Effect Of Anti-inflammatory Treatment Research Articles

Study of the clinical complex efficacy of natural cytokines and antimicrobial peptides in the treatment of patients with inflammatory periodontal diseases

The aim of the work was to determine the anti-inflammatory effectiveness of the use of a complex of natural cytokines and antimicrobial peptides (Superlimf) in the treatment of patients with mild chronic generalized periodontitis.
 Materials and methods: 60 patients were randomized into 2 equal groups. Patients of both groups were removed dental deposits using the Piezon-Master-400 ultrasound machine and the surfaces of the roots of the teeth were polished using periodontal bores (SRP — Scaling, Root Planning), taught the rules of oral hygiene with subsequent three-time control. Resorbable plates of the Superlimf preparation were additionally applied to the gum in the patients of the main group. To assess the intensity of inflammation in periodontal tissues, the clinical indices of Muhlemann and PMA were used.
 Results: The dynamics of the clinical indices of Mulleman and PMA before treatment, 7 days later and 21 days after treatment showed a statistically significant more pronounced anti-inflammatory effect in patients in the main group who were treated with Superlimf in addition to SPR.
 Conclusions: Local use of the drug Superlimf in combination with SRP increases the effect of anti-inflammatory treatment of patients with mild chronic generalized periodontitis.

Effect of Anti-inflammatory Treatment with AMD3100 and CX3CR1 Deficiency on GABAA Receptor Subunit and Expression of Glutamate Decarboxylase Isoforms After Stroke

Following stroke, attenuation of detrimental inflammatory pathways might be a promising strategy to improve long-term outcome. In particular, cascades driven by pro-inflammatory chemokines interact with neurotransmitter systems such as the GABAergic system. This crosstalk might be of relevance for mechanisms of neuronal plasticity, however, detailed studies are lacking. The purpose of this study was to determine if treatment with 1,1′-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and partial allosteric agonist to CXCR7 (AMD3100) alone or in combination with C-X3-C chemokine receptor type 1 (CX3CR1) deficiency, affect the expression of GABAA subunits and glutamate decarboxylase (GAD) isoforms. Heterozygous, CX3CR1-deficient mice and wild-type littermates were subjected to photothrombosis (PT). Treatment with AMD3100 (0.5 mg/kg twice daily i.p.) was administered starting from day 2 after induction of PT until day 14 after the insult. At this time point, GABAA receptor subunits (α3, β3, δ), GAD65 and GAD67, and CXCR4 were analyzed from the peri-infarct tissue and homotypic brain regions of the contralateral hemisphere by quantitative real-time PCR and Western Blot. Fourteen days after PT, CX3CR1 deficiency resulted in a significant decrease of the three GABAA receptor subunits in both the lesioned and the contralateral hemisphere compared to sham-operated mice. Treatment with AMD3100 promoted the down-regulation of GABAA subunits and GAD67 in the ipsilateral peri-infarct area, while the β3 subunit and the GAD isoforms were up-regulated in homotypic regions of the contralateral cortex. Changes in GABAA receptor subunits and GABA synthesis suggest that the CXCR4/7 and CX3CR1 signaling pathways are involved in the regulation of GABAergic neurotransmission in the post-ischemic brain.

Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects.

Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability of numerous therapeutic options, treatment outcome may not be entirely satisfactory and a definitive cure does not exist. This may be due to the fact that the exact VLS etiopathogenesis remains unknown. The objectives of this paper were to review the most up-to-date knowledge on VLS etiopathogenesis and to consider the available therapies through the lens of a plausible pathogenetic model. An electronic search on both VLS etiopathogenesis and its treatment was performed using the National Library of Medicine PubMed database. Based on current knowledge, it is conceivable that various, heterogeneous environmental factors acting on a genetic background trigger an autoimmune, Th-1 response, which leads to a chronic inflammatory state. This, in turn, can determine both tissue and micro-vascular injury and activation of signaling pathways involved in fibroblast and collagen metabolism. This pathogenetic sequence may explain the effectiveness of anti-inflammatory treatments, mostly topical corticosteroids, in improving VLS clinical-pathological changes. Further deepening of the disease pathways will presumably allow key mediators to become new therapeutic targets and optimize the available treatments.

