Vascular Inflammatory Changes Research Articles

Optical coherence tomography angiography to assess for retinal vascular changes in Neuro-Sjögren.

Sjögren's syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP). We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool. Prospective, monocentric pilot-study. OCTA (Heidelberg Engineering OCT SPECTRALIS) of the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus (DCP) of the retina was prospectively performed in Neuro-Sjögren, age-matched CIDP patients (n = 31, each), and healthy controls (n = 30). Vessel density (VD) and foveal avascular zone (FAZ) was measured with Erlangen Angio Tool. Significantly lower VD were found for the DCP and ICP in Neuro-Sjögren and CIDP patients compared to healthy controls (p = 0.0002 and <0.0001). When group comparison was age-adjusted, these differences were not found anymore. Different frequencies of "low" retinal blood flow in each layer comparing Neuro-Sjögren and CIDP patients were not found. FAZ revealed no significant differences between patients with Neuro-Sjögren, CIDP and healthy controls. This study found no significant differences in VD or the foveal avascular zone between Neuro-Sjögren and CIDP patients using OCTA, suggesting that inflammatory vascular changes in the retina are uncommon in Neuro-Sjögren patients.

Stroke risk after varicella-zoster virus infection: a systematic review and meta-analysis.

Varicella-zoster virus (VZV) infection may cause vascular inflammatory changes leading to an increased risk of stroke. Previous studies have focused on the risk of stroke and less on changes in stroke risk and prognosis. We aimed to explore the changing patterns of stroke risk and stroke prognosis after VZV infection. This study is a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies on stroke after VZV infection between January 1, 2000, and October 5, 2022. Relative risks were combined for the same study subgroups using a fixed-effects model and pooled across studies using a random-effects model. 27 studies met the requirements, including 17 herpes zoster (HZ) studies and ten chickenpox studies. There was an increased risk of stroke after HZ, and this risk decreased over time: relative risk 1.80 (95% CI 1.42-2.29) within 14days, 1.61 (95% CI 1.43-1.81) within 30days, 1.45 (95% CI 1.33-1.58) within 90days, 1.32 (95% CI 1.25-1.39) within 180days, 1.27 (95% CI 1.15-1.40) at one year and 1.19 (95% CI 0.90-1.59) after one year, with the same trend in the stroke subtype. The risk of stroke after herpes zoster ophthalmicus was higher, with a maximum relative risk of 2.26 (95% CI 1.35-3.78). The risk of stroke after HZ was higher in patients aged around 40years: relative risk 2.53 (95% CI 1.59-4.02), and similar in men and women. Also, after pooling studies of post-chickenpox stroke, we found that the middle cerebral artery and its branches were most frequently involved (78.2%), with a better prognosis in most patients (83.1%) and less frequent vascular persistence progression (8.9%). In conclusion, the risk of stroke increases after VZV infection, decreasing over time. Post-infection vascular inflammatory changes often occur in the middle cerebral artery and its branches, with a better prognosis in most patients and less frequent persistent progression.

Pathophysiology, cellular and molecular mechanisms of large and small vessel diseases.

Cerebrovascular disease (CVD) is the second most common cause of cognitive impairment and dementia in aged population. CVD presents in a myriad number of clinical ways based on the functional location of pathology. While primary clinical emphasis has been placed on motor, speech and visual deficits, vascular cognitive decline is a vastly under recognized and devastating condition afflicting millions of Americans. CVD, a disease of the blood vessels that supply blood to brain involves an integration between small and large vessels. Cerebral large vessel diseases (LVD) are associated with atherosclerosis, artery-to-artery embolism, intracardiac embolism and a large vessel stroke leading to substantial functional disability. Cerebral small vessel disease (SVD) is critically involved in stroke, brain hemorrhages, cognitive decline and functional loss in elderly patients. An evolving understanding of cellular and molecular mechanisms emphasizes that inflammatory vascular changes contribute to systemic pathologic conditions of the central nervous systems (CNS), with specific clinical presentations including, cognitive decline. Advances in an understanding of pathophysiology of disease processes and therapeutic interventions may help improve outcomes. This review will focus on large and small vessels diseases and their relationship to vascular cognitive decline, atherosclerosis, stroke, and inflammatory neurodegeneration. We will also emphasize the molecular and cellular mechanisms, as well as genetic and epigenetic factors associated with LVD and SVD.

