Degree Of Inflammatory Infiltration Research Articles

Effects of Tolerant Nanoparticles Loaded with Various Regulatory Molecules on the Development of Experimental Autoimmune Encephalomyelitis

This research investigated the effects of tolerating nanoparticles (tNPs) loaded with multiple regulatory molecules on progression of experimental autoimmune encephalomyelitis (EAE). The polylactic acid-glycolic acid copolymer (PLGA), multiple regulatory molecular fragments (Fc) (programmed death receptor ligand 1-Fc (PD-L1-Fc), CD47-Fc), transforming growth factor (TGF-β1), and multiple oligodendrocyte glycoprotein (MOG) antigen peptides (p-MOG) were selected to prepare the tNPs (MRM-tNPs) loaded with various regulatory molecules. Then, the MRM-tNPs were applied in MOG35-55 polypeptide-induced EAE mouse model. According to the treatment methods, the mice were rolled into a group A (BS therapeutic agent), a group B (no-load-NPs), a group C (MOG-tNPs), and a group D (MRM-tNPs). The therapeutic effects were evaluated by the inflammatory infiltration degree (IID), demyelination loss degree (DLD), and apoptosis rate (AR) of CD4+ and CD8+ T cells. The Results showed that the encapsulation rate (ER) of TGF-β1 was 87.65%, and its cumulative release rate (RR) was 58.22%. There were obvious fluorescence signals on MRM-tNPs, MRM-tNPs without PD-L1, and MRM-tNPs without CD47. The neurological function (NF) score in the group D after MRM-tNPs treatment was less than 2 points (P <0.05). The scores of IID and DLD in the brain and spinal cord (SC) of EAE mice in the group D were much lower to those in groups A, B, and C, and the ARs of CD4+ and CD8+ T cells were higher (P <0.05). In conclusion, the tNPs loaded with various regulatory molecules can promote the apoptosis of antigen-specific T cells (AST) and reduce the infiltration and demyelination of inflammatory cells, thus alleviating the EAE.

Evaluation of Inflammatory Infiltration in the Retroperitoneal Space of Acute Pancreatitis Using Computer Tomography and Its Correlation with Clinical Severity.

This paper investigates the correlation between the degree and severity of CT inflammatory infiltration in the retroperitoneal space of acute pancreatitis (AP). A total of 113 patients were included based on diagnostic criteria. The general data of the patients and the relationship between the computed tomography severity index (CTSI) and pleural effusion (PE), involvement, degree of inflammatory infiltration of retroperitoneal space (RPS), number of peripancreatic effusion sites, and degree of pancreatic necrosis on contrast-enhanced CT at different times were studied. The results showed that the mean age of onset in females was later than that in males; 62 cases involved RPS to varying degrees, with a positive rate of 54.9% (62/113), and the total involvement rates of only the anterior pararenal space (APS); both APS and perirenal space (PS); and APS, PS, and posterior pararenal space (PPS) were 46.9% (53/113), 53.1% (60/113), and 17.7% (20/113), respectively. The degree of inflammatory infiltration in the RPS worsened with the increase in CTSI score; the incidence of PE was higher in the group greater than 48 hours than in the group less than 48 hours; necrosis >50% grade was predominant (43.2%) 5 to 6 days after onset, with a higher detection rate than other time periods (P < 0.05). Thus, when the PPS was involved, the patient's condition can be treated as severe acute pancreatitis (SAP); the higher the degree of inflammatory infiltration in the retroperitoneum, the higher the severity of AP. Enhanced CT examination 5 to 6 days after onset in patients with AP revealed the greatest extent of pancreatic necrosis.

The value of enhanced CT features and texture-signatures in assessing the inflammatory infiltration of pancreatic ductal adenocarcinoma.