Recombinant human thrombomodulin for pneumonia-induced severe ARDS complicated by DIC in children: a preliminary study.

PurposeRecombinant human soluble thrombomodulin (rTM) has been used to treat disseminated intravascular coagulation (DIC). Recent studies have shown the efficacy of rTM through its anti-inflammatory effects for treatment of adults with acute respiratory distress syndrome (ARDS). However, the safety and efficacy of rTM in children with severe ARDS complicated by DIC have not been reported. In this preliminary study, we reported the feasibility of using rTM for the treatment of pneumonia-induced severe ARDS complicated by DIC in children.MethodsSix children (age: median 10 months old) with pneumonia-induced severe ARDS complicated by DIC were enrolled in this preliminary study. rTM (380 U/kg) was administered for a maximum of 6 days, in addition to conventional therapies after diagnosis of severe ARDS complicated by DIC. After administration of rTM, we measured changes in the plasma TM concentration and evaluated the clinical course, status of DIC and ARDS, and other laboratory findings, including levels of cytokines, chemokines, and biomarkers.ResultsIn all six children, the plasma concentration of TM increased and DIC scores decreased after administration of rTM. Four of the six children recovered from the severe ARDS complicated by DIC after treatment, and were discharged from the hospital with no complications. In survived children, levels of soluble receptors for advanced glycation end products, interleukin-6, interleukin-8 and monocyte chemotactic protein-1 decreased after administration of rTM compared to those before rTM.ConclusionsThe rTM administration is feasible as an adjunctive therapeutic strategy for children over 2 months with pneumonia-induced severe ARDS complicated by DIC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00540-021-02971-3.

Effects of Anti-Inflammatory Treatment and Surgical Intervention on Endothelial Glycocalyx, Peripheral and Coronary Microcirculatory Function and Myocardial Deformation in Inflammatory Bowel Disease Patients: A Two-Arms Two-Stage Clinical Trial.

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey–Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E’ velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 μm ± 0.05 μm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.

Recombinant sugarcane cystatin CaneCPI-5 down regulates inflammation and promotes angiogenesis and collagen deposition in a mouse subcutaneous sponge model

Cystatins are natural inhibitors of cysteine peptidases that are found practically in all living organisms. CaneCPI-5 is a sugarcane cystatin with inhibitory activity against human cathepsins B, K and L, which are cysteine proteases highly expressed in a variety of pathological conditions, usually marked by persistent inflammation and processing of the extracellular matrix. This work evaluated the effects of daily administration of the recombinant cystatin CaneCPI-5 [0.01, 0.1 or 1.0 μg in 10 μL of Phosphate-Buffered Saline (PBS)] on the inflammatory, angiogenic and fibrogenic components during chronic inflammatory response induced by subcutaneous sponge implants. The anti-inflammatory effect of treatment with CaneCPI-5 was confirmed by reduction of the levels of the pro-inflammatory mediators TNF-α, CXCL1 and CCL2/JE/MCP-1, as well as the activity of the myeloperoxidase and n-acetyl-β-D-glucosaminidase. Treatment with CaneCPI-5 promoted angiogenesis in the implants, increasing the production of cytokines VEGF and FGF and the formation of new blood vessels. Finally, the administration of the recombinant cystatin favored the production of the pro-fibrogenic cytokine TGF-β1 and collagen deposition next to the implants. Together, these results show the potential therapeutic application of CaneCPI-5 as an anti-inflammatory agent, capable of favoring angiogenesis and fibrogenesis processes, necessary for tissue repair.

Predicting Treatment Outcomes Using Explainable Machine Learning in Children with Asthma.

