Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Variable-gain up-converter with current reuse for 5-GHz WLAN applications

A variable-gain up-conversion mixer for 5-GHz WLAN applications is presented, whose input stage is based on a novel variable gain transconductor. The proposed topology features reduced power consumption by exploiting dc current reuse for mixer biasing. Moreover, a new low-consumption control circuit is introduced, which achieves a temperature-stable and linear-in-dB characteristic, providing a 40-dB dynamic range within ±1 dB gain error.     

Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor

Myoclonus of the middle ear is a rare condition characterized by abnormal repetitive muscle contractions of the tympanic cavity. In this paper we describe what we believe is the first reported case of continuous high-frequency objective tinnitus caused by middle ear myoclonus. During exploratory tympanomastoidectomy it was hypothesized that a small dural arteriovenous malformation not identified on previous tests was the cause of the tinnitus. However, complete disappearance of the tinnitus during administration of curare for anesthesia led us to believe that the tinnitus might have been caused by myoclonus of the middle ear. Sectioning of the stapedius and tensor tympani tendons rendered the patient asymptomatic and confirmed the diagnosis of middle ear myoclonus. At follow-up of one year, the patient's quality of life had improved substantially; the tinnitus did not recur and she no longer had vertigo.     

An Implicit Multistage Integration Method Including Projection for the Numerical Simulation of Constrained Multibody Systems

To be efficient, the simulation of multibody system dynamics requires fast and robust numerical algorithms for the time integration of the motion equations usually described by Differential Algebraic Equations (DAEs). Firstly, multistep schemes especially built up for second-order differential equations are developed. Some of them exhibit superior accuracy and stability properties than standard schemes for first-order equations. However, if unconditional stability is required, one must be satisfied with second-order accurate methods, like one-step schemes from the Newmark family.Multistage methods for which high accuracy is not contradictory with stringent stability requirements are then addressed. More precisely, a two-stage, third-order accurate Implicit Runge–Kutta (IRK) method which possesses the desirable properties of unconditional stability combined with high-frequency dissipation is proposed.Projection methods which correct the integrated estimates of positions, velocities and accelerations are suggested to keep the constraint equations satisfied during the numerical integration. The resulting time integration algorithm can be easily implemented in existing incremental/iterative codes. Numerical results indicate that this approach compares favourably with classical methods.     

Anthocyanins and betalains as light-harvesting pigments for dye-sensitized solar cells

We present the photoelectrochemical properties of dye-sensitized solar cells using natural pigments containing betalains and anthocyanins as sensitizers. The dyes extracted from grape, mulberry, blackberry, red Sicilian orange, Sicilian prickly pear, eggplant and radicchio have shown a monochromatic incident photon to current efficiency (IPCE) ranging from 40% to 69%. Short circuit photocurrent densities (J_sc) up to 8.8 mA/cm², and open circuit voltage (V_oc) ranging from 316 to 419 mV, were obtained from these natural dyes under 100 mW/cm² (AM 1.5) simulated sunlight. The best solar conversion efficiency of 2.06% was achieved with Sicilian prickly pear fruits extract. The influence of pH and co-absorbers on natural sensitizers, were investigated and discussed.     

Contribution of major lipophilic antioxidants to the antioxidant activity of basil extracts: an EPR study

BACKGROUND: The present research analyses the contribution of some lipid antioxidants to the antioxidant activity of lipophilic extracts from basil by an electron paramagnetic resonance (EPR) study using the stable free radical 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH). DPPH assay is considered an easy and accurate method with regard to measuring the antioxidant activity of plant extracts and EPR has already been employed to determine antioxidant activities of lipophilic plant extracts. RESULTS: Lipid extracts were obtained from basil grown hydroponically for 20 or 35 days from sowing and in soil for 35 days from sowing. Fast and slow rate constants were distinguishable in the decay kinetics of DPPH mixture added with lipid extract. Antioxidants with kinetics characterized by a fast decay rate were tocopherols and chlorophylls, whereas those characterized by a slow decay rate were carotenoids, among which were β‐carotene, lutein, β‐apo‐8′‐carotenal and zeaxanthin. The 20‐day hydroponically grown sample, which showed higher contents of tocopherol, chlorophyll and carotenoid molecules, was the sample endowed with the higher content of fast lipophilic antioxidants (FLA) and slow lipophilic antioxidants (SLA). CONCLUSION: The three samples showed different compositions of FLA and SLA, giving rise to different decay kinetics. Despite the differences, in all samples tocopherol contributed about 0.3% to the bulk of FLA, whereas the figure for chlorophyll was about 40%, evidencing the relevant but little‐studied role of chlorophyll as an antioxidant. Copyright © 2011 Society of Chemical Industry     

Quantification of glistenings in intraocular lenses using a ballistic-photon removing integrating-sphere method

An alternative method for quantification of glistenings in intraocular lenses (IOLs) using an integrating sphere with an adjustable back aperture to remove ballistic photons is presented. Glistenings in soft IOLs have been known for more than a decade; however, their severity and visual impact are still under investigation. A number of studies have been made to quantitatively describe glistenings in IOLs. Quantization and precise grading of IOLs will provide needed information to evaluate the severity and visual impact of glistenings in patients. We investigated the use of a simple modification of an integrating-sphere method to eliminate ballistic photons to quantitatively measure scattered light from glistenings in IOLs. The method described in this paper provides a simple and effective way to quantitatively characterize glistenings in vitro. It may be especially useful to quantify scattering associated with low-grade glistenings where the density of the scattering centers is low. Finally, the modified integrating-sphere method may also be generally applicable to quantitatively characterize scattering from other optical media.     

Combining Nonstably Infinite Theories

The Nelson–Oppen combination method combines decision procedures for first-order theories over disjoint signatures into a single decision procedure for the union theory. In order to be correct, the method requires that the component theories be stably infinite. This restriction makes the method inapplicable to many interesting theories such as, for instance, theories having only finite models. In this paper, we describe two extensions of the Nelson–Oppen method that address the problem of combining theories that are not stably infinite. In our extensions, the component decision procedures exchange not only equalities between shared variables but also certain cardinality constraints. Applications of our results include the combination of theories having only finite models, as well as the combination of nonstably infinite theories with the theory of equality, the theories of total and partial orders, and the theory of lattices with maximum and minimum. Calogero G. Zarba: Work done by this author at Stanford University and later at LORIA and INRIA-Lorraine.     

A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease

Objective: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease.

Methods: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders.

Results: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as demonstrated through in vitro studies on BALB 3T3 cells.

Conclusions: Prepared hydrogels show a potential application for oral treatment of celiac disease thanks to the possibility to release enzymes able to detoxify the gliadin peptide that induces the immunogenic response.