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Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative central nervous system (CNS) disorder, characterized by focal inflammation, demyelination, irreversible axonal loss and neurodegeneration. The proposed mechanism involves auto-reactive T lymphocytes crossing the blood–brain barrier (BBB), contributing to inflammation and demyelination. Pro-inflammatory Th1 and Th17 lymphocytes are pivotal in MS pathogenesis, highlighting an imbalanced interaction with regulatory T cells. Dysbiosis in the gut microbiota, characterized by microbial imbalance is implicated in systemic inflammation, yet its exact role in MS remains elusive. Short-chain fatty acids (SCFAs), including valerate, butyrate, propionate, and acetate, produced through dietary fiber fermentation by the gut microbiota, modulate inflammation and immune responses. Particularly, butyrate and propionate exhibit pronounced anti-inflammatory effects in both the gut and CNS. These SCFAs influence regulatory T lymphocyte expression and BBB permeability. This review discusses the potential therapeutic implications of SCFA in MS, highlighting their ability to modulate the gut–brain axis and restore immune balance.

Regional anesthesia techniques such as the ultrasound-guided PECS II (pectoral nerve block) block are increasingly employed to optimize perioperative analgesia while minimizing systemic anesthetic exposure. Ropivacaine is commonly used for its favorable pharmacological profile; however, clinical data on its pharmacokinetics and systemic metabolite behavior following interpectoral administration remain limited. This study aimed to characterize the plasma concentration–time profile of ropivacaine and its main active metabolite, 3-OH-ropivacaine, in patients undergoing interpectoral nerve block, using a validated LC-MS/MS (liquid chromatography coupled with mass spectrometry) method. Venous blood samples were collected from 18 patients at predefined time points (0, 1, 3, 6, and 24 h) following a PECS II block performed with a ropivacaine-lidocaine mixture. Plasma concentrations were quantified via a validated LC-MS/MS protocol in accordance with FDA (Food and Drug Administration) and EMA (European Medicines Agency) guidelines. Pharmacokinetic parameters were derived using non-compartmental analysis. Ropivacaine reached a mean peak plasma concentration (Cmax—maximum concentration) of 167.5 ± 28.3 ng/mL at 1.3 ± 0.2 h (Tmax—maximum time). The metabolite 3-OH-ropivacaine peaked at 124.1 ± 21.4 ng/mL at 2.3 ± 0.3 h. The terminal elimination half-life was 19.4 ± 2.8 h for ropivacaine and 29.2 ± 3.1 h for its metabolite. Plasma levels demonstrated prolonged systemic exposure with predictable pharmacokinetics. The PECS II block using ropivacaine results in sustained systemic levels of both the parent drug and its primary metabolite, supporting its role in prolonged perioperative analgesia. These data provide a pharmacokinetic foundation for personalized regional anesthesia protocols. This strategy facilitates the adaptation of anesthetic protocols to the individual characteristics of each patient, aligning with the principles of personalized medicine, particularly in patients with altered metabolic capacity.

Background: Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) are human metabolites which are involved in various biochemical processes and can offer valuable insights and information on various pathological and metabolic issues of patients. Accurate, precise, high-performance bioanalytical methods are important tools in both research and diagnostics of many pathologies, with LC-MS being the most frequently used methodology in modern metabolomics studies. Methods: The current paper describes a complete LC-MS/MS methodology for the accurate quantification of total plasmatic SCFA concentrations in humans using high-resolution QTOF mass spectrometric detection, including sample cleanup, preparation, and derivatization. Results and Conclusions: The method was validated with regard to all relevant parameters (selectivity, sensitivity, accuracy, precision, linearity, recovery, carryover, and reproducibility of sample preparation) according to the current applicable guidelines and tested in an in vivo study to quantify peripheral SCFAs in human patients as biomarkers for gut–brain axis disruption.

