Assessment of Neutrophil Extracellular Traps (NETs) and Macrophage Ratio in the Inner and Outer Area of Carotid Artery Stenosis.

Background & Objective: It is noteworthy that majority of the data links neutrophil extracellular traps (NETs) to human arterial thrombosis. In the current study, extracellular neutrophil networks and macrophage polarization were assessed in the area outside and inside the Carotid artery stenosis. Methods: The sample of Carotid plaque of the patient was divided into two halves with a transverse incision; the terms inner part and outer part were used for the plaque's inner part and the adjacent area. Samples were sorted in 10% formalin for CD163, CD11c, MPO, and histone H3 immunohistochemical assessment, while part of the sample was stored at -80°C for western blotting assay for PDA4 marker. Results: Results of this study showed that the extracellular neutrophil in the inner part of the Carotid plaque was significantly increased (P<0.0001), while the number of M1 and M2 macrophages was higher in the inner part compared with the outer part of the Carotid plaque (P<0.0001). Conclusion: The distribution of NETs and the ratio of macrophages may be different in the inner and outer aspects of arterial plaque.

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series.

BACKGROUND: Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger's disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD. METHODS: Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: Raynaud's phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud's phenomenon (p> 0.05). CONCLUSION: There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.

Different types of cell death in vascular diseases.

In a mature organism, tissue homeostasis is regulated by cell division and cell demise as the two major physiological procedures. There is increasing evidence that deregulation of these processes is important in the pathogenicity of main diseases, including myocardial infarction, stroke, atherosclerosis, and inflammatory diseases. Therefore, there are ongoing efforts to discover modulating factors of the cell cycle and cell demise planners aiming at shaping innovative therapeutically modalities to the therapy of such diseases. Although the life of a cell is terminated by several modes of action, a few cell deaths exist-some of which resemble apoptosis and/or necrosis, and most of them are different from one another-that contribute to a wide range of functions to either support or disrupt the homoeostasis. Even in normal physiological conditions, cell life is severe within the cardiovascular system. Cells are persistently undergoing stretch, contraction, injurious metabolic byproducts, and hemodynamic forces, and a few of cells sustain decade-long lifetimes. The duration of vascular disease causes further exposure of vascular cells to a novel range of offences, most of which induce cell death. There is growing evidence on consequences of direct damage to a cell, as well as on responses of adjacent and infiltrating cells, which also have an effect on the pathology. In this study, by focusing on different pathways of cell death in different vascular diseases, an attempt is made to open a new perspective on the therapeutic goals associated with cell death in these diseases.

The effect of platelet-rich plasma-fibrin glue dressing in combination with oral vitamin E and C for treatment of non-healing diabetic foot ulcers: a randomized, double-blind, parallel-group, clinical trial.

OBJECTIVE: The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS: This randomized controlled trial was performed on 25 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for 8 weeks. RESULTS: Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention and control groups (p < 0.05). This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) , ESR, and hs-CRP was observed in the intervention group compared to the control group (p < 0.05). CONCLUSION: Our results showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).

Cytokine Analysis in Patients with Different Stages of Thromboangiitis Obliterans.

BACKGROUND: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases. OBJECTIVE: The changes in transforming growth factor ß (TGFß), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptoms were investigated in this research. METHODS: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital, from the year 2012 to 2016. They were then categorized into three groups: Mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFß, IL6, TNFα, and IFNγwere determined by the ELISA method and compared among the groups. RESULTS: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFß and IL6 were dysregulated as the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant (p > 0.05). In the multiple logistic regression model, increased TNFα levels were seen in the presence of moderate symptoms as compared to the severe ones (p < 0.05). CONCLUSION: It could be concluded that TNFα, as part of the defining cytokineproduction profile of T helper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.

The Association of HLA-A, B and DRB1 with Buerger's Disease.

