Biological chemistry of organotin compounds: Interactions and dealkylation by dithiols

In this paper, we review our past and current efforts toward the elucidation of the biological chemistry of organotin compounds. In particular, we cover two prominent aspects of organotin compounds: their reactivity toward biological dithiols, and their degradation (or metabolization) mechanism using a combination of experimental and computational techniques.     

Interactions of alkyltin salts with biological dithiols: dealkylation and induction of a regular beta-turn structure in peptides

Organotin compounds specifically target vicinal dithiols, thereby inhibiting the function of essential enzymes. Here, we present the NMR binding studies of trimethyltin (TMT) and dimethyltin (DMT) chlorides with a linear peptide (ILGCWCYLR) derived from the membrane protein stannin (SNN). We show that this peptide is able to dealkylate TMT and bind DMT, adopting a stable type-I beta-turn conformation. Both the NMR data and the calculated structures indicate that the two cysteines coordinate the tin atom in a distorted tetrahedral geometry. The molecular geometries and tin coordination state were confirmed using density functional theory (DFT). In addition, NMR spectral parameters back calculated from the DFT minimized structure compared well with experimental data. These results in conjunction with studies on peptide variants (i.e., C4S, C6S, and Y7F) demonstrate unequivocally the key role of biological dithiols in both the dealkylation and binding of organotin compounds. This peptide serves as a model system for alkyltin-protein interactions and gives new insights into the biological fate of alkyltin compounds.     

Health benefits of pistachios consumption

The health benefits of nuts, mainly in relation to the improvement of dysmetabolic conditions such as obesity, type 2 diabetes mellitus and the related cardiovascular diseases, have been widely demonstrated. Compared to other nuts, pistachios have a lower fat and caloric content, and contain the highest levels of unsaturated fatty acids, potassium, γ-tocopherol, phytosterols and xanthophyll carotenoids, all substances that are well known for their antioxidant and anti-inflammatory actions. This variety of nutrients contributes to the growing body of evidence that the consumption of pistachios improves health, leading to a greater potential of healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. The present review examines the nutrients and phytochemicals present in pistachios as well as the potential health benefits of including pistachios in a diet.     

UWB body area network channel modeling: An analytical approach

The aim of this work is to develop an analytically-based approach for ultra wide band (UWB) body area network (BAN) channel modeling. In detail, the body will be modeled as multi-layered stratified cylinders of infinite length, and the Maxwell's equation will be solved for plane wave and line source excitations. Human-type tissues will be assumed in the multi-layered stratified cylindrical model. Validation of the procedure through measurement results has been provided.     

Trastuzumab quantification in serum: a new,rapid, robust ELISA assay based on a mimetic peptide that specifically recognizes trastuzumab

Trastuzumab, a humanized monoclonal antibody directed against the epidermal growth factor receptor 2 (HER2), is a milestone in the treatment of HER2-overexpressing breast cancer patients. An enzyme-linked immunosorbent assay (ELISA) for trastuzumab has been developed for routine use in the laboratory to support clinical and pharmacokinetic studies to optimize therapy. The method relies on an antigen peptide linked to a 96-well plate via the streptavidin/biotin system. The peptide sequence mimics the extracellular portion of the HER2 receptor that is recognized by trastuzumab. The calibration range of the assay is 10 to 360 ng/mL per well, corresponding to a trastuzumab serum concentration from 5 to 180 μg/mL with a lower limit of quantification of 10 μg/mL. Validation results demonstrate that trastuzumab can be accurately and precisely quantified in human serum using this assay. The procedure was also tested in sera obtained from breast cancer patients to evaluate trastuzumab serum levels, confirming the applicability of method that could be a valid assay to use in daily laboratory practice.     

