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Advances in Therapy Jan 2022This long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to...
INTRODUCTION
This long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to patients with type 2 diabetes mellitus (T2DM) in real-world practice in Japan.
METHODS
Patients with T2DM who were prescribed canagliflozin between December 2014 and September 2016 were registered and observed for up to 3 years. Safety was evaluated in terms of adverse drug reactions (ADRs). Effectiveness was assessed in terms of glycaemic control. Data were also analysed across age subgroups (< 65, ≥ 65 to < 75, and ≥ 75 years old) and the estimated glomerular filtration rate (eGFR) categories for chronic kidney disease (G1-G5 based on eGFR) at baseline.
RESULTS
A total of 12,227 patients were included in the safety analyses and 11,675 in effectiveness analyses. Overall, 7104 patients were treated with canagliflozin for ≥ 3 years. The mean age, haemoglobin A1c (HbA1c), and eGFR at baseline were 58.4 ± 12.5 years, 8.01 ± 1.49%, and 80.04 ± 21.85 mL/min/1.73 m, respectively. There were 1836 ADRs in 1312 patients (10.73%) and 268 serious ADRs in 225 patients (1.84%). The most common ADRs were those related to volume depletion (1.39%), genital infection (1.34%), polyuria/pollakiuria (1.23%), and urinary tract infection (1.19%). The frequencies of ADRs tended to increase with age and stage of chronic kidney disease. The reductions in mean HbA1c after starting canagliflozin were maintained for up to 3 years with a mean change of - 0.68% (n = 6345 at 3 years). Maintained reductions in mean HbA1c were observed in each age subgroup and in patients with G1-G3b renal function.
CONCLUSION
This surveillance in real-world clinical practice showed that canagliflozin provides sustained glucose-lowering effects in patients with T2DM, including elderly patients and patients with moderate renal impairment, without new safety concerns beyond those already described in the Japanese package insert.
TRIAL REGISTRATION
JapicCTI-153048.
Topics: Aged; Aluminum Oxide; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Japan; Product Surveillance, Postmarketing; Treatment Outcome
PubMed: 34853985
DOI: 10.1007/s12325-021-01984-4 -
Clinical Oral Investigations Mar 2022To develop and test the cutting efficiency of a novel degradable glass as an alternative media to alumina powder for air abrasion.
OBJECTIVES
To develop and test the cutting efficiency of a novel degradable glass as an alternative media to alumina powder for air abrasion.
MATERIALS AND METHODS
A zinc-based glass (QMZK2) was designed, produced, and evaluated with a multi-modality imaging analysis. The glass dissolution study was carried out in three acids, using ICP-OES (inductively coupled plasma optical emission spectroscopy) at 5 different time points: 2.5, 5, 10, 60, and 240 min. The cutting efficiency of both materials was tested under the same parameters on slabs of elephant enamel. A stained fissure of a molar tooth was air abraded with the glass and evaluated with X-ray micro-tomography before and after air abrasion.
RESULTS
The particle size distribution of the glass was similar to that of alumina 53 µm but with a slightly greater dispersion of particle size. The shape of the particles was angular, appropriate for cutting purposes. The dissolution study showed that the glass dissolved rapidly in acidic conditions at all time points. Between the two variables, pressure and powder flow, pressure was found to influence the cutting speed to a greater extent than powder flow.
CONCLUSIONS
Alumina powder was found to perform significantly better in 4 of the 9 conditions tested on elephant enamel, QMZK2 in one, and no significant differences were found for the rest of the 4 conditions. The QMZK2 seems to offer promising results as an alternative material to alumina.
CLINICAL RELEVANCE
QMZK2 glass has the potential for replacing aluminum oxide as a degradable material in air abrasion technology.
Topics: Air Abrasion, Dental; Aluminum Oxide; Ceramics; Dental Enamel; Glass; Materials Testing; Powders; Surface Properties
PubMed: 34825281
DOI: 10.1007/s00784-021-04307-7 -
Nanotoxicology Sep 2019Aluminum (Al) can be ingested from food and released from packaging and can reach key organs involved in human metabolism, including the liver via systemic distribution....
