Different role of advanced glycation end products in pathology of transplanted heart in patients with or without diabetes mellitus type 2.

BACKGROUND: Aim of the study was to localize advanced glycation end products (AGEs) in late endomyocardial biopsies (EMBs) of orthotopic heart transplant (OHT) recipients with and without diabetes mellitus (DM) to correlate their presence with acute rejection episodes (ARE) and cardiac allograft vasculopathy (CAV). MATERIALS AND METHODS: Elective EMBs were performed at 3 years post-OHT in 64 subjects, with DM (59 M/5 F), of overall mean age of 49 +/- 8 years and 24 patients, without DM (21 M/3 F), of overall mean age of 42 +/- 10y. Localization of myocardial AGEs in paraffin sections was assessed immunochemically using mouse monoclonal anti-AGE antibodies (clone 6d12) on cardiomyocytes, stromal cells, connective tissue elements and capillaries. RESULTS: The occurrence of AGEs was similar in DM versus non-DM subjects: namely, cardiocytes 73% versus 63%, stroma 33% versus 33%, connective tissue 13% versus 9%, and capillaries 31% versus 33%, respectively. Only in the DM group. The acute rejection episodes and mean EMB score significantly correlated with AGE presence in cardiomyocytes (r = 0.29/0.3; P = .02/.02; Spearman). There was no relation between AGE occurrence and CAV diagnosis among DM subjects, while the time free from angiographically confirmed CAV or a CAV-related event was significantly shorter among non-DM recipients without AGEs in capillaries and/or cardiocytes (P = .014/.017/.014/.03, respectively; log-rank). CONCLUSION: AGE occurrence in OHT recipients with DM was related to ARE, but not to CAV; in contrast, among non-DM patients it was not correlated with ARE, but their absence predicted CAV.

HSP27 diagnostic utility in the fine needle aspirate of breast. Correlation with progesterone and estrogen receptors.

Fine needle aspiration (FNA) is routine diagnostic tool in breast tumors assessment. In some cases, however, limitations of this method do not permit an unequivocal diagnosis. In these, suspected, cases immunocytochemical evaluation of selected biological markers may be of help. The aim of the study was assessment of HSP27 value in diagnosis and discrimination of benign and malignant breast lesions. HSP27 expression was examined by immunocytochemistry in fine needle aspiration smears assessed to C2-C5 categories. In C5 subgroup HSP27 expression was correlated with ER, PR content. Statistically significant differences in HSP27 expression between subsets C2/C5 and C3/C5 were found (p=0.028 and p=0,04, respectively); the differences between C3/C4 categories were not significant. Expression of HSP27 protein in FNA smears can be additional factor, which helps to differentiate benign, and malignant breast lesions, however it is not useful for discrimination of cytological, suspicious lesions.

Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2.

INTRODUCTION: Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT. MATERIAL: The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males. METHODS: We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)). RESULTS: The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV). CONCLUSIONS: The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.