Domain structure and miscibility studies of blends of styrene–butadiene–styrene block copolymers (SBS) and styrene–glycidyl methacrylate statistical copolymers (PS‐GMA) using SAXS and DMTA

The domain structure and miscibility in the solid state of a series of blends of styrene‐butadiene‐styrene (SBS) block copolymers and styrene‐glycidyl methacrylate (PS‐GMA) statistical copolymers with varying molecular weights and compositions were studied using small angle X‐ray scattering and dynamic mechanical thermal analysis. Depending on the molecular characteristics of each component, different types and degrees of solubilization of PS‐GMA in SBS were found which, in addition to the initially SBS phase morphology, lead to materials with multiphase domain morphologies with differences in size and structure. The degree of solubilization of PS‐GMA into the PS domains of SBS was found to be higher for blends containing PS‐GMA with lower molecular weight (M_w = 18 100 g mol^?1) and lower GMA content (1 wt%) and/or for SBS with higher PS content (39 wt%) and longer PS blocks (M_w = 19 600 g mol^?1). Localized solubilization of PS‐GMA in the middle of PS domains of SBS was found to be the most probable to occur for the systems under study, causing swelling of PS domains. However, uniform solubilization was also observed for SBS/PS‐GMA blends containing SBS with composition in the range of a morphological transition (PS block M_w = 19 600 g mol^?1 and 39 wt% of PS) causing a morphological transition in the SBS copolymer (cylinder to lamella). Copyright © 2006 Crown in the right of Canada. Published by John Wiley & Sons, Ltd     

Effects of olive oil and its minor phenolic constituents on obesity-induced cardiac metabolic changes

Background

Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes?

Methods

Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days.

Results

After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO₂) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO₂, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C.

Conclusions

The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

     

Percutaneous stereotactic differential radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia

PURPOSE: The purpose of this study was to evaluate the effectiveness of radiofrequency thermal rhizotomy (RTR) for trigeminal neuralgia, after failure of pharmacological management. PATIENTS AND METHODS: Two hundred fifteen patients underwent RTR from 1991 to 1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face, and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring reoperation, and the type and rate of complications. They were followed-up by serial clinical evaluation and telephone interview. Patients were categorized into groups: 1) Successful result: excellent, good pain relief; and 2) Unsuccessful result: fair, poor, or no pain relief. The RTR group was compared with historical controls. Follow-up ranged from 9 to 68 months (mean, 32 months) and results were evaluated at early and long-term follow-up. RESULTS: At early follow-up (defined as immediately postoperatively to 6 months), pain relief of excellent or good quality (successful result) occurred in 198 of 215 patients (92%). Fair or poor or no pain relief (unsuccessful result) occurred in 17 (8%) patients. At long-term follow-up (>6 months to 68 months), recurrence of pain that required reoperation occurred in 24 patients (11%) and recurrence of pain that did not require reoperation (medically managed) occurred in 34 patients (16%). Dysesthesia developed in 18 patients (8%); seven patients (3%) had dysesthesia alone (medically managed) and 11 patients (5%) had dysesthesia with recurrence of pain (medically or surgically managed). "Anesthesia/analgesia dolorosa" developed in four patients (1.8%) and was medically managed. At long-term follow-up, 83% of patients had good to excellent pain relief (successful result). There were no mortalities, no significant morbidity, and a low rate of minor complications. CONCLUSION: With the use of this specific diagnostic approach and management algorithm, patients with trigeminal neuralgia can be successfully managed.     

A refined kinetic analysis of plasminogen activation by recombinant bovine tissue-type plasminogen activator indicates two interconvertible activator forms

Bovine tissue-type plasminogen activator (tPA) was heterologously expressed in the methylotrophic yeast Pichia pastoris and characterized structurally and kinetically. The bovine single-chain tPA-mediated activation of bovine plasminogen was studied in the presence and absence of fibrinogen fragments. We have proposed a refined new method of kinetic analysis which allows examination of both stationary and prestationary phases of this process. The investigation revealed the presence of two interconvertible forms of the recombinant bovine tPA being in equilibrium at a 1 to 50 ratio. Only the minor form was able to bind and activate plasminogen. Saturation of the whole pool of tPA required high plasminogen concentration (Km >/= 5 microM) in order to reverse the equilibrium between the two forms. Fibrinogen fragments activated the single-chain tPA due to preferential binding and stabilization of the minor "active" form of the enzyme until all the molecules of tPA were converted. The same mechanism could be applied to human tPA as well. The Km values, obtained for recombinant bovine and human tPA in the presence of fibrinogen fragments, were found to be similar (Km = 0.1 microM) while kcat of human tPA was 5-10 times higher.     

