Merz (Germany)

ABSTRACTBackgroundCombining calcium hydroxylapatite‐carboxymethylcellulose (CaHA‐CMC) with hyaluronic acid (HA) products using Cohesive Polydensified Matrix (CPM) technology leverages the volumizing and hydrating effects of HA and draws upon the regenerative properties of CaHA‐CMC, providing a potentially synergistic approach in aesthetic filling treatments. Despite this potential, the rheological and physical properties of these hybrid fillers remain unreported.ObjectiveTo characterize the rheological properties of CaHA‐CMC blended with various CPM‐HA products and identify factors influencing their physical and clinical behavior.MethodsHybrid fillers were prepared by mixing CaHA‐CMC with different CPM‐HA products at varying ratios (1:1 to 1:4 syringe CaHA:syringe CPM). Rheological properties, including storage modulus (G′), loss modulus (G″), complex shear modulus (G*), tan delta (tan δ), and complex viscosity (η*), were measured using an oscillatory rheometer. Extrusion force, cohesivity, stability, and axial strain (εa) were also evaluated.ResultsThe rheological properties of the hybrid fillers varied with the type of HA, mixing ratio, and crosslinking degree. Higher HA concentrations increased G′, G″, and η*, enhancing gel stiffness and resistance to deformation, while increased HA dilution and lower crosslinking favored spread and injectability. The addition of CaHA‐CMC to CPM‐HA products always increased the G′ in a volume‐dependent manner. These properties were closely correlated with the fillers' performance in different tissue planes.ConclusionsThe properties of CaHA‐CMC and CPM‐HA hybrids influence their injection behavior and clinical outcomes. Understanding these factors can guide filler selection and application techniques to maximize safety, efficacy, and patient satisfaction in aesthetic treatments.

ABSTRACTBackground/ObjectivesTwo Phase III randomized controlled trials were conducted in the US (ULTRA I) and Germany (ULTRA II) to investigate the efficacy of incobotulinumtoxinA for simultaneous treatment of upper facial lines (UFLs: glabellar frown lines [GFLs], horizontal forehead lines [HFLs] and lateral canthal lines [LCLs]).Patients/MethodsHealthy adults with moderate to severe GFLs, HFLs, and symmetrical LCLs were enrolled. Participants were randomized 2:1:1 to three groups: placebo, UFLs, and GFLs & HFLs (ULTRA I) or LCLs (ULTRA II). All participants received up to 64 units of incobotulinumtoxinA in the main period (MP) and were eligible for two additional treatment cycles in the open‐label extensions (OLEX). Endpoints included participant‐ and investigator‐assessed Global Aesthetic Improvement Scale (pGAIS and iGAIS, respectively; any improvement defined as ≥ +1 score versus baseline) and the percentage of GFL, HFL, and LCL responders, defined as ≥ 1‐grade improvement in Merz Aesthetics Scale (MAS) score versus baseline at maximum contraction.ResultsFor pGAIS at Day 30, the proportion of participants with any improvement was very high (> 97%) across all three treatment cycles. iGAIS results were similar and slightly higher than pGAIS results. In the MP, investigator and participant MAS assessments were similar, with > 78% of participants showing a positive treatment response for UFLs up to Day 90; responses in the placebo groups remained low at all time points (< 13%). MAS results in the OLEX were consistent with the MP.ConclusionsAdditional endpoints, including pGAIS, iGAIS, and MAS scores, corroborate prior ULTRAI/II findings and demonstrate the efficacy of incobotulinumtoxinA for simultaneous treatment of UFLs.Trial RegistrationULTRA I: NCT04594213; ULTRA II: NCT04622254

Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) are commonly used in nonsurgical aesthetic procedures. This study introduces a novel mixing technique, the foaming technique, aimed at enhancing the homogeneity and distribution of hybrid fillers containing CaHA and HA. This retrospective study, conducted by five expert injectors between January 2022 and January 2024, evaluates the clinical outcomes and microscopic characteristics of the foaming technique. The technique involves premixing CaHA, HA, and lidocaine and subjecting the mixture to repeated negative pressure suctions to create foam, followed by additional mixing passes. The study, conducted between January 2022 and January 2024, treated 1559 patients with hybrid fillers using the foaming technique and revealed no adverse events. Electron microscopy analysis highlighted distinct characteristics of the filler samples (1-CaHA; 2-CaHA, CPM-HA, and lidocaine without foaming; and 3-CaHA, CPM-HA, and lidocaine with foaming), showing a more homogeneous mixture when the foaming technique was applied. Sonography further elucidated unique imaging patterns influenced by the presence of foam, indicative of well-defined borders and the presence of a ring-down artifact. Conversely, in the absence of foam, the imaging typically revealed a band-like product with a less defined border. The foaming technique demonstrates improved homogeneity and distribution of the premixed hybrid filler, along with the absence of adverse events and smoother particle surfaces observed in electron microscopy samples. Sonography further corroborated these findings, revealing a more uniform pattern with the foam, thereby influencing imaging characteristics. This technique signifies a significant advancement in optimizing hybrid filler applications. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Self-assembling Ag dendritic networks provide ultrahigh CO2 permeability, whilst reducing membrane-volume-normalised Ag demand by an order of magnitude.

