Wall Inflammation Research Articles

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms.

BackgroundAbdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture.MethodsExperimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE–/– mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS).ResultsThe size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate.ConclusionPemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

Расширенная резекция брыжейки тонкой кишки при болезни Крона (обзор литературы)

INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel disease characterized by intermittent lesions of the gut wall and transmural inflammation. The disease affects the gastrointestinal tract along the whole length from the mouth to the anus. More than 50% of patients with CD within the first 10 years following established diagnosis develop strictures or fistulas. These complications lead to intestinal obstruction which is a common indication for surgery in the volume of resection of the affected bowel. Surgery for CD complications does not rid the patient of the disease. Endoscopic and clinical recurrence of CD is a common phenomenon after surgical resection of the gut. The surgical approach to treatment of CD have not gained a wide spread since the first description of the disease. It is evident that to reduce the frequency of recurrences, it is necessary to improve surgical tactics. Clarification and better understanding of the anatomy and function of mesentery in recent years has led to the suggestion of its probable role in the pathogenesis of CD. Extended mesenteric resection may improve the outcomes of surgery in CD. Rather than to mobilize and excise the mesentery as in colorectal cancer, the mesentery is usually transected at the level of the intestine and remains in an organism. This review provides the data of recent studies of the role of mesentery in the pathogenesis of CD, which permit to suggest that extended resection of mesentery can significantly improve surgical results in CD and to reduce the frequency of endoscopic and clinical recurrences and reoperations. CONCLUSION: Mesentery is involved in the pathogenesis of Crohns disease and the development of relapse. Further study of its role will lead to a decrease in the frequency of relapses and repeated surgical interventions in Crohns disease.

Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy.

Optimal criteria for diagnosing and monitoring response to treatment for infectious and inflammatory medium–large vessel intracranial vasculitis presenting with stroke are lacking. We integrated intracranial vessel wall MRI with arterial spin labelling into our routine clinical stroke pathway to detect presumed inflammatory intracranial arterial vasculopathy, and monitor disease activity, in patients with clinical stroke syndromes. We used predefined standardized radiological criteria to define vessel wall enhancement, and all imaging findings were rated blinded to clinical details. Between 2017 and 2018, stroke or transient ischaemic attack patients were first screened in our vascular radiology meeting and followed up in a dedicated specialist stroke clinic if a diagnosis of medium–large inflammatory intracranial arterial vasculopathy was radiologically confirmed. Treatment was determined and monitored by a multi-disciplinary team. In this case series, 11 patients were managed in this period from the cohort of young stroke presenters (<55 years). The median age was 36 years (interquartile range: 33,50), of which 8 of 11 (73%) were female. Two of 11 (18%) had herpes virus infection confirmed by viral nucleic acid in the cerebrospinal fluid. We showed improvement in cerebral perfusion at 1 year using an arterial spin labelling sequence in patients taking immunosuppressive therapy for >4 weeks compared with those not receiving therapy [6 (100%) versus 2 (40%) P = 0.026]. Our findings demonstrate the potential utility of vessel wall magnetic resonance with arterial spin labelling imaging in detecting and monitoring medium–large inflammatory intracranial arterial vasculopathy activity for patients presenting with stroke symptoms, limiting the need to progress to brain biopsy. Further systematic studies in unselected populations of stroke patients are needed to confirm our findings and establish the prevalence of medium–large artery wall inflammation.

Ischemic Colitis of the Transverse Colon Induced by 5-Fluorouracil, Leucovorin, and Irinotecan: A Case Report

Gastrointestinal complications are common in chemotherapy patients. Although most patients’ abdominal symptoms can be due to mild chemotherapy adverse reactions, severe or life-threatening complications might occur. Typhlitis or neutropenic enterocolitis is a severe bowel wall inflammation in leukemia or solid tumor chemotherapy in neutropenic patients and may contribute to necrosis and colon perforation. Patients undergoing chemotherapy rarely experience colitis that has no standard typhlitis trait. This ischemic colitis-induced chemotherapy had conducted in patients receiving taxane-based agents. Our study presented ischemic colitis in patients receiving 5-fluorouracil, Leucovorin, and Irinotecan for sigmoid cancer that affected the transverse colon alone, unlikely for both typhlitis and chemotherapy-induced ischemic colitis. Given these findings; it is prominent to consider that life-threatening gastrointestinal complications may develop with these agents, and then surgical intervention is needed.

