Enantioselective syntheses and cytotoxicity of N,O-nucleosides

Enantiomers of 4'-aza-2',3'-dideoxynucleosides have been prepared by two different synthetic approaches, on the basis of 1,3-dipolar cycloaddition of a chiral nitrone. Cytotoxicity and apoptotic activity have been investigated. (5'S)-5-Fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione [(-)-AdFU], while showing low level of cytotoxicity, is a good inductor of apoptosis on lymphoid and monocytoid cells, acting as a strong potentiator of Fas-induced cell death.     

Cord blood endothelin-1 and perinatal asphyxia

Discordant data have been reported on endothelin-1 (ET-1), a potent endothelium-derived vasoconstriction peptide, during the neonatal period, and elevated levels have been found in various neonatal diseases. This study evaluated ET-1 in the cord blood of 74 neonates of different gestational age, birthweight, mode of delivery and 5'-Apgar score. CONCLUSION: Higher ET-1 levels were found in neonates born by emergency caesarean section, and in newborns with low 5'-Apgar score, suggesting that ET-1 could be a marker of perinatal asphyxia.     

Engaged urokinase receptors enhance tumor breast cell migration and invasion by upregulating alpha(v)beta5 vitronectin receptor cell surface expression

We have previously shown that urokinase receptor physically and functionally interacts with alpha(v)beta5 vitronectin receptor, leading to tumor breast cell migration and invasion. Here, the link between these 2 receptors was further investigated by analyzing the expression levels of urokinase receptor and alpha(v)beta5 integrin in 35 human breast carcinomas and 5 benign breast lesions. The occurrence of a positive correlation between urokinase receptor and alpha(v)beta5 protein levels in benign and malignant tumor specimens prompted us to investigate whether engaged urokinase receptors might modulate alpha(v)beta5 expression. Here, we report the receptor-dependent ability of catalytically inactive urokinase to upregulate the alpha(v) and beta5 chains in MDA-MB-231 and MCF-7 breast carcinoma cell lines in a time- and concentration-dependent manner. This effect is dependent on protein kinase C activity and requires new protein synthesis. Accordingly, the availability of assembled alpha(v)beta5 receptors on the cell surface increases upon urokinase treatment, as shown by immunoprecipitation and immunocytochemical analyses. Exposure to urokinase leads to enhanced tumor cell migration and invasion, which is prevented by the "phosphorylation-like" urokinase receptor antagonist His-uPA(138E/303E), the DNA-binding drug mithramycin, the protein kinase C inhibitor calphostin C and anti-alpha(v)beta5 antibodies. Finally, urokinase enables benign breast MCF-10A cells to cross Matrigel in a alpha(v)beta5- and urokinase receptor-dependent manner, indicating that urokinase controls a regulatory circuitry crucial to breast tumor progression.     

Plasminogen activator system modulates invasivecapacity and proliferation in prostatic tumor cells

The malignant phenotype of prostatic tumor cells correlates with the expression of both uPA and itscell-membrane receptor (uPAR); however, there is little information concerning the role of cell-bound uPAin matrix degradation and invasion. Our results suggest that cell-associated uPA plays a key role in regulat-ingthe amount of plasmin present at the surface of prostatic carcinoma (PRCA) cells and show that differ-entialproduction of uPA corresponds with the capacity to bind and activate plasminogen. In addition, weprovide direct evidence that both uPA secretion and the presence of uPA-uPAR complexes characterize theinvasive phenotype of PRCA cells and suggest the existence of several pathways by which tumor cells acquireplasmin activity. LNCaP cells (which do not produce uPA but express uPAR) may activate plasmin throughexogenous uPA. In vivo, the source of uPA may be infiltrating macrophages and/or fibroblasts as observedin several other systems. PAI-1 accumulation in the conditioned medium (CM) limits plasmin action to thepericellular microenvironment. Our results indicate that MMP-9 and MMP-2 are also activated by plasmingenerated by cell-bound but not by soluble, extracellular uPA. Plasmin activation and triggering of the pro-teolyticcascade involved in Matrigel invasion is blocked by antibodies against uPA (especially by anti- A-chainof uPA which interacts with uPAR) and by PA inhibitors such as p-aminobenzamidine which mayregulate levels of cell-bound uPA. uPA may also regulate growth in PRCA cells. Indeed, antibodies againstuPA A-chain (and also p-aminobenzamidine treatment) interfere with the ATF domain and inhibit cell growthin uPA-producing PC3 and DU145 prostate cancer cell lines, whereas exogenous uPA (HMW-uPA with ATF)induces growth of LNCaP prostate tumor cell line. These data support the hypothesis that in prostatic can-cerpatients at risk of progression, uPA/plasmin blockade may be of therapeutic value by blocking both growthof the primary tumor and dissemination of metastatic cells. ©Kluwer Academic Publishers     

The effect of voluntary termination of pregnancy on female sexual and emotional well-being in different age groups

Introduction: To evaluate the impact of voluntary termination of pregnancy (VTOP) on the psycho-sexological well-being of females before/six months after the abortion.