To determine whether early vascular aging may be present in flight attendants with remote in-cabin secondhand smoke (SHS) exposure. Twenty-six flight attendants with a history of in-cabin SHS exposure prior to the airline smoking bans were recruited. Pulse wave analysis, peripheral arterial tonometry, and brachial artery reactivity testing evaluated their arterial compliance and endothelial function. Flight attendants with remote in-cabin SHS exposure have normal blood pressure, pulse wave velocity, and reactive hyperemia index, but abnormal pulse pressure, augmentation index, flow-mediated dilation, and hyperemic mean flow ratio. These preliminary findings suggest that flight attendants with remote in-cabin SHS exposure have preclinical signs of accelerated vascular aging and raise new questions about the relationship between remote SHS exposure and vascular health.

In our previous studies, we found that expression of polyglutamine-expanded huntingtin in HN33 cells induced sensitization of N-methyl-D-aspartate (NMDA) receptors (Sun, Y., Savinainen, A., and Liu, Y. F. (2001) J. Biol. Chem. 276, 24713-24718). Following this study, we investigated whether tyrosine phosphorylation of NMDA receptors might contribute to the altered property of the receptors. Expression of polyglutamine-expanded huntingtin induced elevation of phosphorylated or activated Src and increased targeting of PSD-95 (post-synaptic density 95) and activated Src to cell surface membrane. Expression of the mutated huntingtin also induced tyrosine phosphorylation of NR2B (NMDA receptor 2B) subunits, and co-expression of PSD-95 enhanced the phosphorylation. Treatment of SU6656 (a specific Src inhibitor) or co-expression of a mutated NR2B subunit with mutations of all three major tyrosine phosphorylation sites significantly attenuated neuronal toxicity induced by the mutated huntingtin. Addition of AP-5 did not further inhibit the neuronal toxicity. Taken together, our studies show that polyglutamine-expanded huntingtin increases tyrosine phosphorylation of NMDA receptors via PSD-95 and Src, and increased tyrosine phosphorylation may contribute to the sensitization of the receptors mediated by polyglutamine-expanded huntingtin.

The voluntary withdrawal of cerivastatin (Baycol) from the U.S. market on August 8, 2001, by the manufacturer, in agreement with the Food and Drug Administration (FDA), has prompted concern on the part of physicians and patients regarding the safety of the cholesterol-lowering class of drugs called HMG CoA reductase inhibitors, more commonly known as “statins.” This American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute (ACC/AHA/NHLBI) Clinical Advisory is intended to summarize for professionals the current understanding of statin use, focused on myopathy, and to provide updated recommendations for the appropriate use of statins, including cautions, contraindications, and safety monitoring for statin therapy. Its purpose is not to discourage the appropriate use of statins, which have life-saving potential in properly selected patients, particularly those with established coronary heart disease (CHD) and others at high risk for developing CHD. Included are recent myopathy information compiled by the FDA, information from clinical trials, and summaries from the recently released report of the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP).1 In the literature, the general terminology used to describe muscle toxicity is inconsistent. Therefore, for the purpose of this document, the following terms are used as defined here: Myopathy —a general term referring to any disease of muscles; myopathies can be acquired or inherited and can occur at birth or later in life (Source: NINDS Myopathy Page-http://accessible.ninds.nih.gov/health\_and\_medical/disorders/myopathy.htm). Myalgia —muscle ache or weakness without creatine kinase (CK) elevation. Myositis —muscle symptoms with increased CK levels. Rhabdomyolysis —muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin). Statins are powerful low-density lipoprotein (LDL)-lowering drugs that are widely used in clinical practice. Results from clinical trials with a …

The antiparkinsonian effects of the uncompetitive NMDA antagonists, memantine, amantadine and MK-801, in combination with an acute subthreshold dose of L-Dopa (5 mg/kg) in drug-naive MPTP-treated mice or a suprathreshold dose (20 mg/kg) in L-Dopa tolerant MPTP-treated mice were investigated. In the former case, memantine (locomotion: 3 mg/kg; rearing: 1 mg/kg) and amantadine (locomotion and rearing: 10 mg/kg) injected 60 min before the subthreshold dose of L-Dopa (5 mg/kg), each induced an antiparkinsonian action in hypokinesic MPTP-treated mice that consisted of dose-specific, as opposed to dose-related, elevations of locomotion and rearing behaviour. At the same time, higher doses of memantine reduced further the rearing (10 and 30 mg/kg) and locomotor (30mg/kg) behaviour of the MPTP-treated mice. MK-801 plus L-Dopa elevated locomotion (0.1 mg/kg) but reduced rearing at the 0.3 mg/kg dose. In control, saline-treated mice, memantine (3, 10 and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour but decreased rearing behaviour, while amantadine produced no effects. Memantine increased locomotor (1 and 3 mg/kg, s.c.; 1 mg/kg dose restored activity) and rearing (0.3 and 3 mg/kg) activity in the L-Dopa tolerant MPTP-treated mice, whereas amantadine (3 and 10 mg/kg) restored both locomotor (30 mg/kg significantly increased locomotion but did not restore the activity level) and rearing (3 mg/kg only) activity. MK-801 (0.1 and 0.3 mg/kg, s.c.) also increased significantly locomotor activity of L-Dopa-tolerant MPTP mice although the antikinetic action was not reversed, thereby precluding a restorative effect of the compound. These results, demonstrating both a synergistic and a restorative effect of the NMDA antagonists in coadministration with L-Dopa, demonstrate a putative antiparkinson action by these compounds in a functional animal model that incorporates the "wearing-off" complications of L-Dopa administration in the disorder.