Mast Cell Density Research Articles

Correlation of Mast Cell Density With Angiogenic Cytokines in Patients With Active Multiple Myeloma

PurposeThe aim of the study is to estimate whether bone marrow mast cell density (MCD) in multiple myeloma (MM) correlates with circulating levels of various angiogenic factors. MethodsIn 70 patients with newly diagnosed active MM, we measured MCD using immunohistochemical stain for tryptase and serum levels of matrix metalloproteinase 9 (MMP-9), angiopoietin 2 (ANGIOP-2), and angiogenin (ANG) with ELISA. FindingsLevels of MCD, ANGIOP-2, and ANG were significantly higher in MM patients compared with the control group. The MMP-9 level was higher in MM patients compared with the control group but without statistical significance. All values were increasing in parallel with clinical stages. Furthermore, MCD correlated positively with MMP-9, ANGIOP-2, and ANG. ImplicationsMCs participate in the angiogenic processes of MM, with complex implicated mechanisms. This interplay between MCs and the other participants favors angiogenesis and MM growth.

Dietary treatment modulates mast cell phenotype, density, and activity in adult eosinophilic oesophagitis.

Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic oesophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. To define the phenotype of oesophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. Oesophageal mucosal samples from 10 adult patients with EoE obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analysed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. MC density was significantly increased in EoE compared with controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; P < 0.001). The MCTC subtype predominated in the oesophageal mucosa (90%) in both patients with EoE and controls. Gene expression of MC-related proteases, eotaxins, and SCF were up-regulated in patients with EoE, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (ρ = 0.80) in EoE and correlated with the symptom score (ρ = 0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (P < 0.05). MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment.

The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

BackgroundCardiac mast cell (MC) proteases, chymase and tryptase, increase proliferation and collagen synthesis in cultured cardiac fibroblasts. However, the question as to why preventing individually the actions of either protease prevents fibrosis when both are released upon MC activation remains unanswered. Since tryptase has the ability to activate MCs in noncardiac tissues via the protease-activated receptor-2 (PAR-2), there is the possibility that its, in vivo, fibrotic role is due to its ability to induce MC degranulation thereby amplifying the release of chymase. MethodsThis study sought to delineate the interactions between tryptase and chymase in myocardial remodeling secondary to transverse aortic constriction (TAC) for 5weeks in male Sprague–Dawley rats untreated or treated with either the tryptase inhibitor, nafamostat mesilate or MC membrane stabilizing drug, nedocromil (n=6/group). In addition, ventricular slices from 6 rat hearts were incubated with tryptase, tryptase plus nafamostat mesilate or the chymase inhibitor chymostatin for 24h. Results and conclusionThe results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

Study of Mast Cells and Granules from Primo Nodes Using Scanning Ionic Conductance Microscopy

Acupuncture points have a notable characteristic in that they have a higher density of mast cells (MCs) compared with nonacupoints in the skin, which is consistent with the augmentation of the immune function by acupuncture treatment. The primo vascular system, which was proposed as the anatomical structure of the acupuncture points and meridians, also has a high density of MCs. We isolated the primo nodes from the surfaces of internal abdominal organs, and the harvested primo nodes were stained with toluidine blue. The MCs were easily recognized by their stained color and their characteristic granules. The MCs were classified into four stages according to the degranulation of histamine granules in the MCs. Using conventional optical microscopes details of the degranulation state of MCs in each stage were not observable. However, we were able to investigate the distribution of the granules on the surfaces of the MCs in each stage, and to demonstrate the height profiles and three-dimensional structures of the MCs without disturbance of the cell membrane by using the scanning ion conductance microscopy.

Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness.

In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.

