors at this site, an invasive diagnostic method should be considered first with any unclear changes.

Colon Microbiocenosis and Its Correction in Patients Receiving Programmed Hemodialysis.

The aim of the investigation was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the efficacy of its correction using a new immobilized synbiotic.Materials and Methods.Samples of colon microbiota from 62 patients undergoing programmed hemodialysis were studied before and after a course of diet therapy that included probiotic components, in particular, the immobilized synbiotic LB-complex L. Isolation of microorganisms was carried out according to our original method; for bacteria identification, a MALDI-TOF Autoflex speed mass spectrometer (Bruker Daltonik, Germany) was used in the Biotyper program mode. The results were assessed using the criteria proposed by the authors and based on the OST 91500.11.0004-2003. The efficacy of the immobilized synbiotic was determined based on the clinical data, questionnaires, and bacteriological tests.Results.In patients receiving programmed hemodialysis (before the start of the diet therapy), chronic moderate inflammation and azotemia were found. Dysbiotic changes in microbiocenosis were revealed in all the examined patients; in the absence or suppression of lacto- and bifidoflora, the number and diversity of Bacteroides spp., Clostridium spp., Collinsella spp., Eggerthella spp. and other bacteria increased, which was consistent with the theory of functional redundancy of gut microbiota. From the answers to the questionnaires, a decrease in the quality of life was found (up to 70 points out of 100) according to six of the eight scales used. After the combined therapy using the synbiotic LB-complex L in the study group, 56% of the examined patients showed their microbiocenosis restored to normal; no grade III dysbiosis was detected in any patient. There was a significant decrease in CRP and ESR in these patients and an improvement in the quality of life by criteria reflecting physical health.Conclusion.In patients receiving programmed hemodialysis, the addition of a probiotic component in the diet therapy restores the evolutionarily determined structure of the microbiocenosis, normalizes its functions, and leads to an overall improvement in health and quality of life.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1–1.8) vs. 0.7 (0.6–0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1–1.8) to 1.4 (1.1–1.7), p = 0.17] slightly improved and beta cell function [133% (115–151) to 118% (109–130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

AB1059 A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ANAKINRA IN PATIENTS WITH STILL´S DISEASE

Background:Adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) are rare autoinflammatory disorders associated with an activated IL-1 pathway, characterized by spiking fever, rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. There is a growing understanding that SJIA and AOSD are one disease with different ages of onset, i.e. Still’s disease. The anaSTILLs study (anakinra inStill´sdisease) was designed to further evaluate efficacy and safety of anakinra in patients with Still´s disease across all age groups.Objectives:The primary objective was to demonstrate efficacy of anakinra versus placebo as assessed by ACR30 response with absence of fever at Week 2. Secondary objectives included: early onset of efficacy, sustained efficacy, time to study drug discontinuation, safety, pharmacokinetics, clinical signs and biomarkers.Methods:‘anaSTILLs’ was a randomized, double-blind, placebo-controlled, 12-week study including patients with active and newly diagnosed (6 months) Still´s disease according to adapted ILAR criteria if &lt;16, or Yamaguchi criteria, if ≥16 years of age at disease onset. Patients were randomized to anakinra 2 mg/kg (max 100 mg/day), 4 mg/kg (max 200 mg/day) or placebo.Results:12 patients were randomized and received study drug: 6 anakinra (2 mg/kg n=2, 4 mg/kg n=4) and 6 placebo, the study was terminated early due to slow recruitment. 1 patient on placebo had lymphoma, not Still’s disease, and was excluded; thus in total 11 patients were analyzed for efficacy, 8 were children [median (range) age=4.0 (1-11) years] and 3 were adults [median (range) age=32.0 (25-51) years]. 55% were male and the mean symptom duration was 74.2 days. All patients on anakinra but none on placebo achieved ACR30 response with absence of fever at Week 2 (p-value=0.0022). The efficacy of anakinra was further demonstrated by superiority to placebo in ACR50/70/90 responses with absence of fever at Week 2. All placebo patients discontinued the study within 6 weeks, 2 due to progressive disease, 2 due to lack of efficacy and 1 due to withdrawal by patient. There was a numerically higher proportion with early onset of efficacy (Week 1) in the anakinra group compared to placebo. The ACR30/50/70/90 responses in the anakinra group were sustained throughout the study period. Patients in the anakinra group had a prompt and persistent decrease in CRP and ferritin levels at Week 1, which was not observed in the placebo group. There were no unexpected safety findings. All anakinra patients developed anti-drug antibodies (ADAs) at some timepoint during the study. ADAs were persistent throughout the treatment period, except in one patient. Titers were low to moderate. One placebo patient had low ADA titers at one occasion. No neutralizing antibodies were observed and the ADAs did not appear to impact clinical efficacy or safety.Conclusion:Anakinra is superior to placebo in the treatment of Still’s disease. ADAs occur frequently but do not appear to adversely impact efficacy or safety. These results confirm the benefits of anakinra treatment in patients with active, newly diagnosed Still´s disease across ages.Disclosure of Interests:Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Peter Nigrovic Grant/research support from: Novartis, BMS, Pfizer, Consultant of: Novartis, BMS, Pfizer, Sobi, Miach Orthopedics, Simcere, XBiotech, Quench Bio, Ashley Cooper: None declared, Winn Chatham Grant/research support from: Sobi, Consultant of: Sobi, Shoghik Akoghlanian: None declared, Namrata Singh: None declared, Egla Rabinovich Grant/research support from: AbbVie, UCB Pharma, Janssen Research &amp; Development, Akaluck Thatayatikom: None declared, Alysha Taxter: None declared, Jonathan Hausmann Consultant of: Novartis, Milan Zdravkovic Shareholder of: Sobi, Employee of: Sobi, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Henrik Andersson Employee of: Sobi, Susanna Cederholm Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Rayfel Schneider Grant/research support from: Roche, Novartis, Sobi, Pfizer, Consultant of: Sobi, Novartis, Novimmune, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi

