ADIPONECTIN AS A POTENTIAL BIOMARKER OF LOW BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH METABOLIC SYNDROME.

CONTEXT: Adiponectin is an abundant adipokine, which has antiinflammatory, anti-atherosclerotic and vasoprotective actions, and potential antiresorptive effects on bone metabolism. It seems to be directly involved in the improvement and control of energy homeostasis, protecting bone health and predicting osteoporotic fracture risk. OBJECTIVE: To examine the relationship between adiponectin level and bone mineral density (BMD) in post-menopausal women with metabolic syndrome (MetS) and low BMD, and to estimate the prognostic significance of adiponectin in osteoporosis. DESIGN: Clinical-laboratory cross-sectional study including 120 middle-aged and elder women (average 69.18±7.56 years). SUBJECTS AND METHODS: The anthropometric parameters were measured for all examinees. Lumbar spine and hip BMD, as well as body fat percentage, were measured using a Hologic DEXA scanner. In all subjects serum adiponectin concentration was measured by ELISA method. RESULTS: The level of adiponectin was significantly positively correlated with BMD-total, BMD of the lumbar spine and BMD of the femoral neck (r=0.618, r=0.521, r=0.567; p<0.01). Levels of adiponectin and BMD are significantly lower in post-menopausal women with MetS and osteoporosis compared to patients with osteopenia (856.87±453.43 vs. 1287.32±405.21 pg/mL, p<0.01; BMD, p<0.05), and the highest values in healthy examinees. A cut-off value of adiponectin level for osteoporosis/osteopenia was 1076.22/1392.74 pg/mL. CONCLUSIONS: Post-menopausal women with MetS have significantly lower adiponectin level and low BMD compared to healthy examinees. Adiponectin may be an early, significant and independent predictor of developing osteoporosis in women with MetS, especially in post-menopausal period.

Cytotoxic effects of palladium (II) and platinum (II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl) pentanoic acid on human colon cancer cell lines.

PURPOSE: As novel therapeutic agents relevant to colon cancer therapy are explored continuously, we tested 4 R2edda-type ligand precursors O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid (L1.2HCl-L4.2HCl) and corresponding palladium(II) and platinum(II) complexes against the human colon cancer cell lines CaCo-2, SW480 and HCT116. METHODS: The effects of the tested compounds on cell viability were determined using MTT colorimetric technique. RESULTS: Analysis of cancer cell viability showed that all tested ligand precursors, palladium(II) and platinum(II) complexes were cytotoxic on human colon cancer cells in dose-dependent manner. The cytotoxic activity of all palladium(II) and platinum(II) complexes toward selected cancer cells was significantly higher in comparison to cisplatin. Among the tested platinum(II) and palladium(II) complexes the lowest activity was observed for the compounds with the shortest ester chain and the highest activity was noted for palladium(II) complex No.2 with the n-Pr group in ester chain and for platinum(II) complex No.7 with the n-Bu group in ester chain. CONCLUSION: Palladium(II) complex No.2 and platinum(II) complex No.7 seem to be good candidates for future pharmacological evaluation in the field of colon cancer research and treatment.

A new semiquantitative method for evaluation of metastasis progression.

PURPOSE: Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. METHODS: The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. RESULTS: By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. CONCLUSION: The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

Antioxidant enzymes activities and plasma levels of oxidative stress markers in B-chronic lymphocytic leukemia patients.

PURPOSE: Overproduction of reactive oxygen species (ROS) intermediates above the functional capability of cellular antioxidants may result in instability of important macromolecules and represents the molecular basis of many diseases including inflammation processes, cardiovascular alterations, cancer etc. The purpose of this study was to determine plasma level of superoxide anion, hydrogen-peroxide and malondialdehyde (MDA) as markers of oxidative stress and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as antioxidant enzymes in B-chronic lymphocytic leukemia (B-CLL) patients. METHODS: The study included 29 untreated B-CLL patients in stage A, and 21 in stages B and C, classified according to the Binet system; 31 healthy volunteers formed the control group. After centrifugation of heparinized peripheral blood, plasma levels of all investigated parameters were determined using spectrophotometric methods. RESULTS: Plasma CAT activity was increased in B-CLL patients compared with control subjects; also, progression of disease was related with significantly higher plasma activity of CAT. Also, B-CLL patients showed significantly higher plasma concentration of MDA compared with controls. No statistically significant differences of superoxide anion and hydrogen peroxide as well as plasma activity of SOD and GPx between the tested groups were noted. CONCLUSION: Increase of CAT activity in B-CLL patients indicates that there is stimulation of the antioxidant enzyme system, while the increase of MDA concentration shows increased lipid peroxidation level. According to these results it could be concluded that an imbalance exists between oxidants and antioxidants in the plasma of B-CLL patients.

Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma.

The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma. Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53. Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52+/-47.62 pg/ml vs. mean 101.91+/-22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma. The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.

In vitro induction of apoptotic cell death in chronic lymphocytic leukemia by two natural products: preliminary study.

PURPOSE: B cell chronic lymphocytic leukemia (B-CLL) is an neoplastic disorder characterized by alterations in the pathways of programmed cell death (apoptosis). Deregulation of apoptosis pathways also contributes to chemoresistance of B-CLL cells. Therefore, it is not surprising that induction and acceleration of apoptosis represent key point in novel B-CLL therapeutic protocols. The present study was designed to investigate the effects of two natural products, Immunarc forte and Korbazol on the in vitro survival of leukemic cells. METHODS: peripheral blood mononuclear cells (PBMC) from 20 B-CLL patients and 20 healthy donors were used for cytotoxicity studies. Cytotoxic activity of the tested products were assessed by the MTT colorimetric assay and the type of cell death was determined by flow cytometry. RESULTS: we found that Korbazol was selectively cytotoxic against B-CLL cells, but the cytotoxic activity of Immunarc forte was much weaker. Of note, synergy was shown between these two drugs, and this effect was also selective, without affecting the normal mononuclear cells. According to Annexin-V binding, Korbazol and Immunarc forte induced apoptotic type of cell death in B-CLL cells. Moreover, treatment with Korbazol, but not with Immunarc forte, decreased spontaneous apoptosis in cultured normal polymorphonuclear cells. CONCLUSION: our findings imply that Korbazol is as potential therapeutic agent that induces apoptosis of B-CLL cells. The resistance of normal mononuclear cells and anti-apoptotic effects on normal polymorphonuclear cells, as well as its ability to synergize with Immunarc forte, warrants further investigation and supports their therapeutic application in the treatment of B-CLL.

Endoplasmic reticulum stress associated with caspases-4 and -2 mediates korbazol-induced B-chronic lymphocytic leukemia cell apoptosis.

PURPOSE: B-cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that rapidly develops drug resistance. Therefore there is a need for identifying new agents that will improve the therapeutic outcome. Korbazol is a natural product known to exert cytotoxic effect on the in vitro survival of leukemic cells. The aim of this study was to investigate the mechanism of korbazol-induced apoptosis in B-CLL leukemic cells. METHODS: peripheral blood mononuclear cells from 10 B-CLL patients were used for assessing the effect of caspase inhibitors and chelator of intracellular Ca(2)+. RESULTS: cell death rate induced by the tested compound was decreased with the caspase-3 inhibitor Ac-DEVD-CHO, and the inhibitors of caspase-2 (Z-VDVAD-FMK) and -4 (ZYVAD- FMK), but not with the caspase-9 inhibitor z-LEHD-FMK and caspase-8 inhibitor z-IETD-FMK. No significant release of cytochrome C (cyt C) from mitochondria to the cytosol of B-CLL cells treated with korbazol was observed. Moreover, chelating of intracellular Ca(2)+ with BAPTA-AM almost completely abolished the cytotoxic effect of korbazol. CONCLUSION: engagement of caspases-2 and -4 and mobilization of intracellular Ca(2)+ indicate involvement of endoplasmic reticulum (ER) stress in apoptosis induced by korbazol.

The cytotoxic effects of some selected gold(III) complexes on 4T1 cells and their role in the prevention of breast tumor growth in BALB/c mice.

PURPOSE: to investigate the cytotoxic activity of newly synthesized gold(III) complexes [AuCl(2)(en)](+), [AuCl(2) (SMC)](+), [AuCl(2)(DMSO)(2)(+) (en: ethylenediamine, SMC: S-methyl- L-cysteine and DMSO: for dimethylsulfoxide) in 4T1 mouse breast cancer cell line in vitro and in vivo and to compare their antitumor characteristics with cisplatin complex [PtCl(2)(NH(3))(2)]. METHODS: the in vitro, effects of the tested complexes on 4T1 cell viability were determined using MTT colorimetric technique. In vivo, progression of mouse breast tumor growth in BALB/c mice was measured by using external caliper. RESULTS: among the tested gold(III) complexes, [AuCl(2) (en)](+) showed best cytotoxic effects in vitro. The cytotoxic effects of [AuCl(2)(en)](+) and [PtCl(2)(NH(3))(2)] were similar at all concentrations. The data from the in vivo experiment showed that among the tested gold(III) complexes only [AuCl(2)(en)](+) can prevent the primary breast tumor growth. [AuCl(2)(en)](+) was tolerated well and much better than [AuCl(2)(DMSO)(2)(+), [AuCl(2)(SMC)](+) and [PtCl(2)(NH(3))(2)] complex which was confirmed by weight gain in mice that received [AuCl(2)(en)](+). In addition, mice that received [AuCl(2)(en)](+) showed better survival time in comparison with mice that received [PtCl(2) (NH(3))(2)] complex. CONCLUSION: [AuCl(2) (en)](+) complex seems to be good candidate for future pharmacological evaluation in breast cancer research.