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies-except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended-CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease.

OP16 The first virtual chromoendoscopy artificial intelligence system to detect endoscopic and histologic remission in Ulcerative Colitis

Abstract Background Endoscopic and histologic activity are important therapeutic targets in ulcerative colitis (UC). The Paddington International Virtual ChromoendoScopy ScOre (VCE-PICaSSO)1 demonstrated that enhanced visualisation of subtle mucosal and vascular inflammatory changes correlated strongly with histology. However, without adequate training, the subjective evaluation of white light (WL) and VCE endoscopic scores varies between observers. We aimed to develop an artificial intelligence (AI) system for objective assessment of endoscopic disease activity and predict histology related to both white light and VCE videos. Methods 469 endoscopy videos (48512 frames) from 235 patients representative of all grades of inflammation, from our prospective PICaSSO multicentre study1 were used to develop a convolutional neural network (CNN). 316 videos were divided into training (254) and validation (62) sets. 153 additional videos (78 patients) were used as test cohort. The videos were edited to separate clips with WL and with VCE, and assessed using Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO, respectively. The classification stage of a pre-trained ResNet50 CNN classifier was trained to predict the healing or active inflammation on video frames. One network was trained to predict endoscopic remission (ER) as UCEIS≤1 from WL frames, and a second network was trained to predict PICaSSO≤3 from VCE. Histological remission (HR) was defined as Robarts Histological Index (RHI) ≤3 with no neutrophils in lamina propria or epithelium. Results In the validation cohort, our system predicted ER (UCEIS ≤1) in WL videos with 82% sensitivity (Se), 94% specificity (Sp) and an area under the ROC curve (AUROC) of 0.92. For the detection of remission in VCE videos (PICaSSO ≤3) Se was 74%, Sp 95%, and AUROC 0.95. In the testing cohort of independent videos, the diagnostic performance for both cut offs of ER remained similar. Our system also had an excellent diagnostic performance for the prediction of HR in the validation set, with Se, Sp, and Accuracy of 92%, 83%, and 85% respectively, using VCE, and 83%, 87%, and 86% respectively, with WL. In the testing set performance declined modestly while remaining good. Of note, the algorithm’s prediction of histology was similar with VCE and WL videos. Table 1 Table 2 Conclusion Our AI system accurately recognize endoscopic remission in videos and predict histological remission equally well. This is the first AI model developed to analyse inflammation and endoscopic remission in VCE through the PICaSSO score, and the first multi-domain system providing a complete endoscopic and histologic assessment. Reference 1. Iacucci et al. Gastroenterology 2021

Fundus imaging features of purified protein derivative and T-spot positive tubercular serpiginous-like choroiditis

Objective: To summarize the clinical and fundus imaging features of purified protein derivative and T-spot positive tubercular serpiginous-like choroiditis (PTP-SLC) patients. Methods: This retrospective study consecutively enrolled 13 PTP-SLC patients (21 eyes) in Beijing Tongren Hospital from November 2015 to November 2017. There were 8 males and 5 females with an average age of (45.2±12.1) years. Medical history and results of systemic and ophthalmological examinations, such us fundus autofluorescence photography, optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and indocyanine green angiography, were evaluated. Results: Eight patients had binocular disease with an average interval time of (8.4±7.9) years. The average visual acuity of all patients was 0.3, and 4 patients had a clear history of exposure to tuberculosis. The active lesions in the PTP-SLC patients were homogeneous and creamish-yellow with unclear boundaries. Fundus autofluorescence showed an ill-defined, diffuse hyperautofluorescent zone. OCT showed punctate hyperreflexes between the choroidal stroma, destruction of the outer retinal structure with intraretinal edema and discrete vitreal hyper-reflective spots. FFA showed hypofluorescence in the active lesion at early stage and diffuse hyperfluorescence with leakage. Indocyanine green angiography showed persistent hypofluorescence. Conclusions: PTP-SLC fundus lesions are mainly manifested as homogeneous creamish-yellow lesions with unclear boundaries and high in autofluorescence. The involvement of the choroid and the outer layer of the retina can be observed on OCT. FFA can find more retinal vascular inflammatory changes. It is difficult to distinguish PTP-SLC from serpiginous choroiditis simply based on clinical and epidemiological characteristics. The pathogenic examination of tuberculosis is still the key to differential diagnosis (Chin J Ophthalmol, 2020, 56: 914-919).

