Pomegranate extract affects fungal biofilm production: consumption of phenolic compounds and alteration of fungal autoinducers release

Candida albicans expresses numerous virulence factors that contribute to pathogenesis, including its dimorphic transition and even biofilm formation, through the release of specific quorum sensing molecules, such as the autoinducers (AI) tyrosol and farnesol. In particular, once organized as biofilm, Candida cells can elude conventional antifungal therapies and the host’s immune defenses as well. Accordingly, biofilm-associated infections become a major clinical challenge underlining the need of innovative antimicrobial approaches. The aim of this in vitro study was to assess the effects of pomegranate peel extract (PomeGr) on C. albicans growth and biofilm formation; in addition, the release of tyrosol and farnesol was investigated. The phenolic profile of PomeGr was assessed by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis before and after exposure to C. albicans. Here, we showed that fungal growth, biofilm formation and AI release were altered by PomeGr treatment. Moreover, the phenolic content of PomeGr was substantially hampered upon exposure to fungal cells; particularly pedunculagin, punicalin, punicalagin, granatin, di-(HHDP-galloyl-hexoside)-pentoside and their isomers as well as ellagic acid–hexoside appeared highly consumed, suggesting their role as bioactive molecules against Candida. Overall, these new insights on the anti-Candida properties of PomeGr and its potential mechanisms of action may represent a relevant step in the design of novel therapeutic approaches against fungal infections

Wrist electrogoniometry: are current mathematical correction procedures effective in reducing crosstalk in functional assessment?

BACKGROUND: The recording of human movement is an essential requirement for biomechanical, clinical, and occupational analysis, allowing assessment of postural variation, occupational risks, and preventive programs in physical therapy and rehabilitation. The flexible electrogoniometer (EGM), considered a reliable and accurate device, is used for dynamic recordings of different joints. Despite these advantages, the EGM is susceptible to measurement errors, known as crosstalk. There are two known types of crosstalk: crosstalk due to sensor rotation and inherent crosstalk. Correction procedures have been proposed to correct these errors; however no study has used both procedures in clinical measures for wrist movements with the aim to optimize the correction. OBJECTIVE: To evaluate the effects of mathematical correction procedures on: 1) crosstalk due to forearm rotation, 2) inherent sensor crosstalk; and 3) the combination of these two procedures. METHOD: 43 healthy subjects had their maximum range of motion of wrist flexion/extension and ulnar/radials deviation recorded by EGM. The results were analyzed descriptively, and procedures were compared by differences. RESULTS: There was no significant difference in measurements before and after the application of correction procedures (P<0.05). Furthermore, the differences between the correction procedures were less than 5° in most cases, having little impact on the measurements. CONCLUSIONS: Considering the time-consuming data analysis, the specific technical knowledge involved, and the inefficient results, the correction procedures are not recommended for wrist recordings by EGM

CYP2D6 and CYP2C8 pharmacogenetics and pharmacological interactions to predict imatinib plasmatic exposure in GIST patients

Patients on treatment with oral fixed dose imatinib are frequently under- or overexposed to the drug. We investigated the association between the gene activity score (GAS) of imatinib-metabolizing cytochromes (CYP3A4, CYP3A5, CYP2D6, CYP2C9, CYP2C19, CYP2C8) and imatinib and nor-imatinib exposure. We also investigated the impact of concurrent drug-drug-interactions (DDIs) on the association between GAS and imatinib exposure

Collagen Biomimetic Nanofibers reconstituted by a Novel Electrospinning Method

Collagen nanofibers mats have been obtained using a novel electrospinning method in water solution in the absence of organic solvents. The reconstituted collagen electrospun fibers exhibit pysico-chemical properties very close to the natural ones; their structure, morphology, thermal stability and mechanical behaviour allow to consider them really biomimetic. These properties make them particularly suitable for biomedical applications

A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting

Biomimetic reconstituted collagen fibers from molecular suspensions

Collagen is the main structural component of extracellular matrix (ECM) in many biological tissues. On the basis of its peculiar physico-chemical properties it is considered the highest module protein in connective tissue. Reconstituted collagen fibers have been obtained from single molecule collagen suspensions telopeptides-free following three different routes: either by changing the pH solution or by electrochemically assisted deposition or by electrospinning methods. For all the applications, type I collagen was extracted from horse Achilles tendon using the standardized manufacting method of OPOCRIN SpA and made clear of glycosaminoglycan fraction. The first route is based on the collagen auto-assembling properties using a sol/gel type reaction to yield collagen fibrils, identified by SDS-PAGE analysis, which organize in network through freeze-drying. The second route leads to electrochemically-assisted deposition of collagen fibrils on Ti plates by an electrolytic process: to purely helical collagen molecules suspended in 0.9 wt% NaCl water solution a constant current for different periods of time is apllied at room temperature