Aluminum (Al) can be ingested from food and released from packaging and can reach key organs involved in human metabolism, including the liver via systemic distribution. Recent studies discuss the occurrence of chemically distinct Al-species and their interconversion by contact with biological fluids. These Al species can vary with regard to their intestinal uptake, systemic transport, and therefore could have species-specific effects on different organs and tissues. This work aims to assess the hepatotoxic hazard potential of three different relevant Al species: soluble AlCl and two nanoparticulate Al species were applied, representing for the first time an investigation of metallic nanoparticles besides to mineral bound γ-AlO on hepatic cell lines. To investigate the uptake and toxicological properties of the Al species, we used two different human hepatic cell lines: HepG2 and differentiated HepaRG cells. Cellular uptake was determined by different methods including light microscopy, transmission electron microscopy, side-scatter analysis, and elemental analysis. Oxidative stress, mitochondrial dysfunction, cell death mechanisms, and DNA damage were monitored as cellular parameters. While cellular uptake into hepatic cell lines occurred predominantly in the particle form, only ionic AlCl caused cellular effects. Since it is known, that Al species can convert one into another, and mechanisms including 'trojan-horse'-like uptake can lead to an Al accumulation in the cells. This could result in the slow release of Al ions, for which reason further hazard cannot be excluded. Therefore, individual investigation of the different Al species is necessary to assess the toxicological potential of Al particles.
Topics: Aluminum Chloride; Aluminum Oxide; Biological Transport; Cell Survival; DNA Damage; Hep G2 Cells; Humans; Liver; Metal Nanoparticles; Microscopy, Electron, Transmission; Oxidative Stress
PubMed: 30938204
DOI: 10.1080/17435390.2019.1593542 -
International Journal of Biological... Nov 2023Curcumin (CUR) is among the most natural and effective antitumor drugs for cancer treatment. These drugs have low solubility and short half-lives that reduce their...
Curcumin (CUR) is among the most natural and effective antitumor drugs for cancer treatment. These drugs have low solubility and short half-lives that reduce their effectiveness in drug release systems. Herein, a hydrogel nanocarrier containing chitosan (CS), alumina (γ-AlO), and carbon quantum dots (CQDs) was prepared by the water-in-oil-in-water (W/O/W) double nanoemulsion method. DLS revealed a nanocarrier size of 227 nm, with a zeta potential of -37.8 mV, which corroborates its stability. FE-SEM showed its quasi-spherical shape, FT-IR and XRD confirmed the presence of all the components in the nanocomposite and gave information about the intermolecular interactions between them and the crystalline nature of the nanocarrier, respectively. The drug loading (48 %) and entrapment efficiency (86 %) were higher than those reported previously for other CUR nanocarriers. The drug release profile revealed a controlled and stable release, and a pH-sensitive behavior, with faster CUR release in an acid environment. The breast cancer cell line was examined by cytotoxicity and cell apoptosis analyses. The results showed that the slow release over time and the programmed cell death were due to interactions between CUR and the nanocarrier. Considering the results obtained herein, CS/γAlO/CQDs/CUR can be considered as a promising new nanosystem for tumor treatment.
Topics: Chitosan; Quantum Dots; Humans; Drug Carriers; Aluminum Oxide; Carbon; Curcumin; Hydrogels; Drug Liberation; Drug Delivery Systems; Apoptosis; Cell Line, Tumor; MCF-7 Cells; Nanocomposites; Nanoparticles; Antineoplastic Agents
PubMed: 37591420
DOI: 10.1016/j.ijbiomac.2023.126280 -
Journal of Ultrasound Dec 2016In this work we provide measurements of speed of sound () and acoustic impedance () of some doped/non-doped rubber-based materials dedicated to the development of...
PURPOSE
In this work we provide measurements of speed of sound () and acoustic impedance () of some doped/non-doped rubber-based materials dedicated to the development of ultrasound phantoms. These data are expected to be useful for speeding-up the preparation of multi-organ phantoms which show similar echogenicity to real tissues.
METHODS
Different silicones (Ecoflex, Dragon-Skin Medium) and polyurethane rubbers with different liquid (glycerol, commercial detergent, -propanol) and solid (aluminum oxide, graphene, steel, silicon powder) inclusions were prepared. of materials under investigation was measured in an experimental setup and was obtained by multiplying the density and the of each material. Finally, an anatomically realistic liver phantom has been fabricated selecting some of the tested materials.