To explore the predictive value of computed tomography (CT) imaging features and CT-based texture analysis in assessing inflammatory infiltration in pancreatic ductal adenocarcinoma (PDAC). A total of 43 patients with PDAC confirmed by surgical pathology were included in the study. The clinical, radiological, surgical, and pathological features of the patients were analyzed retrospectively using the chi-square test or Spearman's correlation. Receiver operating characteristic (ROC) curves were utilized to assess the overall predictive ability of the tumor enhancement degree on triphasic contrast-enhanced CT images for the inflammatory infiltration degree in PDAC. Furthermore, all CT data were uploaded to the RadCloud platform for region of interest (ROI) delineation and feature extraction. Then, the Variance Threshold and SelectKBest algorithms were used to find the optimal CT features. Binary logistic regression was employed to analyze the selected features in all three contrast-enhanced CT phases, and regression equations were formulated. ROC analysis was performed to evaluate the predictive effectiveness of each equation. The analysis revealed a statistically significant correlation between the degree of differentiation and radiological findings such as necrosis and cystic degeneration, vascular invasion, and the presence of ascites (P < 0.05). The enhancement degree of the tumor in both the arterial and venous phases was significantly correlated with the inflammatory infiltration degree (P < 0.05); however, the areas under the ROC curve (AUCs) of arterial and venous enhancement were 0.570 and 0.542, respectively. Regression equations based on the texture features of triphasic contrast-enhanced tumors were formulated, and their AUCs were 0.982, 0.643, and 0.849. Conventional radiological features are not significantly correlated with the degree of inflammatory infiltration in PDAC. The enhancement degrees in both the arterial phase and venous phase were statistically correlated with the inflammatory infiltration level but had poor predictive value. The texture features of PDAC on contrast-enhanced CT may show a better assessment value, especially in the arterial phase.

Marcadores de proliferação celular e de apoptose como fatores preditivos à eletroquimioterapia em carcinoma de células escamosas cutâneo de gatos

ABSTRACT: Determining cell proliferation rates and tumor apoptosis through immunohistochemistry allows the evaluation of the biological behavior of the tumor, optimizing the patient’s clinical course. This study aimed to analyze the immunohistochemical expression of Ki-67, COX-2 and caspase-3 and correlate them with the type of response to ECT in feline cutaneous squamous cell carcinoma (SCC), thus determining the predictive potential of these variables. For this, 13 samples of feline cutaneous SCC were evaluated before ECT, and statistical analyses of the correlation intensity between the variables were performed using the Spearman correlation coefficient, with a significance level of 95%. The results indicate a significant negative correlation between histopathological grade and response to ECT (ρ=-0.6; p=0.03); there was no significant correlation between Ki-67, COX-2 and caspase-3 immunoexpression with the response to ECT (ρ=-0.18; p=0.54/ρ=-0.23; p=0.44/ρ=-0.12; p=0.69, respectively). Therefore, the study shows that the histopathological grade, tumor size and staging, degree of cellular pleomorphism and degree of inflammatory infiltrate can be considered negative prognostic factors for cutaneous SCC and negative predictors for response to ECT. However, the markers Ki-67, COX-2 and caspase-3 are not considered predictive factors for the type of response to ECT. In addition, no relationship between these immunoexpressions and greater tumor aggressiveness was observed. The SCCs evaluated in this study showed significant COX-2 labeling, indicating a potential therapeutic target. ECT has been shown to be safe and effective for local control of feline cutaneous SCC but with reduced effectiveness in larger and invasive lesions.

Effect of Valproic Acid on NLR Family Pyrin Domain Containing 1/3 (NLRP1/3) Inflammasome in Rats with Acute Spinal Cord Injury

Our study assesses valproic acid’s effect on NLRP1/3 inflammasome in rats with acute spinal cord injury (SCI). SD rats were clamped by aneurysm clips to establish SCI model followed by analysis of functional recovery by BBB score, degree of inflammatory infiltration, by H&amp;E staining, NLRP1/NLRP3 and P2X7 level by western blot, IL-1β and IL-18 level by ELISA, blood spinal cord barrier by EVANS blue method. After SCI, the lower limb motor function of rats decreased and recovered after valproic acid treatment (P &lt; 0.05). Inflammatory cell infiltration of SCI group increased and decreased after treatment. After SCI, NLRP1/3 level increased and P2X7 protein level elevated which were reversed after valproic acid treatment (P &lt; 0.05). In rats with SCI, IL-1β level in spinal cord was higher than sham operation and lower after treatment (P &lt; 0.05) without difference of IL-18 between injury group and treatment group (P &gt; 0.05). In addition, fluorescence was higher in injury group than sham operation group and lower in valproic acid injection group than injury group. In conclusion, Valproic acid can promote motor function recovery in rats after SCI and inhibit inflammasome 1 and 3 expression, thereby inhibiting the maturation and release of IL-1β, and reducing P2X7 level after SCI.