Asthma in children is a heterogeneous disease manifested by various phenotypes and endotypes. The level of disease control, as well as the effectiveness of anti-inflammatory treatment, is variable and inadequate in a significant portion of patients. By applying machine learning algorithms, we aimed to predict the treatment success in a pediatric asthma cohort and to identify the key variables for understanding the underlying mechanisms. We predicted the treatment outcomes in children with mild to severe asthma (N = 365), according to changes in asthma control, lung function (FEV1 and MEF50) and FENO values after 6 months of controller medication use, using Random Forest and AdaBoost classifiers. The highest prediction power is achieved for control- and, to a lower extent, for FENO-related treatment outcomes, especially in younger children. The most predictive variables for asthma control are related to asthma severity and the total IgE, which were also predictive for FENO-based outcomes. MEF50-related treatment outcomes were better predicted than the FEV1-based response, and one of the best predictive variables for this response was hsCRP, emphasizing the involvement of the distal airways in childhood asthma. Our results suggest that asthma control- and FENO-based outcomes can be more accurately predicted using machine learning than the outcomes according to FEV1 and MEF50. This supports the symptom control-based asthma management approach and its complementary FENO-guided tool in children. T2-high asthma seemed to respond best to the anti-inflammatory treatment. The results of this study in predicting the treatment success will help to enable treatment optimization and to implement the concept of precision medicine in pediatric asthma treatment.

Effects of anti-inflammatory treatment and surgical intervention on endothelial glycocalyx, peripheral and coronary microcirculation and myocardial deformation in inflammatory bowel disease patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): EOMIFNE (Hellenic Society of IBD study) Introduction IBD alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process which leads to significant arterial endothelial dysfunction and modification of cardiac structure and function. This study is performed to test the hypothesis that treatment with TNF-a inhibitor or surgical intervention improves cardiovascular function through anti-inflammatory mechanisms. Methods 57 IBD patients (45 CD and 12 UC, 40 ± 8 years, 57% male) were examined at baseline and 4 months after pharmaceutical (antiTNF-a) or surgical intervention. Subjects with a history of established cardiovascular risk factors were excluded. We measured a) carotid-femoral pulse wave velocity (PWV - Complior SP ALAM) and augmentation index (AI), b) flow mediated dilatation (FMD) of the brachial artery), c) perfused boundary region (PBR) of the sublingual arterial microvessels, d) LV longitudinal strain (GLS) and (PWV/GLS) as a marker of ventricular-arterial coupling, e) peak LV twisting, peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, f) mitral annulus velocities by tissue doppler imaging (S’ and E’) and mitral inflow velocity (E), g) coronary flow reserve (CFR) by Doppler echocardiography, h) C-reactive protein (CRP), white blood cells (WBC). IBD severity was quantified using Mayo score and Harvey-Bradshaw Index (HBI) for UC and CD respectively. Results At baseline, the disease severity score and the WBC values were significantly correlated with peripheral PWV (r = 0.3, p &amp;lt; 0.05 and r = 0.364, p &amp;lt; 0.05), while central arterial AI was associated with median arterial pressure (r = 0.479, p &amp;lt; 0.05), lateral and septal mitral E’ velocity (r=-0.651, p &amp;lt; 0.05 and r=-0.587, p &amp;lt; 0.05). Four months after treatment, there was a reduction of CRP (13 ± 2.8 mg/L vs 3.9 ± 1.2 mg/L, p &amp;lt; 0.05), CFR (2.5 ± 0.08 vs 3.1 ± 0.11, p &amp;lt; 0.05) and PBR5-25 (2.27 ± 0.06 vs 2.09 ± 0.05 μm, p &amp;lt; 0.05) more significantly in pharmaceutical group (p &amp;lt; 0.05 vs p = 0.23). Moreover, there was an improvement of GLS (-18.6 ± 0.37 vs -20 ± 0.34, p &amp;lt; 0.05), LS-4ch (-18.3 ± 0.47 vs -19.3 ± 0.41, p &amp;lt; 0.05), GcircS (-18.1 ± 0.7 vs -20.1 ± 0.9, p &amp;lt; 0.05) and FMD (7.2%±0.6 vs 11.8%±1.4, p &amp;lt; 0.05). Moreover, there was an overall improvement of PWV/GLS (-0.49 ± 0.02 vs -0.43 ± 0.02, p &amp;lt; 0.05). It was greater after with anti-TNFa therapy compared to surgery (p &amp;lt; 0.05 vs p = 0.1) and particular for the GLS component (p &amp;lt; 0.05 vs p = 0.07). The difference in PBR5-25 was significantly correlated with the difference in GLS (r=-0.403, p &amp;lt; 0.05) and PWV/GLS (r = 0.421, p &amp;lt; 0.05). Conclusion IBD severity is associated with vascular and diastolic dysfunction, with significant improvement after anti-inflammatory treatment. Systemic anti-TNFa inhibition leads to significant improvement in myocardial deformation, endothelial and coronary microcirculatory function compared with local intestinal surgical intervention, possibly through a systemic reduction of excess inflammatory burden.

