Core Cross-Linked Amphiphilic Star-Block Copolymers with (Meth)acrylic Acid Shells Prepared by Atom Transfer Radical Polymerization

Core cross-linked amphiphilic star-block copolymers were prepared by hydrolysis of the outer shell of star-block copolymers prepared using copper mediated atom transfer radical polymerization (ATRP). In an arm-first approach, linear poly(tert-butyl methacrylate) macroinitiators (PtBMA-Cl) were extended with styrene to yield PtBMA-b-PS-Cl and then cross-linked with divinylbenzene (DVB) in order to yield (PtBMA-b-PS)_arms-PDVB_core star-block copolymers. Then, PMAA-b-PS block and (PMAA-PS)_arms-PDVB_core star-block copolymers were obtained by hydrolysis of the PtBMA blocks in both linear and cross-linked copolymers, as confirmed by ¹H NMR analyses. The amphiphilic character of these copolymers was confirmed by solubilisation in water. Several factors affecting the polymer aggregation and solubility such as the length, the composition of the arms and the catalyst used were studied. An acrylate analogue, that is, (PAA-b-PS)_arms-PDVB_core, was also prepared for comparison purposes. Atomic force microscopy (AFM) and differential scanning calorimetry (DSC) were used to elucidate the morphology and the thermal behaviour of the star-block copolymers.     

Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

Miscibility and morphology of poly(vinylidene fluoride)/poly[(vinylidene fluoride)‐ran‐trifluorethylene] blends

This study presents an investigation of the effect of the different crystalline phases of each blend component on miscibility when blending poly(vinylidene fluoride) (PVDF) and its copolymer poly[(vinylidene fluoride)‐ran‐trifluorethylene] [P(VDF–TrFE)] containing 72 mol % of VDF. It was found that, when both components crystallized in their ferroelectric phase, the PVDF showed a strong effect on the crystallinity and phase‐transition temperature of the copolymer, indicating partial miscibility in the crystalline state. On the other hand, immiscibility was observed when both components, after melting, were crystallized in their paraelectric phase. In this case, however, a decrease in crystallization temperatures suggested a strong interaction between monomers in the liquid state. Blend morphologies indicated that, in spite of the lack of miscibility in the crystalline state, there is at least miscibility between PVDF and P(VDF–TrFE) in the liquid state, and that a very intimate mixture of the two phases on the lamellar level can be maintained upon crystallization. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1362–1369, 2002     

Effect of Silicon Substitution on the Sintering and Microstructure of Hydroxyapatite

The substitution of between 0 and 1.6 wt% silicon (Si-HA) in hydroxyapatite (HA) inhibited densification at low temperatures (1000°–1150°C), with these effects being more significant as the level of silicon substitution was increased. For higher sintering temperatures (1200°–1300°C), the sintered densities of HA and Si-HA compositions were comparable. Examination of the ceramic microstructures by scanning electron microscopy (SEM) showed that silicon substitution also inhibited grain growth at higher sintering temperatures (1200°–1300°C). The negative effect of silicon substitution on the sintering of HA at low temperatures (1000°–1150°C) was reflected in the hardness values of the ceramics. However, for higher sintering temperatures, e.g., 1300°C, where sintered densities were comparable, the hardness values of Si-HA compositions were equal to or greater than that of HA, reflecting the smaller grain sizes observed for the former.     

Dielectric behavior of PVDF/POMA blends that have a low doped POMA content

The real (ε′) and imaginary (ε″) components of the complex permittivity of blends of PVDF [poly(vinylidene fluoride)] with POMA [poly(o‐methoxyaniline)] doped with toluenosulfonic acid (TSA) containing 1, 2.5, and 5 wt % POMA–TSA were determined in the frequency interval between 10² and 3 × 10⁶ Hz and in the temperature range from ?120 up to 120°C. It was observed that the values of ε′ and ε″ had a greater increase with the POMA–TSA content and with a temperature in the region of frequencies below 10 kHz. This effect decreased with frequency and it was attributed to interfacial polarization. This polarization was caused by the blend heterogeneity, formed by conductive POMA–TSA agglomerates dispersed in an insulating matrix of PVDF. The equation of Maxwell–Garnett, modified by Cohen, was used to evaluate the permittivity and conductivity behavior of POMA–TSA in the blends. A strong decrease was observed in POMA–TSA conductivity in the blend, which was bigger the lower the POMA–TSA content in the blend. This decrease could have been caused either by the POMA dedoping during the blend preparation process or by its dispersion into the insulating matrix. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 752–758, 2003     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

Design,Synthesis, and Evaluation of WC5 Analogues as Inhibitors of Human Cytomegalovirus Immediate‐Early 2 Protein,a Promising Target for Anti‐HCMV Treatment

Although human cytomegalovirus (HCMV) infection is mostly asymptomatic for immunocompetent individuals, it remains a serious threat for those who are immunocompromised, in whom it is associated with various clinical manifestations. The therapeutic utility of the few available anti‐HCMV drugs is limited by several drawbacks, including cross‐resistance due to their common mechanism of action, i.e., inhibition of viral DNA polymerase. Therefore, compounds that target other essential viral events could overcome this problem. One example of this is the 6‐aminoquinolone WC5 , which acts by directly blocking the transactivation of essential viral Early genes by the Immediate‐Early 2 (IE2) protein. In this study, the quinolone scaffold of the lead compound WC5 was investigated in depth, defining more suitable substituents for each of the scaffold positions explored and identifying novel, potent and nontoxic compounds. Some compounds showed potent anti‐HCMV activity by interfering with IE2‐dependent viral E gene expression. Among them, naphthyridone 1 was also endowed with potent anti‐HIV activity in latently infected cells. Their antiviral profile along with their innovative mechanism of action make these anti‐HCMV quinolones a very promising class of compounds to be exploited for more effective antiviral therapeutic treatment.     

Preparation of 2H‐1,4‐Benzoxazin‐2‐one Derivatives under Heterogeneous Conditions via Domino Process

Carbonate on polymer is a valuable solid supported reagent (SSR) to promote, under eco‐friendly conditions, the preparation of 2H‐1,4‐benzoxazin‐2‐one derivatives starting from β‐nitroacrylates and aminophenols via a domino process.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.