Effect of 5-ALA-mediated photodynamic therapy on mast cell and microvessels densities present in oral premalignant lesions induced in rats

Acute inflammatory response after photodynamic therapy is frequently described, and increase on mast cell degranulation is also present during this process. The mast cell activation may improve angiogenesis, and this fact has been associated with progression of oral premalignant lesions (OPL). The aim of this study was to evaluate whether photodynamic therapy (PDT) increases mast cell density (MCD) and microvessels density (MVD) in 4-nitroquinoline-1-oxide(4NQO)-induced OPL in rats. 4NQO-induced OPL were treated or not with 5-ALA followed by laser irradiation (PDT group and 4NQO groups, respectively). Mast cells and CD34+ microvessels were counted. Both PDT and 4NQO groups had MCD and MVD that were higher than normal mucosa (p<0.05). The 4NQO group had the lowest number of non-degranulated MCD in comparison to experimental periods of PDT (PDT 6h – p=0.020; 24h – p=0.016; 48h – p=0.003; 72h – p=0.033). Only in the PDT group did MCD and MVD have a significant correlation (r=0.6219, p=0.010). 5-ALA-mediated PDT modified the MCD and MVD in the induced OPL, leading to degranulation of mast cells and angiogenesis. A PDT protocol with an efficient eradication of the OPL must be adopted considering the angiogenesis potential associated with the mast cell activation after the therapy.

Regular exercise modulates cardiac mast cell activation in ovariectomized rats.

It is well accepted that regular exercise is a significant factor in the prevention of cardiac dysfunction; however, the cardioprotective mechanism is as yet not well defined. We have examined whether regular exercise can modulate the activity of cardiac mast cells (CMC) after deprivation of female sex hormones, as well as the density and percentage degranulation of mast cells, in ventricular tissue of ovariectomized (OVX) rats after an 11-week running program. A significant increase in CMC density with a greater percentage degranulation was induced after ovarian sex hormone deprivation. Increased CMC density was prevented by estrogen supplements, but not by regular training. To the contrary, increased CMC degranulation in the OVX rat heart was attenuated by exercise training, but not by estrogen supplement. These findings indicate a significant correlation between the degree of CMC degranulation and myocyte cross-section area. However, no change in the expression of inflammatory mediators, including chymase, interleukin-6, and interleukin-10, was detected. Taken together, these results clearly indicate one of the cardioprotective mechanisms of regular aerobic exercise is the modulation of CMC activation.

Abstract A70: Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key?

Abstract The goal of the current study is to establish the mechanism by which mast cells may serve as a prognostic factor in and possibly explain the racial disparity associated with prostate cancer. There is increasing evidence for a strong association between chronic inflammation and prostate cancer, and the role of mast cells in prostate cancer are of particular interest as they have been suggested to influence cancer progression and immune modulation. It is well established that prostate cancer presents with significant racial disparities, with African American (AA) men being 65% more likely to be diagnosed with prostate cancer than Caucasian American (CA) men and more than two times as likely to die as a result of prostate cancer. In addition, studies have shown AA men to be significantly more likely to present with inflammation in prostate biopsy samples negative for prostate cancer, while microarray data has suggested that inflammatory pathways are highly represented in the differentially expressed mRNA in the tumors of AA vs CA men. Complicating these results, it is probable that inflammatory cells play varied and multiple roles in different regions and grades within the same cancer. With this in mind, we are currently using immunohistochemistry (IHC) and in-situ hybridization techniques to directly visualize and localize mast cells in the prostate microenvironment. These studies are aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Our preliminary results in a 10 case tissue microarray (TMA) are consistent with other reports in the literature indicating that there are higher mast cell densities in better differentiated cancers; however, we are examining this further in a larger full slide cohort in relation to Gleason grade and stage. We are currently utilizing this image analysis technology on a TMA cohort designed to explore differences in mast cell density in AA vs CA men. Furthermore, we aim to examine differences in mast cell subtypes between benign and malignant regions of the prostate and between AA and CA men. Our goal is to establish the mechanism by which mast cells may serve as a prognostic factor in prostate cancer and may help to explain prostate cancer racial disparities. Citation Format: Heidi A. Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Angelo M. De Marzo, Karen S. Sfanos. Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key? [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A70.

Effects of nerve growth factor antagonist K252a on peritoneal mast cell degranulation: implications for rat postoperative ileus.

Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (POI). Nerve growth factor (NGF) mediates MC degranulation. The aim of the study was to evaluate whether NGF receptor antagonist K252a acts as a MC stabilizer in vitro and in vivo model of POI. Peritoneal mast cells (PMCs) were obtained from Sprague-Dawley rats and were incubated with K252a and exposed to NGF or Compound 48/80 (C48/80). MC degranulation was assessed by β-hexosaminidase assay. POI was induced in rats by intestinal manipulation (IM). Rats were pretreated with K252a (100 μg/kg sc) 20 min prior to POI induction. At 20 min after IM, release of rat mast cell protease 6 (RMCP-6) was evaluated in peritoneal lavage. At 24 h, intestinal transit (IT) and gastric emptying (GE) were evaluated. Ileal inflammation was assessed by myeloperoxidase (MPO) activity, expression of IL-6, NGF, TrkA, RMCP-2 and 6, and MC density within the full-thickness ileum. C48/80 and NGF evoked degranulation of PMCs in a dose-dependent manner. K252a prevented NGF-evoked, but not C48/80-evoked, MC degranulation. IM evoked the release of peritoneal RMCP-6 and subsequently delayed IT and GE. IM increased MPO activity and expression of IL-6. In IM rats, K252a prevented upregulation of IL-6 expression and reduced TrkA. IT, GE, and inflammation were not affected by K252a. K252a inhibited NGF-evoked degranulation of PMCs in vitro. In vivo, K252a decreased IL-6 and PMC degranulation. This may be of relevance for the development of new therapeutic targets for POI.

Histochemical Study of Heparin-positive Mast Cells in the Terminal Part of Porcine Ductus Choledochus and Papilla Duodeni Major.

The study presented in detail the localization and density of mast cells (MCs) in the intramural part of the common bile duct (CBD) and in the major duodenal papilla (MDP) of domestic swine. MCs' density (number/mm(2) ) in different layers of both of the duct and papilla was evaluated after toluidine blue staining. Their number was higher in the lamina propria mucosae than in the tunica muscularis of the studied structures. The localization of berberine-positive, (heparin containing) MCs and the ratio between them and toluidine blue-positive MCs with γ-ma metachromasia was also established. Ratios of heparin-containing MCs in comparison with all toluidine blue-positive MCs were found as follows: ductus choledochus - 32% in the subglandular connective tissue of lamina propria mucosae in the intramural part of the duct; m. sphincter ductus choledochus - 31% in the circular and 0.06% in the longitudinal muscle layer; subserosa - 59%; papilla duodeni major - 0.03% in the subepithelial connective tissue and 34% in the subglandular connective tissue of lamina propria mucosae, respectively. The established large difference in heparin-positive MCs in both the subepithelial and subglandular connective tissues of CBD and MDP, respectively, is an evidence for the existence of mucosal and connective tissue MCs.

Mast cells in relation Helicobacter pylori and chronic active gastritis

Background: Gastritis is commonly reported using several parameters such as infiltration by neutrophils, lymphocytes, intestinal metaplasia, atrophy and Helicobacter pylori. In recent years, mast cells are also suggested in several studies to play central role in development of gastritis. This study tires to look at the relation between the mast cell count and infiltration by neutrophils and Helicobacter pylori.Materials and methods: This is a retrospective study which includes endoscopic gastric biopsies received at the histopathology department of GRP polyclinic that have been diagnosed as chronic gastritis. Clinical information regarding associated gastrointestinal symptoms and conditions were obtained from the medical database. Patients taking antibiotics, proton-pump inhibitors, H2- antagonists, nonsteroidal anti-inflammatory drugs or corticosteroids were excluded from the study. Also excluded are patients with dysplasia or carcinoma. Sections were then stained by H&amp;E and Giemsa for the evaluation of H pylori infection and inflammation. These sections were examined by two pathologists. Mast cells were counted in 1000 epithelial cells in 40x.Three different counts were performed by each pathologists and an average score was taken for every case.Result: A total of 534 cases were included in the study. Mast cells were detected in all the cases. However, mast cells were seen mostly in mild grade 60%. 98% of our cases showed H.pylori positivity and 72% of cases had active gastritis. A positive correlation was found between mast cells density and infiltration by neutrophils as well as Helicobacter pylori infection with significant P value of 0.0001 in each.Conclusion: Mast cells are seen in a significant number of biopsies with gastritis showing positive correlation with neutrophilic infiltration and Helicobacter pylori infection.