Thermo-mechanical reliability during technology development of power chip-on-board assemblies with encapsulation

In this paper we examine the thermo-mechanical reliability of polymer-encapsulated chip-on-board (COB) assemblies for power applications by simulation and experiment. Thereby the focus is set on the low cycle fatigue failure behaviour of the die-attach material under thermal cycling conditions. As die-attach material different solder materials and Ag-filled thermal adhesives have been used. The encapsulation was performed with a soft silicone-based and hard silica-reinforced epoxy-based material, respectively. An other process variable takes into account die-tilt. The study was carried out as a feasibility analysis in the course of a COB technology development. To this end lifetime models have been employed to correlate crack growth in the, i.e. attach to a computational accumulative failure criterion which allows to consistently describe ad predict quantitatively the lifetime of the assemblies. Thereby a considerable influence of the encapsulation was found. In particular it could be shown that a hard encapsulation largely increases reliability for solder die-attach.

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Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis

PURPOSE: To investigate prospectively the utility of plasma transforming growth factor beta1 (TGFbeta1) as a marker for the development of symptomatic radiation pneumonitis. MATERIALS AND METHODS: Seventy-three patients with lung cancer treated with curative intent are reported herein. Plasma TGFbeta1 samples were obtained before, weekly during, and at each follow-up after radiation therapy (RT). TGFbeta1 was extracted using an acid/ethanol method. An enzyme-linked immunosorbent assay was used to quantify plasma TGFbeta1 concentrations. The TGFbeta1 level at the end of RT was considered "normal" if it was both < or = 7.5 ng/ml and less than the pretreatment value. All patients were followed for at least 6 months, unless symptomatic pneumonitis developed sooner. Pneumonitis was defined by National Cancer Institute (NCI) common toxicity criteria. RESULTS: Fifteen of the 73 patients (21%) developed symptomatic pneumonitis and the remaining 58 (79%) did not. A normal plasma TGFbeta1 by the end of RT, as defined above, was more common in patients who did not develop pneumonitis. A return of the plasma TGFbeta1 to normal accurately identified patients who would not develop pneumonitis with both a sensitivity and positive predictive value of 90%. CONCLUSION: Plasma TGFbeta1 levels appear to be a useful means to identify patients at low risk for the development of pneumonitis from thoracic RT. Thus, monitoring of plasma TGFbeta1 levels may identify candidates for dose escalation studies in the treatment of lung cancer.     

Acquisition of word-object associations by 14-month-old infants

The following experiments were designed to determine the age at which infants can first readily learn word--object pairings with only minimal exposure and without social or contextual support. To address this question, 8- to 14-month-old infants were tested on their ability to form word--object associations in a "switch" design. Infants were habituated to 2 word--object pairings and then tested with 1 trial that maintained a familiar word--object pairing and 1 that involved a familiar word and object in a new combination. Across 6 experiments, only 14-month-old infants formed word--object associations under these controlled testing conditions but appeared to do so only when the objects were moving. Although 8- to 12-month-olds did not form the associations, they appeared to process both the word and the object information. These studies provide strong evidence that 14-month-old infants can rapidly learn arbitrary associations between words and objects, that this ability appears to develop at about 14 months of age, and that the Switch design is a useful method for assessing word--object learning in infancy.     

Beta-adrenergic receptors, voltage-operated Ca(2+)-channels, nuclear triiodothyronine receptors and triiodothyronine concentration in pig myocardium after long-term low-dose amiodarone treatment