Oxidative stress accelerates spontaneous apoptosis of B-chronic lymphocytic leukemia lymphocytes.

PURPOSE: B-chronic lymphocytic leukemia (B-CLL) is characterized by the progressive accumulation of small immature B lymphocytes which do not undergo apoptosis due to an underlying defect. One potential mechanism of defective apoptosis could be irregular oxidative stress. The goal of our investigation was to determine in vitro production of oxidative stress markers by lymphocytes of B-CLL patients. PATIENTS AND METHODS: 30 untreated stage A B-CLL patients, as well as 20 stage B and C patients and 30 healthy volunteers as a control group were examined. Nitric oxide (NO), superoxide anion, hydrogen peroxide and malondialdehyde (MDA) were measured by spectrophotometry in supernatants of lymphocytes cultures of all 3 investigational groups. The method applied for detecting apoptosis was fluorescence microscopic analysis using acridine orange/ethidium bromide (AO/EB) double staining. RESULTS: In vitro lymphocyte production of superoxide anion, hydrogen peroxide and MDA was increased in B-CLL patients, while there were no statistical significantly differences of NO production among the tested groups. Compared with the spontaneous apoptosis observed in control subjects lymphocytes, B-CLL lymphocytes showed increased percentages of apoptotic cells after incubation for 24 h. Disease progression was not followed with significant differences in spontaneous apoptosis of B-CLL lymphocytes. CONCLUSION: This intensive oxidative stress markers production in cultures of B-CLL lymphocytes could be one of the potential mechanisms in the pathogenesis of abnormal apoptosis.

Inflammation at the interface of innate and acquired immunity.

This is the short summary of the presentation at the 2nd Belgrade Meeting on Immunoregulation entitled "Inflammation at the interface of Innate and Acquired Immunity" held recently under the auspice of European Federation of Immunological Societies and organized by Medical School, University of Kragujevac.

Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice.

Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3(+/+) and Gal-3(-/-) mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-alpha, IFN-gamma, IL-17, and iNOS in pancreatic lymph nodes. Gal-3(+/+) mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3(-)/(-) mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-gamma and complete absence of TNF-alpha, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-alpha and NO in Gal-3(-/-) mice. Thus, Gal-3 is involved in immune mediated beta cell damage and is required for diabetogenesis in this model of disease.

HER-2 expression in uterine cervix carcinogenesis.

PURPOSE: To assess the expression and clinical significance of HER-2 protooncogene in the uterine cervix carcinogenesis. PATIENTS AND METHODS: We examined 69 tissue samples of low grade cervical squamous intraepithelial lesions (SIL) (n=16), high grade SIL (n=11) portio vaginalis uteri (PVU) carcinoma in situ (n=11) and PVU invasive carcinoma, stage IA-IIA (n=13; study group) and 18 samples without SIL or malignancy (control group). The expression of HER-2 was detected immunohistochemically using a monoclonal antibody. Fisher's exact test was used to assess statistical significance. By establishing sensitivity and specificity of the test, the level of reliability of these analyses was determined as a possible screening method for early detection of changes in the uterine cervix. RESULTS: Overexpression of HER-2 was found to increase in direct relation to the grade of the cervical lesions. Statistically significant difference was found in the frequency of overexpression in patients with high grade SIL, PVU carcinoma in situ and PVU invasive carcinoma compared with the control group. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be concluded that in patients with HER-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. CONCLUSION: Our results indicate that overexpression of HER-2 oncogene may play an important role in cervical carcinogenesis. However, more extensive series of samples is required to establish the prognostic significance of HER- 2 in cervical carcinogenesis.

Relationship of serum levels of tumor markers with tissue expression of gene products in ovarian carcinoma.

