Nitric oxide delivery by ultrasonic cracking: some limitations

Nitric oxide (NO) has been implicated in smooth muscle relaxation. Its use has been widespread in cardiology. Due to the effective scavenging of NO by hemoglobin, however, the drug has to be applied locally or in large quantities, to have the effect desired. We propose the use of encapsulated microbubbles that act as a vehicle to carry the gas to a region of interest. By applying a burst of high-amplitude ultrasound, the shell encapsulating the gas can be cracked. Consequently, the gas is released upon which its dissolution and diffusion begins. This process is generally referred to as (ultra)sonic cracking. To test if the quantities of released gas are high enough to allow for NO-delivery in small vessels (?<200 microm), we analyzed high-speed optical recordings of insonified stiff-shelled microbubbles. These microbubbles were subjected to ultrasonic cracking using 0.5 or 1.7 MHz ultrasound with mechanical index MI>0.6. The mean quantity released from a single microbubble is 1.7 fmol. This is already more than the NO production of a 1mm long vessel with a 50 microm diameter during 100 ms. However, we simulated that the dissolution time of typical released NO microbubbles is equal to the half-life time of NO in whole blood due to scavenging by hemoglobin (1.8 ms), but much smaller than the extravascular half-life time of NO (>90 ms). We conclude that ultrasonic cracking can only be a successful means for nitric oxide delivery, if the gas is released in or near the red blood cell-free plasma next to the endothelium. A complicating factor in the in vivo situation is the variation in blood pressure. Although our simulations and acoustic measurements demonstrate that the dissolution speed of free gas increases with the hydrostatic pressure, the in vitro acoustic amplitudes suggest that the number of released microbubbles decreases at higher hydrostatic pressures. This indicates that ultrasonic cracking mostly occurs during the expansion phase.     

Electron energy-dependent product state distributions in the dissociative recombination of O2+

We present product state distributions and quantum yields from the dissociative recombination reaction of O2+ in its electronic and vibrational ground states as a function of electron collision energy between 0 and 300 meV. The experiments have been performed in the heavy-ion storage ring, CRYRING, and use a cold hollow-cathode discharge source for the production of cold molecular oxygen ions. The branching fractions over the different dissociation limits show distinct oscillations while the resulting product quantum yields are largely independent of electron collision energy above 40 meV. The branching results are well reproduced assuming an isotropic dissociation process, in contrast with recent theoretical predictions.     

Raman spectroscopic study of Lactarius spores (Russulales, Fungi)

Fungi are important organisms in ecosystems, in industrial and pharmaceutical production and are valuable food sources as well. Classical identification is often time-consuming and specialistic. In this study, Raman spectroscopy is applied to the analysis of fungal spores of Lactarius, an economically and ecologically important genus of Basidiomycota. Raman spectra of spores of Lactarius controversus Pers.: Fr., Lactarius lacunarum (Romagn.) ex Hora, Lactarius quieticolor Romagn. and Lactarius quietus (Fr.: Fr.) Fr. are reported for the first time. The spectra of these species show large similarity. These spectra are studied and compared with the Raman spectra of reference substances known to occur in macrofungi, including saccharides, lipids and some minor compounds that may serve as specific biomarkers (adenine, ergosterol and glycine). Most Raman bands could be attributed to specific components. In agreement with the biological role of fungal spores, high amounts of lipids were observed, the main fatty acid being oleate. In addition to different types of lipids and phospholipids, the polysaccharides chitin and amylopectin could be detected as well. The presence of trehalose is not equivocally shown, due to overlapping bands. Raman band positions are reported for the observed bands of the different species and reference products.     

Visible-light triggered templated ligation on surface using furan-modified PNAs

Oligonucleotide-templated reactions are frequently exploited for target detection in biosensors and for the construction of DNA-based materials and probes in nanotechnology. However, the translation of the specifically used template chemistry from solution to surfaces, with the final aim of achieving highly selective high-throughput systems, has been difficult to reach and therefore, poorly explored. Here, we show the first example of a visible light-triggered templated ligation on a surface, employing furan-modified peptide nucleic acids (PNAs). Tailored photo-oxidation of the pro-reactive furan moiety is ensured by the simultaneous introduction of a weak photosensitizer as well as a nucleophilic moiety in the reacting PNA strand. This allows one to ensure a localized production of singlet oxygen for furan activation, which is not affected by probe dilution or reducing conditions. Simple white light irradiation in combination with target-induced proximity between reactive functionalities upon recognition of a short 22mer DNA or RNA sequence that functions as a template, allows sensitive detection of nucleic acid targets in a 96 well plate format.

Pinpoint production of singlet oxygen was exploited for a self-contained light-triggered activation of a pro-reactive furan moiety, allowing selective and templated surface modification by recognition of short 22mer oligonucleotides.     