Cardiac resynchronization therapy devices, implantable cardioverter defibrillators, and pacemakers are used to treat advanced systolic heart failure, ventricular tachyarrhythmias, and bradyarrhythmia. Over the past ten years, there has been a notable rise in the number of cardiac implanted electronic device implants because of mounting evidence of better survival and quality of life among specific patient populations. Appropriate analgesia and sedation throughout the implantation procedure is crucial for the patient’s stability. This paper aims to describe the advantages of both interpectoral plane block (PECS I) and interpecto-seratus plane block (PECS II) for the implantation of cardiac devices.Combining PECS I and PECS II blocks provides advantages for the thoracic wall procedures. While the PECS I block anesthetizes the medial and lateral pectoral nerves, PECS II extends coverage to upper intercostal nerves (T2-T7), as well as the long thoracic and thoracodorsal nerves, covering areas that are not anesthetize adequately by PECS I alone. Minimizing the need for opioids, leading to fewer opioid related side effects contributing to shorter recovery time and nonetheless creating less discomfort for the patient.This combined regional technique offers comfort to the patient due to its sole puncture needed for performance and by offering an extensive anesthesia at the site of the procedure.

Background: Amyotrophic lateral sclerosis (ALS) evolution is influenced by many dietary factors, biochemical and hormonal inter-relations and gut microbiota. This study focuses on dynamics by conducting a plasmatic quantitative analysis of six of the main short-chain fatty acids (SCFAs) for ALS patients and the shifts in circulating SCFA profiles during ALS progression as well as their potential responsiveness or change due to dietary modulation. Methods: A 12-month prospective study in parallel with control group determinations was conducted. The patients diagnosed with ALS were evaluated at the start of the study (T0) followed by a six-month observation time frame (T1) and after another six months of a Mediterranean diet intervention (T2). Plasma SCFAs were determined using liquid chromatography coupled to mass spectrometry to showcase the plasmatic profiles. Correlation between plasma levels of SCFAs and patients’ clinical characteristics next to correlations between plasma SCFA levels at T1 and T2 were performed. Results: A significant increase between control group and patients at T0 was observed for acetic, propionic, butyric and hydroxy-butyric acid. Hexanoic acid levels stagnated and 4-methyl-valeric acid concentrations decreased. Evolutions from T1 and T2 impacted acetate, propionate and 4-methyl-valerate. Conclusions: The study offers a better understanding regarding the differences in SCFA levels in ALS patients. The Mediterranean diet may impact the levels of acetic and propionic acid, indicating the modulation of SCFA production by gut microbiota.

Knowledge of drug pharmacokinetics and tissue distribution is precious for ensuring patient safety and optimizing treatments. The varied use of local anesthetics, as well as the fact that anesthetics can sometimes have low therapeutic indices and numerous adverse drug reactions, makes any novel pharmacokinetics information valuable. The present manuscript describes a pharmacokinetic study of ropivacaine carried out after plane block anesthesia on an animal model, using high sensitivity, accurate, and precise LC-MS/MS bioanalysis. Both plasmatic concentrations and tissue distribution of ropivacaine and its primary active metabolite were determined. The results showed a tissue affinity of the anesthetics, a clearance of ropivacaine mainly by hepatic metabolism, and the final, mainly renal excretion of the hydroxylated metabolite. While the results cannot simply and directly be transposed to human pharmacokinetics, they offer a valuable basis for future studies and can contribute to a better understanding of the bioavailability and toxicology of the widely used modern anesthetic.

In this study, orodispersible films (ODFs) were developed as fast-releasing formulations for pediatric patients suffering from Lennox-Gastaut or Dravet syndrome, with cannabidiol (CBD) selected as the active pharmaceutical ingredient (API). The properties of the ODFs were evaluated both before and after casting, with a focus on establishing a correlation between the properties of colloidal dispersion/suspension and ODFs to enhance understanding of the manufacturing process. Two blank colloidal dispersions were characterized for spreadability, viscosity, tangential stress, and pH, and their properties were correlated with those of blank ODFs, including mass uniformity, thickness, folding endurance, thickness-normalized crushing strength, disintegration time (evaluated through two different methods) and adhesivity. The strength and direction of the correlation were established via the Pearson coefficient. The same statistical approach was applied to assess correlation between CBD suspension (DCBD1, DCBD2) properties and CBD-ODF parameters. For the suspensions, particle size evaluation was also considered. Although few statistically significant positive or negative correlations were observed, a notable finding of this study was the dissolution behavior of CBD-ODF2, where nearly 100% of the API was released at 30 min, which is consistent with the disintegration behavior evaluated through the pharmacopeial method. Notably, CBD is classified as a Biopharmaceutical Classification System (BCS) Class II compound.

