Abstract WP284: Pro-inflammatory Response Elicited by Porphyromonas Gingivalis Lipopolysaccharide Exacerbates the Rupture of Experimental Cerebral Aneurysms

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Takeshi Miyamoto ◽  
Keiko T Kitazato ◽  
Yoshiteru Tada ◽  
Kenji Shimada ◽  
Kenji Yagi ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Porphyromonas Gingivalis ◽  
Intracranial Aneurysms ◽  
Renal Hypertension ◽  
Saline Control ◽  
High Morbidity ◽  
Aneurysmal Rupture ◽  
Porphyromonas Gingivalis Lipopolysaccharide ◽  
Group 2 ◽  
Group 1

Introduction: Subarachnoid hemorrhage (SAH) is a catastrophic event with high morbidity and a poor prognosis. To prevent SAH, its pathogenesis must be understood. Dental infection may play a part in the pathophysiology of intracranial aneurysms. In our newly established rat model of aneurysms, the vascular inflammatory response was associated with their rupture. Therefore we hypothesized that the inflammatory response exacerbated by periodontal pathogens affects experimental cerebral aneurysm rupture. Methods: Aneurysms were induced in 10-week-old female Sprague-Dawley rats by eliciting estrogen deficiency, renal hypertension, and hemodynamic stress. Two weeks later they were divided into 2 groups; group 1 (n=13) was treated with Porphyromonas gingivalis lipopolysaccharide (LPS), group 2 (n=17) was the saline control. Both groups were intraperitoneally injected once a week. Results: During the 90-day observation period, 7 group 1 (54%) and 6 group 2 rats (35%) suffered aneurysmal rupture. The incidence of rupture within 60 days was significantly higher in group 1 than group 2 (38% vs 6%, p<0.05), indicating that LPS promoted experimental aneurysmal rupture. The administration of LPS increased the plasma level of IL-1β and MMP-9 and the mRNA level of TLR2, IL-1β, and MMP-9 in the vascular wall prone to rupture on day 60. In our in vitro studies, IL-1β mRNA was increased in vascular smooth muscle cells exposed to LPS. These results suggest that LPS enhances the rupture of intracranial aneurysms via the promotion of local and systemic pro-inflammatory responses. Conclusion: Our study first documents that in rats, Porphyromonas gingivalis LPS exacerbates vascular inflammation and enhances the rupture of intracranial aneurysms.

Abstract P117: Hydralazine Prevents the Rupture of Experimental Cerebral Aneurysms in Hypertensive Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Takeshi Miyamoto ◽  
Keiko T Kitazato ◽  
Yoshiteru Tada ◽  
Kenji Shimada ◽  
Kenji Yagi ◽  
...  
Keyword(s):  
Renal Hypertension ◽  
Cerebral Aneurysms ◽  
Vascular Wall ◽  
Abnormal Behavior ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Down Regulation ◽  
Group 2 ◽  
Group 1 ◽  
Cerebral Vascular

Introduction: Subarachnoid hemorrhage (SAH) is a catastrophic event with high morbidity and a poor prognosis. While epidemiological studies showed that hypertension is a risk factor for aneurysmal rupture, it remains unclear whether lowering the blood pressure (BP) prevents the rupture of aneurysms. Under the hypothesis that lowering the BP prevents the rupture of experimental cerebral aneurysms, we investigated whether hydralazine reduces the incidence and rupture of aneurysms in our rat model. Methods: In 10-week-old female Sprague-Dawley rats (n=34) we elicited estrogen deficiency, renal hypertension, and hemodynamic stress. Two weeks later, they were divided into 2 groups; group 1 (n=17) was treated perorally with hydralazine (100 mg/kg/day), group 2 (n=17) was the vehicle control. We recorded their death or abnormal behavior in the course of 90 days and inspected ruptured aneurysms. Results: At 2 weeks, both groups manifested an increase in the systolic BP (SBP) (group 1, 205 mmHg; group 2, 207 mmHg). After 30-, 60-, and 90-days, the SBP was lower in group 1 than group 2 (150 vs 210 mmHg, 163 vs 211 mmHg, and 173 vs 210, mmHg, respectively). In the course of 90 days, 9 group 2 (53%) and 8 group 1 rats (47%) developed cerebral aneurysms. The rupture rate was lower in group 1 (3/8, 38%) than group 2 rats (9/9: 100%). While hydralazine did not prevent the development of aneurysms, it prevented their rupture. qRT-PCR performed on day 35 showed the down-regulation of MCP-1 and MMP-9 in the cerebral vascular wall of group 1 rats. Conclusion: Our findings suggest that lowering the SBP may prevent the rupture of cerebral aneurysms via the down-regulation of MCP-1 and MMP-9 in the cerebral vascular wall.

Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats

2007 ◽  
Vol 107 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Mohammad A. Jamous ◽  
Shinji Nagahiro ◽  
Keiko T. Kitazato ◽  
Tetsuya Tamura ◽  
Hani Abdel Aziz ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intracranial Aneurysm ◽  
Intracranial Aneurysms ◽  
Morphological Changes ◽  
Renal Hypertension ◽  
Endothelial Injury ◽  
High Morbidity ◽  
Corrosion Casts ◽  
Aneurysm Formation ◽  
Vascular Corrosion Casts

Object Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. Methods The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague–Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery–olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohis-tochemically by using antibodies against endothelial nitric oxide synthase, α–smooth muscle actin, macrophages, and matrix metalloproteinase–9. Results Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). Conclusions This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.

Investigation of TAp63 gene Expression and Follicle Count Using Melatonin in Cisplatin-induced Ovarian Toxicity

2020 ◽  
Author(s):  
Hacı Öztürk Şahin ◽  
Mehmet Nuri Duran ◽  
Fatma Sılan ◽  
Ece Sılan ◽  
Duygu Sıddıkoglu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Female Rats ◽  
Histological Evaluation ◽  
Saline Control ◽  
Control Group ◽  
Ovarian Toxicity ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats. Twenty nine female rats were divided to three groups: Saline control group (Group 1), cisplatin group (Group 2), and cisplatin+melatonin group (Group 3). While the rats in Groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in Group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapited. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-mullerian hormone (AMH) values were measured with enzyme immune-assay technology. Results: While primordial follicles were seen to decrease in Group 2 as compared to Group 1 (p:0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to Group 2 (p:0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p:0.102 and p:0.411, respectively). While TAp63 gene expression significantly increased in Group 2 as compared to control group (p:0.001), we did not detect a statistically significant difference in cisplatin+melatonin group, although gene expression decreased (p:0.34). Conclusion: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage.

scholarly journals The Effects of Insufflation Conditions on Rat Mesothelium

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Andrew K. Davey ◽  
Jessica Hayward ◽  
Jean K. Marshall ◽  
Anthony E. Woods
Keyword(s):  
Inflammatory Response ◽  
Mesothelial Cell ◽  
Surface Group ◽  
Control Group ◽  
Cell Nuclei ◽  
Tissue Samples ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Aim. The aim of this investigation was to examine the alterations in the peritoneum after cold dry CO2, heated dry CO2, and humidified heated CO2at pressures equivalent to intraperitoneal pressures used in human laparoscopy.Methods. Eighteen rats were divided into 4 treatment groups—group 1: untreated control; group 2: insufflation with cold dry CO2; group 3: insufflation with heated, dry CO2; group 4: insufflation with heated and humidified CO2. The abdomen was insufflated to 5 mm/Hg (flow rate 50 mL/min) for 2 h. Twelve hours later, tissue samples were collected for analysis by light microscopy (LM) and scanning electron microscopy (SEM).Results. Group 1: no abnormalities were detected. Group 2: specimens revealed an inflammatory response with loss of mesothelium and mesothelial cell nuclei showing lytic change. Cells were rounded with some areas of cell flattening and separation. Group 3: some animals showed little or no alteration, while others had a mild inflammatory response. Mesothelial cells were rounded and showed crenation on the exposed surface. Group 4: specimens showed little change from the control group.Conclusions. The LM results indicate that insufflations with heated, humidified CO2are the least likely to induce mesothelial damage.

scholarly journals Stent treatment for basilar artery dissection: A single-center experience of 21 patients

2016 ◽  
Vol 22 (3) ◽  
pp. 260-265 ◽  
Author(s):  
Li Li ◽  
Tianxiao Li ◽  
Jiangyu Xue ◽  
Ziliang Wang ◽  
Weixing Bai ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Artery Dissection ◽  
High Morbidity ◽  
Single Center Experience ◽  
Post Operation ◽  
Pre Treatment ◽  
Group 2 ◽  
Partially Occluded ◽  
Group 1