Применение эозинофильно-нейтрофильного индекса ЭНИ и показателя степени интенсивности воспалительной инфильтрации для оценки воспалительного процесса при полипозном риносинусите

Introduction. Identification of the cellular composition of polyps in polypous rhinosinusitis (PRS) is important. In practice, to determine the quantitative indicators of the number and ratio of eosinophilic and neutrophilic leukocytes in polyp tissue, the eosinophil-neutrophil index (ENI) was introduced, which is equal to the ratio of the arithmetic mean number of eosinophils to the arithmetic mean number of neutrophils in 10 considered fields of view at a magnification of the microscope ×400, and the indicator degree of cellular inflammatory infiltration. Objective. To conduct a pathomorphological study of the tissue of resected nasal polyps with the determination of ENI parameters and the degree of cellular inflammatory infiltration in various PRS phenotypes and evaluate the possibility of using these indicators as predictors of PRS drug control. Materials and methods. We examined 292 people (126 men, 166 women), mean age 52.12±13.04 years, with bilateral PRS, which were divided into 4 phenotypic groups: I group: PRS without concomitant bronchial asthma (BA) and respiratory allergies; IIa group: PRS + allergic BA (aBA) and allergic rhinitis (AR); IIb group: PRS + AR without BA; III group: PRS + nonallergic BA (nBA). During pathological examination, polyps were divided into 3 histological types: «eosinophilic,» «neutrophilic,» and «mixed»; the ENI index was determined, 3 degrees of inflammatory infiltration were established: weak (I degree) when the arithmetic mean of eosinophils, lymphocytes, neutrophils, macrophages, histiocytes, and mast cells in 10 representative fields of view does not exceed 200 cells; moderate (II degree) when the arithmetic mean varies from 201 to 400 cells; and significant (III degree) where the arithmetic mean is &gt; 400 cells. In the PRS+BA groups, the state of BA control was determined using the ACQ-7 (Asthma Control Questionnaire). An analysis of the dynamics of ENI indicators and the degree of inflammatory infiltration was carried out depending on the effectiveness of conservative therapy with topical glucocorticoids (GCs) during the observation period of 1 year. The patients were divided into 3 groups: group 1, patients with positive dynamics, with a decrease in the degree of nasal polyps; group 2, the severity of polyps remained at the same level; group 3, the prevalence of polyps was higher than a year ago. Results. In all phenotypes of PRS, the eosinophilic type of inflammation prevails. The minimum indicators of ENI (11 [6;16]) and the degree of inflammatory infiltration (1 [1; 1]) were in the PRS +AR group, the highest intensity of inflammation was found in the PRS+nBA group (2.03 [2; 2]). According to the cellular composition of polyps in group 1, eosinophilic polyps were 87%; neutrophilic, 8%; mixed type, 5%; in group 2a, 97% of eosinophilic and 3% of mixed type in the absence of neutrophilic polyps, in group 2b ORS + AR, eosinophilic polyps were detected in 100%; in group 3, eosinophilic 88%, neutrophilic 6%, and mixed polyps 6% were diagnosed. Changes in ENI parameters and the intensity of inflammatory infiltration depending on the effectiveness of conservative therapy were revealed. In the group with positive dynamics, there was a decrease in these two indicators after 6 months of using intranasal GCs, in the absence of dynamics during therapy there were no changes in these indicators, and with low drug control, their increase was noted, which after the next 12 months was manifested by aggressive growth of polyps. At the same time, a correlation was found between the increase in the magnitude of indicators of local inflammation of the tissue of nasal polyps with a deterioration in the degree of control of BA of any etiology and the absence of significant correlations between blood eosinophilia and the level of eosinophilic infiltration of polypous tissue. Conclusions. 1. During the pathological examination of the surgical material, it is necessary to establish the histological type of nasal polyps (eosinophilic, neutrophilic, and mixed) to determine the further tactics of treating patients with PRS. 2. Pathological determination of the density of the inflammatory infiltrate in the tissue of resected nasal polyps with the calculation of ENI in clinical practice is necessary to control the dynamics of the course of inflammation, predict the possibility of relapse, and adjust the treatment of patients with PRS. 3. Correlation analysis in patients with PRS did not reveal a significant relationship between the severity of tissue eosinophilic infiltration of polyp tissue and the level of eosinophils in the peripheral blood, so the determination of peripheral blood eosinophilia is not enough to characterize local inflammation in PRS. 4. A decrease in ENI and the degree of density of the inflammatory infiltrate in nasal polyps in dynamics indicates the effectiveness of the ongoing conservative therapy. 5. An increase in the intensity of inflammatory infiltration in the tissues of polyps is accompanied by a deterioration in the medical control of asthma in phenotypes of PRS in combination with aBA and nBA.

