Triactome: neuro-immune-adipose interactions. Implication in vascular biology.

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

Morphological characteristics of neonatal adipose tissue.

The aim of the present work was to study the morphological characteristics of neonatal adipose tissue using rats as an animal model. The results revealed that the subcutaneous adipose tissue of newborns consists of packets of unilocular adipose cells (one large lipid drop occupying the whole cell and pushing the cytoplasm and the nucleus to the cell periphery) and some multilocular fat cells (several lipid droplets of different size and an almost centrally located nucleus). All the adipocytes demonstrated positive immunohistochemical expression for leptin, whereas the multilocular adipose cells were positive for cyclin D1. These findings suggest that the multilocular adipose cells are preadipocytes that have not yet finished proliferation and differentiation and could under some external and/or internal stimuli conclude their development and become mature unilocular adipocytes, thus increasing fat mass.

Adipoparacrinology--vascular periadventitial adipose tissue (tunica adiposa) as an example.

Human adipose tissue is partitioned into two large depots (subcutaneous and visceral), and many small depots associated with internal organs, e.g. heart, blood vessels, major lymph nodes, pancreas, prostate gland and ovaries. Since the adipose 'Big Bang' led to the discovery of leptin (Zhang, Proenca, Maffei, Barone, Leopold and Friedman, Nature 1994;372:425-32), adipose tissue has been seen not merely as a lipid store, but as a secretory - endocrine and paracrine - organ, particularly in the pathogenesis of a number of diseases. Accordingly, two major sub-fields of adipobiology have emerged, viz. adipoendocrinology and adipoparacrinology, the latter herein being illustrated by PAAT (periadventitial adipose tissue) in vascular walls. A long-standing paradigm holds that the vascular wall consists of three coats, tunica intima, tunica media and tunica adventitia. It is now imperative that 'to further elucidate vascular function, we should no longer, as hitherto, separate adventitia and PAAT from the vascular wall, but keep them attached and in place, and subject to thorough examination' (Chaldakov, Fiore, Ghenev, Stankulov and Aloe, Int Med J 2000;7:43-9; Chaldakov, Stankulov and Aloe, Atherosclerosis 2001;154:237-8; Chaldakov GN, Stankulov IS, Fiore M, Ghenev PI and Aloe L, Atherosclerosis 2001;159:57-66). From the available data, we propose that it is time to rethink about vascular wall composition, and suggest that the PAAT may be considered the fourth and outermost vascular coat, hence, tunica adiposa (regarding the proximal segment of coronary artery, it is the innermost part of the EAT (epicardial adipose tissue) situated around the coronary adventitia). Its significance in the pathogenesis and therapy of CMDs (cardiometabolic diseases), particularly atherosclerosis and hypertension, requires further basic, translational and clinical studies.

[Morphometrical analysis of bone marrow metamyelocyte in pernicious anemia].

INTRODUCTION: In pernicious anemia besides the presence of megaloblasts in the bone marrow, changes in myeloid series were seen; being the most evident among the metamyelocyte. The aim of this study was to perform the quantification of metamyelocyte of the bone marrow in pernicious anemia. MATERIAL AND METHODS: Between 2000-2006 in the Clinic of Hematology-Nis, 68 patients with pernicious anemia were examined and 30 with dyspeptic syndrome (control group). The group of patients with pernicious anemia in relation to pathohistologic changes of gastric mucosa was divided into three sub-groups. Morphometrical analysis of metamyelocyte of the bone marrow was carried out by the application of the double netlike system (B100). The following parameters were used: relative surface, contour length, absolute surface of nucleus and cytoplasm, absolute contour nucleus and cytoplasm density, shaped nucleus and cytoplasmic factor and nuclear-cytoplasmatic ratio of metamyelocytes. RESULTS: Relative surface, contour length, absolute surface and contour density of nucleus and cytoplasm of metamyelocytes increased simultaneously with the degree of atrophic gastritis. Shaped nucleus and cytoplasmic factor and nuclear-cytoplasmatic ratio of metamyelocytes decreased in all examined groups in relation to the control group. CONCLUSION: Not only are bone marrow erythroid elements scoped with megaloblastic changes but the changes on the level of leukocyte cells as well. The result of this is the phenomena of giant metamyelocytes.

