Complex Evaluation of Tissue Factors in Pediatric Cholesteatoma

The aim of this study was to describe the appearance and distribution of tissue remodeling markers (MMP-2, MMP-9, TIMP-2, TIMP-4), Sonic hedgehog gene protein (Shh), pro- and anti-inflammatory cytokines (IL–1, IL–10), transcription factor (NF-κβ), proliferation marker (Ki–67), angiogenetic factor (VEGF), tissue defensins (HβD–2, HβD–4) of the pediatric cholesteatoma. Sixteen cholesteatoma samples were obtained from children, eleven skin controls from cadavers. Tissues were stained for MMP-2, MMP-9, TIMP-2, TIMP-4, Shh, IL–1, IL–10, NF-κβ, Ki–67, VEGF, HβD–2, HβD–4. Non-parametric statistic, Mann–Whitney, and Spearman’s coefficient was used. A statistically significant difference was seen between Shh and HβD–2 in perimatrix and control connective tissue, between NF-κβ in cholesteatoma and control skin, and between HβD–4 in matrix and skin epithelium. Complex intercorrelations between MMPs, NF-κβ and VEGF cause the intensification of angiogenesis in cholesteatoma. The persistent increase in Shh gene protein expression in cholesteatoma perimatrix suggests the stimulation of the cholesteatoma growth in children. Similar expression of IL-1 and IL-10 and their intercorrelation, proves there is a balance between pro- and anti-inflammatory cytokines. NF-κβ, and not Ki-67, seems to be the main inducer of cellular proliferation. The main antimicrobial protection is provided by HβD-2.

Analysis of the Chemical Profiles and Anti-S. aureus Activities of Essential Oils Extracted from Different Parts of Three Oregano Cultivars

The use of antibiotics in the food industry is highly regulated owing to the potential harmful effects of antibiotics on human health. Therefore, it is crucial to seek alternatives for ensuring food safety. Essential oils (EOs) extracted from plants of the genus Origanum exhibit a wide range of chemical and antibacterial activities. Species and tissue factors shape the production and accumulation processes of EOs in Origanum plants, thereby affecting their bactericidal activity. In this study, the morphologies and EO yields from the inflorescences, leaves, and stems of three oregano cultivars were evaluated. In addition, the chemical compositions and antibacterial abilities of oregano EOs (OEOs) were assessed. The results showed that OEOs from the different parts of the plant displayed only minor differences in chemical composition, whereas the yield of EOs varied considerably. Additionally, the chemical profiles of OEOs differed significantly among cultivars. The carvacrol content in the OEOs was closely related to its activity against Staphylococcus aureus; the antibacterial properties of the OEOs were further verified using carvacrol. These findings suggested that OEOs possessing high antibacterial activity may have the potential to be developed as bactericides in the food industry.

Metastatic carcinoma of the lung presenting as jugular venous thrombosis: a valuable clinical lesson

Thromboses of the upper extremity and neck are rare and not as commonly seen as lower extremity deep vein thrombosis (DVT). Internal jugular vein thrombosis (IJVT) is a serious condition with a potentially fatal outcome. Jugular vein thrombosis refers to the formation of intraluminal thrombi anywhere from the intracranial part of the jugular vein to the junction between the internal jugular vein (IJV) and subclavian vein. The relationship between malignancy and thromboembolic disorders has been well established, as Trousseau first described it in 1865. Tumor cells are known to promote hypercoagulability by expressing tissue factors that activate clotting cascades and procoagulants while promoting interactions between the tumor cells, platelets, and endothelial cells via different cytokines, tumor antigens, and their immune complexes. We are reporting our encounter with a patient who presented with extensive left internal jugular vein thrombosis as the first presenting sign of primary lung malignancy.

Management of peri-prosthetic joint infection and severe bone loss after total hip arthroplasty using a long-stemmed cemented custom-made articulating spacer (CUMARS)