Subclinical atherosclerosis evolution during 5 years of anti-TNF-alpha treatment in psoriatic arthritis patients.

Our aim was to evaluate subclinical atherosclerosis progression during 5 years of anti-tumour necrosis factor (TNF)-α treatment in psoriatic arthritis (PsA) patients. Thirty-two consecutive PsA patients starting TNF-α inhibitors were enrolled and evaluated at baseline (T0), 2 years (FU1) and 5 years (FU2) of treatment. Arterial structural properties were evaluated by B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each segment (common, bulb, internal), bilaterally. Endothelial function was assessed by post-occlusion flow-mediated dilation (FMD) of the brachial artery using high-sensitivity ultrasonography. Treatment response was studied through DAS28 (disease activity score) and inflammatory biomarkers (C-reactive protein, TNF-α, osteoprotegerin). Metrologic and metabolic data were collected. At T1, a significant decrease of DAS28 (4.2±0.7 vs. 2.3±0.8, p<0.001) and CRP (11.25±9.16 vs. 2.91±1.72, p<0.01) was observed. Efficacy was preserved at FU2 (DAS28 2.4±0.9, CRP 2.73±2.51; p=ns vs. FU1). Systolic blood pressure and BMI remained stable throughout the follow-up, while diastolic blood pressure decreased significantly from FU1 to FU2 (80±10 vs. 74±7 mmHg, p=0.001). From T0 to FU1 there was an increase of IMT-mean and M-MAX (0.7±0.1 vs. 0.9±0.4 and 0.9±0.2 vs. 1.1±0.4, p<0.01). At FU2, IMT-mean and M-max did not change significantly (0.9±0.3 and 1.1±0.3, p=ns vs. FU1). No significant variation in FMD values was observed during the study period. A slight progression of subclinical atherosclerosis in PsA was observed in the first 2 years of anti-TNF-α treatment. This process seemed to decelerate in follow-up extension to 5 years.