BACKGROUND: Thromboangiitis obliterans (TAO), also known as Burger's disease, is a devastating disease affecting the arteries and veins of the upper and lower distal limbs most commonly afflicting young male smokers of low socioeconomic status. The expression of human leukocyte antigen (HLA)-A, B and -DRB1 genes have been implicated in the pathogenesis of TAO. Our study aimed to examine the association of different HLA-A, B and -DRB1 genes in TAO patients in the Iranian population. METHODS: A case-control study examining 55 Iranian patients with TAO and 500 healthy subjects was performed in Imam Reza hospital, Mashhad, Iran. The prevalence of major histocompatibility complex (MHC) class I (-A, -B) and class II (-DRB) alleles were determined for each participant. RESULTS: Our results revealed the HLA-A*03 (odds ratio [OR]=5.394), HLA-A*24 (OR=5.143), HLA-A*31 (OR=4.251), HLA-A*11 (OR=3.034), HLA-B*27 (OR=6.680), HLA-B*15 (OR=3.959), HLA-B*07 (OR=3.698), HLA-B*51 (OR=3.370), HLA-B*44 (OR=3.326), HLA-DRB1*16 (OR=20.583), HLADRB1* 04 (OR=8.960), HLA-DRB1*14 (OR=3.746), HLA-DRB1*03 (OR=2.303), and HLA-DRB1*15 (OR=2.111) alleles to occur at a significantly higher frequency in TAO patients compared to controls (p<0.05). The HLA-A*25, HLA-A*66, HLA-DRB1*08, HLA-DRB1*10, and HLA-DRB1*12 alleles resulted in infinite OR, and was associated with an increased risk of TAO. However, the alleles HLA-A*30, HLA-B*08, HLA-B*45, HLA-B*46, and HLA-B*53 were associated with a protective role against TAO with an OR = 0. CONCLUSION: This is the first study examining the HLA pattern in patients with Burger's disease in the Iranian population. Our findings have revealed an association between HLA class I and II alleles with TAO.

Molecular mechanisms regulating immune responses in thromboangiitis obliterans: A comprehensive review.

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive as well as an inflammatory peripheral vascular disease with unknown etiology. Recent evidence has supported the immunopathogenesis of the disease, however, the factors contributing to the altered immune function and vascular tissue inflammation are still unclear. This review was intended to collate the more current knowledge on the regulatory molecules involved in TAO from an immunoreactive perspective. The homeostasis of the immune system as well as a variety of progenitor cell populations appear to be affected during TAO and these alterations are associated with intrinsic signaling defects that are directing to an improved understanding of the crosstalk between angiogenesis and the immune system, as well as the potential of new co-targeting strategies applying both immunotherapy and angiogenic therapy.

Limb complaints after autogenous arteriovenous fistula creation in chronic hemodialysis patients.

Placement of autogenous arteriovenous fistula (AVF) is one of the basic needs in hemodialysis patients. Although many studies have investigated the complications of AVF placement, the complaints expressed by patients have not been studied in a long-term study. The purpose of this study was to evaluate the incidence of complaints after placement of autogenous AVF in patients undergoing chronic hemodialysis. This cohort study was conducted on patients with end-stage renal disease undergoing AVF placement who were referred to Imam Reza hospital in Mashhad, Iran, from January 2015 to June 2016. The AVFs were placed in all patients and incidence rates of expressed complaints, including pain, paresthesia, and edema, were assessed up to three periods 1 month after surgery and three periods 2 months after starting use of the AVF. Data were analyzed using SPSS software, version 19. The relationship of AVF types with each of the outcomes was analyzed via χ2 test. Three hundred and eighty-eight patients (222 males and 166 females; mean age 54.3 ± 16.0 years) were studied. AVF was established in the cubital site of 230 patients, in snuff box of 103 patients, and distal forearm of 55 patients. Total incidence rate of pain within six follow-up periods and incidence rates of paresthesia and edema were determined as 18.1%, 2.6%, and 5.4%, respectively. A statistically significant relationship was observed between types of AVF and pain and paresthesia (P < .05). According to results from this study, pain and then edema were the most common complaints, followed by AVF placement in the patients. Paresthesia had lower incidence rates compared to other complaints.

Serum Lipid Changes after Short Term SIPC Therapy for Lower Limb Lymphedema.

Lymphedema is a ubiquitous chronic disease with various suggested treatment options, but no definite treatment. Using (Sequential) Intermittent Pneumatic Compression (SIPC) is one of the most appropriate non-surgical treatments without any noticeable complications. In this study, we evaluated the serum lipids changes following SIPC. Participants included 40 lower limb lymphedema patients who underwent High Pressure SIPC for a period of 48 hrs. Pre and Post SIPC serum lipids changes were evaluated. Though, there was some increase in the serum level of cholesterol and triglyceride, none of the patients had the values above the normal range. We concluded that, the fluid entering the serum during SIPC, contain large molecules such as lipids, which increases serum lipid levels. However this phenomenon does not have any significant complication for the patients.