IS THERE A PLACE FOR CHOLANGIOSCOPIC EVALUATION OF BILIARY ANASTOMOTIC STRICTURE AFTER DECEASED DONOR LIVER TRANSPLANT?

Biliary complications remain one of the most important causes of morbidity and graft loss after liver transplant (LT). Endoscopic therapy of biliary complications has proven to be effective over time, leaving surgical treatment restricted to only very few cases. However, we cannot yet predict which patients will have the greatest potential to benefit from endoscopic treatment. On this premise we decide to conduct this study to evaluate the role and safety of single operator cholangioscopy (SOC) in the endoscopic treatment of post-LT biliary anastomotic strictures (AS). Between March/2016 and June/2017, 20 consecutive patients referred for endoscopic treatment for biliary anastomotic stricture were included in this prospective observational cohort study. Inclusion criteria were age over 18 years old, and a deceased LT performed within at least 30 days. Exclusion criteria were non-anastomotic biliary stricture, biliary leakage, cast syndrome, any previous endoscopic therapy, pregnancy and inability to provide informed consent. All patients underwent SOC before endoscopic therapy with fully covered self-expandable metal stent (FCSEMS) and after stent removal. At pre-treatment SOC, stricture orifice and fibrotic changes could be visualized in all patients, vascular changes and surgical sutures in 60% and acute inflammatory changes in 30%. SOC was essential for guidewire placement in five cases. FCSEMS was successfully deployed in all patients. Stricture resolution rate was 44.4% (median stent indwelling 372 days). Stricture recurrence was 12.5% (median follow-up of 543 days). Adverse events were distal (66.6%) and proximal (5.5%) stent migration, stent occlusion (16.6%), severe abdominal pain (10%) and mild acute pancreatitis (10%). SOC was repeated after FCSEMS removal. Post-treatment SOC showed fibrotic changes in all but one patient; vascular and acute inflammatory changes were less frequent in comparison to index procedure. The disappearance of suture material was remarkable. None of the cholangioscopic findings were statistically correlated to treatment outcome or stricture recurrence. Endoscopic retrograde cholangiography with SOC is feasible in post-LT patients with AS. Cholangioscopic findings can be classified into fibrotic, vascular and acute inflammatory changes. Cholangioscopy may be helpful to assist guidewire passage, but Its overall role for changing management is post-LT patients was not demonstrated.

Recent Advances in Vascular Imaging.

Recent advances in vascular imaging have enabled us to uncover the underlying mechanisms of vascular diseases both ex vivo and in vivo. In the past decade, efforts have been made to establish various methodologies for evaluation of atherosclerotic plaque progression and vascular inflammatory changes in addition to biomarkers and clinical manifestations. Several recent publications in Arteriosclerosis, Thrombosis, and Vascular Biology highlighted the essential roles of in vivo and ex vivo vascular imaging, including magnetic resonance image, computed tomography, positron emission tomography/scintigraphy, ultrasonography, intravascular ultrasound, and most recently, optical coherence tomography, all of which can be used in bench and clinical studies at relative ease. With new methods proposed in several landmark studies, these clinically available imaging modalities will be used in the near future. Moreover, future development of intravascular imaging modalities, such as optical coherence tomography-intravascular ultrasound, optical coherence tomography-near-infrared autofluorescence, polarized-sensitive optical coherence tomography, and micro-optical coherence tomography, are anticipated for better management of patients with cardiovascular disease. In this review article, we will overview recent advances in vascular imaging and ongoing works for future developments.

World Trade Center-Cardiorespiratory and Vascular Dysfunction: Assessing the Phenotype and Metabolome of a Murine Particulate Matter Exposure Model

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-PET), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flow-velocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M post-exposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after PM-exposure. Similarly, α-smooth muscle actin(α-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. Our study shows persistent WTC-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after PM exposure. Early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets.

Retinal vascular inflammatory and occlusive changes in infectious and non-infectious uveitis.

Retinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated. Retrospective. We investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal necrosis, cytomegalovirus retinitis, human T-cell lymphotropic virus type 1-associated uveitis, toxoplasmic retinitis, syphilitic uveitis, rubella virus-associated uveitis, fungal endophthalmitis, and bacterial endophthalmitis) or NIU (sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada disease, human leukocyte antigen-B27-associated uveitis, systemic lupus erythematosus retinopathy, psoriatic uveitis, rheumatoid arthritis/collagen disease-associated uveitis, multiple sclerosis-associated uveitis, and sympathetic ophthalmia). All patients underwent fluorescein angiography (FA) and color photography examinations of the fundus. Presence of inflammatory and occlusive changes was determined by FA images. Significantly higher positive ratios of phlebitis, vein sheathing, vein occlusion, arteritis, artery sheathing, artery occlusion, and avascular areas were observed in the IU group than in the NIU group (p < 0.05). Notably, the discrepancy between IU and NIU was prominent with regard to retinal arterial changes (arteritis [57.9% vs 11.2%], inflammatory artery sheathing [33.7% vs 0%], and artery occlusion [22.1% vs 3.7%], respectively; p < 0.0001). Findings of vasculitis and occlusion, especially in retinal arteries, in FA strongly suggest an infectious origin of active uveitis.

Comparative study on hemato-biochemical alterations and selected acute phase protein response in native sheep experimentally infected with bluetongue virus serotypes 10 and 24

Bluetongue (BT) is an infectious, non-contagious, insect-transmitted viral disease of sheep, other domestic, and wild ruminants caused by bluetongue virus (BTV), a prototype species of the genus Orbivirus of the family Reoviridae. The study was designed to determine the hematological and biochemical alterations and acute phase protein response in BTV sero-negative sheep experimentally infected with bluetongue virus serotype-10 and 24. The BTV-infected group comprising of 18 animals, 6 each inoculated with 6 ml of clarified virus containing 1 × 106/ml TCID50 of BTV-10 or 24 by intradermal route, 6 animals inoculated with equal volumes of BTV-10 and 24 and 4 animals with 6 ml of mock infected culture fluid served as uninfected control group. The blood and serum samples were analyzed at 0, 1, 3, 7, 11, and 16 days post-infection (DPI). Hematological findings in this study showed a significant decrease in the total number of white blood cells in BTV-10 infected group, a significant increase in circulating neutrophils decrease in lymphocytes in all the infected groups, in PCV in BTV-24 and co-infected groups, and RBC count in only BTV-24-infected group at 11 DPI. The results of serum biochemical analyses of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) exhibited increased levels in BTV-24 and co-infected animals. A significant rise in the serum level of creatine kinase (CK) was observed from 3 DPI in the infected groups. Serum levels of total proteins decreased significantly at 11 DPI in BTV-24 infected animals. Significant increase in CRP and fibrinogen levels was observed at 7 and 11 DPI in the infected groups. The significantly decreased levels of TLC, hemoglobin, PCV, CK, and acute phase proteins such as fibrinogen and CRP indicated the inflammatory changes associated with the virus replication and the consequent vascular damage and inflammatory changes in the tissues. Further, the variations in the hemato-biochemical and acute phase response observed between the two serotypes BTV-10 and 24 probes to the difference in virulence and pathogenesis of the serotypes in infected sheep.

SSeCKS/Gravin/AKAP12 Inhibits PKCζ-Mediated Reduction of ERK5 Transactivation to Prevent Endotoxin-Induced Vascular dysfunction.

SSeCKS/Gravin/AKAP12 is a protein kinase C (PKC) substrate that inhibits the activity of PKC through binding with it. SSeCKS is expressed in vascular endothelial cells (ECs). The atypical PKC isoform ζ (PKCζ) is a pathologic mediator of endothelial dysfunction. However, the functional significance of SSeCKS/PKCζ dimerization in the vascular endothelium remains poorly understood. Given this background, we investigated the effects of SSeCKS on endothelial dysfunction and elucidated the possible mechanism involved. Vascular endothelial dysfunction and inflammatory changes were induced by treatment with bacterial endotoxin lipopolysaccharide (LPS, a vascular endothelial toxicity inducer). LPS can increase the level of SSeCKS. However, we also found that depletion of SSeCKS aggravated the LPS-induced vascular endothelial dysfunction, upregulated pro-inflammatory proteins and phosphorylation level of PKCζ, increased ROS formation, decreased extracellular-signal-regulated kinase 5 (ERK5) transcriptional activity, and reduced eNOS expression. Further examination revealed that depletion of SSeCKS increased PKCζ/ERK5 dimerization. These findings provide preliminary evidence that the expression of SSeCKS induced by LPS, as a negative feedback mechanism, has the potential to improve endothelium-dependent relaxation in vascular disease conditions by inhibiting PKCζ-mediated reduction of ERK5 transactivation.