Immune checkpoint inhibitor myocarditis: elucidating the spectrum of disease through endomyocardial biopsy.

Although immune checkpoint inhibitor (ICI) myocarditis carries a high reported mortality, increasing reports of smoldering myocarditis suggest a clinical spectrum of disease. Endomyocardial biopsy (EMB) remains the gold standard for diagnosis of ICI myocarditis, but different pathologic diagnostic criteria exist. The objective of this study was to classify the spectrum of ICI myocarditis and myocardial inflammation by pathology findings on EMB and correlate this with clinical outcomes. All patients who had EMB at MD Anderson Cancer Center between January 2018 and August 2019 for suspected ICI myocarditis were retrospectively reviewed. A grading system (Grades 0-2) based on the degree of inflammatory infiltrate was developed by pathologists. Cardiovascular outcomes and treatment were compared between grades of pathology. We identified 28 patients who had EMB for suspected ICI myocarditis, of which 18 were positive for myocarditis/inflammation. There were four deaths (two in Grade 2 and two in Grade 1), but only one was attributable to myocarditis. Grade 2 patients had no myocarditis-associated deaths despite having the highest troponin T values (median 2063 pg/mL). Four patients with Grade 1 myocardial inflammation continued ICI without any immunomodulation, and all were alive without adverse cardiovascular events at follow-up. We defined an EMB grading system for ICI myocarditis encompassing a spectrum of histologic findings of inflammatory infiltrates. A subset of low-grade myocardial inflammation patients were able to continue ICI without immunosuppressive therapy. Further studies are needed to identify low-risk patients who can be safely treated with ICI.

Cathepsin-B involved in effect of electroacupuncture by inhibiting the activation of NLRP3 inflammasome in rats with acute gouty arthritis

To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA. A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg-1·d-1), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1β(IL-1β) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score，the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1β,IL-18 were significantly increased (P<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1，IL-1β,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (P<0.01, P<0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (P<0.05). EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.

Наш досвід лікування хворих на бактеріальний кератит

Introduction. In recent years, the emergence of bacterial strains resistant to antibiotics used in medical practice significantly reduced the effectiveness of chemoprophylaxis and therapy. Following data indicates the need to search for new antibacterial drugs and ways of treating patients with bacterial keratitis. The aim of research is improvement of clinical parameters in patients with bacterial keratitis using hyperbaric oxygenation. Materials and Methods. We observed 68 patients (68 eyes) with bacterial keratitis aged 18 to 75 years. There were 36 men and 32 women. The patients were divided into 2 groups: main group (38 patients) and control group (30 patients). All the patients received antibiotic therapy, mydriatics, tissue-based products, vitamins. In addition, patients of the main group underwent hyperbaric oxygenation. The severity of the inflammatory response was evaluated using objective indicators: the presence and type of discharge into the conjunctival cavity, the severity of the mixed injection, corneal edema, the degree of inflammatory infiltration of the surface layers of the cornea. Results. The changes of clinical parameters in patients of the main and control groups were evaluated and scored (conjunctival discharge in the cavity, the severity of the mixed injection, corneal edema and inflammatory infiltration). The therapy contributed to faster disappearance of discharge into the conjunctival cavity and mixed injection, regression of edema, resorption of infiltrates (p &lt;0.001). Conclusions. Hyperbaric oxygenation in comprehensive treatment of patients with bacterial keratitis is highly efficient, provides stable clinical and functional results in the main group compared with the control group. Keywords: bacterial keratitis, hyperbaric oxygenation, comprehensive treatment, clinical parameters in points.

Arenaria kansuensis attenuates pulmonary fibrosis in mice via the activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.

Pulmonary fibrosis is a key feature of COVID-19, Chinese herbal medicine Arenaria kansuensis has been used for curing pulmonary disease and antivirus for a long time and it has the potential against COVID-19. In this work, protective effect of A. kansuensis ethanol extract (AE) on pulmonary fibrosis was evaluated through paraquat (PQ)-induced pulmonary fibrosis animal model. Results showed that AE could significantly improve the survival rate, increase the body weight and reduce the lung index of mice at the raw drug doses of 700 and 350 mg/kg. Histopathological observation results showed that the destruction degree of lung tissue structure in mice was significantly improved with the increase of AE dosage. Collagen deposition in lung interstitium was significantly reduced. The marker protein alpha-SMA involved in PF were significantly inhibited through repressing TGF-beta1/Smads pathway. The degree of inflammatory infiltration was significantly reduced and inflammatory cytokines were significantly inhibited in mice through inhibiting the NF-kB-p65. Besides, oxidant stress level including upregulated ROS and down-regulated SOD and GSH was efficiently improved by AE through upregulation of Nrf2 and downregulation of NOX4. In summary, this study firstly showed that the protective effect of AE on pulmonary fibrosis was partly due to activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.

Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model.

Background.Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-inflammatory and immune-regulatory properties that mitigate tissue damage. This study explores the protective effects of AAT in the setting of IRI utilizing a rat lung transplant model.Methods.Orthotopic left single lung transplantation was performed from Lewis to Sprague-Dawley rats; recipients did not receive systemic immunosuppression. Before transplantation, the donor lungs were primed with either albumin (control) or AAT. Starting the day of transplantation, recipient rats also received either albumin (control) or AAT with subsequent doses administered over the next 7 days. On the eighth postoperative day, lung allografts were recovered and analyzed.Results.Degree of inflammatory infiltrate, as quantified by the allograft weight (g)/body weight (kg) ratio, was significantly reduced in the AAT-treated group compared with controls (3.5 vs 7.7, respectively, P < 0.05). Treatment with AAT also significantly decreased allograft necrosis in treated animals, as measured by a semiquantitative score that ranged from 0 to 4 (1.25 vs 4, P < 0.05). In addition, lymphocytes isolated from recipients treatment group showed significant proliferative inhibition via a mixed lymphocyte response assay in response to donor antigens.Conclusions.AAT attenuates acute allograft injury and necrosis in a rat model of lung transplantation, suggesting that AAT may play a role in reducing IRI-induced inflammation.

Genistein can ameliorate hepatic inflammatory reaction in nonalcoholic steatohepatitis rats

Genistein plays an active role in improving nonalcoholic fatty liver disease (NAFLD). This study is designed to investigate the effect of genistein on liver inflammation in rats with nonalcoholic steatohepatitis (NASH). Forty SPF male SD rats were randomly divided into normal group, model group, genistein low-dose group (0.1% wt/wt) and high-dose group (0.2% wt/wt) with 10 rats in each group. After 12 weeks’ feeding, liver tissues and serum samples of rats were taken, and HE staining was used to perform pathological examination of liver tissues, then the degree of inflammatory infiltration was observed and NAFLD activity score(NAS) was calculated. With corresponding kits, several indicators were detected, namely, serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), liver TC and TG, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose and serum endotoxin. The levels of tumor necrosis factor (TNFα) in liver and insulin in blood of rats were detected by enzyme linked immunosorbent assay (ELISA), then the HOMA-IR index was calculated. Immunohistochemistry staining was used to observe the expression level of TLR4 protein and the RT-PCR was used to detect Tlr4 mRNA expression in liver tissue. The results showed that genistein could reduce TLR4 protein and gene expression, decrease the endotoxin and TNFα, alleviate the inflammatory reaction and make the indicators detected in blood and liver stay near normal in NASH rats. In conclusion, genistein can ameliorate hepatic inflammatory reaction in nonalcoholic steatohepatitis rats.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n=16) or AAA (n=14), while the control group was formed by cadaveric organ donors (n=10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P<0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P<0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA.