Morphological and inflammatory changes in the skin of autopsied fetuses according to the type of stress

IntroductionThe fetal skin acts on the development and activation of the immune response via immune–neuroendocrine communication coordinated by corticotropin-releasing hormone. ObjectiveThis study aimed to evaluate the morphological and inflammatory changes in the skin due to acute stress and chronic stress, associated with perinatal asphyxia, ascending infection and congenital malformation. MethodsWe measured dermal and epidermal thickness, the diameter of keratinocytes, and the percentage of collagen and elastic fibers. Immunohistochemistry was used to evaluate both Langerhans cell and mast cell density, and corticotropin-releasing hormone expression in the epidermis, sebaceous gland, sebaceous duct, sudoriparous gland and in the hair follicle. ResultsThe epidermis was thinner in the cases with perinatal asphyxia, ascending infection and chronic stress. The diameter of keratinocytes was smaller in ascending infection and chronic stress. Mast cell density showed an indirect correlation with gestational age. Corticotropin-releasing hormone expression was significantly higher in ascending infection and chronic stress. ConclusionsChronic stress is associated with immunological and morphological changes in the skin of fetuses with perinatal asphyxia and ascending infection. Thus, corticotropin-releasing hormone seems to play a vital role in the differentiation and activation of innate and adaptive immune cells of the skin of fetuses.

Density of Tryptase-Positive Mast Cells Correlated with the Presence of H. pylori in Gastric Neoplasia.

Gastric cancer continues to be a platoon leader of mortality causes. A significant number of recent studies show direct or indirect involvement of mast cells (MC), with a complex role both pro- and anti-tumor growth. To objectify the correlations between expression of MC and presence of Helicobacter pylori (HP) infection depending on neoplastic nature of the gastric damage. The study was carried out on archival samples of gastric wall from 30 patients with gastric cancer versus 30 age and sex-matched subjects with gastric surgery for non-neoplastic diseases. The inclusion criteria for the case group were histologically proven stage T3/T4 malignancies with regional lymph node metastases. For each case of the study group, distribution and number of MC tryptase positive (DMC-TP) were analyzed in five different areas from the same gastrectomy specimen: intratumor area, deep and side tumor invasion front, normal gastric tissue sample 5-10 cm or more distant from the tumor and furthest resection margin. Independently of HP infection, the study recorded a significantly lower value of DMC-TP in male patients. In regions with inflammatory lesions and preneoplastic changes and in control cases with non-gastric neoplasia, the DMC-TP level was higher than controls with HP-related inflammatory pathology, thus removing bacterial etiology from the forefront of MC mobilizing causes. The presence of H. pylori infection was not found to cause significant changes in terms of mobilizing mast cells in the gastric wall with advanced tumors, with minimal stage III TNM.

Mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea

Abstract The aim of the study was to evaluate the distribution and number of mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea. The highest density of mast cells was found in cystic papillary adenocarcinomas of grade II. Eosinophils were detected only in the cystic papillary adenocarcinoma of grades I and II, in non-invasive cribriform adenocarcinoma and comedo-type carcinoma. Mast cell populations were observed perivascularly in the tumour stroma, in the host tumour interface, as well as in necrotic areas of neoplasms. Mast cells were observed to be intact according to their morphological changes, collectively referred to as degranulation. The obtained results indicate that mast cells and eosinophils play an important role in tumour micro-environment formation. The increased density of these cells in experimentally-induced rat mammary gland tumours suggests a poor prognosis in these cancers. Our results also confirmed that rat mammary gland tumours are good models for the study of breast cancers.