Evaluation of melatonin therapy on improving the metabolic disorders associated to obesity in rats

Obesity is a worldwide epidemic and there are many diseases associated with it. Recent studies suggested that melatonin may be involved in the regulation of body mass and metabolic homeostasis through different mechanisms.To this purpose, we conducted an experimental study on 24 adults male Wistar rats, separated into 2 control groups and 1 test group. Our experimental protocol took place in three phases, an obesity induction phase in which the rats were subjected to a hyper fat diet “Cafeteria diet”. A therapeutic phase in which the control group received NaCl as a placebo, the test group was treated with melatonin at a dose of 5mg/kg/day. The groups were randomized and received treatment intraperitoneally for 6 weeks. A Biological blinded evaluation for lipidic, glucidic, and inflammatory (CRP) assessments were performed for each group.The results of our study showed that the Cafeteria diet significantly increased body weight with a gain of up to 126g (p=0.00). The biological analysis of the blood of rats treated with melatonin showed a decrease in blood glucose levels, triglycerides, LDL, HDL, CRP and total cholesterol compared to the initial values. Plasma analysis results obtained at the end of the therapeutic phase between melatonin and placebo‐treated rats showed a significant decrease in total cholesterol (p=0.002), LDL (p=0.005), HDL (p=0.014) and blood glucose (p=0.013). The difference between the two groups for CRP (p=0.084) and triglycerides (p=0.116) was not significant.Based on our results melatonin seems to have a beneficial effect against metabolic disorders related to obesity.Support or Funding InformationN/A

The Contribution of Hormone Replacement Therapy in Postmenopausal Women to Prevent Periodontal Disease

Aim: We investigated the possible association of hormone replacement therapy (HRT) administration and periodontitis in postmenopausal women by testing of systematic inflammatory parameters. Participants and Methods: 169 postmenopausal women participated in a prospective clinical study. They were divided into two groups: Group HRT (n=69) received HRT and Group no-HRT (n=100) did not receive HRT, but continued with body exercise and daily suitable natural food diet. We measured in the serum: Interleukin-1a (IL-1a); Interleukin-1b (IL-1b); Interleukin-6 (IL-6); Τumor necrosis factor (TNF-α); C-reactive protein of serum (CRP); Alkaline phosphatase (ALP); and Activin A. We also examined: oropharyngeal cavity microbial cultures; use of periodontal probe; depth of pocket; and bone mineral density. Results: The laboratory analyses showed statistical significant decrease of TNF-a (p<0.001), IL-6 (p<0.001), IL-1a (p<0.001), IL-1b (p<0.001), alkaline phosphatase (p<0.001) and CRP (p<0.001) in Group HRT compared to no-HRT. Activin A was also reduced but not statistically significantly (p=0.549). Oropharyngeal cavity cultures were all negative in Group HRT. Conclusion: We conclude that post-menopausal women after administration of HRT are protected of oral cavity health problems periodontitis and other local symptoms,

773 The Natural Course of Inflammatory Bowel Disease After Bariatric Surgery

INTRODUCTION: Approximately 32–52% of inflammatory bowel disease (Crohn's disease [CD] and ulcerative colitis [UC]) patients have obesity or are overweight. Bariatric surgery (BS) is a recommended and widely used approach to address severe obesity and its related comorbidities. However, data on the effect of BS on IBD are equivocal. We aimed to assess the course of IBD after BS. METHODS: Using ICD-9 codes all IBD patients who underwent BS (Roux-en-Y gastric bypass [RYGB], sleeve gastrectomy [SG] or gastric band/balloon [GB]) at a major referral center between January 2000-June 2018 were identified. Data on baseline demographics, co-morbidities and concomitant medications was collected. Laboratory data, endoscopic data (Mayo score for UC and Simple Endoscopy score [SES] for CD), patient reported outcomes (PROs) and medications at baseline and 6-12 months after BS were collected. We also assessed exacerbation of IBD, hospitalization and adverse events after BS. RESULTS: A total of 58 IBD patients (46.6% CD and 53.4% UC) underwent BS (79.3% GS, 15.5% RYGB and 5.2% GB) during the study period. Our cohort consisted of 74% females and 81% were Caucasians. At the time of BS, mean age was 47.8 ± 12.2 years, mean BMI was 43.5 ± 7, and 36.2% were active smokers. Compared to baseline, 6 months after BS, a decrease in WBC (8.6 ± 3 vs. 7.2 ± 2), CRP (0.7 vs. 0.6), aspartate aminotransferase (34.1 ± 28 vs. 23.5 ± 10) and alanine aminotransferase (34.4 ± 28 vs. 20.2 ± 11) and an increase in vitamin D (25.5 ± 15 vs. 20.2 ± 11) (P &lt; 0.05 for all) was noted. Beside the significant decrease in BMI (43.5 ± 7 vs. 36.3 ± 7) and HbA1C (5.6 vs. 5.2), extraintestinal manifestation of IBD also improved (50% vs. 5.2%) (P &lt; 0.05 for all). There was no differences in PROs, IBD therapy, and endoscopy scores (Table 1). Five patients (8.6%) had IBD exacerbation (all after GS) of which two had active disease at the time of BS, only two required hospitalization and intravenous steroids, but none of the patients required any further surgery or intervention. CONCLUSION: To date, our study is the largest on the natural course of IBD after bariatric surgery. A significant improvement in BMI, HbA1c, liver enzymes and IBD-related extraintestinal manifestations were noted after bariatric procedures. Longer follow-up is required, but based on these results; bariatric surgery for obesity appears to be safe in IBD patients.