Pecularities of the ischemic heart disease clinical course in patients with different provision of vitamin D, residents of St. Petersburg: an association with a complex of genotypes of vitamin D receptor

Background. Vitamin D has been shown to reduce the risk of atherosclerosis development. Vitamin D receptors (VDRs) mediate the protective effects of vitamin D on immune inflammation in the vascular wall. Polymorphisms of the VDR gene are involved in the regulation of the stability of its mRNA. The carriage of some polymorphisms may affect the development of atherosclerosis.Objective. To study the availability of vitamin D in patients with coronary artery disease (CAD) with various VDR polymorphisms.Design and methods. The vitamin D level in blood serum was determined by enzyme immunoassay. The genotypes of the VDR gene were determined in 302 patients with CAD and in 196 patients without CAD by PCR.Results. The level of vitamin D in patients with CAD was lower than in controls. The presence of the studied VDR polymorphisms was not associated with an increased risk of CAD. The content of vitamin D was higher in patients with the BB vs. bb genotype of the VDR gene (BsmI), in carriers of the AA vs. aa genotype (ApaI), in carriers of TT vs. tt genotype of the VDR gene (TaqI).Conclusion. TaqI, FokI, ApaI and BsmI polymorphisms are not associated with the risk of CAD. Vitamin D level in the CAD patients with BB and AA genotype of the VDR gene was higher compare with bb and aa genotypes.

Animal Models of Atherosclerosis-Supportive Notes and Tricks of the Trade.

Atherosclerotic cardiovascular disease is a major cause of death among humans. Animal models have shown that cholesterol and inflammation are causatively involved in the disease process. Apolipoprotein B-containing lipoproteins elicit immune reactions and instigate inflammation in the vessel wall. Still, a treatment that is specific to vascular inflammation is lacking, which motivates continued in vivo investigations of the immune-vascular interactions that drive the disease. In this review, we distill old notions with emerging concepts into a contemporary understanding of vascular disease models. Pros and cons of different models are listed and the complex integrative interplay between cholesterol homeostasis, immune activation, and adaptations of the vascular system is discussed. Key limitations with atherosclerosis models are highlighted, and we suggest improvements that could accelerate progress in the field. However, excessively rigid experimental guidelines or limiting usage to certain animal models can be counterproductive. Continued work in improved models, as well as the development of new models, should be of great value in research and could aid the development of cardiovascular disease diagnostics and therapeutics of the future.

Do Antiseptic Coated Sutures Reduce Colo-Colonic Anastomotic Leaks?

Colorectal anastomotic leaks remain one of the most significant complications following colorectal surgery. Various interventions to reduce anastomotic leaks have been investigated, however few have resulted in a significant improvement. To date antiseptic coated monofilament sutures for sutured bowel anastomoses have not been assessed, hence this study was undertaken to investigate whether or not triclosan impregnated polydioxanone suture material (PDS) results in fewer anastomotic leaks. A rabbit colo-colonic anastomotic model was developed to compare the tensile strength and local inflammatory response between triclosan coated PDS and uncoated PDS. Of the 42 anastomoses there were 4 (9.5%) leaks. Of the remaining 38 anastomoses neither the leak pressures, degree of bowel wall inflammation or fibrosis were statistically different (P = .11; .813 and .658 respectively) when comparing the two suture materials. In an animal model, triclosan coated PDS is as safe as uncoated PDS in performing colo-colonic anastomosis.

Differential diagnosis of acute and chronic colitis in mice by optical coherence tomography.