Retrospective Study of Pneumony by Aelurostrongylus abstrusus in Cats

Background: Aelurostrongylus abstrusus is a lungworm of cats with worldwide distribution. The adult forms of this parasite live in terminal bronchioles and alveoli, and can cause an asymptomatic disease or predominantly respiratory clinical signs, which can be occasionally cause of death. The aim of this study is to describe the epidemiological and pathological findings of infection by A. abstrusus through a necropsy retrospective study.Materials, Methods &amp; Results: the necropsy records from the Department of Veterinary Pathology of the Universidade Federal do Rio Grande do Sul were recovered and cats diagnosed with lungworm by Aelurostrongylus abstrusus were selected since January 1998 until December 2015. General data, such as age, sex, breed, clinical signs, and macroscopic lesions, were analyzed and compiled. The histological slides were reviewed by optical microscopy and detailed the microscopic aspects. In this study, were identified 22 cats with varying degrees of lungworm by A. abstrusus, and in 45.5% of the cases, this was the cause of death. Most part of the cats were mixed breed (19/22), and there were no sex predisposition. The age of the cats ranged from four months to 11 years old, and the most frequent age group was three to six years, with nine cases reported. In 37.5% of the cases were reported respiratory clinical signs, such as dyspnea and nasal discharge, and in 62.5%, clinical signs were not specific. The gross findings of the lungs ranged from reddish, or yellowish or white areas, and presence of multiples small, firm, and whitish nodules, measuring more than two centimeters in diameter, with multifocal distribution in the lung surface. Histologically, there was varied amount of parasites in different stages in the alveolar spaces, associated with the inflammatory infiltrate composed of lymphocytes, plasma cells, macrophages, neutrophils and occasional multinucleated giant cells, and hypertrophy and hyperplasia of the pulmonary smooth muscle and the wall of the arteries.Discussion: Aelurostrongylus abstrusus is the principal parasite of lung of cats, with worldwide distribution. In this study, we observed that 40.9% of cases were reported as of 2012, and may be due to a larger propagation of definitive intermediate and paratenic hosts, climate changes and/or the increase of rearing cats, and the consequent increase of hospital routine. Agreeing with the others authors, there is no sex predilection, but differ in the age group, in to the present study, the most frequent age group was between “3 to 6 years” of age (52.9%). The gross findings observed were similar to those described by other authors. Histologically was observed varied amount of parasites, and the degree of inflammatory infiltrate were very similar, but with a slight difference in discrete infiltration (36.4%). Others researchers have identified predominantly severe inflammatory infiltrate (57.9%). Hypertrophy and hyperplasia of pulmonary smooth muscle and the wall of the arteries was moderate (50%), however, in previous studies were severe. The diagnosis of aelurostrongilosis through parasitological tests have proven the occurence this lung parasite in the study region, highlighting the importance of this study by adding epidemiological and pathological data on the disease.

Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes

Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance. We attempted to transplant Aire-overexpressing bone marrow-derived DCs (Aire-BMDCs) to treat type 1 diabetes (T1D) and to explore a new strategy for autoimmune disease treatment. We observed that the onset of T1D in recipient mice was delayed; insulin autoantibody (IAA) production was significantly decreased; the structure of islets was protected; and the degree of inflammatory infiltration was lower. Furthermore, we found that Aire-BMDCs can promote apoptosis and induce autoreactive CD4+ T cell clonal anergy, inhibit Th1 and Th17 production, and induce Treg production. These results suggest that transplantation of Aire-BMDCs will be a manipulation and effective method for preventing or treating T1D.

Expression of hypoxia-induced semaphorin 7A correlates with the severity of inflammation and osteoclastogenesis in experimentally induced periapical lesions

ObjectiveWhile hypoxia and inflammation are intimately linked, the effects of inflammatory hypoxia on the pathogenesis of periapical lesions remain largely unknown. The aim of this study was to examine hypoxia during the progression of experimentally induced rat periapical lesions, and to derive correlations between hypoxia-induced Semaphorin 7A (Sema7a) expression, severity of inflammation, and osteoclastogenesis in the lesions. DesignPeriapical lesions were developed after mandibular first molar pulp exposure in forty Sprague-Dawley rats. The animals were randomly divided into four groups and sacrificed at 0, 7, 14, and 28days after pulpal exposure. The bilateral mandibles containing the first molar were obtained and routinely prepared for histological, immunohistochemical, enzyme histochemical analyses and quantitative polymerase chain reaction detecting Sema7a mRNA expression. Data were analysed by one-way analysis of variance and the Pearson’s correlation and linear tendency test. ResultsPeriapical tissues become hypoxic during the development of experimentally induced periapical lesions, with steadily increasing numbers of HIF-1α-positive cells that positively correlate with the expression of Sema7a mRNA in the lesions. Furthermore, significant positive correlates were derived for the expression of Sema7a and the degree of inflammatory infiltration and osteoclast number, respectively. ConclusionsHypoxia-induced Sema7a participates in the pathogenesis of periapical lesions, providing a novel therapeutic target for the treatment of this inflammatory disease in the future.