Histomorphometric Comparative Analysis between Oral Dysplastic Potentially Malignant Disorders and Oral Squamous Cell Carcinoma

Objective This study aimed to determine the correlation between the vascular mast cells and inflammatory changes in the potentially malignant disorders, compared to the oral squamous cell carcinoma (OSCC) in varying degrees of dysplasia. Materials and Methods Thirty samples were selected: 10 of OSCC, 10 of oral leukoplakia, and 10 of actinic keratosis. The toluidine blue technique was used on the mast cells, and hematoxylin and eosin were used for analyzing the lymphocytes, mitosis, and vessels. The quantification was performed using the ImageJ software after obtaining the images by light microscopy with a × 40 objective. Analysis of variance with p < 0.05 was considered for statistical significance. Results Mast cells ( p < 0.0158), vessels ( p < 0.9431), lymphocytes ( p < 0.0001), and mitoses ( p < 0.0009) were found in OSCC. In potentially malignant disorders, a lower density of these structures and a higher concentration of mitosis in the actinic keratosis were observed. Conclusion The results showed evidence of a positive correlation between mast cells and vascularization in the OSCC, suggesting the aggression of the disease. Intense inflammatory infiltrate indicates that other molecular events are involved in the carcinogenesis process, and further studies are necessary for a better understanding of it.

Involvement of P2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion.

Antiplatelet drugs, frequently used for cardiovascular events with thrombotic involvement, are also regarded as possible promising agents for cardiovascular primary prevention. The roles of P2Y12, an ADP receptor and the target of thienopyridine antiplatelet drugs, are not satisfactorily known in the vascular wall. We investigated the hypothesis that vascular smooth muscle cell (VSMC) P2Y12 is involved in vascular wall inflammatory changes by upregulating monocyte chemoattractant protein-1 (MCP-1) and promoting monocyte adhesion. ADP at 10(-5) M induced a 3.6 ± 0.3-fold upregulation of MCP-1 mRNA in cultured rat VSMCs, which was significantly inhibited by R-138727, the active metabolite of P2Y12 inhibitor prasugrel and siRNAs against P2Y12. ADP also induced MCP-1 protein upregulation, which was diminished by R-138727 and P2Y12 siRNAs. JNK (c-Jun NH2-terminal kinase) inhibition attenuated ADP-induced MCP-1 mRNA and protein upregulation. R-138727 and P2Y12 siRNAs inhibited ADP-induced JNK activation. The reactive oxygen species (ROS) inhibitors N-acetylcysteine (NAC), diphenyleneiodonium (DPI), and Tempol also diminished MCP-1 upregulation and JNK activation induced by ADP. ADP induced MCP-1 promoter activation, which was inhibited by R-138727 and P2Y12 siRNAs. Nuclear factor-κB (NF-κB) consensus sites in the MCP-1 promoter region were involved in this activation. ADP-induced NF-κB pathway activation, examined by a plasmid containing multiple NF-κB sites, was diminished by P2Y12 inhibition. For cellular function analysis, stimulation of VSMC with ADP increased subsequent THP-1 monocyte adhesion. P2Y12 siRNAs and CCR2 antagonism diminished this ADP-induced monocyte adhesion. These data suggested that ADP, via the VSMC P2Y12 receptor, induces vascular inflammatory changes by upregulating MCP-1 and promoting monocyte adhesion.