[Gastrointestinal stromal tumors--microscopic and immunihistochemical features].

BACKGROUND/AIM: Gastrointestinal (GI) stromal tumors (GIST) are the most common mesenchymal tumors of GI tract. The most frequent localization is gastric (60-70%) followed by intestinal localization (20-30%). The histogenesis, classification, diagnostic criteria and biological behavior of GIST are still discussable. Gastrointestinal stromal tumors are thought to originate from interstitial pacemaker intestinal cells of Cajal. Histologic appearance of a GIST is complicated and biologic potential unpredictable. The aim of of tha study was to investigate anatomic localization, the size of the tumor, incapsulation, microscopic and immunohistochemical characteristics. METHODS: The study involved 21 GIST taken by a complete resection in the period from 1994-2006. The analysed parameters were the localization, size, microscopic (mitotic index, nectosis, bleeding, invasivity) and immunohistochemical characteristics (CD117 (c-kit), CD34, desmin, vimentin, smooth muscle actin and s-100 protein expression. RESULTS: Gastrointestinal stromal tumors (n=21) size varied from 10-150 mm were most frequently gastric localised with predominance of malignant tumors (85.72%). Most GIST were comprised of a uniform spindle cell population, but some were dominated by epitheloid cells. Eosinophilic cells stained CD117, CD34 and vimentin positively, were usually arranged in fascicles with the presence of skeinoid fibers. Positive correlation of biologic potential and tumor size, haemorrhagia and mitotic index were found, so as negative correlation of biologic potential and incapsulation. CONCLUSION: The above results, a specially localization, tumor size, mitotic index, CD117, CD34 and vimentin positivity, may be helpful for setting of a widespread criteria for diagnostic and differential diagnosis of GIST and their use in practice and therapy.

[Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia].

BACKGROUND/AIM: Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA), as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like (ECL) carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. METHODS: During the period from 2000-2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE); histochemical AB-PAS (pH 2.5), cytochemical argyrophilic Servier-Munger's and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA) method. The obtained results were statisticaly calculated by using Student's t test. RESULTS: Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05) as well as an average number of ECL cells. CONCLUSION: We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia.

[Expression of nuclear Ki-67 antigen in prostatic high grade intraepithelial neoplasia and prostatic carcinoma].

BACKGROUND/AIM: Prostatic intraepithelial high grade neoplasia (PINHG) is accepted as preneoplastic lesion in prostatic carcinoma. One of the fundamental events in early oncogenesis is the disruption of proliferative activity. One of the numerous regulatory proteins is Ki-67 expressed in all proliferating cells. Index Ki-67 is considered to have prognostic significance. The aim of the study was to compare the level of proliferation in hyperplastic epithelium, prostatic carcinoma (Gleason score > 6) and PINHG. METHODS: Micromorphological examination was done in 85 patients. Pathohistological analysis was performed on standard histologic specimens with the estimation of Gleason score and the presence of PINHG in its surroundings. Nuclear proliferative activity was analyzed immunohistochemically in 19 cases, using a monoclonal anti-Ki-67 antibody. RESULTS: PINHG was found in prostatic carcinoma surrounding in 30% of the patients. In hyperplastic epithelia Ki-67 proliferative activity was 1,08, in PINHG 2,25 (p < 0,05), while in prostatic cancer, Ki-67 index was 17,64. Proliferative activity in prostatic carcinoma was significantly higher than in PINHG (p < 0,001) and hyperplasia (p < 0,001). CONCLUSION: This study confirmed that high grade PIN lesion predominately appears in the surrounding of poor or moderately differentiated prostate carcinoma, and that it represents progressive disorder of proliferation in preneoplastic and neoplastic prostatic epithelium.