The differential diagnosis of acute and chronic colitis remains a common clinical problem. Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technique that can be used to measure morphological changes in the intestinal wall and estimate intestinal inflammation. We aimed to conduct an ex vivo experiment on a mouse model investigate the value of OCT as a tool for the differential diagnosis of acute and chronic colitis. Mice were administered dextran sulfate sodium salt (DSS) to construct acute and chronic colitis models. Acutely- and chronically-affected intestinal walls were scanned by OCT, and then the scanned colonic tissue samples were stained with hematoxylin and eosin (HE). Structural and morphological changes indicating inflammation in the intestinal wall were evaluated in the HE sections and OCT images using different parameters. The parameters were used in one-way analysis of variance (ANOVA) to screen for a differential diagnosis of acute or chronic colitis. For the HE sections, the angle of the mucosal folds, length of the basilar part, and submucosal height and area were statistically significant parameters in the comparisons between the mice with acute colitis and the control-group mice (P<0.05). In the comparisons between chronic colitis mice and control-group mice, the angle of the mucosal folds, length of the basilar part, submucosal height and area, muscularis thickness, submucosal height + muscularis thickness, and mucosal thickness were statistically significant parameters (P<0.05). Finally, in the comparisons between acute colitis mice and those with chronic colitis, the angle of the mucosal folds, submucosal height and area, muscularis thickness, submucosal height + muscularis thickness, and mucosal thickness were statistically significant parameters (P<0.05). For the OCT images, only the length of the basilar part and submucosal height + muscularis thickness were statistically significant parameters between the acute colitis mice and control-group mice (P<0.05). The length of the basilar part and submucosal height + muscularis thickness were statistically significant between chronic colitis mice and control-group mice (P<0.05). In the comparisons between acute colitis mice and those with chronic colitis, only submucosal height + muscularis thickness was a statistically significant parameter (P<0.05). Certain intestinal wall parameters in OCT can be used to make a differential diagnosis between acute and chronic colitis possible. This study contributes to constructing a potential diagnostic system for evaluating colorectal inflammation using OCT.

Large Vessel Vasculitides: Giant Cell Arteritis and Takayasu Arteritis - Similarities and Differences

Large Vessel Vasculitides: Giant Cell Arteritis and Takayasu Arteritis - Similarities and Differences Abstract. According to the Chapel Hill Consensus Conference Nomenclature of 2012, giant cell arteritis (GCA) and Takayasu arteritis (TAK) belong to the idiopathic large vessel vasculitides. While GCA is a typical disease of the elderly, TAK begins in adolescence and young adulthood, sometimes even in childhood. In both diseases, immune-mediated granulomatous vascular wall inflammation of the aorta and its major branches leads to the formation of stenoses, occlusions, and aneurysms. The reduced blood flow to downstream organs causes the characteristic symptoms such as visual disturbance, ischemic muscle pain, and dysesthesias. Typically, a pronounced systemic reaction with constitutional symptoms such as temperature elevation, fatigue, and weight loss is present. If GCA or TAK is suspected, vasculitis should always be confirmed by imaging (ultrasound, MRI, or PET-CT) and/or histology. In addition to induction therapy with glucocorticoids, steroid-sparing immunosuppressants such as tocilizumab and infliximab have become increasingly important in recent years, prompting the EULAR to update its recommendations for the management of large-vessel vasculitis in 2018.

The relationship between the level of Lр(а) and the prevalence of atherosclerosis among young patients

