Ultraviolet photofragmentation spectroscopy of alkaline earth dication complexes with pyridine and 4-picoline (4-methyl pyridine)

A detailed experimental and theoretical study has been undertaken of the UV photofragmentation spectroscopy of the alkaline earth metal dications Mg(2+), Ca(2+), and Sr(2+) complexed with pyridine and 4-methyl pyridine (4-picoline). The ion complexes have been prepared using the pick-up technique and held in an ion trap where their internal temperature has been reduced to <150 K. Exposure of the trapped ions to tunable UV laser radiation leads to the appearance of photofragments with intensities that show significant variation as a function of wavelength. For all three metal dications, the resultant spectra show evidence of resolved features. Time-dependent density functional theory (TDDFT) has been used to identify possible electronic transitions that might be present in the [M(pyridine)(4)](2+) complexes (M = Mg, Ca, and Sr) within the wavelength range studied. These calculations show that the spectra are dominated by strong π* ← π and weaker π* ← n transitions localized on the pyridine ligands. The calculations correctly identify those regions of the experimental spectra where UV transitions begin to occur in the complexes and also the wavelengths at which absorption maxima are reached; however, more subtle features of the spectra are difficult to assign with confidence.     

Effect of tretinoin inclusion in dimethyl-beta-cyclodextrins on release rate from a hydrogel formulation

The aim of this work was to study the release, permeation and skin retention profiles of 0.05% tretinoin hydrogel formulations in which tretinoin was in free form or complexed with dimethyl-beta-cyclodextrin in a stoichiometry of 1:4. Theoretically, this complexation will mainly allow to: overcome drug’s low water solubility and low stability; enhance the drug permeation by promoting skin absorption and alleviate drug inducing local irritation. In vitro release, permeation and skin retention tests were performed in both formulations in order to compare the main advantages of this complexation. The influence of the thermodynamic activity on the drug release profile was also investigated. This study proved that tretinoin inclusion complexes formulation with excess of cyclodextrins had better release profile than the free tretinoin formulation. It was concluded that in this study, thermodynamic activity was not the driving force for the release rate improvement observed with cyclodextrins. Probably, this improvement was due to the increased availability of tretinoin near the membrane surface. In fact, the percentage of total drug that had been retained in the skin was 0.41?±?0.08% for complexed tretinoin gel and 0.17?±?0.04% for the free tretinoin gel.     

Hepatic sarcoidosis: MR appearances in patients with chronic liver disease

Purpose

To describe the MR appearances of hepatic sarcoidosis in patients with chronic liver disease and correlate the results with clinical stage of disease as measured with the Mayo end-stage liver disease (MELD) score.

Materials and methods

Twenty patients with chronic liver disease and histopathological diagnosis of hepatic sarcoidosis who underwent MR imaging were included in this study. Two abdominal radiologists retrospectively reviewed all images for the presence of cirrhosis, imaging pattern of the liver, intrahepatic biliary dilatation, presence of areas of parenchymal atrophy, presence of splenic nodules and lymphadenopathy. Imaging findings were correlated with the MELD score.

Results

Of the patients, 14/20 had imaging findings of cirrhosis, 9/20 had a large macronodular pattern of liver cirrhosis and 5/20 had a diffuse pattern of liver cirrhosis. Peripheral wedge-shaped areas of parenchymal atrophy were observed in 10 patients. The combination of a central macronodular pattern and peripheral atrophy was observed in 9/20 patients. The pattern of cirrhosis had statistically significant correlation with the presence of wedge-shaped areas of parenchymal atrophy (p < 0.005). No statistically significant difference was revealed between the clinical score of patients who had imaging findings consistent with cirrhosis and those who did not.

Conclusion

MR imaging appearances of chronic sarcoid liver disease are diverse and do not appear to correlate with severity of clinical disease. Large central regenerative nodules and wedge-shaped areas of peripheral parenchymal atrophy are frequent findings and may help to suggest the diagnosis.     

Catalytic Chain Transfer (co‐)Polymerization: Unprecedented Polyisoprene CCG and a New Concept to Tune the Composition of a Statistical Copolymer

Borohydrido‐halflanthanidocene/dialkylmagnesium combinations are found to be powerful catalytic systems for the chain transfer polymerization of isoprene and its copolymerization with styrene. A behavior close to a lanthanide catalyzed polyisoprene chain growth on magnesium is reported. Transmetalation is further shown to occur in the course of the statistical copolymerization of isoprene and styrene. For the same monomer feed, the amount of styrene inserted in the copolymer can be increased by a factor 3 using 10 equiv. dialkylmagnesium versus 1 in the range of our experimental conditions. Chain transfer in the course of a metal catalyzed statistical copolymerization may thus be viewed as a new and original way for the control of the composition of a copolymer.