Cardiometabolic and Inflammatory Benefits of Sympathetic Down-Regulation with Zamicastat in Aged Spontaneously Hypertensive Rats.

The hyperactivity of the sympathetic nervous system (SNS) plays a major role in the development and progression of several cardiovascular diseases. One strategy to mitigate the SNS overdrive is by restricting the biosynthesis of norepinephrine via the inhibition of dopamine β-hydroxylase (DBH). Zamicastat is a new DBH inhibitor that decreases norepinephrine and increases dopamine levels in peripherally sympathetic-innervated tissues. The cardiometabolic and inflammatory effects of sympathetic down-regulation were evaluated in 50 week old male spontaneously hypertensive rats (SHRs) receiving zamicastat (30 mg/kg/day) for 9 weeks. After 8 weeks of treatment, the blood pressure (BP) and heart rate (HR) were assessed by tail cuff plethysmography. At the end of the study, 24 h urine, plasma, heart, and kidney were collected for biochemical and morphometric analyses. Zamicastat-induced sympathetic down-regulation decreased the high BP in SHRs, with no observed effect on HR. The heart-to-body weight ratio was lower in SHRs treated with zamicastat, whereas the body weight and kidney-to-body weight ratio were similar between both SHR cohorts. Zamicastat-treated SHRs showed reduced 24 h urine output, but the urinary amount of protein excreted and creatinine clearance rate remained unchanged. Zamicastat treatment significantly decreased plasma triglycerides, free fatty acids, and aspartate aminotransferase levels. Aged SHRs showed higher plasma levels of inflammatory markers as compared with age-matched normotensive Wistar-Kyoto rats. The inflammatory benefits attained with DBH inhibition were expressed by a decrease in CRP, MCP-1, IL-5, IL-17α, GRO/KC, MIP-1α, and RANTES plasma levels as compared with untreated SHRs. In conclusion, DBH inhibition decreased norepinephrine levels, reduced end-organ damage, and improved cardiometabolic and inflammatory biomarkers in aged male SHRs.

Effects of the Systemic Administration of Omega -3 Polyunsaturated Fatty Acid on Experimental Periodontitis

Objective: The present study was aimed to investigate and evaluate the effects of eicosapentaenoic acid (EPA) on ligature induced periodontitis in rats through the biochemical analysis for rat’s serum level of CRP, ALP and MDA.&#x0D; &#x0D; Methods: Periodontitis was induced for the studied animals by ligation around the upper central incisor. Twenty five animals were used as a control and gavaged by water only, and one hundred animals with the induced periodontitis were divided into four equal groups according to the treatment used which was started at time of ligation removal: Water (P/W), scaling/root planing (P/SRP), 60mg/kg EPA(P/EPA), and scaling/root planing together with EPA(P/SRP+EPA). Blood was taken by cardiac puncture, after three hours, 24 hours, three days, one week and two weeks for biochemical analysis.&#x0D; Results: The P/SRP+EPA treatment group showed significant decrease (p&lt;0.05) in serum CRP, significant increase in serum ALP, significant decrease in serum MDA after one week, three days, and three hours respectively in comparison with the P/W treatment group.&#x0D; Conclusion: The treatment by SRP with 60mg/kg EPA is better than each one alone and can be used for treatment of periodontitis.

