Skeletonized bilateral internal mammary arteries for non-elective surgical revascularization in unstable angina.

OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients with unstable angina (UA) undergoing non-elective myocardial revascularization. METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12 years, underwent non-elective coronary artery bypass grafting (CABG) for unstable angina. Two hundred and five (27%) were operated emergently and 503 (73%) urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M). RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow-up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P = 0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35% (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non-elective CABG for UA is safe and effective. Mid-term outcome, however, are superior with improved freedom from cardiac death, from coronary reintervention and from myocardial infarction.     

Osteocyte dendrogenesis in static and dynamic bone formation: an ultrastructural study

The present ultrastructural investigation into osteocyte dendrogenesis represents a continuation of a previous study (Ferretti et al., Anat. Embryol., 2002; 206:21-29), in which we pointed out that, during intramembranous ossification, the well-known dynamic bone formation (DBF), performed by migrating osteoblast laminae, is preceded by static bone formation (SBF), in which cords of stationary osteoblasts transform into osteocytes in the same site where they differentiated. The research was carried out on the perichondral center of ossification surrounding the mid shaft level of various long bones of chick embryos and newborn rabbits. Transmission electron microscope observations showed that the formation of osteocyte dendrites is quite different in the two types of osteogenesis, mainly depending on whether or not osteoblast movement occurs. In DBF, osteoblasts transform into small ovoidal/ellipsoidal osteocytes and their dendrites form in an asynchronous and asymmetrical manner in concomitance with, and depending on, the advancing mineralizing surface and the receding osteogenic laminae. In SBF, stationary osteoblasts give rise to big globous osteocytes, located inside confluent lacunae, with short and symmetrical dendrites that can radiate simultaneously all around their cell body because they are completely surrounded by unmineralized matrix. Contacts and gap junctions were observed between all osteocytes (both SBF- and DBF-derived) and between osteocytes and osteoblasts. Finally, a continuous osteocyte network extends throughout the bone, regardless of its static or dynamic origin. This network has the characteristic of a functional syncytium, potentially capable of modulating, by wiring transmission, the cells of the osteogenic lineage covering the bone surfaces.     

Long distance transport of ragweed pollen as a potential cause of allergy in central Italy.

BACKGROUND: Ambrosia pollen is an important allergen in North America and, as recently discovered, in some European countries. In Italy, the most affected area is the northeast, whereas ragweed has not been reported in the central and southern parts of the country. OBJECTIVE: To identify the source of ragweed pollen detected in Florence and Pistoia in central Italy. METHODS: Ragweed pollen data were collected in Florence and Pistoia for a 6-year period (1999-2004). The relationship between pollen counts and local ground prevalent wind directions was evaluated with analysis of variance and the least significant difference test. Weather conditions were also evaluated on a large-scale circulation pattern by analyzing weather maps and air mass back trajectories. RESULTS: A highly statistically significant relationship between daily prevailing wind direction and pollen count was found in the period under investigation; the ragweed pollen peaks were recorded when winds from northeast in Florence and north-northeast in Pistoia were observed. The synoptic weather situation and the path of back trajectories suggest an area around southern Hungary as a possible source of Ambrosia pollen. Furthermore, the pollen count was above the clinical threshold several times in both Florence and Pistoia. CONCLUSIONS: Several factors indicate that the detection of ragweed pollen in central Italy is due to long distance transport. Taking into consideration the high allergenicity of Ambrosia pollen, the present findings, if confirmed, suggest that the number of sensitized individuals might significantly increase in the near future.     

D-Serine differently modulates NMDA receptor function in rat CA1 hippocampal pyramidal cells and interneurons

The organization of the neuronal hippocampal network depends on the tightly regulated interaction between pyramidal cells (PCs) and interneurons (Ints). NMDA receptor (NMDAR) activation requires the binding of glutamate and co-activation of the 'glycine site'. It has been reported that d -serine is a more potent endogenous agonist than glycine for that site. While many studies have focused on NMDAR function in PCs, little is known regarding the modulation of NMDARs in Ints. We studied the modulatory effect of d -serine on NMDAR EPSCs in PCs and in stratum radiatum Ints using whole-cell patch-clamp recording in rat acute hippocampal slices. We found that d -serine enhances NMDAR function and differently modulates NMDAR currents in both cell types. The augmentation of NMDAR currents by d -serine was significantly larger in PCs compared with Ints. Moreover, we found differences in the kinetics of NMDAR currents in PCs and Ints. Our findings indicate that regulation of NMDAR through the 'glycine site' depends on the cell types. We speculate that the observed differences arise from assemblies of diverse NMDAR subunits. Overall, our data suggest that d -serine may be involved in regulation of the excitation-inhibition balance in the CA1 hippocampal region.     

Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.     

Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency

Factor XIII (FXIII) deficiency is a very rare severe autosomal bleeding disorder with a frequency of 1:2,000,000 in the general population and only a few patients have been genetically characterized so far. We report a phenotype-genotype characterization of 10 unrelated Iranian patients. Two FXIII (transglutaminase) activity assays showed no FXIII activity, except a conserved residual activity in patients receiving prophylactic substitution treatment. FXIII antigen concentrations measured by two immunoassays were comparable. Genotype characterization identified four novel mutations (2 missense and 2 small deletions) and two previously reported missense mutations in the FXIII A subunit gene (F13A). Molecular modeling was carried out to reveal the structural consequences of the missense mutations, that caused the replacement of an arginine residue involved in the formation of structurally important extensive hydrogen-bonded network. The replacements [c.320G>A (p.Arg77His) in the beta-sandwich, c.868C>T (p.Arg260Cys), c.869G>A (p.Arg260His) and c.1236G>T (p.Arg382Ser) in the core domain] resulted in the loss or impairment of such H-bonded network. Energy decomposition analysis demonstrated that this situation leads to the instability and perhaps to the incorrect folding of the A subunit, that would explain the development of severe FXIII deficiency.     

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by ¹H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg⁻¹ i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.