     

Novel Antiretroviral Therapeutic Strategies for HIV

When the first cases of HIV infection appeared in the 1980s, AIDS was a deadly disease without any therapeutic alternatives. Currently, there is still no cure for most cases mainly due to the multiple tissues that act as a reservoir for this virus besides the high viral mutagenesis that leads to an antiretroviral drug resistance. Throughout the years, multiple drugs with specific mechanisms of action on distinct targets have been approved. In this review, the most recent phase III clinical studies and other research therapies as advanced antiretroviral nanodelivery systems will be here discussed. Although the combined antiretroviral therapy is effective in reducing viral loading to undetectable levels, it also presents some disadvantages, such as usual side effects, high frequency of administration, and the possibility of drug resistance. Therefore, several new drugs, delivery systems, and vaccines have been tested in pre-clinical and clinical trials. Regarding drug delivery, an attempt to change the route of administration of some conventional antiretrovirals has proven to be successful and surpassed some issues related to patient compliance. Nanotechnology has brought a new approach to overcoming certain obstacles of formulation design including drug solubility and biodistribution. Overall, the encapsulation of antiretroviral drugs into nanosystems has shown improved drug release and pharmacokinetic profile.     

Design of a Nasal Spray Based on Cardiospermum halicacabum Extract Loaded in Phospholipid Vesicles Enriched with Gelatin or Chondroitin Sulfate

The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg/mL) or chondroitin sulfate from catshark cartilages (Scyliorhinus canicula, 20 mg/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30°. Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state.     

Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.     

Comprehensive Two-Dimensional Gas Chromatography as a Powerful Strategy for the Exploration of Broas Volatile Composition

Broa is a Portuguese maize bread with characteristic sensory attributes that can only be achieved using traditional maize varieties. This study intends to disclose the volatile compounds that are mainly associated with the baking process of broas, which can be important contributors to their aroma. Twelve broas were prepared from twelve maize flours (eleven traditional maize varieties and one commercial hybrid). Their volatile compounds were analyzed by GC×GC–ToFMS (two-dimensional gas chromatography coupled with time-of-flight mass spectrometry) for an untargeted screening of the chemical compounds mainly formed during baking. It was possible to identify 128 volatiles that belonged to the main chemical families formed during this stage. Among these, only 16 had been previously detected in broas. The most abundant were furans, furanones, and pyranones, but the most relevant for the aroma of broas were ascribed to sulfur-containing compounds, in particular dimethyl trisulfide and methanethiol. Pyrazines might contribute negatively to the aroma of broas since they were present in higher amounts in the commercial broa. This work constitutes the most detailed study of the characterization of broas volatile compounds, particularly those formed during the Maillard reaction. These findings may contribute to the characterization of other maize-based foodstuffs, ultimately improving the production of foods with better sensory features.     

Sustainable Valorization of Tomato By-Products to Obtain Bioactive Compounds: Their Potential in Inflammation and Cancer Management

Tomato producing and processing industries present undoubted potential for industrial discarded products valorization whether due to the overproduction of fresh tomatoes or to the loss during processing. Although tomato by-products are not yet considered a raw material, several studies have suggested innovative and profitable applications. It is often referred to as “tomato pomace” and is quite rich in a variety of bioactive compounds. Lycopene, vitamin C, β-carotene, phenolic compounds, and tocopherol are some of the bioactives herein discussed. Tomato by-products are also rich in minerals. Many of these compounds are powerful antioxidants with anti-inflammatory properties besides modulating the immune system. Several researchers have focused on the possible application of natural ingredients, especially those extracted from foods, and their physiological and pharmacological effects. Herein, the effects of processing and further applications of the bioactive compounds present in tomato by-products were carefully reviewed, especially regarding the anti-inflammatory and anti-cancer effects. The aim of this review was thus to highlight the existing opportunities to create profitable and innovative applications for tomato by-products in health context.     

Spectroscopic investigation of interactions between dipeptides and vanadate(V) in solution

The reaction of vanadate(V) with a series of dipeptides (Val-Gln, Ala-Gln, Gly-Gln, Gly-Glu, and Ala-Gly) was investigated by UV-visible spectroscopy and multinuclear ((51)V, (14)N, (13)C) NMR spectroscopy in solution. It was possible to evaluate the formation constants of the corresponding complexes for which a molecular structure was proposed. Complex formation is favored by the presence of a functionalized or a sterically demanding side chain. The Val-Gln dipeptide which combines both properties exhibits one of the highest formation constant reported so far for dipeptides.