Biosynthetic homeostasis and resilience of the complement system in health and infectious disease.

BackgroundThe complement system is a central component of the innate immune system. Constitutive biosynthesis of complement proteins is essential for homeostasis. Dysregulation as a consequence of genetic or environmental cues can lead to inflammatory syndromes or increased susceptibility to infection. However, very little is known about steady state levels in children or its kinetics during infection.MethodsWith a newly developed multiplex mass spectrometry-based method we analyzed the levels of 32 complement proteins in healthy individuals and in a group of pediatric patients infected with bacterial or viral pathogens.FindingsIn plasma from young infants we found reduced levels of C4BP, ficolin-3, factor B, classical pathway components C1QA, C1QB, C1QC, C1R, and terminal pathway components C5, C8, C9, as compared to healthy adults; whereas the majority of complement regulating (inhibitory) proteins reach adult levels at very young age. Both viral and bacterial infections in children generally lead to a slight overall increase in complement levels, with some exceptions. The kinetics of complement levels during invasive bacterial infections only showed minor changes, except for a significant increase and decrease of CRP and clusterin, respectively.InterpretationThe combination of lower levels of activating and higher levels of regulating complement proteins, would potentially raise the threshold of activation, which might lead to suppressed complement activation in the first phase of life. There is hardly any measurable complement consumption during bacterial or viral infection. Altogether, expression of the complement proteins appears surprisingly stable, which suggests that the system is continuously replenished.FundEuropean Union's Horizon 2020, project PERFORM, grant agreement No. 668303.

Serum soluble urokinase plasminogen activator receptor (suPAR) in adults with growth hormone deficiency.

Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.

POTENTIAL HOLISTIC PREVENTIVE AND THERAPEUTIC EFFECTS OF GARCINIA MANGOSTANA EXTRACT OR ISOLATES IN TYPE 2 DIABETES MELLITUS: A REVIEW

Objective: The need for long-term medication in diabetes mellitus has led to a search for herbal medicines as alternative treatments. Several studies have shown that extract or isolates of Garcinia mangostana can help prevent and treat type 2 diabetes mellitus (T2DM).&#x0D; Methods: This review was conducted by searching various databases, including PubMed, ClinicalKey, ScienceDirect, and EBSCOhost. We analyzed papers published within the previous 10 y.&#x0D; Results: All in vitro, in vivo, and clinical studies that evaluated the pharmacological effects of extract or isolates of G. mangostana in T2DM were reviewed. G. mangostana was found to suppress adipogenesis and regulate lipid homeostasis, thus improving lipid profiles and preventing T2DM. G. mangostana also demonstrated hypoglycemic properties, including the ability to decrease fasting blood glucose and mildly increase pancreatic β-cell numbers and activity. The mangosteen-treated group in one study showed a decrease in Homeostatic Model Assesment for Insulin Resistance (HOMA-IR), indicating improved insulin sensitivity, along with a significant decrease in the high-sensitivity CRP (hs-CRP) levels. Histopathology showed that the α-mangostin-treated group had less damage to pancreatic β cells, healthier hepatocytes and central veins, and less glomerular and tubular epithelial necrosis than the diabetic control group. Moreover, the antioxidant effect of G. mangostana was shown to protect against the micro-and macrovascular damage caused by T2DM.&#x0D; Conclusion: Extract or isolates of G. mangostana possess strong potential to prevent and treat T2DM. Further research evaluating long-term outcome biomarkers in humans is needed to confirm the drug’s glycemic control capacity.