Basilar artery dissection is a rare disease with high morbidity and mortality. No well-established management strategy exists for this lesion. Endovascular reconstructive therapy using stents (with or without coiling) may be the optimum strategy. We describe our center’s experience for this treatment strategy in 21 patients with basilar artery dissection from January 2009 to July 2014 (17 men, four women; age range, 18–70 years; median age, 56 years). We divided patients into two groups: Group 1 patients received stent-assisted coiling treatment, and Group 2 patients received stent-only treatment. Pre-treatment, peri-operation and follow-up evaluation were investigated for complications, clinical outcome and angiographic results. The median follow-up time was 20 months (range, 3–67 months). All patients were treated endovascularly by stent-assisted coiling (14 patients) or stent only (seven patients). Immediate angiography showed: in Group 1, five of 14 lesions were completely occluded, five were partially occluded, four revealed retention of contrast media; in Group 2, all patients (seven of seven) had contrast retention. At the follow-up visit (median seven months, 3–29 months), the aneurysms were angiographically improved in five of 13 patients in Group 1 compared with immediately post-operation, while six of sevenimproved in Group 2. Five patients (all in Group 1) had ischemic or hemorrhage peri-operation complications. Long-term good clinical outcomes (modified Rankin Scale score (mRS) ≤ 2) were achieved in all patients except three death cases (two in Group1, one in Group 2). In our experience, endovascular reconstructive therapy using stents (with or without coiling) for basilar artery dissection is effective and safe. Stent-only treatment seems have a better safety profile during the peri-operation period.

Inoculation of Balb/c mice with live attenuated tachyzoites protects against a lethal challenge ofNeospora caninum

Parasitology ◽  
2007 ◽  
Vol 135 (1) ◽  
pp. 13-21 ◽  
Author(s):  
P. M. BARTLEY ◽  
S. WRIGHT ◽  
F. CHIANINI ◽  
D. BUXTON ◽  
E. A. INNES
Keyword(s):  
Protective Immunity ◽  
Neospora Caninum ◽  
High Morbidity ◽  
Post Challenge ◽  
Lethal Challenge ◽  
Secondary Challenge ◽  
Group 3 ◽  
Group 2 ◽  
Severe Pathology ◽  
Group 1

SUMMARYNeospora caninumtachyzoites attenuated through passage in tissue culture were tested for their ability to induce protective immunity against a lethal challenge dose of parasites. Balb/c mice were each inoculated with either 1×106live virulent tachyzoites (Group 1) or 1×106live attenuated tachyzoites (Group 2), while (Group 3) received a control inoculum. All mice were each challenged 28 days later with 5×106virulent parasites. Histopathological lesions in the brains including necrosis and microgliosis were observed following post-mortem on day 28 post-challenge (p.c.) in 71% of Group 1 and 56% of Group 2. Immunohistochemistry (IHC) of these lesions showed tachyzoites andNeosporaantigens to be associated with moderate brain lesions in 17% of Group 1, while in 11% of Group 2N. caninumtissue cysts were detected, but these were not associated with lesions, Parasite DNA was detected by PCR in the brains of 86% of mice in Group 1 and 56% of mice in Group 2. Following challenge the mice in Group 3 showed high morbidity and 100% mortality within 17 days p.c. Positive IHC forN. caninumwas seen in 88% of the Group 3 mice and parasite DNA was detected in all brain samples. This study shows that it is possible to protect against a lethal challenge ofN. caninumthrough inoculation with attenuated or virulent tachyzoites. However, more severe pathology developed in mice initially inoculated with virulent parasites following a secondary challenge, compared to mice initially inoculated with attenuated parasites.

scholarly journals Sitagliptin Attenuates Porphyromonas Gingivalis Virulence and Inflammatory Response in Macrophage on Titanium

2021 ◽  
Author(s):  
Weilong Tang ◽  
Minquan Du ◽  
Shuang Zhang ◽  
Han Jiang
Keyword(s):  
Inflammatory Response ◽  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Flow Cytometry Assay ◽  
Related Factors ◽  
Qrt Pcr ◽  
Inhibiting Effect ◽  
Porphyromonas Gingivalis Lipopolysaccharide ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract BackgroundIn peri-implantitis, porphyromonas gingivalis and macrophage play central roles. The aim of this study was to detect the attenuating effect of an anti-diabetic drug sitagliptin on porphyromonas gingivalis virulence and inflammatory response in macrophage on titanium discs. Materials and methodsPorphyromonas gingivalis and macrophage were cultured on titanium discs. Antibacterial and antibiofilm activities of sitagliptin were assessed and the morphology of porphyromonas gingivalis were observed by SEM. Bacterial early adhesion, aggregation, hemagglutination, hemolysis and porphyromonas gingivalis virulence factors mRNA expression were assessed to preliminarily investigate the mechanisms of action. Flow cytometry assay, qRT-PCR and Western Blot were used to assess the anti-inflammatory effect of sitagliptin on porphyromonas gingivalis lipopolysaccharide-stimulated macrophage. ResultsThe present study demonstrated the inhibiting effect of sitagliptin on the growth, biofilm, phenotypic behavior and virulence factors of porphyromonas gingivalis and the protective effect on the porphyromonas gingivalis lipopolysaccharide-induced polarization in macrophage. And we also confirmed the anti-inflammatory effect of sitagliptin on the secretion of inflammation-related factors in macrophage by inhibiting the MAPK and AKT signaling pathways. ConclusionsSitagliptin possesses the attenuating effect on porphyromonas gingivalis virulence and inflammatory response in porphyromonas gingivalis lipopolysaccharide-stimulated macrophage on titanium.

