Metabolomic fingerprint of Hamamelis virginiana L. gallotannins by suspect screening analysis with UHPLC-qToF and their semiquantitative evaluation.

The evolution of the regulatory framework for medical devices in the EU (Reg 2017/745) has opened the study of complex systems emerging properties. This makes necessary to identify new analytical approaches able of characterizing complex natural substrates as completely as possible. Therefore, omics approaches and advanced analytical methods for the determination of metabolite classes appear to be at the forefront to meet this need. In this perspective, a new approach based on the suspect screening was developed to detect gallotannins. Gallotannins are a class of phenols with a polymeric nature; thus, there are no pure analytical standards available for all possible structures and their quali-quantitative determination in complex natural substrates can be a challenge. A new UHPLC-qToF method was developed and used to create an "in-house tannin database" with a dual purpose: (1) as a classic list of suspects and (2) to identify core fragments common to gallotannins to have another list of putative suspects based on the common fragment. The method was validated. The application of the method to a "system of molecules" extracted from the leaves of Hamamelis virginiana L. (Witch-hazel) allowed to the characterization of a total of 29 phenols by a suspect screening approach. Therefore, 15 gallotannins were putatively annotated while another 3 were confidently identified. All the gallotannins were semiquantified according to external regression curves of gallic acid and hamamelitannin based on core fragments at m/z 125.0244 and m/z 169.0142, the building blocks of the polymers. This new method provides a practical fit-to-purpose approach for the quali-quantitative screening evaluation of gallotannins, useful for creating multivariate control charts applicable in process development of complex natural systems or in quality control. The approach is innovative, and after specific checks, it can in principle be suitable for metabolomic fingerprint analysis of gallotannins among witch-hazel extract (WHE) samples.

Prescribing Practices in Geriatric Patients with Cardiovascular Diseases.

Inappropriate prescribing (IP) increases the risk of adverse medication reactions and hospitalizations in elderly patients. Therefore, it is crucial to evaluate prescribing patterns among this population. This study was designed to assess the prevalence of potentially inappropriate medication (PIMs) use and potential prescribing omissions (PPOs) among geriatrics with cardiovascular diseases (CVDs). In addition, it determined the predictors for IP in this population. A multi-center study was performed retrospectively on 605 patients' medical records collected randomly from seven governmental hospitals in Kuwait. Three of these hospitals have specialized cardiac centers (tertiary care). Inclusion criteria were age ≥ 65 years, diagnosed with at least one CVD, and attended the outpatient clinic during the last 6 months before data collection. A total of 383 patients (63.3%; 95% CI: 59.3-67.1%) were found using at least one PIM or having PPO or both, based on STOPP/START criteria. Three hundred and ninety-one patients (64.6%; 95% CI: 60.7-68.4%) were prescribed PIMs categorized as C and/or D medicines according to the Euro-FORTA list. Over one-quarter (28.8%; 95% CI: 25.2-32.6%) of the patients had drug-drug interactions class D that require therapy modification and/or X that should be avoided. Patients taking ≥ five medications had significantly higher PIMs based on STOPP and FORTA criteria, drug-drug interactions (p < 0.001), and significantly higher PPOs based on START criteria (p = 0.041). Patients with three or more chronic diseases had significantly higher PIMs based on STOPP and FORTA criteria and PPOs based on START criteria (p-values: 0.028, 0.035, and 0.005, respectively). Significantly higher PIMs based on STOPP criteria and PPOs based on START criteria were found in general hospitals compared to specialized cardiac centers (p= 0.002, p= 0.01, respectively). These findings highlight the need to develop and implement multifaceted interventions to prevent or minimize inappropriate prescribing among the geriatric population with CVDs in Kuwait.

Intra-Articular Route for the System of Molecules 14G1862 from Centella Asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis.

Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2-2 mg mL-1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 µg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.