Similar features during chronic amiodarone treatment and hypothyroidism suggest that amiodarone induces a state of "triiodothyronine (T3)-resistance" or "cardiac hypothyroidism", which may predispose the heart to pump failure under conditions with severe strain, such as recovery after cardiac surgery. Disagreements exists as to how amiodarone, and possibly its main metabolite desethylamiodarone, act upon the various receptor systems in the heart. The aim of the present study was to elucidate whether chronic amiodarone treatment leads to a functional reduction in the number of myocardial nuclear T3 receptors, the myocardial tissue T3 concentration and the number of beta-receptors and voltage-operated Ca(2+)-channels. Finally, special attention was drawn to any changes that could contribute to explain previous reports on reduced haemodynamic reserve in animals exposed to severe cardiac strain, such as cardiac surgery. Pigs (72 +/- 2 kg) were assigned randomly to amiodarone treatment (20 mg.kg-1.day-1 for 30 +/- 1 days, N = 8); controls received no medical treatment (N = 6). The left ventricle was evaluated for beta-adrenergic receptors, voltage-operated Ca(2+)-channels, T3 nuclear receptors and tissue T3 concentration. Maximum binding capacity for beta-receptors and Ca(2+)-channels was reduced in amiodarone-treated pigs (by 38%, p < 0.05, and by 52%, p < 0.01) and correlated with tissue drug concentrations for both receptor types (p < 0.05). No changes were observed concerning nuclear T3 receptors. In vitro competition studies revealed that amiodarone, but not desethylamiodarone, possessed binding properties to Ca(2+)-channels, whereas neither of the compounds bound to beta-receptors. Desethylamiodarone, but not amiodarone, competitively inhibited T3 binding to its nuclear receptors. Myocardial T3 was undetectable (< 0.05 nmol/kg wet wt) in amiodarone-treated pigs. From our observations we suggest that the active metabolite desethylamiodarone, rather than the parent drug, is mainly responsible for the observed local hypothyroid-like effects during amiodarone treatment. The observed changes after treatment with low-dose amiodarone in pigs are likely to have biological implications. Functionally, the changes may imply reduced cardiac reserve during conditions of extraordinary strain.     

ATF3-Induced Mammary Tumors Exhibit Molecular Features of Human Basal-Like Breast Cancer

Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse models with tumors that resemble BLBC is important for human therapeutic development. ATF3 is a potent oncogene that is aberrantly expressed in most human breast cancers. In the BK5.ATF3 mouse model, overexpression of ATF3 in the basal epithelial cells of the mammary gland produces tumors that are characterized by activation of the Wnt/β-catenin signaling pathway. Here, we used RNA-Seq and microRNA (miRNA) microarrays to better define the molecular features of BK5.ATF3-derived mammary tumors. These analyses showed that these tumors share many characteristics of human BLBC including reduced expression of Rb1, Esr1, and Pgr and increased expression of Erbb2, Egfr, and the genes encoding keratins 5, 6, and 17. An analysis of miRNA expression revealed reduced levels of Mir145 and Mir143, leading to the upregulation of their target genes including both the pluripotency factors Klf4 and Sox2 as well as the cancer stem-cell-related gene Kras. Finally, we show through knock-down experiments that ATF3 may directly modulate MIR145/143 expression. Taken together, our results indicate that the ATF3 mouse mammary tumor model could provide a powerful model to define the molecular mechanisms leading to BLBC, identify the factors that contribute to its aggressiveness, and, ultimately, discover specific genes and gene networks for therapeutic targeting.     

Modulation of the antitumor activity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosoure a by O(6)-methyl-2'-deoxyguanosine--a new inhibitor of O(6)-alkylguanine-DNA-alkyltransferase

O6-Methyl-2'-deoxyguanosine (O6-MedG), a novel inhibitor of O6-alkylguanine-DNA alkyltransferase (O6-AGT), has been synthesized. The ability of O6-MedG to deplete the O6-AGT activity in leukemia L1210 and melanoma B16 cells in vivo has been studied. After intraperitoneal administration of O6-MedG to mice bearing leukemia L1210 or melanoma B16, the activity of O6-AGT in tumour cells decreased by 50%. Pretreatment of leukemia L1210 bearing mice with O6-MedG (200 mg/kg) 24 hours prior to ACNU (15 mg/kg) administration resulted in six out of seven 60-day survivors. Treatment of mice with ACNU (15 mg/kg) alone increased the life span by 200%. Treatment of melanoma B16 bearing mice with O6-MedG and 3 hours thereafter with ACNU resulted in a 50% inhibition of tumour growth, whereas the inhibiting effect of ACNU alone was 16%. There was no difference in leukemia growth when L1210/BCNU bearing mice were treated with O6-MedG followed by ACNU treatment. In vivo ACNU (15 mg/kg) produced a deep and prolonged inhibition of DNA, RNA and protein synthesis in leukemia L1210 cells. The DNA synthesis in leukemia L1210/BCNU cells was shown to recover more rapidly than in L1210 cells. The activities of DNA-polymerases alpha and beta and, especially, of O6-AGT were elevated in ACNU-resistant leukemia cells as compared with ACNU-sensitive cells. The activation of some repairing enzymes, such as O6-AGT, DNA-polymerases alpha and beta as well as increased levels of GSH may play a role in the development of drug resistance to ACNU.