The Inflammatory Preatherosclerotic Remodeling Induced by Intermittent Hypoxia Is Attenuated by RANTES/CCL5 Inhibition

The highly prevalent obstructive sleep apnea syndrome (OSA) with its main component intermittent hypoxia (IH) is a risk factor for cardiovascular mortality. The poor knowledge of its pathophysiology has limited the development of specific treatments, whereas the gold standard treatment, continuous positive airway pressure, may not fully reverse the chronic consequences of OSA and has limited acceptance in some patients. To examine the contribution of IH-induced inflammation to the cardiovascular complications of OSA. We investigated systemic and vascular inflammatory changes in C57BL6 mice exposed to IH (21-5% Fi(O(2)), 60-s cycle) or normoxia 8 hours per day up to 14 days. Vascular alterations were reassessed in mice treated with a blocking antibody of regulated upon activation, normal T-cell expressed and secreted (RANTES)/CC chemokine ligand 5 (CCL5) signaling pathway, or with the IgG isotype control throughout the IH exposure. IH induced systemic inflammation combining increased splenic lymphocyte proliferation and chemokine expression, with early and predominant RANTES/CCL5 alterations, and enhanced splenocyte migration toward RANTES/CCL5. IH also induced structural and inflammatory vascular alterations. Leukocyte-endothelium adhesive interactions were increased, attested by leukocyte rolling and intercellular adhesion molecule-1 expression in mesenteric vessels. Aortas had increased intima-media thickness with elastic fiber alterations, mucoid depositions, nuclear factor-κB-p50 and intercellular adhesion molecule-1 overexpression, hypertrophy of smooth-muscle cells overexpressing RANTES/CCL5, and adventitial-periadventitial T-lymphocyte infiltration. RANTES/CCL5 neutralization prevented both intima-media thickening and inflammatory alterations, independently of the IH-associated proatherogenic dyslipidemia. Inflammation is a determinant mechanism for IH-induced preatherosclerotic remodeling involving RANTES/CCL5, a key chemokine in atherogenesis. Characterization of the inflammatory response could allow identifying at-risk patients for complications, and its pharmacologic manipulation may represent a potential complementary treatment of sleep apnea consequences.

POC07 Central nervous graft-vs-host disease causing intracranial vasculopathy

Graft-vs-host-disease (GVHD) can complicate allogeneic bone marrow transplantation (BMT) and usually targets host skin, liver and gut. Reports of central nervous system (CNS) GVHD are very rare and diagnosis is...

The Biochemical Basis of Hydroxymethylglutaryl-CoA Reductase Inhibitors as Neuroprotective Agents in Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) has the highest morbidity and mortality rates of all types of stroke. Many aneurysmal SAH patients continue to suffer from significant neurological morbidity and mortality directly related to delayed cerebral ischemia. Pilot clinical studies of the use of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) in aneurysmal SAH patients have reported a reduction in delayed cerebral ischemia and better clinical outcomes. We review the biochemical effects of statins on endothelium vascular function, glutamate-mediated neurotoxicity, inflammatory changes, and oxidative injuries, with reference to their possible neuroprotective effects in aneurysmal SAH.

Takayasu's arteritis with associated aortic insufficiency and coronary ostial obliteration

To describe the presentation, assessment, and management of Takayasu's arteritis (TA), a rare vascular condition exhibited predominantly in females in their second and third decades of life. Thorough review of current scientific literature was obtained from electronic databases and medical journals (CINAHL and PubMed). A case study is presented to illustrate TA, which was reviewed and approved by the Human Subjects Committee for the release of protected health information. Clinical presentation of TA varies depending on the location of vessel involvement. Diagnosis is challenging because of the complex pathogenesis of TA. The chronic nature of TA requires ongoing evaluation and adjustment of medication regimens. The patient's quality of life is improved with maintenance of TA in a quiescent state. Presentation of a young woman with symptoms suggestive of vascular inflammatory changes should prompt consideration of TA within the differential diagnosis.

Transient cortical blindness after heart surgery in a child patient -A case report-

Visual loss occurring after pediatric cardiac surgery employing cardiopulmonary bypass (CPB) is relatively rare but the risk is substantial. Compromised cerebral perfusion due to a CPB related micro-embolization and inflammatory vascular changes as well as reduced oxygen carrying capacity in hemodilution and hypothermia during CPB might be major contributing factors to the development of postoperative visual loss after cardiac surgery with CPB. A case of immediate but transient postoperative visual loss was encountered in a 21-month-old male who underwent tricuspid valve surgery. Despite routine intraoperative measures to maintain an adequate perfusion pressure throughout the procedure, postoperative computed tomography revealed a subacute infarct in his occipital lobe. Recovery began on postoperative day 28, and the patient's vision was restored by 31 days.

Astrocytic and microglial response and histopathological changes in the brain of horses with experimental chronic Trypanosoma evansi infection

This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.