PURPOSE: The aim of this prospective study was to determine serum levels and tissue expression of CA125, CA 15-3, p53, HER-2 and nm23 tumor markers, which are used in the detection and follow up of patients with ovarian carcinoma. PATIENTS AND METHODS: 19 patients with malignant and benign ovarian tumors were included in this study. Serum levels of CA125, CA 15-3 and p53 tumor markers were detected in preoperative and postoperative blood samples using ELISA technique. Tissue expression of p53, HER-2 and nm23 were examined using immunohistochemistry. RESULTS: All serum tumor markers were elevated in patients with ovarian carcinoma. Serum level of CA 15-3 was increased in patients with ovarian carcinoma (median 48.33 U/ml, normal range 0-36), while it was normal in patients with benign ovarian tumors (median 20.67 U/ml; p >0.05). CA125 serum values were strikingly increased in ovarian carcinoma (median 264.16 IU/ml, normal range 0-35) and benign ovarian tumors (median 119.59 IU/ml; p <0.05). Serum levels of p53 in patients with ovarian carcinoma were increased (median 0.69 U/ml, normal range 0-0.50) compared to patients with benign tumors (0.32 U/ml; p <0.05). Histological HER-2 overexpression was detected in 7 cases, including 4 with strong (score 3+ and 2+) and 3 with weak or no HER-2 expression (score 1+ and 0) in ovarian carcinoma tissue; in benign tumors HER-2 overexpression was detected in 1 case (p >0.05). Strong overexpression of p53 was detected in 3 cases with malignant and none with benign tumors (p >0.05); and strong overexpression of nm23 was detected in 5 cases with malignant and 2 with benign tumors (p >0.05). CONCLUSION: Serum levels of CA125, CA 15-3 and p53 are strikingly increased, as well as the expression of HER-2 and p53 in carcinomatous tissue. Detection and analysis of multiple tumor-specific markers in serum and tissue can give useful clinical information for the management of ovarian carcinoma and can also improve the sensitivity and specificity of these markers.

In vitro assay for the quantitative measurement of apoptotic lymphocytes phagocytosis by peripheral blood monocytes.

Currently used assays for the quantification of apoptotic cells uptake by phagocytes have several methodological problems. Our assay overcomes some of these problems. As a source of apoptotic cells we used peripheral blood lymphocytes obtained from the patients with chronic lymphoblast leukaemia. Apoptosis was induced by incubating cells with cycloheximide for up to 24 h. The assay was performed in suspension of peripheral blood mononuclear cells. For the visualisation of the phagocytes and phagocyted cells and discrimination of phagocyted from bound apoptotic cells we used Acridine orange/Ethidium bromide double staining. Here we offer a simple test which enables reliable measurement and it can show the difference of phagocytic potential between different individuals.

Preliminary study of mononuclear phagocytosis during breast cancer therapy.

PURPOSE: To evaluate the eventual changes in the number and phagocytic functions of blood monocytes in breast cancer patients during surgical treatment and chemotherapy. MATERIALS AND METHODS: The absolute and relative number of peripheral blood leukocytes and monocyte phagocytic functions were determined at the time of diagnosis (I), following surgery (II), during (III) and after chemotherapy (IV) in 30 patients diagnosed with breast cancer. The control group consisted of 30 age-matched healthy women. RESULTS: The mean number of monocytes was significantly lower in cancer patients at diagnosis, while they increased following surgery reaching the control values. There were no postchemotherapy changes in the number of monocytes. Monocyte phagocytic activity was decreased at the time of diagnosis. Following surgery, the capacity of phagocytosis (CP) recovered to normal values, but the index of phagocytosis (IP) remained decreased. During and after chemotherapy, as well as one year after surgery, the IP still remained decreased. CONCLUSION: Our results showed that some properties of monocytes' phagocytic activity in cancer patients were decreased at diagnosis, returning back to normal range after surgical therapy. However, time is needed to confirm whether the alteration of IP may provide additional information when monitoring breast cancer patients.

Serum HER2 and CA 15-3 in breast cancer patients.

PURPOSE: The HER2 oncogene encodes a transmembrane tyrosine kinase receptor. This molecule could be a new marker for prognosis and response to therapy in patients with advanced breast cancer. However, the extracellular domain of c-erbB-2 (HER2) transmembrane receptor undergoes proteolytic cleavage from the fulllength protein by metalloproteases, and is shed into the blood as a circulating antigen. To determine the clinical utility of this oncoprotein, the soluble form of HER2 was assayed in the serum of breast cancer patients. PATIENTS AND METHODS: Serum levels of breast carcinoma antigens CA 15-3 and HER2 were determined in 60 patients, 40 with localized (group A) and 20 with metastatic (group B) breast carcinoma. CA 15-3 measurements served as "gold standard" to which HER2 diagnostic and/or prognostic value was compared. Sera from 10 healthy women served as controls. RESULTS: Serum levels of the tested tumor markers HER2 and CA 15-3 were significantly higher in cancer patients compared to controls. CA 15-3 correlated with bulky initial tumor, whereas HER2 showed no differences between healthy individuals and group A patients. The serum levels of the tested markers in group B patients were significantly higher (p <0.001) than the serum levels of patients in group A. Striking increase in serum levels of HER2 was found in 52.7% and CA 15-3 in 52.9% of patients with metastatic cancer. A combination of markers was more sensitive than using one marker alone. In this regard, 90% of the patients with metastasis had at least one of the markers increased. CONCLUSION: The results of this study suggest that the HER2 oncoprotein may be potentially useful in detecting recurrence of breast cancer. However, to improve sensitivity and specificity in the diagnosis and monitoring of breast cancer, the use of multiple tumor markers should be employed.

