Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: Physicochemical and magnetic properties, in vitro and in vivo drug release

Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint. Two molecular weights of poly(lactic-co-glycolic acid) (PLGA) were used, 12 and 19 kDa. The prepared batches were similar in size (around 10 μm), inner morphology, surface morphology, charge (neutral) and superparamagnetic behaviour. The SPION distribution in the microparticles assessed by TEM indicates a homogeneous distribution and the absence of aggregation, an important factor for preserving superparamagnetic properties. DXM release profiles were shown to be quite similar in vitro (ca. 6 days) and in vivo, using a mouse dorsal air pouch model (ca. 5 days).     

Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance

Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. We have recently demonstrated that spinal ceramide, a sphingolipid signaling molecule plays a central role in the development of morphine antinociceptive tolerance. We now report that ceramide upregulation in dorsal horn tissues in response to chronic morphine administration is associated with significant neuronal apoptosis. Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain.     

An in vitro study on the maturation of conventional glass ionomer cements and their interface to dentin

The objective of the study was to investigate the influence of long-term storage (up to 1 year) and coating on the variation of micro-mechanical properties of four conventional restorative glass ionomer cements (GICs) within 3.5 mm deep class I cavities. Four commercially available GICs (Riva Self Cure (SDI), ChemFil Rock (Dentsply), Fuji IX Fast and Fuji IX GP Extra/Equia (GC)) were applied to 100 teeth. In each tooth, two similar 3.5 mm deep class I cavities were prepared and filled with the GICs, with and without resin coating. The samples were stored in artificial saliva at 37 °C for 1 week, 1 month, 3 months, 6 months and 1 year. The variation in mechanical properties (indentation modulus (E) and Vickers hardness (HV)) were determined in 100 μm steps starting from the filling surface, through the intermediate layer in between dentine and GIC, and ending 100 μm in dentin. HV and E were strongly influenced by the material (P < 0.05, partial eta-squared η_P² = 0.31 and 0.23) but less by aging duration (P < 0.05, η_P² = 0.02 and 0.12) and resin coating (P < 0.05, η_P² = 0.02 and 0.03). The depth of measurement (0–2 mm) has no influence on HV (P = 0.789). HV shows a gentle increase over the 1 year storage period (P = 0.002). A ～300 μm GIC zone at the areas close to dentin with weaker properties as those measured in dentin or GIC was identified in all fillings, irrespective of the presence of coating, and at all storage periods. The thickness of this zone is more strongly influenced by storage (P < 0.05, η_P² = 0.081) than by material type (P < 0.05, η_P² = 0.056), while coating showed no influence (P = 0.869). Filler morphology and dimension were similar to upper parts of the GIC filling; however, the amount of low cations was higher. We concluded that the development of an intermediate layer in between dentine and GIC with lower mechanical properties might be responsible for the bond quality of GIC to dentine. Moreover, class I GIC restorations are unlikely to feature constant mechanical properties throughout the cavity, regardless of conditions such as aging and coating.     

Short-Term Impact of a Multimedia Communication Campaign on Children’s Physical Activity Beliefs and Behavior

To examine the short-term impact of the WIXX multimedia communication campaign on children’s physical activity (PA) beliefs and behaviors, 3 repeated cross-sectional telephone surveys were conducted before, 9 months after, and 21 months after the launch of the campaign. A random-digit dialing procedure was used to recruit children ages 9 to 13 years. Children’s PA beliefs, behaviors, and recall of the WIXX ads were self-reported. Logistic regression models showed that girls exposed to the WIXX ads were more likely to believe that PA would help to make new friends (odds ratio [OR] = 1.4, 95% confidence interval [CI] [1.0, 1.9]) and that they can be active even if too busy (OR = 1.4, 95% CI [1.0, 1.8]) compared to girls not exposed. Boys exposed were more likely to believe that PA would help to spend time with friends (OR = 1.4, 95% CI [1.1, 1.9]). Boys (OR = 1.5, 95% CI [1.1, 2.0.]) and girls (OR = 1.4, 95% CI [1.1, 1.8]) exposed were more likely to report having tried new PAs. No significant impact of the campaign was observed on overall PA after we controlled for confounders. Recall of the WIXX ads was associated with a significant, albeit modest, impact on some PA beliefs and intermediate PA behaviors.     

Intra-articular drug delivery systems for the treatment of rheumatic diseases: A review of the factors influencing their performance

Osteoarthritis and rheumatoid arthritis are rheumatic diseases for which a curative treatment does not currently exist. Their management is directed towards pain relief achieved with different classes of drugs among which non-steroidal and steroidal anti-inflammatory substances are the most frequently used agents. Nevertheless, the oral or systemic administration of such drugs is hindered by numerous side effects, which could be overcome by their intra-articular (i-a.) administration as dosage forms capable of gradually releasing the active substance. The present review article summarises the research done in the field of drug delivery systems for i-a. injection vs. current management of osteoarthritis or rheumatoid arthritis. Aspects such as the influence of size, shape, polymer matrix or targeted drug on the i-a. retention time, phagocytosis and biological activity will be discussed. Finally, we will comment on the need for adapted delivery systems for the novel and very potent anti-inflammatory drugs, such as inhibitors of the p38 mitogen-activated protein kinase or the IL-1β conversion enzyme, which to date cannot be properly used due to the severe side effects associated with their systemic administration.     

Magnesium Orotate and the Microbiome–Gut–Brain Axis Modulation: New Approaches in Psychological Comorbidities of Gastrointestinal Functional Disorders

Magnesium orotate has been cited in the medical literature for the past three years as a possible adjuvant in some pediatric and adult gastroenterological disorders associated with dysbiosis. Studies also focus on the possibility of adding magnesium orotate in psychiatric disorders’ treatment, such as major depression and anxiety. The most relevant element in these studies is the efficiency of magnesium orotate therapy in cases with both gastroenterological and psychiatric symptoms. This article proposes a literature review, focused on the studies published in the last three years, targeting magnesium orotate treatment and probiotic supplementation in patients with both digestive and psychiatric symptoms. Moreover, this review will compare the efficiency of magnesium orotate and probiotics within both the pediatric and adult communities, focusing on the possibility of gut–brain axis modulation and its involvement in the clinical evolution of these patients.     

Reducing Friction in Orthodontic Brackets: A Matter of Material or Type of Ligation Selection? In-Vitro Comparative Study

(1) Background: Orthodontic appliances have changed and improved with the increasing demand for orthodontic treatment of the general population. Patients desire for shorter orthodontic treatments and for the wearing of more aesthetic devices has led to the technological development of orthodontic brackets; these were manufactured from aesthetic materials (ceramics, composite polymers) and presented different designs regarding the way archwires are ligated to the bracket. The aim of this study was to determine whether there were any differences between the static frictional forces generated by stainless steel (metallic) and polycrystalline alumina (ceramics) conventional and self-ligating brackets. (2) Methods: Static friction assessment was carried out in vitro with a universal testing machine, HV-500N-S (Schmidt Control Instruments, Hans Schmidt & Co. GmbH), intended for measuring compression and traction forces. (3) Results: The study revealed significant differences in static frictional forces at the bracket-archwire interface between the tested brackets. Stainless steel brackets produced lower static friction forces than polycrystalline alumina and self-ligating brackets generally produced lower static frictional forces than conventional brackets. The reduction of frictional forces was noticeable in the first stages of treatment, when thin, flexible orthodontic archwires (0.016” NiTi) are used. Engaged with large rectangular stainless steel archwires, (0.019 × 0.025” SS), the frictional forces produced by conventional and self-ligating metal brackets were similar, no significant differences being observed between the two types of metallic design. However, in the case of tested ceramic brackets, the results showed that the self-ligating type allows a reduction in frictional forces even in advanced stages of treatment compared to conventionally ligation. (4) Conclusions: From the perspective of an orthodontic system with low frictional forces, metal brackets are preferable to aesthetic ones, and self-ligating ceramic brackets are preferable to conventional ceramic brackets.     

Laser Processed Hybrid Lead-Free Thin Films for SAW Sensors

In this study we report the specific interaction of various gases on the modified surface of acoustic wave devices for gas sensor applications, using the piezoelectric ceramic material BaSrTiO₃ (BST), with different concentrations of Sr. For enhancing the sensitivity of the sensor, the conductive polymer polyethylenimine (PEI) was deposited on top of BST thin films. Thin films of BST were deposited by pulsed laser deposition (PLD) technique and integrated into a test heterostructure with PEI thin films deposited by matrix assisted pulsed laser evaporation (MAPLE) and interdigital Au electrodes (IDT). Further on, the layered heterostructures were incorporated into surface acoustic wave (SAW) devices, in order to measure the frequency response to various gases (N₂, CO₂ and O₂). The frequency responses of the sensors based on thin films of the piezoelectric material deposited at different pressures were compared with layered structures of PEI/BST, in order to observe differences in the frequency shifts between sensors. The SAW tests performed at room temperature revealed different results based on deposition condition (pressure of oxygen and the percent of strontium in BatiO₃ structure). Frequency shift responses were obtained for all the tested sensors in the case of a concentration of Sr x = 0.75, for all the analysed gases. The best frequency shifts among all sensors studied was obtained in the case of BST50 polymer sensor for CO₂ detection.