Peri-Procedural Tight Glycemic Control during Early Percutaneous Coronary Intervention Is Associated with a Lower Rate of In-Stent Restenosis in Patients with Acute ST-Elevation Myocardial Infarction

Objective: We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI). Research Design and Methods: A total of 165 hyperglycemic patients (glucose ≥140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary angiography was performed at study entry and at 6-month follow-up. Blood samples for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF-α), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine) were collected immediately before and 24 h, 30 and 180 d after PCI. Results: After insulin infusion, mean plasma glucose during the peri-procedural period was greater in the CGC group than in the IGC group (CGC, 191 ± 15 mg/dl; IGC, 145 ± 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein, TNF-α), and monocyte chemoattractant-protein-1 were significantly higher in CGC patients compared with IGC patients. Moreover, ICG during PCI reduces restenosis by half (48 and 24%) at 6 months. During follow-up, there was no difference in mortality rates, glucose, inflammatory and oxidative stress markers among the groups. In-stent restenosis was positively associated with mean plasma glucose levels as well as oxidative stress and inflammatory markers during the insulin infusion period. Conclusions: In hyperglycemic patients with STEMI, optimal peri-procedural glycemic control by reducing oxidative stress and inflammation may improve the outcome after PCI.     

Mis-sorting of procathepsin D in metastogenic tumor cells is not due to impaired synthesis of the phosphomannosyl signal

Synthesis, processing and sorting of pro-cathepsin D (proCD), the precursor of a lysosomal protease involved in tumor-cell proliferation and invasion, were compared in various human tumor cell lines. In cultures of HepG2, HT29 and MCF7 cells the extracellular CD activity was up to 10 times higher than in cultures of U937 and MG63 cells. Ammonium chloride, which disrupts the pH-dependent receptor-mediated transport of lysosomal enzymes, exerted a differential effect on the secretion of CD activity in these cells. As judged by metabolic labeling and immunoprecipitation, the secretion of CD synthesized in 24 hr in MG63 and U937 cells was enhanced 4- to 10-fold by ammonium chloride, while it was only slightly increased in HepG2, HT29 and MCF7 cells. In all tumor cells examined, a portion of proCD was segregated into the endosomal-lysosomal pathway in the presence of ammonium chloride. However, the intralysosomal maturation of CD was only inhibited by this drug in HT29 and MCF7 cells. The Golgi-associated processing of proCD, leading to the synthesis of uncovered phosphomannosyl groups, proceeded with comparable efficiency in all tumor cells examined. These results suggest that hypersecretion of proCD in HepG2, HT29 and MCF7 cells is linked to transport mechanisms, as yet unidentified, which are independent of mannose-6-phosphate.Int. J. Cancer 70:561–566. © 1997 Wiley-Liss Inc.     

Characterization of Porous Scaffolds Fabricated by Joining Stacking Based Laser Micro-Spot Welding (JS-LMSW) for Tissue Engineering Applications

A novel manufacturing approach was used to fabricate metallic scaffolds. A calibration of the laser cutting process was performed using the kerf width compensation in the calculations of the tool trajectory. Welding defects were studied through X-ray microtomography. Penetration depth and width resulted in relative errors of 9.4%, 1.0%, respectively. Microhardness was also measured, and the microstructure was studied in the base material. The microhardness values obtained were 400 HV, 237 HV, and 215 HV for the base material, HAZ, and fusion zone, respectively. No significant difference was found between the microhardness measurement along with different height positions of the scaffold. The scaffolds’ dimensions and porosity were measured, their internal architecture was observed with micro-computed tomography. The results indicated that geometries with dimensions under 500 µm with different shapes resulted in relative errors of ~2.7%. The fabricated scaffolds presented an average compressive modulus ~13.15 GPa, which is close to cortical bone properties. The proposed methodology showed a promising future in bone tissue engineering applications.     

A 67 kDa non-hormone binding estradiol receptor is present in human mammary cancers

The presence of large amounts of a 67 kDa estradiol receptor that does not bind hormone was observed in 8 of 37 human mammary tumors (34 malignant and 3 benign). This form of receptor was detected by its conversion to hormone binding receptor by an endogenous tyrosine kinase in vitro. All 8 tumors were malignant. In these, the incubation of cytosol with ATP was seen to cause a 1- to 5-fold increase in estradiol-specific binding sites. These sites bound estradiol with physiological affinity, and their appearance was associated with tyrosine phosphorylation of estradiol receptor. The enzyme converting the non-hormone binding receptor into the hormone binding receptor is largely present in cytosol and scarce in membranes. It has been extensively purified. It is a 67 kDa protein under denaturating conditions, binds calmodulin-Sepharose in a Ca²⁺-dependent manner, is stimulated by Ca²⁺ and calmodulin, phosphorylates exogenous actin, is activated by the estradiol-receptor complex. The enzyme interacts with antibodies directed against the carboxy-terminal and catalytic domains of c-src. Therefore, it is a putative new member of the large c-src-related kinase family. Human mammary cancers with significant amounts of 67 kDa non-hormone binding receptor show relatively low levels of hormone binding estradiol receptor. The presence of non-hormone binding receptor that can be activated by in vitro tyrosine phosphorylation suggests that functional interaction of estradiol receptor with tyrosine kinases is altered in malignant tumors and has bearing on loss of hormone dependence and progression of the mammary cancer malignancy. © 1996 Wiley-Liss, Inc.     