Hyperlipoproteinemia (a) is an independent and cause risk factor for atherosclerotic cardiovascular diseases (ASCVD). The correlation between lipoprotein (a) Lp(a) and inflammation in the vessel wall was actively studied during the past few years. C-reactive protein (CRP) plays an important role in ASCVD. To analyze the relationship between hyperlipoproteinemia (a), inflammatory markers, and the early development of stenosing atherosclerosis (AS) in several vascular pools. 76 patients, 55 men aged 18 to 55 years and 21women 18 to 60 years, with the results of instrumental examination of coronary, carotid and lower extremities vascular pools were enrolled. Three groups: with stenosing (50%) AS of only one (group 1, n=29); two or three (group 2, n=21) vascular pools. 26 patients without coronary heart disease and AS were included in the control group. All patients in groups 1 and 2 and 65% of those in the control group took statins. The concentrations of Lp(a), CRP, lipids and blood count were determined. The patients of the three groups did not differ in age. In the groups with AS (79% in group 1 and 85% in group 2), there were more men (relative to 54% in the control group). Diabetes mellitus was more common only in patients with multifocal AS. The absolute number of blood monocytes and leukocytes, the neutrophil-lymphocyte ratio, as well as Lp(a) level were higher in patients of groups 1 and 2 relative to the control. The maximum Lp(a) level (median [25%; 75%]) was observed in patients with lesions of two or more vascular pools vs the control group (49 [4; 96] mg/dL, vs 10 [4; 21] mg/dL, p=0.02). The CRP level was significant elevated in patients from group 2 7.2 [4.0; 9.7] mg/L, relative to group 1 2.5 [1.0; 4.7] mg/L, and the control group 2.9 [1.2; 4.9] mg/L, p0.05. The Lp(a) and CRP concentration, or the presence of diabetes mellitus in patients, regardless of other risk factors, were associated with severe stenosing AS in young and middle age. An elevated concentration of Lp(a) (30 mg/dL) determines the presence of both isolated and multifocal stenosing AS in the examined patients. A simultaneous increase in the concentration of both Lp(a) and CRP, as well as the presence of diabetes mellitus, are associated with the premature development of stenosing atherosclerotic lesions in several vascular regions at once. Measurement of these predictors in young and middle-aged patients makes it possible to use them as biochemical markers to assess the likelihood of multifocal lesions of the vascular pool.

Role of Vaginal Mucosa, Host Immunity and Microbiota in Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is a prevalent gynaecological disease characterised by vaginal wall inflammation that is caused by Candida species. VVC impacts almost three-quarters of all women throughout their reproductive years. As the vaginal mucosa is the first point of contact with microbes, vaginal epithelial cells are the first line of defence against opportunistic Candida infection by providing a physical barrier and mounting immunological responses. The mechanisms of defence against this infection are displayed through the rapid shedding of epithelial cells, the presence of pattern recognition receptors, and the release of inflammatory cytokines. The bacterial microbiota within the mucosal layer presents another form of defence mechanism within the vagina through acidic pH regulation, the release of antifungal peptides and physiological control against dysbiosis. The significant role of the microbiota in maintaining vaginal health promotes its application as one of the potential treatment modalities against VVC with the hope of alleviating the burden of VVC, especially the recurrent disease. This review discusses and summarises current progress in understanding the role of vaginal mucosa and host immunity upon infection, together with the function of vaginal microbiota in VVC.

POS0249 FIBROBLAST ACTIVATION PROTEIN AS A LINK BETWEEN INFLAMMATION AND VASCULAR REMODELING IN GIANT CELL ARTERITIS

BackgroundGiant cell arteritis (GCA) can present with serious complications such as blindness, stroke and aortic aneurysm that are related to both inflammation and remodeling of the vessel wall. GCA frequently overlaps with polymyalgia rheumatica (PMR). The pathogenesis of GCA starts in the adventitia where fibroblasts are the major stromal cell population. A preliminary study [1] reported the migration of adventitial fibroblasts to the intima, contributing to intimal hyperplasia in GCA. Fibroblast activation protein (FAP) is a non-classical serine protease which can be present in both a membrane-bound form and a soluble form and has been demonstrated to promote inflammation and fibrosis in coronary artery disease and rheumatoid arthritis [2-3]. We hypothesize that FAP is involved in GCA vasculopathy due to its pro-inflammatory and pro-fibrotic effects.ObjectivesAs a first step to unravel the contribution of FAP to the vasculopathy in GCA, we determined FAP plasma levels and FAP protein expression at the site of vascular inflammation in GCA.MethodsIn our prospective cohort of GCA, PMR and healthy elderly (GPS), we measured the plasma FAP levels with ELISA in new-onset, treatment-naïve GCA (N=62), and PMR (N=63) patients and 42 age-matched healthy controls (HC). In addition, we measured the plasma FAP levels at follow-up (3-months, 1-year, 1.5-year and treatment-free remission (TFR)). Temporal artery biopsies (TAB) from treatment-naïve GCA patients (n=9) and non-GCA patients (n=9), aorta samples from GCA-related aneurysm (n=9) and atherosclerosis (n=11) were stained for FAP using immunohistochemistry. Immunofluorescence staining for CD90, CD68, αSMA and FAP was performed to detect FAP expression in fibroblasts, macrophages and vascular smooth muscle cells (VSMC), respectively.ResultsBaseline plasma FAP levels were significantly lower in GCA patients (52.72±2.93 ng/ml) than in PMR patients (66.42±2.86 ng/ml) and HC (80.47±3.38 ng/ml). FAP levels at baseline correlated inversely with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin (IL)-6, macrophage-associated protein YKL-40 (Chitinase 3-like 1/CHI3L1) levels and monocyte counts. Plasma FAP levels in GCA patients decreased even further at 3 months (37.23±2.10 ng/ml) upon glucocorticoid-induced remission, and gradually increased to the level of HC (76.84±5.43 ng/ml) when patients were in TFR. Increased FAP expression in GCA TAB (adventitia, media, intima) and aorta (media) compared with tissues from non-GCA was documented. FAP was abundantly expressed in fibroblast- and macrophage-rich areas but not in VSMC-rich areas in TAB and aorta of GCA patients.ConclusionFAP expression is clearly modulated both in plasma and at the site of vascular inflammation in GCA and may represent a pathogenic link between the inflammatory and remodeling processes in GCA. As such, FAP may have utility as a biomarker and should be further investigated as target for therapeutic intervention.