Synthesis of DOTA-conjugated multivalent cyclic-RGD peptide dendrimers via 1,3-dipolar cycloaddition and their biological evaluation: implications for tumor targeting and tumor imaging purposes

This report describes the design and synthesis of a series of alpha(V)beta(3) integrin-directed monomeric, dimeric and tetrameric cyclo[Arg-Gly-Asp-d-Phe-Lys] dendrimers using "click chemistry". It was found that the unprotected N-epsilon-azido derivative of cyclo[Arg-Gly-Asp-d-Phe-Lys] underwent a highly chemoselective conjugation to amino acid-based dendrimers bearing terminal alkynes using a microwave-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition. The alpha(V)beta(3) binding characteristics of the dendrimers were determined in vitro and their in vivoalpha(V)beta(3) targeting properties were assessed in nude mice with subcutaneously growing human SK-RC-52 tumors. The multivalent RGD-dendrimers were found to have enhanced affinity toward the alpha(V)beta(3) integrin receptor as compared to the monomeric derivative as determined in an in vitro binding assay. In case of the DOTA-conjugated (111)In-labeled RGD-dendrimers, it was found that the radiolabeled multimeric dendrimers showed specifically enhanced uptake in alpha(V)beta(3) integrin expressing tumors in vivo. These studies showed that the tetrameric RGD-dendrimer had better tumor targeting properties than its dimeric and monomeric congeners.     

Injectable peptide-based hydrogel formulations for the extended in vivo release of opioids

To overcome drawbacks related to repeated opioid administration during the treatment of chronic pain, several controlled-drug delivery systems of opioids have been designed. In order to address some of the limitations of the existing systems, injectable peptide-based hydrogels represent a promising alternative. This work reports on the design and synthesis of short amphipathic peptide-based hydrogels as controlled-drug delivery systems for opioids. Based on the lead sequence H-FEFQFK-NH₂, a new set of peptide hydrogelators was designed including β-homo and d-amino acids, mainly aiming at enhancing proteolytic resistance of the peptides, and which hypothetically allows an extension of the drug release period. After self-assembly in aqueous media, the resulting hydrogels were characterized by dynamic rheometry, cryogenic transmission electronic microscopy and their cytotoxicity was assessed. The cryoTEM images of drug loaded hydrogels show the association of microcrystals of the loaded drug along the axes of the fibres, suggesting that the peptide fibres play a key-role as nucleating site for the drug crystals. Hydrogelators devoid of cytotoxicity were considered for further in vivo evaluation. Upon encapsulation of morphine and 14-methoxymetopon, two opioid analgesics, the applicability of the peptide hydrogels as controlled-drug delivery platforms was validated in vivo using the mouse tail-flick test. A sustained antinociceptive effect was observed after subcutaneous injection of the drug loaded gels and, in comparison with the lead sequence H-FEFQFK-NH₂, novel sequences revealed extension of the in vivo antinociception up to 72–96 h post injection.     

Separating Growth from Nucleation for Facile Control over the Size and Shape of Palladium Nanocrystals

In order to maximize the performance of nanocrystals in a specific application, it is necessary to control both their size and shape. Here we report a one-pot protocol that allows us to separate growth from nucleation for achieving better control over the size and shape of Pd nanocrystals. The two processes are temporally separated from each other, although the synthesis is carried out in the same reaction container. Size control is achieved by simply varying the ratio between the amounts of precursor allocated to the growth and nucleation processes. With the involvement of seeds at a fixed number, increasing the amount of precursor for growth leads to increasingly larger nanocrystals. Shape control is made possible by varying the capping agent, with bromide leading to a cubic shape and citrate inducing the formation of an octahedral shape. The synthesis can also be scaled up by at least tenfold without compromising the quality.     

Saturated long linear aliphatic chain sodium monocarboxylates for the corrosion inhibition of lead objects—an initiative towards the conservation of our lead cultural heritage

In this study, sodium salts of saturated linear carboxylic acids with the general formula CH₃(CH₂) _n?2COONa (n = 14, 18)—labeled NaC₁₄ and NaC₁₈—were used to inhibit the corrosion of metallic lead via the development of protective coatings for lead heritage objects. The salts were dissolved in water/ethanol 1:1 (V/V) mixture at 50 °C to increase their solubility, and the coatings were formed by immersing lead samples in the resulted solutions for 24 h. The coatings were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. A hydrophobic layer of lead carboxylates appeared to form on the metal surface, and its corrosion inhibition properties were examined by linear sweep voltammetry and electrochemical impedance spectroscopy in a corrosive solution simulating the environment of museums with uncontrolled conditions. The lead carboxylates formed a protective barrier that inhibited further lead corrosion.

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