Background There is little evidence on techniques for management of peri-prosthetic infection (PJI) in the context of severe proximal femoral bone loss. Custom-made articulating spacers (CUMARS) utilising cemented femoral stems as spacers was described providing better bone support and longer survival compared to conventional articulating spacers. We retrospectively report our experience managing PJI by adaptation of this technique using long cemented femoral stems where bone loss precludes use of standard stems. Methods Patients undergoing 1st stage revision for infected primary and revision THA using a cemented long stem (> 205 mm) and standard all-polyethylene acetabulum between 2011 and 2018 were identified. After excluding other causes of revision (fractures or aseptic loosening), Twenty-one patients remained out of total 721 revisions. Medical records were assessed for demographics, initial microbiological and operative treatment, complications, eradication of infection and subsequent operations. 2nd stage revision was undertaken in the presence of pain or subsidence. Results Twenty-one patients underwent 1st stage revision with a cemented long femoral stem. Mean follow up was 3.9 years (range 1.7–7.2). Infection was eradicated in 15 (71.4%) patients. Two patients (9.5%) required repeat 1st stage and subsequently cleared their infection. Three patients (14.3%) had chronic infection and are on long term suppressive antibiotics. One patient (4.8%) was lost to follow up before 2 years. Complications occurred in seven patients (33%) during or after 1st stage revision. Where infection was cleared, 2nd stage revision was undertaken in 12 patients (76.5%) at average of 9 months post 1st stage. Five (23.8%) CUMARS constructs remained in-situ at an average of 3.8 years post-op (range 2.6–5.1). Conclusions Our technique can be used in the most taxing of reconstructive scenarios allowing mobility, local antibiotic delivery, maintenance of leg length and preserves bone and soft tissue, factors not afforded by alternative spacer options.

The Pathology of Lymphocytes, Histiocytes, and Immune Mechanisms in Mycobacterium tuberculosis Granulomas

Granuloma formation is the pathologic hallmark of tuberculosis. Few studies have detailed the exact production of cytokines in human granulomatous inflammation and little is known about accessory molecule expressions in tuberculous (TB) granulomas. We aimed to identify some of the components of the immune response in granulomas in HIV-positive and -negative lymph nodes. We investigated the immunohistochemical profiles of CD4+, CD8+, CD68+, Th-17, Forkhead box (FOXP3) cells, accessory molecule expression (human leukocyte antigen [HLA] classes I and II), and selected cytokines (interleukins 2, 4, and 6 and interferon-γ) of various cells, in granulomas within lymph nodes from 10 HIV-negative (−) and 10 HIV-positive (+) cases. CD4+ lymphocyte numbers were retained in HIV− granulomas, whereas CD4+:CD8 + cell were reversed in HIV+ TB granulomas. CD68 stained all histiocytes. Granulomas from the HIV+ group demonstrated a significant increase in FOXP3 cells. Interleukin-2 cytoplasmic expression was similar in both groups. Interferon-gamma (IFN-γ) expression was moderately increased, IL-6 was statistically increased and IL-4 expression was marginally lower in cells from HIV− than HIV+ TB granulomas. Greater numbers of cells expressed IFN-γ and IL-6 than IL-2 and IL-4 in HIV− TB granulomas. This study highlights the varied cytokine production in HIV-positive and -negative TB granulomas and indicates the need to identify localized tissue factors that play a role in mounting an adequate immune response required to halt infection. Although TB mono-infection causes variation in cell marker expression and cytokines in granulomas, alterations in TB and HIV coinfection are greater, pointing toward evolution of microorganism synergism.

EXPRESSION OF MARKERS OF HYPOXIA, ANGIOGENESIS, AS MICROCIRCULATORY-TISSUE FACTORS IN PROLIFERATIVE PROCESSES OF THE ENDOMETRIUM

The aim of the study – to learn the expression of VEGF and HIF-1α in physiological, hyperplastic, atypical endometrium at different ages of women. Materials and Methods. Evaluation of VEGF expression and HIF-1α performed in endometrial tissue samples in 458 women of late reproductive, perimenopausal and postmenopausal age. Expression of VEGF and HIF-1α was performed at the mRNA level by polymerase chain reaction of cDNA obtained by reverse transcription. The results were processed by the method of variation statistics with the assessment of reliability according to the Student's criterion using standard computer systems. Results and Discussion. Analyzing the data of the presented work, higher VEGF expression rates were found in atypical hyperplasia in all age categories, but probably higher rates were found in the postmenopausal period, in atypical endometrial hyperplasia, which indicates the need for vigilance in detecting this process in the appropriate age category. Studies have shown that HIF-1α can potentiate the activation of vasomotor genes that are required for the vascular response to hypoxia. These studies demonstrate the informativeness of the method of determining HIF-1α in the examination of patients with endometrial hyperplastic processes (EHP). The introduction of this method in practical medicine will not only understand the details of the changes occurring in the body (pathological, physiological), but also develop strategic maneuvers for possible therapeutic or surgical treatments. Conclusions. Expression of VEGF and HIF-1α levels in endometrial tissue cells as a marker can be a promising method for diagnosing the risk of proliferative conditions and their prognosis, especially in combination with other markers that characterize immunohistochemical and molecular genetic cellular parameters. Hypoxia and its relationship with indicators of angiogenesis may have some promising significance. Because the development of pathological conditions develops at a certain stage of hypoxic conditions. Under certain conditions, as a result of disruption of tissue processes, possibly metabolic, changes in angiogenesis are reduced with increasing hypoxia, which may in the long run provoke atypical disorders.