Soluble CD36 Concentration in Diabetic Hypertensive Patients with Coronary Atherosclerosis.

Atherosclerosis is a chronic condition defined by cholesterol retention and arterial wall inflammation. CD36 is indeed a membrane protein found in the monocyte-macrophage systems and endothelial cells involved in the cellular uptake of oxidized low-density lipoproteins and long-chain fatty acids with a crucial role in the pathophysiology of atherosclerosis. The purpose of this research is to compare the diagnostic usefulness of soluble CD36 (sCD36) to high sensitivity C reactive protein (hs-CRP) in diabetic hypertensive individuals with coronary atherosclerosis and the correlation between these parameters in research groups. One hundred individuals with coronary atherosclerosis were divided into four groups based on diabetes mellitus (DM) and/or hypertension (HTN), with 100 participants with routine angiography serving as a control group. The serum levels of sCD36 and hs-CRP were quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) for sCD36 and a particle-enhanced immune turbidimetric assay for hs-CRP, respectively. A study group's lipid profiles, hematological markers, and clinical aspects were compared. Compared to the control, sCD36 and hs-CRP levels in patients increased considerably (p<0.05). The sCD36 level varied substantially between groups (p<0.05), with the DM-HTN group having the highest sCD36 level among the patient groups. Further, the hs-CRP level indicated a significant difference among patients and controls (p<0.05). CD36 correlated significantly and positively with the following terms BMI, hs-CRP, Total cholesterol and non-HDL-C (p<0.05).

Capsule Endoscopy versus Magnetic Resonance Enterography for Evaluation of Pediatric Small Bowel Crohn’s Disease: Prospective Study

Background: Magnetic resonance enterography (MRE) and capsule endoscopy (CE) are currently used for the evaluation of small bowel involvement in pediatric Crohn’s disease (CD). Several studies have been conducted to investigate the usefulness and diagnostic accuracy of each test. However, only a few studies have been conducted to compare the performance of both tests in the assessment of pediatric small bowel CD upon diagnosis and during follow-up. Therefore, the purpose of this study was to assess the diagnostic accuracy and diagnostic consistency of CE and MRE for the evaluation of pediatric small bowel CD at the time of diagnosis and during follow-up. Methods: Fifteen patients with pediatric CD were recruited for this study. They underwent MRE and CE concomitantly at the time of diagnosis and 10–12 weeks and one year after induction therapy for CD. MRE was interpreted using MRE global score (MEGS) and bowel wall inflammation severity diffusion-weighted imaging score (BWI-DWIS), whereas CE was interpreted using Lewis’s score (LS). The two diagnostic modalities were then compared. Results: Eleven patients completed MRE and CE at the time of diagnosis. Analysis of the results showed that LS had a strong correlation with MEGS and BIS-DWIS (ρ = 0.633, p = 0.037, and ρ = 0.629, p = 0.038, respectively). Nine patients completed three MREs and three CEs. LS significantly decreased throughout the sessions (p = 0.044), whereas MEGS and BIS-DWIS did not show any statistically significant changes. When LS was compared with MEGS and BIS-DWIS, both MRE indicators showed statistically significant differences throughout the sessions. Conclusions: At the time of diagnosis, the severity indexes of MRE and CE showed very good agreement. However, throughout management, MRE and CE did not show consistent changes.

