Combined differentiating therapy for myelodysplastic syndromes: a phase II study

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.     

Low temperature delamination of plastic encapsulated microcircuits

Plastic encapsulated microcircuits (PEMs) are increasingly being used in applications requiring operation at temperatures lower than the manufacturer’s recommended minimum temperature, which is 0°C for commercial grade components and −40°C for industrial and automotive grade components. To characterize the susceptibility of PEMs to delamination at these extreme low temperatures, packages with different geometries, encapsulated in both biphenyl and novolac molding compounds, were subjected to up to 500 thermal cycles with minimum temperatures in the range −40 to −65°C in both the moisture saturated and baked conditions. Scanning acoustic microscopy revealed there was a negligible increase in delamination at the die-to-encapsulant interface after thermal cycling for the 84 lead PQFPs encapsulated in novolac and for both 84 lead PQFPs and 14 lead PDIPs encapsulated in biphenyl molding compound. Only the 14 lead novolac PDIPs exhibited increased delamination. Moisture exposure had a significant effect on the creation of additional delamination.     

Use of the polymerase chain reaction in the diagnosis of leprosy

A case is described in which a pericardial branch of a nongrafted left internal mammary artery communicated directly with the distal left anterior descending artery, following saphenous vein bypass grafting. This type of collateralization following coronary artery bypass surgery seems to be very rare, and perhaps could protect the myocardium from severe ischemia.     

The effect of support morphology on the reaction of oxidative dehydrogenation of ethane to ethylene at short contact times

The oxidative dehydrogenation of ethane is carried out in short contact time reactors over Pt and LaMnO₃ based catalysts supported on a large number of different ceramic substrates (45, 60 and 80 ppi foam monoliths and 200, 400, 600, 900 and 1200 cpsi honeycomb monoliths). Experimental results, obtained under the same conditions at varying the C₂H₆/O₂ ratio, showed that the highest performance in terms of ethylene selectivity and yield is always attained on LaMnO₃ catalysts. Furthermore, the results are significantly influenced by the morphology and cell density of the support, with 45 and 60 ppi foams and 400 and 600 cpsi honeycombs giving the best performance. The experimental results are explained by means of geometrical and fluid dynamic considerations on the support, and by means of a 2D mathematical model, which clearly indicates an optimal intermediate cell density for maximising ethylene selectivity and yield.     

On the Use of the Flickermeter to Limit Low-Frequency Interharmonic Voltages

The possibility of using the IEC flickermeter for the assessment of the limits of low frequency interharmonic voltages is critically analyzed. The response of flickermeters to interharmonic components is analytically investigated, obtaining approximation formulas for the calculation of Pst in the presence of couples of components at frequencies that are symmetric with reference to the fundamental and in the presence of one or more single components. The instrument characteristics and limitations are also highlighted, using the results obtained from a numerical implementation of the IEC flickermeter. Finally, the general problem of the limits of low frequency interharmonic voltages is discussed and practical solutions are proposed.     

EGF/EGF-R system and benign breast disease during and following the treatment of gynaecological pathologies with an analogue of LH-RH

Clinical and pathological changes of the mammary gland have been studied in 64 women affected by symptomatic Benign Breast Disease (BBD) coexisting with endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They were evaluated clinically and ultrasonographically before and after treatment to find possible changes of BBD as well as of endometriosis or uterine leiomyomata. Mammary biopsies were performed before and after treatment in all the patients to study the changes of EGF-R expression. Results showed that clinical improvement is accompanied with a reduction of EGF-R expression.     

Degradation of lincomycin in aqueous medium: Coupling of solar photocatalysis and membrane separation

The photocatalytic oxidation of a common antibiotic, the lincomycin was carried out in aqueous suspensions of polycrystalline TiO₂ Degussa P25 irradiated by sunlight. In order to improve the performance of the lincomycin degradation a hybrid system consisting of a solar photoreactor with the photocatalyst in suspension coupled with a membrane module, used to confine both photocatalyst and pollutants in the reaction environment, was tested.A preliminary study was carried out in order to determine some kinetics parameters of the drug photodegradation. The influence of initial substrate concentration on the lincomycin photooxidation rate was investigated. The photooxidation rate follows a pseudo-first order kinetics with respect to the lincomycin concentration under the used experimental conditions. The presence of the membrane reactor allows the catalyst separation and to operate in continuous mode as the membranes rejection for lincomycin and its oxidation products was quite high.     

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.