Eosinophil: A central player in modulating pathological complexity in asthma

Eosinophils are the major inflammatory cells which play a crucial role in the development of allergic and non-allergic asthma phenotypes. Eosinophilic asthma is the most heterogeneous phenotype where activated eosinophils are reported to be significantly associated with asthma severity. Activated eosinophils display an array of cell adhesion molecules that not only act as an activation marker, suitable for assessing severity, but also secrete several tissue factors, cytokines and chemokines which modulate the clinical severity. Eosinophil activations are also strictly associated with activation of other hetero cellular populations like neutrophils, macrophages, mast cells, and platelets which culminate in the onset and progression of abnormal phenotypes such as bronchoconstriction, allergic response, fibrosis instigated by tissue inflammation, epithelial injury, and oxidative stress. During the activated state, eosinophils release several potent toxic signaling molecules such as major basic proteins, eosinophil peroxidase, eosinophil cationic protein (ECP), and lipid mediators, rendering tissue damage and subsequently leading to allergic manifestation. The tissue mediators render a more complex manifestation of a severe phenotype by activating prominent signaling cross-talk. Here, in the current review with the help of search engines of PubMed, Medline, etc, we have tried to shed light and explore some of the potent determinants regulating eosinophil activation leading to asthma phenotype.

Characterization of Pro- and Anti-Inflammatory Tissue Factors in Rosacea: A Pilot study

Rosacea is a chronic inflammatory skin disease mainly affecting the facial skin. Our aim was to determine the appearance of pro- and anti- inflammatory cytokines in rosacea-affected facial tissue. Materials and Methods: Rosacea tissue were obtained from eight patients (aged 35 to 50 years). The control group (CG) included four facial skin samples (49 to 70 years). Routine staining and immunohistochemistry for IL-1, IL-10, LL-37, HBD-2, and HBD-4 proceeded. Results: Inflammation was observed in all the rosacea samples. A statistically significant difference was seen between epithelial HBD-2 positive cells in comparison to the control. There was a strong positive correlation between HBD-4 in the epithelium and HBD-4 in the connective tissue, IL-10 in the epithelium and IL-1 in the connective tissue, and IL-1 in the epithelium and IL-10 in the connective tissue. Conclusion: Increased levels of IL-10 and decreased levels of IL-1 show the balance between anti- and pro-inflammatory tissue responses. A significant amount of HBD-2 in the epithelium proves its important role in the local immune response of rosacea-affected tissue. The last effect seems to be intensified by the elevated level of LL-37 in the epithelium.

Evaluating the levels of D-dimer as a primary marker in oral cancers using immunoturbidimetric assay: The original research

Objectives: Oral cancer is major health threat; with 90% mortality and ranks sixth among worldwide cancers. So to overcome this mortality; newer bio-markers are explored and one of such biomarker is D-dimer, which is end product of fibrinogen formed by plasmin. The raised levels of D-dimer play significant role in proliferation and progress of cancer cells. In cancers D-dimer is formed by dual action, where UPA (Urokinase type Plasminogen Activator) and Tissue factor play important role simultaneously. To understand correlation between D- dimer and oral cancers, by immunoturbidimetry; quantitative assay. Material and Methods: After obtaining consents of patients and Institutional ethical clearance, we randomly selected; age and sex matched; 216 samples. Further these samples were subdivides as oral cancer group and control group, consisting 108 samples in each group respectively. Results: Statistical analysis was done; using SPSS version 20, unpaired -T test, and one way ANOVA were applied. Plasma D-dimer levels were; 497.32±872.28μl/ml and 165.30±150.43 28μl/ml, among cancer and control groups respectively, (P≤ 0.0001), which was statistically highly significant. Conclusion: D-dimer is altered during carcinogenesis by activation of UPA and Tissue factors, and this distinguishes form routine levels of D-dimer. This suggests that, cancer cell biology is greatly affected by D-dimer levels during growth and spread of cancers. So raised levels of D-dimer can be considered during interventions of cancers, and incorporated as a biomarker. However for its scientific applications; there is need of further study, with collaborative approach and larger samples, to restrict cancer related mortalities.