Histological Changes in Nasolabial Cutaneous Flaps Employed in Intraoral Reconstruction

Nasolabial cutaneous flaps have been routinely used to reconstruct intraoral defects. The purpose of this study was to study histological changes that may occur in the skin flap as a result of its exposure to a new environment. Thirteen patients took part in this study. Fusiform tissue specimens were obtained from the intraoral cutaneous portion of the flap. Biopsy specimens were also taken from the skin of nasolabial region and from the buccal mucosa to serve as control. Thickness of stratum corneum, degree of inflammatory infiltration and number of skin appendages were evaluated. Periodic-acid Schiff (PAS) staining was also performed to identify the presence of hyphae. The characteristic features of the skin are almost always maintained, although the thickness of stratum corneum and the number of skin appendages are often significantly reduced. In two patients the inflammatory infiltration was intense and accompanied by elimination of skin appendages and stratum corneum. These flaps tend to mimic mucosa macroscopically. In four patients fibrosis was histologically demonstrated. These flaps resembled atrophic skin macroscopically. Hyphae could not be identified with PAS staining in this study. Koilocytes, which are indicative of HPV infection, were identified in two flap specimens. Intraorally placed nasolabial flaps may undergo a variety of histological and macroscopical changes. In the majority of cases the intraoral cutaneous flap maintains skin features, except if it becomes heavily infiltrated with inflammatory cells. Inflammation occurs for unknown reasons and results in a mucosa-like microscopic and macroscopic appearance of the intraorally placed flap.

Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling.

Purpose. Kawasaki disease (KD) is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs) in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE) to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs) was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

Healing after Root-end Microsurgery by Using Mineral Trioxide Aggregate and a New Calcium Silicate–based Bioceramic Material as Root-end Filling Materials in Dogs

IntroductionThe purpose of this study was to compare healing after root-end surgery by using grey mineral trioxide aggregate (MTA) and EndoSequence Root Repair Material (RRM) as root-end filling material in an animal model. MethodsApical periodontitis was induced in 55 mandibular premolars of 4 healthy beagle dogs. After 6 weeks, root-end surgeries were performed by using modern microsurgical techniques. Two different root-end filling materials were used, grey MTA and RRM. Six months after surgery, healing of the periapical area was assessed by periapical radiographs, cone-beam computed tomography (CBCT), micro computed tomography (CT), and histology. ResultsMinimal or no inflammatory response was observed in the majority of periapical areas regardless of the material. The degree of inflammatory infiltration and cortical plate healing were not significantly different between the 2 materials. However, a significantly greater root-end surface area was covered by cementum-like, periodontal ligament–like tissue, and bone in RRM group than in MTA group. When evaluating with periapical radiographs, complete healing rate in RRM and MTA groups was 92.6% and 75%, respectively, and the difference was not statistically significant (P = .073). However, on CBCT and micro CT images, RRM group demonstrated significantly superior healing on the resected root-end surface and in the periapical area (P = .000 to .027). ConclusionsLike MTA, RRM is a biocompatible material with good sealing ability. However, in this animal model RRM achieved a better tissue healing response adjacent to the resected root-end surface histologically. The superior healing tendency associated with RRM could be detected by CBCT and micro CT but not periapical radiography.

Perforin Expression in Plaque Psoriasis: An Immunohistochemical Study

ABSTRACTPsoriasis (PsO) is T-cell-mediated disease resulting from aberrant activation of both innate and adaptive immunity. Perforin is a multi-domain, pore-forming protein. It is located within the cytoplasm of CD 8 cytotoxic T cells (CTLs) and natural killer cells (NK). The aim of this study was to evaluate the immunohistochemical (IHC) expression of perforin in lesional and perilesional skin of chronic plaque psoriatic patient and correlate its expression with the standard clinico-pathological variables. This prospective case–control study was conducted on 50 PsO patients and 30 age- and gender-matched healthy subjects as a control group. There were high-significant differences between lesional and perilesional skin of plaque PsO patients as regards to IHC perforin status and localization (p < 0.001 for both). There was a high-significant difference between positive and negative perforin cases as regards to psoriasis area severity index (PASI) (p < 0.000). There were significant differences between mild and moderate-to-severe intensity of IHC perforin expression as regards to triggering factors and PASI (p = 0.02 and 0.03, respectively). Localization of IHC perforin positive lymphocytes in both epidermis and dermis was significantly associated with higher degree of acanthosis and higher degree of inflammatory infiltrates in comparison with positive cells located in dermis (p = 0.001 for both). Perforin might have a putative signaling in early and late plaque PsO. Plaque psoriatic patients with positive perforin expression could be a candidate for a future target therapy to stop the proposed scenario and achieve a therapeutic response.