Abstract 2342: Characterization of inflammatory markers and mast cells in association with prostate cancer

Abstract Evidence suggests that there is a strong association between chronic inflammation and prostate cancer development and/or progression. While chronic inflammation is known to serve as an “enabling characteristic” in many cancers, the mechanism whereby it contributes to carcinogenesis and progression is still very controversial. This is particularly true for cells of the innate immune system, such as mast cells, that have been shown to possess both pro- and anti-tumor properties. The role of mast cells in prostate cancer is of particular interest, as evidence suggests that they influence cancer progression and immune modulation. The current study seeks to characterize mast cell density and mast cell-to-epithelial ratio in relation to prostate cancer recurrence using a unique set of tissue microarrays (TMAs) from a case-control study nested in a cohort of prostate cancer patients who underwent radical prostatectomy. These studies are aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Our preliminary results, obtained via analysis of a prostate cancer TMA containing matched cancer and benign tissues from 727 cases of radical prostatectomy patients, correlated with the literature in that the mast cell density (mast cell number/total tissue area) was significantly higher in cancer versus benign (p = 0.0016). We will expanded this study to determine if mast cell number correlates with epithelial area in the same cohort and to examine mast cell density in correlation to the presence, grade, or progression of prostate cancer. Furthermore, we will be examining this in a large full tissue slide cohort in relation to Gleason grade and stage. Finally, we are expanding this study to explore a possible role for mast cells in the racial disparity in prostate cancer incidence and prognosis. Citation Format: Heidi Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Elizabeth A. Platz, Angelo M. DeMarzo, Karen S. Sfanos. Characterization of inflammatory markers and mast cells in association with prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2342. doi:10.1158/1538-7445.AM2015-2342

Abstract 356: Angiotensin II as a Paracrine Factor in Heart Environment

Besides its potent vasoconstrictor action, the Angiotensin II (Ang II) has other important biological roles as autocrine and paracrine actions, being fundamental in cardiovascular homeostasis. Changes in the levels of this substance in the pericardial fluid (PF) are associated with the development of cardiovascular diseases. The aim of this study was to evaluate the presence of members of the classical and alternative pathways of the Renin Angiotensin System (RAS), as well as one of its main effectors peptides, Ang II, in PF of patients with coronary artery disease and assess the role of Ang II as a factor able to promote the process of epithelial-mesenchymal transition epicardial mesothelial cells in genetically modified mice. Male and female patients with coronary artery disease and controls patients were involved in this study. The ELISA’s results showed significant amounts of Ang II, Angiotensin Converting Enzyme (ACE) and chymase in PF coronary artery disease male patients. Chymase positive mast cells were identified by immunohistochemical and quantitative analysis demonstrated a greater density of mast cells in this group. Expression of AT1 and AT2 was detected by immunohistochemistry in patients of male and female groups with coronary artery disease and controls. The scaling of the parietal mesothelium is a process seen in all groups, although when quantified showed no significant differences between them. Ang II was not able to increase the epithelial-mesenchymal transition of the epicardial cells in infarcted mice genetically modified. The presence of constituents of the classical and alternative pathways of RAS in the PF suggest an important role for this fluid as a modulator of cardiac functions. Specifically in relation to Ang II, their biological roles in the cardiovascular system still need to be further investigated. The identification in the cardiovascular microenvironment of paracrine factors and your action mechanisms, which stimulate and promote cardiac repair, may allow a better understanding of heart disease and the development of new therapies.