The bark resulted after the industrial processing of wood represents a byproduct of the forestry industry, used in many suboptimal ways, being considered a natural waste. Currently, it has been highlighted that the bark of different woody plants may be an important source of several bioactive compounds, with various beneficial biological functions. The aim of this study is to evaluate and compare the chemical composition and biological activities of two different pine species (Pinus nigra and Pinus sylvestris) bark extracts. Ultrasound (UAE) and microwave (MAE) assisted extractions were performed in order to obtain the extracts. The total polyphenol (TPC) and total tannin (TTC) contents of the extracts were assessed via the Folin–Ciocâlteu method. The volatile and polyphenolic compounds were identified and quantified via a GC/MS analysis and an UPLC-PDA analysis, respectively. The antioxidant activity (AOA) was evaluated using the DPPH and ABTS assays, while the antibacterial activity was assessed using the minimum inhibitory concentration (MIC) protocol. The results showed that the Pinus sylvestris bark extracts obtained by UAE had a higher TPC, TTC and AOA, while the Pinus nigra bark extracts obtained by MAE had higher volatile compounds content (mainly α-pinene and β-pinene). Moreover, the inhibition of the bacterial growth was more efficient in the case of Pinus sylvestris extracts, Gram-positive bacteria being the most affected, while Gram-negative strains presented a relative resistance to the tested extract concentrations. These results may indicate the potential use of the pine bark extracts as antioxidant or antibacterial agents.

: Cannabidiol (CBD) is a non-psychoactive compound found in the plant. Due to its broad therapeutic potential, CBD is often incorporated into various pharmaceutical formulations. This study aimed to evaluate homogenous (oil-based) and heterogeneous (emulsion-based) liquid preparations of CBD using different fatty oils and provide a comprehensive comparative framework for the development of stable liquid dosage forms of cannabidiol (CBD), with direct applications in pharmaceutical formulations. : The oils and emulsions were qualitatively analysed to assess their stability and suitability as CBD carriers. Ultraviolet (UV) spectrophotometry and High-Performance Liquid Chromatography (HPLC) were employed for quantifying CBD in the formulations and also characterising them in terms of product quality. : The results indicated that sunflower oil is the most stable and analytically compatible matrix, with CBD recovery close to 100% and minimal degradation over time. Conversely, linseed and pumpkin seed oils exhibited significant analytical interference and oxidative instability. Oil-in-water emulsions prepared with a 4% Tween 80/Span 80 mixture demonstrated optimal physical stability and droplet size distribution. : Overall, both formulations can be regarded as suitable pharmaceutical carriers for CBD delivery.

Alterations in intestinal permeability and microbiota dysregulation have been linked to the development of multiple sclerosis (MS). Short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are products of gut bacteria fermentation which are involved in immune regulation processes. In MS, SCFA have important immunomodulatory properties both in the periphery and the central compartment. Interferon β (IFNβ) was the first disease-modifying therapy approved for the treatment of MS and its effects on the gut microbiota are not fully elucidated. We performed a prospective observational study aimed to assess peripheral levels of SCFA and MCFA in 23 newly diagnosed, treatment-naïve MS patients (nMS) before and after one year of IFNβ treatment and 23 healthy controls (HC). We investigated their associations with inflammation, interleukin-10 (IL-10), and blood-brain barrier permeability, matrix metalloproteinase 9 (MMP9). No significant differences in SCFA/MCFA levels were observed between baseline and after IFNβ treatment. Caproic acid levels were significantly higher in nMS compared to HC (1.64 vs 1.27 µM, p=0.005). The butyric acid/caproic acid ratio was higher in HC compared to nMS (5.47 vs 2.55, p=0.005). Correlation analysis revealed associations between SCFA/MCFA levels and inflammatory biomarkers. nMS have a higher gut-inflammatory activity as seen by the caproic acid ratio as opposed to HC. In this cohort, IFNβ does not appear to modify the peripheral SCFA/MCFA levels after one year of treatment. The quantifications of peripheral SCFA/MCFA may prove to be a useful biomarker for gut-brain axis disruption in MS patients.