Sonicated Diagnostic Immunoblot for Bartonellosis

Two simple Bartonella bacilliformis immunoblot preparation methods were developed. Antigen was prepared by two different methods: sonication of whole organisms or glycine extraction. Both methods were then tested for sensitivity and specificity. Well-defined control sera were utilized in the development of these diagnostic immunoblots, and possible cross-reactions were thoroughly examined. Sera investigated for cross-reaction with these diagnostic antigens were drawn from patients with brucellosis, chlamydiosis, Q fever, and cat scratch disease, all of whom were from regions where bartonellosis is not endemic. While both immunoblots yielded reasonable sensitivity and high specificity, we recommend the use of the sonicated immunoblot, which has a higher sensitivity when used to detect acute disease and produces fewer cross-reactions. The sonicated immunoblot reported here is 94% sensitive to chronic bartonellosis and 70% sensitive to acute bartonellosis. In a healthy group, it is 100% specific. This immunoblot preparation requires a simple sonication protocol for the harvesting of B. bacilliformis antigens and is well suited for use in regions of endemicity.     

Medical-legal evaluation of cardiac transplantation]

Heart transplantation is a curative surgical-medical procedure capable of radically modifying the prognosis of patients in the terminal phase who are non-responsive to other treatments and whose life expectancy is < 1 year, thus greatly increasing survival and distinctly improving their quality of life. The authors illustrate the numerous welfare and social security services, guaranteed by our Social Security System for such patient categories, with an overview of damage parameters within the medical-legal field, encompassing areas of civil responsibility. They therefore illustrate the changes, determined by the graft, on the patient's quality of life, while considering both the psycho-physical aspect and the family, social and working relationships before finally elaborating medical-legal guidelines for the assessment of such patients, for both biological damage and in their capacity for work, based on the pathophysiology of the transplanted heart.     

Neural networks in astronomy.

In the last decade, the use of neural networks (NN) and of other soft computing methods has begun to spread also in the astronomical community which, due to the required accuracy of the measurements, is usually reluctant to use automatic tools to perform even the most common tasks of data reduction and data mining. The federation of heterogeneous large astronomical databases which is foreseen in the framework of the astrophysical virtual observatory and national virtual observatory projects, is, however, posing unprecedented data mining and visualization problems which will find a rather natural and user friendly answer in artificial intelligence tools based on NNs, fuzzy sets or genetic algorithms. This review is aimed to both astronomers (who often have little knowledge of the methodological background) and computer scientists (who often know little about potentially interesting applications), and therefore will be structured as follows: after giving a short introduction to the subject, we shall summarize the methodological background and focus our attention on some of the most interesting fields of application, namely: object extraction and classification, time series analysis, noise identification, and data mining. Most of the original work described in the paper has been performed in the framework of the AstroNeural collaboration (Napoli-Salerno).     

AAV-mediated Tyrosinase Gene Transfer Restores Melanogenesis and Retinal Function in a Model of Oculo-cutaneous Albinism Type I (OCA1)

Oculo-cutaneous albinism type 1 (OCA1) is characterized by congenital hypopigmentation and is due to mutations in the TYROSINASE gene (TYR). In this study, we have characterized the morpho-functional consequences of the lack of tyrosinase activity in the spontaneous null mouse model of OCA1 (Tyr^c-2j). Here, we show that adult Tyr^c-2j mice have several retinal functional anomalies associated with photoreceptor loss. To test whether these anomalies are reversible upon TYR complementation, we performed intraocular administration of an adeno-associated virus (AAV)–based vector, encoding the human TYR gene, in adult Tyr^c-2j mice. This resulted in melanosome biogenesis and ex novo synthesis of melanin in both neuroectodermally derived retinal pigment epithelium (RPE) and in neural crest–derived choroid and iris melanocytes. Ocular melanin accumulation prevented progressive photoreceptor degeneration and resulted in restoration of retinal function. Our results reveal novel properties of pigment cells and show that the developmental anomalies of albino mice are associated with defects occurring in postnatal life, adding novel insights on OCA1 disease pathogenesis. In addition, we provide proof-of-principle of an effective gene-based strategy relevant for future application in albino patients.