Mesenteric Lymphatic-Perilymphatic Adipose Crosstalk: Role in Alcohol-Induced Perilymphatic Adipose Tissue Inflammation

The digestive tract lymphatics transport approximately two-thirds of all lymph produced in the body and have a key role in mucosal immunity through their contribution to antigen transport and immune cell trafficking. Mesenteric lymphatic pumping function integrity is critical for maintaining homeostasis and lipid transport. We previously demonstrated that acute alcohol intoxication (AAI) increases mesenteric lymphatic amplitude of contraction and ejection fraction, enhancing the ability of the lymphatic vessels to pump lymph. AAI has been shown to disrupt intestinal barrier integrity, which would be expected to increase the endotoxin content of mesenteric lymph. In this study, we tested the prediction that AAI increases lymphatic permeability directly affecting perilymphatic adipose tissue (PLAT) milieu. Male Sprague Dawley rats received an intragastric infusion of 2.5g/kg of alcohol. Isovolumic administration of water (vehicle) served as control. PLAT was isolated for the determination of Evans Blue extravasation (permeability), cytokine content, and immunohistochemistry for inflammatory cell infiltration at 30minutes and 24hours after alcohol administration. PLAT isolated from AAI animals had greater Evans Blue concentrations and cytokine expression (24hours post-AAI) and mast cell and neutrophil density than that isolated from controls. AAI resulted in significantly higher plasma lipopolysaccharide (endotoxin) levels, lower plasma adiponectin levels (at 30minutes), and unchanged plasma visfatin levels. The data indicate that AAI induces mesenteric lymphatic hyperpermeability, promotes PLAT inflammatory milieu and disrupts the systemic adipokine profile. These findings suggest an association between alcohol-induced lymphatic hyperpermeability and early manifestations of metabolic dysfunction as a result of alcohol abuse. We propose that crosstalk between lymph and PLAT results in adipose inflammation and adipokine dysregulation during AAI.

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by bone marrow infiltration from malignant plasma cells. Mast cells play an important role in inflammation and angiogenesis in malignant diseases. The aim of the study was to evaluate the mast cell density in bone marrow of untreated MM patients with markers of disease activity such as serum interleukin-6 (IL-6), B2M, and C-reactive protein (CRP), the grade of bone marrow infiltration, and the levels of produced paraprotein. We studied 86 newly diagnosed MM patients (46 males, 40 females, mean age 59 ± 13.7 years). Thirty of them reached plateau phase after chemotherapy and 20 healthy volunteers. According to the criteria of International Staging System (ISS) staging system, 23 patients had stage I, 30 had stage II, and 33 had stage III. The serum concentrations of CRP, B2M, and IL-6, and the mast cell density (MCD) values were significantly higher in MM patients' group (1.6 ± 1.8, 4.3 ± 2.9, 7.1 ± 5.1, and 9 ± 4.8), in comparison with those found in control group (0.4 ± 0.1, 1.5 ± 0.6, 1.1 ± 0.5, and 1.9 ± 0.7; p < 0.001 in all the cases). Significant differences were found between the grade of infiltration in bone marrow, and the paraprotein values in patients' serum before and after chemotherapy. Furthermore, there was a significant correlation between the MCD values and the prognostic markers CRP (r = 0.452, p < 0.0001), IL-6 (r = 0.475, p < 0.0001), bone marrow infiltration (r = 0.333, p < 0.0002), and serum paraprotein levels(r = 0.221, p < 0.04). High MCD values strengthen the hypothesis that mast cells participate in the pathogenesis of disease progression and may be used as an indicator of the disease activity.

Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan.

Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1β concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process.

Galectin-9 as an important marker in the differential diagnosis between oral squamous cell carcinoma, oral leukoplakia and oral lichen planus

ObjectivesTo evaluate the expression of Galectins (Gal) 1, 3 and 9, Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients with potentially malignant disorders (PMD) and oral squamous cell carcinomas (OSCC) by comparison with the controls. Study designWe selected 40 cases of PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry was performed for Gal-1, Gal-3, Gal-9 and MMP-3. ResultsGal-9 was significantly higher in patients with OSCC than in others groups (p<0.001). Gal-1 expression was significantly lower in patients with leukoplakia than those with OSCC and controls (p=0.0001). Gal-3 was significantly lower in patients with OSCC than those with leukoplakia (p=0.03). MMP-3 was lower in patients with leukoplakia in comparison with the lichen planus group (p=0.013). ConclusionThe increased expression of Gal-9 may be helpful to differentiate of OSCC from other oral cavity lesions.