The lipopolysaccharide model for the experimental induction of transient lameness and synovitis in Standardbred horses

An established lipopolysaccharide (LPS) model previously described in Warmbloods, was inconsistent in Standardbred horses, where lameness was not detected despite the presence of synovitis. The present study aimed to determine the dose of LPS from E. coli O55:B5 required to induce mild to moderate lameness following middle carpal joint injection in Standardbred horses and to quantitate the induced lameness over time, with and without anti-inflammatory pre-treatment. In a baseline trial, eight healthy, clinically sound Standardbred horses were used in a rule-based dose-escalation design trial, starting at a dose of 10 endotoxin units (EU). Lameness at trot was evaluated visually and quantitatively (using an inertial-sensor system and pressure plate analysis). Synovial fluid aspirates were analysed for total nucleated cell counts, total protein and prostaglandin E2 (PGE2). Following 2 months wash-out, the effective LPS-dose determined in the baseline trial was used to evaluate the effect of anti-inflammatory treatment. A mixed model for repeated measures with horse as random effect was used for analysis.After injection of 10 EU LPS, the desired degree of lameness was observed in the baseline trial, with maximal lameness at post-injection hour (PIH) 4, followed by a rapid decline and return to baseline by PIH 48. No lameness was observed following pre-treatment with meloxicam. In synovial fluid, PGE2 was significantly higher at PIH 8 and PIH 24 in the baseline trial compared with following meloxicam pre-treatment. In conclusion, injection of the middle carpal joint with 10 EU LPS consistently induces a transient lameness and synovitis in Standardbred horses.

Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients.

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].

The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial

BackgroundLow back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes.Methods/designThe BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18–65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients’ clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes.DiscussionFinding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes.The study is registered at ClinicalTrials.gov under the identifier NCT03704363. The EudraCT Number: 2017–004861-29.

A New Insight into Meloxicam: Assessment of Antioxidant and Anti-Glycating Activity in In Vitro Studies.

Meloxicam is a non-steroidal anti-inflammatory drug, which has a preferential inhibitory effect to cyclooxyganase-2 (COX-2). Although the drug inhibits prostaglandin synthesis, the exact mechanism of meloxicam is still unknown. This is the first study to assess the effect of meloxicam on protein glyco-oxidation as well as antioxidant activity. For this purpose, we used an in vitro model of oxidized bovine serum albumin (BSA). Glucose, fructose, ribose, glyoxal and methylglyoxal were used as glycating agents, while chloramine T was used as an oxidant. We evaluated the antioxidant properties of albumin (2,2-di-phenyl-1-picrylhydrazyl radical scavenging capacity, total antioxidant capacity and ferric reducing antioxidant power), the intensity of protein glycation (Amadori products, advanced glycation end products) and glyco-oxidation (dityrosine, kynurenine, N-formylkynurenine, tryptophan and amyloid-β) as well as the content of protein oxidation products (advanced oxidation protein products, carbonyl groups and thiol groups). We have demonstrated that meloxicam enhances the antioxidant properties of albumin and prevents the protein oxidation and glycation under the influence of various factors such as sugars, aldehydes and oxidants. Importantly, the antioxidant and anti-glycating activity is similar to that of routinely used antioxidants such as captopril, Trolox, reduced glutathione and lipoic acid as well as protein glycation inhibitors (aminoguanidine). Pleiotropic action of meloxicam may increase the effectiveness of anti-inflammatory treatment in diseases with oxidative stress etiology.

Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows

Systemic inflammation (SI) is increasingly studied in several species because it may be central in many metabolic disturbances and be a risk factor for clinical disease. This proof-of-concept study evaluated the effects of the anti-inflammatory drug meloxicam on markers of SI and energy metabolism, polymorphonuclear neutrophil (PMN) function, and endometritis in clinically healthy postpartum dairy cows. Cows received meloxicam (0.5 mg/kg of body weight; n = 20) once daily for 4 days (10–13 days postpartum) or were untreated (n = 22). Blood samples were collected −7, 1, 3, 5, 7, 10, 11, 12, 13, 14, 18, 21, 28, and 35 days relative to calving to measure serum concentrations of metabolic and inflammatory markers. Function of peripheral blood PMN were evaluated at 5, 10, 14, and 21, and proportion of PMN in endometrial cytology were performed at 5, 10, 14, 21, 28 and 35 days postpartum. Meloxicam decreased serum haptoglobin from the second until the last day of treatment, and improved indicators of energy metabolism (lesser β-hydroxybutyrate and greater insulin-like growth factor-1 during treatment, and greater glucose at the end of treatment than control cows). This improved PMN function at 14 days postpartum, but the endometrial inflammatory status was not affected.

Microcirculatory changes in periodontal tissues of patients with periodontitis in the dynamics of physical therapy

Relevance . The prevalence of periodontal diseases among the population of different countries remains at a high level every year. The study of pathogenetic mechanisms of the disease and the search for effective treatment methods for patients with chronic generalized periodontitis remain relevant. Important in the pathogenetic treatment of periodontitis are methods aimed at normalizing hemodynamics in periodontal tissues. Physiotherapeutic methods of treatment are widely used. Today, a large number of modern physiotherapy equipment has appeared on the dental market. However, in the budget health care institutions of the Udmurt Republic, the staffing of routine devices remains quite high. Purpose . The aim is to study the hemodynamic parameters of periodontal tissues in the dynamics of treatment of patients with chronic generalized periodontitis using routine and innovative methods of physical therapy. Materials and methods . The study was conducted in 500 patients with chronic generalized periodontitis of moderate severity. Аll the examined patients were divided into 5 groups of 100 people each: in the control group, only professional hygiene was performed using ultrasound and zone – specific scalers; in the first main group, after professional hygiene, a course of physiotherapy was prescribed using a Picasso led laser with a wavelength of 810 nm; the second main group course of physical treatment of periodontitis conducted by the device “ОzoneDTA”; in the first group comparison physiotherapy treatment included the effect on the tissues of the periodontal apparatus “Optodan”, and the second comparison group used darsonvalization unit “Iskra-1”. Professional hygiene was performed once every 3 months, and physical therapy was performed once every 6 months for 12 months of follow-up. The monitoring of clinical indicators was carried out in time: before treatment, 3.6 and 12 months after the start of follow-up. Microcirculation of periodontal tissues during physiotherapy was evaluated by photoplethysmography using the method of Z. M. Segal (1984) with a computer device. Results . It was found that during physiotherapy treatment, microcirculation in periodontal tissues increases in the nearest time (after a week and 3 months), while maintaining stable hemodynamics for 12 months of follow-up, while in the control group, where physiotherapy was not performed, but professional hygiene was prolonged once every 3 months, improvement of hemodynamics was noted only at the end of the follow-up period-in a year. The most favorable clinical indicators were also observed in the groups where the devices were used during treatment. Аfter 12 months, especially significant differences were observed in the PMA index. Conclusion . Physiotherapy methods help to increase hemodynamics in periodontal tissues. Modern physiotherapy devices – the Picasso diode laser and the Ozonedta device-have a more intensive effect on the linear systolic blood flow rate.they also significantly increase the anti-inflammatory effect of treatment of chronic generalized periodontitis in patients.

Time dependent dual effect of anti-inflammatory treatments on sarin-induced brain inflammation: Suggested role of prostaglandins

A common consequence of exposure to organophosphate nerve agents is the centrally mediated seizure activity that appears even after conventional treatment with atropine and oximes. We have previously demonstrated a major inflammatory response with subsequent brain damage which was correlated with the duration of the sarin-induced seizures (Chapman et al., 2006). In the present work seizures were induced by the nerve agent sarin (1.2 LD50) insufficiently treated 1 min later by atropine and trimedoxime bromide (TA), with additional midazolam treatment either 5 or 30 min after continuous seizure activity. The efficacy of both steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as other drugs that were reported as beneficial in neuroprotection, were evaluated for their contribution as adjunct treatment against sarin induced seizures and the ensuing inflammatory brain damage. Results show that both steroids and NSAIDs were harmful when administered during convulsions, and steroids were at best ineffective if administered at their termination. However, if administered at termination of convulsions, the NSAID ibuprofen, the selective COX 2 inhibitor nimesulide and the PLA2 inhibitor quinacrine were partially effective in reducing brain inflammatory markers. Administration of exogenous analogs of prostaglandins (PGE2) immediately following sarin-induced convulsions was found to have a beneficial effect in reducing brain inflammatory markers measured at 24 h and one week post sarin exposure. These findings support the hypothesis that elevated levels of PGE2 have a beneficial role immediately following sarin induced seizures, and that early inhibition of PGE2 production by both steroids and NSAID is contraindicative.

Effects of anti-inflammatory treatment on fibroblast growth factor-21 in obesity and metabolic syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of anti-inflammatory treatment on Sever’s disease management

Effect of anti-inflammatory treatment on Sever’s disease management

The prognosis of ocular inflammation index after pterygium surgery based on Oculus Keratograph® 5M and Visual analogue scale

Objective To investigate the characteristics of ocular surface inflammation index after pterygium excision by using Oculus Keratograph® 5M and Visual analogue scale and evaluated the effectiveness of anti-inflammatory treatment. Methods A prospective case control study was performed.Eighteen patients (6 males and 12 females) who suffered from primary pterygium were recruited in Zhongshan Ophthalmic Center from June to September 2016.All patients were treated with monocular pterygium excision combined with amniotic membrane transplantation.Anti-inflammatory treatment was given after surgery, and the ocular inflammation index was evaluated at preoperative and 1st, 3rd, 7th, 10th, 30th and 60th day postoperative.The temporal conjunctival hyperemia index (TCHI) was assessed by Oculus Keratograph® 5M with a red eye index analysis software.Ocular symptom scores (OSS) and visual analogue scale (VAS) were used to analyze the subjective symptoms of the patients.Fluorescein staining was used to detect the epithelization of corneal and scleral wound.The best corrected visual acuity (BCVA), intraocular pressure and complications were evaluated in this study.This study was approved by the Medical Ethics Committee of Zhongshan Ophthalmic Center of Sun Yat-sen University (2016KYPJ024). All patients signed informed consent for clinical research. Results No drug-related ocular and systemic adverse events were found during the follow-up.Corneal epithelial defect was recovered on 10th day, and conjunctival epithelization was observed in sclera exposed area on 30th day.The BCVA on the 60th day was 0.12±0.17, which was significantly lower than 0.34±0.36 preoperatively (t=3.401, P=0.003). Compared with those before surgery, OSS and VAS were significantly increased on 1st day (OSS: Z=-4.255, P=0.000; VAS: Z=-5.256, P=0.000). The OSS on 7th day was not significantly different from that before surgery (Z=-0.958, P=0.372). VAS decreased to baseline on 30th day.The OSS on 60th day after surgery was significantly lower than that before surgery (Z=-2.397, P=0.037). TCHI was higher than 1.2 preoperatively, and increased to the highest on 1st day after surgery, with significant difference between them (t=-6.620, P=0.000). The TCHI decreased to baseline on 7th day, no significant difference were obtained when compared with preoperative TCHI (t=-1.050, P=0.310), and TCHI on 60th day after surgery was lower than that before surgery, with significant difference between them (t=2.758, P=0.020). Conclusions The subjective symptoms combined with conjunctival hyperemia can be more accurate assessment of ocular surface inflammation in the perioperative period of pterygium surgery, which can be used as an evaluation index to assess the effectiveness of anti-inflammatory treatment. Key words: Pterygium; Ocular inflammation; Hyperaemia index; Symptom score; Visual analogue scale

US Molecular Imaging of Acute Ileitis: Anti-Inflammatory Treatment Response Monitored with Targeted Microbubbles in a Preclinical Model.