Blood monocytes and tumor-associated macrophages in human cancer: differences in activation levels.

This study was performed to investigate functional properties of mononuclear phagocytes isolated from ascitic fluid in patients with peritoneal carcinomatosis (PC), and potential immunomodulatory effects of soluble factors produced or induced by human metastatic malignant cells. Phagocytic activity and nitric oxide production of peripheral blood monocytes (PBMo) and tumor-associated macrophages (TAM) or peritoneal macrophages (PEM) were synchronously examined in cancer patients and control individuals. Our results showed that contrary to peripheral blood monocytes, where phagocytic activity was not altered, TAM had impaired phagocytic activity. Moreover, dilutions of crude supernatant from short-term cultures of the peritoneal cells obtained from ascitic fluid of patient with PC, cause a significant, dose dependent inhibition of control PBMo and PEM phagocytosis, comparable to those in TAM, indicating that a soluble factor(s) plays a prominent role in this alteration. Next, we investigated the potential of cancer patients mononuclear phagocytes to produce nitric oxide (NO). It was found that TAM produce fourfold lower levels of NO than PEM from control subject, whereas monocytes produce NO at levels comparable to those of corresponding controls. These data support the hypothesis that depressed TAM function may contribute to the mechanisms of tumor escape from immune destruction.

Systemic response of peripheral blood leukocytes and their phagocytic activity during acute myocardial infarction.

OBJECTIVES: To determine changes in leukocyte counts and phagocytic activity of peripheral blood mononuclear (MN) and polymorphonuclear (PMN) cells as potential cellular markers of systemic immunological events in acute myocardial infarction (AMI). PATIENTS AND METHODS: Thirty patients with a first AMI and 30 healthy volunteers were examined. Immunological analyses were performed at admission and repeated at one and seven days after the acute event. MN and PMN cells were obtained from heparinized whole blood after centrifugation and separation on a density gradient, and incubated with a fixed number of heat-inactivated and labelled yeast particles. Total leukocyte counts, leukocyte populations and some parameters of phagocytic activity were determined: percentage phagocytosis, phagocytic index, absolute phagocytic index, count of phagocytes in a fixed volume of peripheral blood (CP) and phagocytic capacity. RESULTS: Patients with AMI had increased total leukocyte counts accompanied by increased PMN counts, while there were no significant differences in total MN count and MN populations. Except for the phagocytic index, all phagocytic parameters of MN and PMN cells were increased in patients with AMI at admission and on the first day of disease. On the seventh day after AMI only the CP of MN cells had increased significantly in patients with AMI, while percentage phagocytosis, CP and capacity of phagocytosis of PMN cells increased during the acute phase of AMI. CONCLUSIONS: These data suggest that AMI was followed with a strongly systemic inflammatory response to myocardial damage. Furthermore, activated MN and PMN cells may be a significant source of free radicals that may be involved in lipid peroxidation and produce tissue damage in the early postinfarction period.

Quantitative analysis of the immunocompetent cells in periapical granuloma: correlation with the histological characteristics of the lesions.

Granuloma formation includes an immune response in oral tissues to various microorganisms and their products. The immunocompetent cells of both series (T and B) are present in the periapical lesions. In order to further analyze the relative contribution and pathophysiological significance of the T cell subsets in granuloma formation, we undertook the quantitative analysis of the CD3-positive, CD4-positive, CD8-positive and Ig-positive cells in these lesions by using indirect immunofluorescence. Evidence is provided showing predominance of T cells in diffuse and B cells in focal mononuclear infiltrates. CD8-positive cells were more frequent in diffuse infiltrates and in particular in granulomas with distinct epithelium while CD4-positive cells were more numerous in focal infiltrates. It appears that the presence and ratios of different subsets of immunocompetent cells reflects the pathogenesis of granuloma and transformation to cyst.