PHRONESIS: A One-Shot Approach for Sequential Assignment of Protein Resonances by Ultrafast MAS Solid-State NMR Spectroscopy

Solid-state NMR (ssNMR) spectroscopy has emerged as the method of choice to analyze the structural dynamics of fibrillar, membrane-bound, and crystalline proteins that are recalcitrant to other structural techniques. Recently, ¹H detection under fast magic angle spinning and multiple acquisition ssNMR techniques have propelled the structural analysis of complex biomacromolecules. However, data acquisition and resonance-specific assignments remain a bottleneck for this technique. Here, we present a comprehensive multi-acquisition experiment (PHRONESIS) that simultaneously generates up to ten 3D ¹H-detected ssNMR spectra. PHRONESIS utilizes broadband transfer and selective pulses to drive multiple independent polarization pathways. High selectivity excitation and de-excitation of specific resonances were achieved by high-fidelity selective pulses that were designed using a combination of an evolutionary algorithm and artificial intelligence. We demonstrated the power of this approach with microcrystalline U-¹³C,¹⁵N GB1 protein, reaching 100 % of the resonance assignments using one data set of ten 3D experiments. The strategy outlined in this work opens up new avenues for implementing novel ¹H-detected multi-acquisition ssNMR experiments to speed up and expand the application to larger biomolecular systems.     

Analysis of Realistic Ultrawideband Indoor Communication Channels by Using an Efficient Ray-Tracing Based Method

A fundamental step in ultrawideband (UWB) communication system design involves the characterization of the indoor propagation channel. In this paper, we show that the UWB propagation channel parameters can be accurately predicted by employing ray tracing (RT) simulation carried out at various frequencies over the signal bandwidth. It is important to note that the determination of the rays reaching a given location is made only once, as the RT algorithm is independent of frequency. A parallel ray approximation (PRA) is used to significantly improve the computational efficiency of the RT based method. Moreover the accuracy of the approximation is verified through a measurement campaign.     

Extraction and analysis of cosmetic active ingredients from an anti-cellulitis transdermal delivery system by high-performance liquid chromatography

A new transdermal delivery system that controls cellulitis is evaluated using reversed-phase high-performance liquid chromatography coupled with photodiode array detection. An extraction procedure and the validation of the analytical method to assay the active excipients from the Centella asiatica plant (asiaticoside, madacessic acid, and asiatic acid) are described. Excellent results ae obtained in terms of linearity, accuracy, and specificity of the analytical method.     

Bernoulli Elliptical Stadia

 Let Q _a,h be a convex region of the plane whose boundary consists of two semiellipses joined by two (straight) lines parallel to the major axis of the semiellipses (elliptical stadium). The axes of the semiellipses have length 2 and 2a,a>1, and the lines have length 2h. For and we give a complete proof of the following result: the billiard map in the elliptical stadium Q _a,h is ergodic, K-mixing and Bernoulli with respect to the natural billiard measure. Received: 10 May 2002 / Accepted: 24 June 2002 Published online: 10 January 2003 RID="*" ID="*" Present address: Department of Mathematics, Instituto Superior Técnico, 1049-001 Lisbon, Portugal. E-mail:delmagno@math.ist.utl.pt Communicated by G. Gallavotti     

Complexation of Manidipine with Cyclodextrins and their Derivatives

Manidipine (MDP,(±)-2-[-(diphenylmethyl)-1-piperazinyl]ethylmethyl-1,4-dihydro-2,6-dimethyl-4(m-nitrophenyl)-3,5-pyridinedicarboxylate methyl-ester) is a poorlysoluble (<1 g/mL) long acting antihypertensive drug. Salt formingwith citric or tartaric acid results in a 400 to 600 fold solubilityenhancement, respectively, which can be further increased by an order ofmagnitude with cyclodextrins. Dimethyl-CD alone results in a more than8000 fold solubility enhancement. Besides the strongly enhanced solubility¹HNMR spectroscopy also proves the inclusion-type interactionbetween Manidipine and cyclodextrins. From the attained 5-8 mg/mL solubilityof the drug in water an improved bioavailability and pharmacokinetics isexpected.