scholarly journals Atopic Biomarker Changes after Exposure to Porphyromonas gingivalis Lipopolysaccharide: A Small Experimental Study in Wistar Rat

2021 ◽  
Author(s):  
Sindy Cornelia Nelwan ◽  
Ricardo Adrian Nugraha ◽  
Anang Endaryanto ◽  
Asti Meizarini ◽  
Udijanto Tedjosasongko ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Wistar Rat ◽  
Periodontal Pathogen ◽  
Rapid Decline ◽  
Group 4 ◽  
Area Of Interest ◽  
Before And After ◽  
Porphyromonas Gingivalis Lipopolysaccharide ◽  
Group 3 ◽  
Group 2

BackgroundIgE and IgG4 are implicated in atopic development and clinically utilized as major biomarkers. Atopic responses following certain pathogens such as Porphyromonas gingivalis is currently an area of interest for further research.PurposeThe aim of this study is to measure the level of IgE, IgG4, and IgG4/IgE ratio periodically after exposure of periodontal pathogen Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS).MethodsWe used 16 wistar rats (Rattus norvegicus) randomly subdivided into 4 groups, group 1 were injected by placebo, group 2 by LPS Pg 0.3 μg/mL,group 3 by LPS Pg 1 μg/mL, and group 4 by LPS Pg 3 μg/mL. Sera from both groups were taken from retro-orbital plexus before and after exposure.ResultsLevel of IgE and IgG4 increased significantly following exposure of LPS Pg at day-4 and day-11. Greater increase of IgE rather than IgG4 contributes to rapid decline of IgG4/IgE ratio, detected in the peripheral blood at day-4 and day-11.ConclusionModulation of atopic responses following exposure to LPS Pg is reflected by decrease in IgG4/IgE ratio that accompanies an increase of IgE.Clinical significancePorphyromonas gingivalis, a keystone pathogen during periodontal disease, may have a tendency to disrupt atopic biomarkers.

Biomarkers of system inflammation in local and diffuse peritonitis

2020 ◽  
Vol 66 (5) ◽  
pp. 411-418
Author(s):  
E.V. Mikhalchik ◽  
I.V. Borodina ◽  
I.V. Vlasova ◽  
T.V. Vakhrusheva ◽  
N.P. Gorbunov ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Healthy Volunteers ◽  
Normal Values ◽  
Diffuse Peritonitis ◽  
Surgical Operation ◽  
Neutrophil Activity ◽  
Plasma Antioxidant Capacity ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

In cases of any acute surgical abdominal disease the progression of purulent inflammation can lead to local or diffuse peritonitis. The indicators of the degree and specificity of the inflammatory response in blood such as cytokine concentration, neutrophil activity, plasma antioxidant capacity (thiols concentration) could be considered as potential predictors of complications. The luminol-dependent chemiluminescence (CL) response of blood activated by the phorbol ester (PMA), and the concentration of cytokines IL-6, IL-8, IL-10, myeloperoxidase (MPO) and thiols in plasma were measured in patients with uncomplicated condition (group 1, n=8), local peritonitis (group 2, n=9) or diffuse peritonitis (group 3, n=9) at admission to surgery (before surgical operation, b/o), immediately after surgical operation (a/o) and a day after surgery (1 day) as well as in healthy volunteers (norm, n=12). In all time-points the cytokines and MPO concentrations measured by ELISA, in group 3 were higher than in healthy volunteers and in patients in groups 1 and 2. Blood CL demonstrated a more than 5-fold increase above the normal values in all patients, and was also higher in group 2 as compared to group 1 (b/o and a/o). Patients in group 3 had shown both maximum and minimum of CL values, which could be a consequence of neutrophil priming or exhaustion (“immune paralysis”), respectively. The same patients' plasma exhibited low thiol concentration (≤30% vs normal values). In patients with fatal outcomes (group 3, n=2) within a day after surgery, either a decrease of the CL to zero values concurrently with elevated IL-8 and IL-6 concentrations and low thiol levels was observed, or CL exceeded normal values more than 20 times with concurrent complete exhaustion of the plasma thiol pool. No clear dependency between the plasma parameters and neutrophil activity was found. Hence a parameter set for prognosis and/or early diagnosis of infectious complications in acute abdominal pathology should include different biomarkers of the inflammatory response: cytokine profile (IL-6, IL-8, IL-10), MPO and neutrophil activity, antioxidant plasma capacity (e.g., total thiols concentration).

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