Methods: A sample of 194 women was recruited from three obstetrics and gynaecological divisions. The women were evaluated for the variables “sexual functioning” with the Female Sexual Function Index (FSFI), “depression” with the Beck Depression Inventory (BDI-II), and “anxiety state” with the Self-Rating Anxiety Scale (SAS) at time 0 (the beginning of the abortion procedure) and time 1 (six months after the abortion). Since 24 women refused to fill out the questionnaires, the final sample was composed of 170 women.

Results: The women showed a slight although significant improvement in the mean FSFI score from time 0 (16.7?±?12.9) to time 1 (20.9?±?13.8) (p?p?=?0.0241). The sub-group of younger women (18–25) showed a lesser increase in FSFI score from time 0 to time 1. In addition, both depression (p?=?0.048) and anxiety (p?Discussion: Voluntary TOP may influence the sexuality of younger females differently from how it influences that of older women. Hence, the sexuality of younger female should be regularly supervised in follow-up examinations.     

Composites based on carbon fibers and liquid crystalline epoxy resins, 1 Monomer synthesis and matrix curing

The synthesis and physical characterization of a novel liquid crystalline epoxy resin, used as a matrix for carbon fiber‐reinforced composites is presented in this paper. The curing reaction was monitored by means of calorimetric and rheological measurements. Calorimetric analysis indicates that the presence of carbon fibers does not affect the reaction rate. A conventional isotropic epoxy resin is used as a model compound in the rheological analysis. According to the patent literature, two different formulations of the model compound were used, characterized by a stoichiometric ratio of epoxy and an epoxy excess, respectively, with respect to the curing agent.     

Covid-19 Infection in Cancer Patients: The Management in a Diagnostic Unit

BackgroundCOVID-19 infection is particularly aggressive in frail patients, as cancer patients. Therefore, the more suitable management of the oncological patient requires a multidisciplinary assessment, to identify which patients should be treated, as inpatients or outpatients, and which treatments can be procrastinated.ConclusionsThe role of radiologist is crucial, and, all cancer patients who need an imaging evaluation will need to be studied, using the most appropriate imaging tools related to the clinical question and paying a special attention to preserve public health. Guidelines are necessary in the correct organization of a radiology unit to manage patients with suspected or confirmed COVID-19 infection, and whenever possible, a satellite radiography center with dedicated equipment should be used to decrease the transmission risk.Key words: COVID-19 infection, cancer patients, diagnostic unit, management, guideline     

Glutamate receptors in striatum and substantia nigra: Effects of medial forebrain bundle lesions

We examined NMDA-sensitive [³H]glutamate, [³H]AMPA, [³H]kainate and metabotropic-sensitive [³H]glutamate binding sites in neostriatum and substantia nigra pars reticulata (SNr) in rats after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. One week after the lesion, NMDA, AMPA, kainate and metabotropic receptors were decreased in the ipsilateral neostriatum, whereas at three months NMDA receptors were increased while AMPA, kainate and metabotropic receptors were not changed. In the SNr at one week, only AMPA and metabotropic receptors were significantly decreased whereas three months after the lesion NMDA, AMPA and kainate binding sites were decreased. The early decrease of excitatory amino acid receptors in the striatum is likely to reflect degeneration of dopaminergic fibers, suggesting that specific subpopulations of excitatory amino acid binding sites are located on dopaminergic terminals.     

Ligasure versus Ultracision® in thyroid surgery: a prospective randomized study

PURPOSE: New hemostatic technologies (NT) are often employed in thyroid surgery in the effort to reduce operating time and complications. The aim of this study is to compare three different hemostatic techniques. METHODS: This is a prospective randomized study. There were 150 patients, aged 56 +/- 14 years, randomized for total thyroidectomy with conventional technique (CT), Ligasure vessel sealing system (LI) or Harmonic Scalpel (HS) at the university surgical department. One hundred thirty-five patients had benign diseases; 15 had malignancies. RESULTS: Mean postoperative hospital stay was 2.6 days. Mean operation time was 113 +/- 31 min; in HS patients, it was significantly shorter (p < 0.001). Morbidity was 43.3%; mortality was nil. Morbidity was significantly different between CT and NT groups (p = 0.0002); HS and LI groups had a higher morbidity (p = 0.0001 and p = 0.02, respectively). Mean postoperative calcemia was 1.12 +/- 0.1 mmol/l with a significant difference between groups; NT patients had a significantly lower calcemia (p < 0.05). There was no difference in recurrent laryngeal nerve palsies and in intraoperative blood losses (p = ns). CONCLUSIONS: According to our experience, the only real advantage of new hemostatic technologies was a shorter operation time with HS.