Possible Association between Serum Hepcidin and Hemostatic Parameters in Chronic Renal Failure Rat Model: Influence of Inhibition of Angiotensin Converting Enzyme

AbstractBackground: Chronic renal failure (CRF) is usually asso-ciated with abnormal coagulation profile. Hepcidin is a major regulator of iron metabolism and was reported to have an impact on anemia, insulin resistance, dyslipidemia, inflam-mation and oxidative stress which were all reported to play a potential role in CRF induced coagulopathy. Renin angi-otensin system (RAS) is involved in the pathophysiology of CRF and can affect coagulation profile.Aim of Study: To evaluate changes in coagulation profile in a rat model of chronic renal failure and the possible asso-ciation of these changes with serum hepcidin level in relation to some metabolic, inflammatory and oxidative stress param-eters and to evaluate whether changes in these parameters induced by inhibition of angiotensin converting enzyme (ACE) can affect serum hepcidin level.Material and Methods: Forty adult male albino rats divided into: Group I (n=8): Control group: Rats received subcutaneous injection with the vehicle (0.3M NaHCO3, 5ml/Kg) once weekly for 5 weeks. Group II (n=16): Chronic renal failure-induced group (CRF): Rats received subcutaneous injection with folic acid (300mg/kg in 5ml) once weekly (dissolved in 0.3M NaHCO3) for 5 weeks. Group III (n=16): (CRF + captopril): Chronic renal failure was induced by folic acid as in group II with concomitant administration of the ACE inhibitor; captopril in a daily dose of (100mg/kg/day) orally by gastric gavage. The following was measured in all groups: Blood pressure, Kidney function, haematological and haemo-static parameters, HOMA-IR, lipid profile, CRP, IL6, MDA, SOD and histopathological examination was made.Results: There was a significant increase in serum hepcidin level in group II compared to control which was correlated positively with serum creatinine, blood urea and negatively with creatinine clearance, while its level decreased significantly in group III compared to group II. A significant increase in bleeding time, WBCT, PT, APTT, INR, FDPs, D dimer and protein C was found in group II compared to control with an increase in HOMA-IR, CRP, IL6, MDA, systolic and diastolic blood pressure and a significant decrease in Hb, MCV, MCH, platelet count, MPV and SOD. In group III, bleeding time, WBCT and protein C remained significantly elevated versus control and further increase in APTT was found versus group II. A significant decrease in FDPs and D dimer was found in group III versus group II with a significant decrease in HOMA-IR, TG, LDL, VLDL, CRP, IL6, MDA, systolic and diastolic BP.Conclusion: Chronic renal failure induced significant increase in hepcidin level associated with an abnormal coag-ulation profile. Hepcidin can indirectly affect coagulation profile through its effect on anaemia, IR, oxidative stress and inflammatory mediators. Inhibition of ACE by captopril caused significant improvement of renal function with significant decrease in hepcidin level and significant decrease in hyper-coagulopathy.

Lipopolysaccharide and inflammatory cytokines levels decreased after sleeve gastrectomy in Chinese adults with obesity.

Obesity is linked to a low-grade systemic inflammation and lipopolysaccharide (LPS) is a key factor. Sleeve gastrectomy (SG) can significantly cause weight loss, but few reports have looked into the changes of LPS and inflammatory cytokines after surgery. To explore the potential short-term impact of SG on LPS and inflammatory cytokines and their relationship to early metabolic changes in obesity. 30 Chinese adults with obesity (BMI 39.37 ± 8.22 kg/m2, 25 female) receiving SG were included in this study. Fasting blood samples were collected at baseline and 30 days after SG. Serum LPS markedly reduced from 336.50 (73.54, 500) pg/mL to 5.00 (5.00, 5.24) pg/mL at 1 month after SG (p < 0.05). There was a significant decrease in plasma IL-6, IL-8, and serum CRP after SG (all p < 0.05). Insulin resistance improved remarkably after surgery as displayed by reductions in fasting insulin level (FINS, p < 0.001), and HOMA-IR (p < 0.001). In addition, visceral fat area (VFA) decreased from 209.70 ± 39.96 cm2 to 193.28 ± 43.68 cm2 after SG (p < 0.001). LPS was positively correlated with FINS (r = 0.391, p = 0.033) and HOMA-IR (r = 0.38, p = 0.038) before SG. Meanwhile, VFA was positively associated with CRP (r = 0.388, p = 0.034) before surgery. When assessing 30-days postoperative changes, a positive correlation was found between the variations of LPS, IL-8 and the reduction of VFA. After multivariate analyses, only the reduced IL-8 level was independently associated with the reduction of VFA (p = 0.015). In conclusion, SG can significantly relieve the inflammation in obesity in the short term and LPS might be an earlier predictor of inflammatory changes after surgery.