Purpose To evaluate whether dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in an acute terminal ileitis model in swine. Materials and Methods The Institutional Animal Care and Use Committee approved all animal studies. Fourteen swine with chemically induced acute terminal ileitis (day 0) were randomized into the following groups: (a) an anti-inflammatory treatment group (n = 8; meloxicam, 0.25 mg per kilogram of body weight; prednisone, 0.5 mg/kg) and (b) a control group (n = 6; saline). US molecular imaging was performed with a clinical US machine after intravenous injection of clinically translatable dual P- and E-selectin-targeted microbubbles (5 × 108/kg). Three inflamed bowel segments per swine were imaged at baseline, as well as on days 1, 3, and 6 after treatment initiation. At day 6, bowel segments were analyzed ex vivo for selectin expression levels by using quantitative immunofluorescence. Results After induction of inflammation, US molecular imaging signal increased at day 1 in both animal groups (P < .001). At day 3, signal in the treatment group decreased (P < .001 vs day 1), while signal in control animals did not significantly change (P = .18 vs day 1) and was higher (P = .001) compared with that in the treatment group. At day 6, signal in the treatment group further decreased and remained lower (P = .02) compared with that in the control group. Immunofluorescence confirmed significant (P ≤ .04) downregulation of both P- and E-selectin expression levels in treated versus control bowel segments. Conclusion Dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in a large-animal model of acute ileitis. This supports further clinical development of this quantitative and radiation-free technique for monitoring inflammatory bowel disease. © RSNA, 2018 Online supplemental material is available for this article.

Abstract 448: Stress Granule Formation as a Molecular Indicator of Atherosclerotic and Vascular Disease Progression

The molecular mechanisms by which atherogenic stress contributes to the pathophysiology of disease remain to be fully characterized. RNA-binding proteins (RBPs) regulate vascular cell (VSMCs and ECs) response to inflammatory stimuli by fine-tuning mRNA stability, and protein abundance. RBPs such as HuR and FXR1 regulate mRNA transcript abundance by binding AU-rich elements (AREs) in the 3’UTR permitting the transcript stabilization or destabilization, respectively. Most inflammatory transcripts including TNFα contain conserved AREs in their 3’UTR, and inflammatory stimuli activate RBPs to alter the landscape of inflammatory mediators. This post-transcriptional regulation of inflammatory transcripts by RBPs islocalized to structures called stress granules (SGs), which are mRNA-protein assemblies formed from non-translating mRNAs, ribosomal subunits, among other components. The manner by which these complexes form between mRNA and RBPs (mRNPs) under inflammatory or pathological conditions remains unknown, particularly with respect to vascular inflammatory disease. We hypothesize that the presence and quantity of stress granules are a critical cellular response to atherogenic stimuli. We identified SGs in cultured VSMCs and ECs treated with clotrimazole, a known inducer of SGs by co-staining for PABP, a SG marker, along with RBPs HuR and FXR1, both known to co-localize to SGs. VSMC treated with clotrimazole had increased eIF2α phosphorylation. LDLR-/- mice fed high fat diet for 14 weeks also demonstrated significantly increased PABP expression in the smooth muscle and endothelial cells of the aortic arch as compared to WT control. Atherogenic and hypoxic stimuli induced the formation of SGs in cultured primary human VSMCs and ECs. Interestingly, we found VSMCs pre-treated with anti-inflammatory cytokine IL-19 followed by clotrimazole significantly reduced the formation of SGs per cell in a time dependent manner (n=50, p&lt;0.05) as well as reduction in PABP expression, suggesting anti-inflammatory treatment effects SG formation. Taken together, these results have led to the hypothesis that SG formation in atherosclerosis is driven by inflammatory stimuli, and that anti-inflammatory treatment may lessen atherosclerosis progression and plaque formation by reduction of SGs.