Omalizumab treatment reduces asthma exacerbations regardless of airway bronchodilator reversibility

In asthma, the type 2 inflammatory response mediated by IgE leads to airway remodeling and subsequent symptom presentation.1 Blocking the action of IgE can decrease airway remodeling, including reducing wall thickness and inflammation.2,3 Airway smooth muscle thickness and vascularity are inversely correlated with postbronchodilator FEV1.4 In patients with allergic asthma, bronchodilator reversibility can indicate pulmonary function and is associated with lung function improvement during omalizumab therapy.

Combination of UNet++ and ResNeSt to classify chronic inflammation of the choledochal cystic wall in patients with pancreaticobiliary maljunction.

The aim of this study was to establish an automatic classification model for chronic inflammation of the choledoch wall using deep learning with CT images in patients with pancreaticobiliary maljunction (PBM). CT images were obtained from 76 PBM patients, including 61 cases assigned to the training set and 15 cases assigned to the testing set. The region of interest (ROI) containing the choledochal lesion was extracted and segmented using the UNet++ network. The degree of severity of inflammation in the choledochal wall was initially classified using the ResNeSt network. The final classification result was determined per decision rules. Grad-CAM was used to explain the association between the classification basis of the network and clinical diagnosis. Segmentation of the lesion on the common bile duct wall was roughly obtained with the UNet++ segmentation model and the average value of Dice coefficient of the segmentation model in the testing set was 0.839 ± 0.150, which was verified through fivefold cross-validation. Inflammation was initially classified with ResNeSt18, which resulted in accuracy = 0.756, sensitivity = 0.611, specificity = 0.852, precision = 0.733, and area under curve (AUC) = 0.711. The final classification sensitivity was 0.8. Grad-CAM revealed similar distribution of inflammation of the choledochal wall and verified the inflammation classification. By combining the UNet++ network and the ResNeSt network, we achieved automatic classification of chronic inflammation of the choledoch in PBM patients and verified the robustness through cross-validation performed five times. This study provided an important basis for classification of inflammation severity of the choledoch in PBM patients. We combined the UNet++ network and the ResNeSt network to achieve automatic classification of chronic inflammation of the choledoch in PBM. These results provided an important basis for classification of choledochal inflammation in PBM and for surgical therapy.

Efficacy and Safety of Fevipiprant in Asthma: A Review and Meta-Analysis.

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population.A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value < 0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic.A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p<0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p<0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

Biodegradable PTX-PLGA-coated magnesium stent for benign esophageal stricture: An experimental study

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 μg/mL at pH = 7.4 and 176 ± 12 μg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. Statement of significanceWe designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture.

Molecular Pharmacology of Inflammation Resolution in Atherosclerosis.

Atherosclerosis is one of the most important problems of modern medicine as it is the leading cause of hospitalizations, disability, and mortality. The key role in the development and progression of atherosclerosis is the imbalance between the activation of inflammation in the vascular wall and the mechanisms of its control. The resolution of inflammation is the most important physiological mechanism that is impaired in atherosclerosis. The resolution of inflammation has complex, not fully known mechanisms, in which lipid mediators derived from polyunsaturated fatty acids (PUFAs) play an important role. Specialized pro-resolving mediators (SPMs) represent a group of substances that carry out inflammation resolution and may play an important role in the pathogenesis of atherosclerosis. SPMs include lipoxins, resolvins, maresins, and protectins, which are formed from PUFAs and regulate many processes related to the active resolution of inflammation. Given the physiological importance of these substances, studies examining the possibility of pharmacological effects on inflammation resolution are of interest.

Syndecan-1 Is Overexpressed in Human Thoracic Aneurysm but Is Dispensable for the Disease Progression in a Mouse Model.

Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA (p = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, p = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA.