Inflammatory response to percutaneous coronary intervention in stable coronary artery disease

Percutaneous coronary intervention (PCI) can be regarded as a model for mechanical induced plaque rupture. The objective of this study was to evaluate the inflammatory response to PCI in stable coronary artery disease (CAD) by analysing plasma levels of a wide range of inflammatory mediators. Consecutively, we included 36 patients with stable angina pectoris after successful revascularization by PCI with implantation of a bare metal stent (BMS) or a drug eluting stent (DES). Patients were followed for 7 days with serial measurements of inflammatory mediators in plasma. C-reactive protein (CRP) and Pentraxin 3 showed a statistical significant early increase after PCI peaking at 3 days and 3 h, respectively. Vascular cell adhesion molecule-1 (VCAM-1) increased significantly with a peak at 3 days, while E-selectin showed a statistical significant gradual decrease. Markers of platelet mediated inflammation showed increasing (CD40 ligand) and decreasing (P-selectin) levels after PCI. While monocyte chemoattractant protein, CCL21 and CXCL16 increased rapidly in response to PCI, Interleukin-8, CCL19 and RANTES decreased. Patients with DES had significantly lower levels of VCAM-1 and RANTES compared to those with BMS. A femoral access site was associated with higher CRP levels than a radial access site. The use of glycoprotein-IIb/IIIa-inhibitors was associated with significantly higher CD40L and RANTES levels. Our findings underscore the complex nature of the inflammatory responses during PCI in stable CAD, and suggest that simultaneous measurements of several markers may be needed to characterize these PCI-related responses. The responses were only in a minor degree influenced by stent type, access site and the use of glycoprotein-IIb/IIIa-inhibitors.     

Laminin alpha2 deficient congenital muscular dystrophy: prenatal diagnosis.

Laminin alpha2 chain-deficient congenital muscular dystrophy (CMD) is diagnosed by genetic analysis and by immunohistochemistry. Since laminin alpha2 chain is expressed in placental trophoblasts, the demonstration of its deficiency in chorionic villi is a useful aid to prenatal diagnosis. We present our experience with the use of the immunohistochemical method for prenatal diagnosis in four women, all of whom had at least one child with laminin alpha2 chain-deficient CMD. Immunohistochemistry provided a rapid procedure for prenatal diagnosis, and follow-up of these four cases confirmed its reliability.     

Housing conditions in childhood and cause-specific adult mortality: the effect of sanitary conditions and economic deprivation on 55,761 men in Oslo

AIMS: To examine indices of two plausible pathways linking housing conditions in childhood and adult cause-specific mortality: sanitary conditions and economic deprivation. To investigate if the effects of these are explained by education. METHODS: Linked register study (housing information from the 1960 Census, the educational register in 1990 and the death register 1990-998). A Sanitary Conditions Index (SCI) and an Economic Deprivation Index (EDI) were constructed from the housing conditions variables. PARTICIPANTS: All men aged 30-54 years (n = 55,761) who were residents in Oslo on 1 January 1990 with complete information on housing conditions (80%). RESULTS: Both SCI and EDI were related to all-cause mortality independently of each other. Education explained to a large extent these effects. In a sub-sample, 24% of the effects could be explained by parental education and 31% by own education. The effects found for causes of death failed to give a heterogeneous pattern between the two indices. In the fully adjusted model psychiatric causes of death appeared to be more related to EDI than SCI. CONCLUSIONS: The two indices of childhood social circumstances, sanitary conditions and economic deprivation, appeared to be independently associated with all-cause mortality. The effect of both could to a large extent be explained by parental and own education.     

Cardiac papillary fibroelastoma of the mitral chorda

We describe a case of cardiac papillary fibroelastoma in a 33-year-old man. The diagnosis was established by echocardiography. Computerised tomographic angiography gave no evidence of coronary stenosis, but illustrated a radiopaque filling defect in the left ventricle. The papillary fibroelastoma was removed together with the involved chorda, and an artificial chord was implanted under cardiopulmonary bypass. Histological study confirmed the diagnosis of papillary fibroelastoma. Due to the potentials of cerebral and coronary embolisation, surgical management to the patients with a papillary fibroelastoma is highly recommended.     

Effects of selective somatostatin analogs and cortistatin on cell viability in cultured human non-functioning pituitary adenomas

Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors.     

Evidence for acyl-ghrelin modulation of growth hormone release in the fed state

CONTEXT: The timing and frequency of GH secretory episodes is regulated by GHRH and somatostatin. This study provides evidence for amplification of these GH pulses by endogenous acyl-ghrelin. DESIGN: Blood was sampled every 10 min for 26.5 h during a fed admission with standardized meals and also during the final 24 h of a 61.5-h fast. GH secretion profiles were derived from deconvolution of 10-min sampling data, and full-length acyl-ghrelin levels were measured using a newly developed two-site sandwich assay. SETTING: The study was conducted at a university hospital general clinical research center. PARTICIPANTS: Participants included eight men with mean (+/- sd) age 24.5 +/- 3.7 yr (body mass index 24 +/- 2.1 kg/m(2)). RESULTS: Correlations were computed between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-min interval preceding each GH burst. In the fed state, the peak correlations were positive for all subjects and significantly higher than in the fasting state when acyl-ghrelin levels declined [mean (+/- sem): 0.7 (0.04) vs. 0.29 (0.08), P = 0.017]. In addition, long-term fasting was associated with an increase in the GH secretory pulse mass and amplitude but not frequency [fed vs. fasting pulse mass: 0.22 (0.05) vs. 0.44 (0.06) microg/liter, P = 0.002; amplitude: 5.2 (1.3) vs. 11.8 (1.9) microg/liter/min, P = 0.034; pulses per 24 h: 19.4 (0.5) vs. 22.0 (1.4), P = 0.1]. CONCLUSION: Our data support the hypothesis that under normal conditions in subjects given regular meals endogenous acyl-ghrelin acts to increase the amplitude of GH pulses.     

Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells

Advanced glycation end products (AGEs) are considered as biomarkers of ageing and are associated with several degenerative diseases. Besides endogenous formation, significant amounts of AGEs are taken up with food. Although nutritional AGEs are considered as undesirable, proinflammatory agents, they may also enclose potentially beneficial antioxidants. We used rodent cardiac cells to evaluate if food AGEs, present in bread crust, can modify the cellular antioxidant defence. Mice were fed with bread crust containing diet to prove the in-vivo relevance for the heart. In mouse cardiac fibroblasts, bread crust extract induced a moderate elevation of ROS production causing an activation of p42/p44^MAPK, p38^MAPK and NF-κB, followed by increased expression of antioxidative enzymes. Preconditioning studies demonstrated that this was sufficient to protect cardiac fibroblasts and rat adult cardiac myocytes against severe oxidative stress. Furthermore, mice, fed a bread crust containing diet, exhibited a similarly improved cardiac expression of antioxidative defence genes. The consumption of AGEs can therefore contribute to an improved antioxidant status of the heart, thus exhibiting cardioprotective effects in case of severe oxidative stress as in ischemia reperfusion injury. Also, these data show that the exclusive interpretation of circulating AGEs as pathophysiological biomarkers of ageing might be misleading.     

HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease

Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T cells from celiac patients to map DQ2 and DQ8 epitopes within 2 representative gluten proteins, alpha-gliadin AJ133612 and gamma-gliadin M36999. For alpha-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of 2 separate regions. For gamma-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of the same region. Some gamma-gliadin peptides were recognized by T cells in the context of DQ2 or DQ8 when bound in exactly the same registers, but with different requirements for deamidation; deamidation at peptide position 4 (P4) was important for DQ2-restricted T cells, whereas deamidation at P1 and/or P9 was important for DQ8-restricted T cells. Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes.