Is There Association between Altered Adrenergic System Activity and Microvascular Endothelial Dysfunction Induced by a 7-Day High Salt Intake in Young Healthy Individuals

This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines’ level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.     

Skin oxygenation after topical application of liposome-entrapped benzyl nicotinate as measured by EPR oximetry in vivo: Influence of composition and size

New and improved drug delivery systems are the important subject of much scientific research. The development of formulations that increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with healing processes affected by the level of oxygen. We have use EPR oximetry in vivo to compare the influence of liposomal formulations of different size and composition with that of hydrogel with respect to the action of the entrapped benzyl nicotinate (BN). Following the topical application of BN onto the skin of mice, pO₂ increase was measured by low-frequency EPR as a function of time. The effect of BN was evaluated by 3 different parameters: lag-time, time needed for maximum pO₂ increase, and overall effectiveness expressed by the area under the response-time curve. An increase in skin oxygenation was observed after BN application. The results show that the effect of BN incorporated in liposomes is achieved more rapidly than the effect from hydrophilic gel. The composition of the liposomes significantly affects the time at which BN starts to act and, to a lesser extent, the maximum increase of pO₂ in skin and the effectiveness of BN action. However, the size of the liposomes influences both the effectiveness of BN action and the time at which BN starts to act. After repeated application of liposomes, the pO₂ baseline increased and the response of the skin tissue was faster. Our results demonstrate that EPR oximetry is a useful method for evaluating oxygen changes after drug application and for following the time course of their action.     

Correction to: Comparison of the 1-year clinical outcome of a novel cryoballoon to an established cryoballoon technology

Journal of Interventional Cardiac Electrophysiology -     

Validation of flavonoids as potential dipeptidyl peptidase III inhibitors: Experimental and computational approach

Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III with the IC₅₀ values ranging from 22.0 to 437.2 μm . Our 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity, while the higher percentage of hydrophobic surfaces has negative impact on enzyme inhibition. Furthermore, molecular dynamics (MD) simulations of the complex of hDPP III with one of the most potent inhibitors, luteolin, were performed, and binding mode analysis revealed that the 3′ and 4′ hydroxyl group on B‐ring as well as 5 and 7 hydroxyl group on A‐ring helps luteolin to interact with the Asn391, Asn406, Tyr417, His450, Glu451, Val447, Glu512, Asn545, Gln566, and Arg572 residues. The MD results clearly provide valuable information explaining the importance of flavonoid hydroxyl groups in the mechanism for the binding pattern at the active site of hDPP III.     

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220^?CD3^?CD11b^–/loCD115⁺CD117⁺CX3CR1⁺ and possibly also Ter119^?CD11c^?CD135^loLy6C⁺RANK^?. In peripheral blood the OCP population bears the monocytoid phenotype B220^?CD3^?NK1.1^?CD11b⁺Ly6C^hiCD115⁺CX3CR1⁺, presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3^?CD19^?CD56^?), within immature monocyte subset (CD11b⁺CD14⁺CD16^?), expressing receptors for M-CSF and RANKL (CD115⁺RANK⁺). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3^?CD19^?CD56^?CD11b⁺CD14⁺, and the disease activity score (DAS28) in the follow-up samples from patients with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption. Control of the activity and migratory behaviour of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.     

Outcomes from the International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) project

Aims: The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) study evaluated the implementation of opioid dependence treatment across different countries to assess treatment delivery, quality of care and outcomes. Methods: A questionnaire-based survey was used to gather data in nine countries across Central and Eastern Europe, South Africa and South-East Asia, from patients with opioid dependence receiving medication-assisted treatment (MAT), healthcare professionals (HCPs) who cared for opioid-dependent patients and opioid users not receiving MAT. Findings: There was substantial variation between countries, but overall results suggest that several aspects of MAT can be improved, such as access to treatment (conditions to start or remain in treatment), quality of care (availability/awareness of treatment options and appropriate medication dosing) and treatment outcomes (on-top use, misuse and diversion). Conclusions: This analysis highlights key priorities that should improve the quality of opioid dependence care and access to treatment. These priorities include: acknowledging opioid dependence as a chronic medical condition requiring long-term treatment; recognition by policymakers of the cost-effectiveness of treatment; making available, to those who want them, psychosocial interventions and educating HCPs to prescribe the safest, least divertible forms of medications available at optimal doses in order to reduce opioid use, misuse and diversion.     

Incorporation of Copper-Doped Mesoporous Bioactive Glass Nanospheres in Experimental Dental Composites: Chemical and Mechanical Characterization

Experimental dental resin composites incorporating copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were designed to impart antibacterial and remineralizing properties. The study evaluated the influence of Cu-MBGN on the mechanical properties and photopolymerization of resin composites. Cu-MBGN were synthesized using a microemulsion-assisted sol–gel method. Increasing amounts of Cu-MBGN (0, 1, 5, and 10 wt %) were added to the organic polymer matrix with inert glass micro- and nanofillers while maintaining a constant resin/filler ratio. Six tests were performed: X-ray diffraction, scanning electron microscopy, flexural strength (FS), flexural modulus (FM), Vickers microhardness (MH), and degree of conversion (DC). FS and MH of Cu-MBGN composites with silica fillers showed no deterioration with aging, with statistically similar results at 1 and 28 days. FM was not influenced by the addition of Cu-MBGN but was reduced for all tested materials after 28 days. The specimens with 1 and 5% Cu-MBGN had the highest FS, FM, MH, and DC values at 28 days, while controls with 45S5 bioactive glass had the lowest FM, FS, and MH. DC was high for all materials (83.7–93.0%). Cu-MBGN composites with silica have a potential for clinical implementation due to high DC and good mechanical properties with adequate resistance to aging.