RESULTS
and evaluation for different rubber materials and formulations are reported. The presence of liquid additives appears to increase the , while solid inclusions generally reduce the . The ultrasound images of realized custom fabricated heterogeneous liver phantom and a real liver show remarkable similarities.
CONCLUSIONS
The development of new materials' formulations and the knowledge of acoustic properties, such as speed of sound and acoustic impedance, could improve and speed-up the development of phantoms for simulations of ultrasound medical procedures.
Topics: 1-Propanol; Aluminum Oxide; Detergents; Equipment Design; Glycerol; Graphite; Humans; Liver; Models, Biological; Phantoms, Imaging; Polyurethanes; Rubber; Silicon; Silicones; Sound; Steel; Ultrasonography
PubMed: 27965715
DOI: 10.1007/s40477-016-0204-7 -
Journal of Experimental Botany Feb 2018Arabidopsis has been reported to respond to phosphate (Pi) stress by arresting primary root growth and increasing lateral root branching. We developed a system to buffer...
Arabidopsis has been reported to respond to phosphate (Pi) stress by arresting primary root growth and increasing lateral root branching. We developed a system to buffer Pi availability to Arabidopsis in gel media systems by charging activated aluminum oxide particles with low and sufficient concentrations of Pi, based on previous work in horticultural and sand culture systems. This system more closely mimics soil chemistry and results in different growth and transcriptional responses to Pi stress compared with plants grown in standard gel media. Low Pi availability in buffered medium results in reduced root branching and preferential investment of resources in axial root growth. Root hair length and density, known responses to Pi stress, increase in low-buffered Pi medium. Plants grown under buffered Pi conditions have different gene expression profiles of canonical Pi stress response genes as compared with their unbuffered counterparts. The system also eliminates known complications with iron (Fe) nutrition. The growth responses of Arabidopsis supplied with buffered Pi indicate that the widely accepted low-Pi phenotype is an artifact of the standard gel-based growth system. Buffering Pi availability through the method presented here will improve the utility and accuracy of gel studies by more closely approximating soil conditions.
Topics: Aluminum Oxide; Arabidopsis; Buffers; Phosphates
PubMed: 29304231
DOI: 10.1093/jxb/erx454 -
Journal of Colloid and Interface Science Dec 2022Understanding the microscopic driving force of water wetting is challenging and important for design of materials. The relations between structure, dynamics and hydrogen...
HYPOTHESIS
Understanding the microscopic driving force of water wetting is challenging and important for design of materials. The relations between structure, dynamics and hydrogen bonds of interfacial water can be investigated using molecular dynamics simulations.
EXPERIMENTS AND SIMULATIONS
Contact angles at the alumina (0001) and (112‾0) surfaces are studied using both classical molecular dynamics simulations and experiments. To test the superhydrophilicity, the free energy cost of removing waters near the interfaces are calculated using the density fluctuations method. The strength of hydrogen bonds is determined by their lifetime and geometry.
FINDINGS
Both surfaces are superhydrophilic and the (0001) surface is more hydrophilic. Interactions between surfaces and interfacial waters promote a templating effect whereby the latter are aligned in a pattern that follows the underlying lattice of the surfaces. Translational and rotational dynamics of interfacial water molecules are slower than in bulk water. Hydrogen bonds between water and both surfaces are asymmetric, water-to-aluminol ones are stronger than aluminol-to-water ones. Molecular dynamics simulations eliminate the impacts of surface contamination when measuring contact angles and the results reveal the microscopic origin of the macroscopic superhydrophilicity of alumina surfaces: strong water-to-aluminol hydrogen bonds.
Topics: Aluminum Oxide; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Molecular Dynamics Simulation; Water
PubMed: 35964442
DOI: 10.1016/j.jcis.2022.07.164 -
International Journal of Environmental... Dec 2022To apply coal fly ash to the remediation of heavy-metal-contaminated soil, an alumina-silica nano-amendment (ASNA) was synthesized from coal fly ash and was used for the...
To apply coal fly ash to the remediation of heavy-metal-contaminated soil, an alumina-silica nano-amendment (ASNA) was synthesized from coal fly ash and was used for the immobilization of lead and zinc in contaminated soil. The investigation on the synthesis of the ASNA shows that the ASNA can be obtained under a roasting temperature of 700 °C, a ratio of alkali to coal fly ash of 1.2:1, and a molar ratio of silicon to aluminum of 1:1. The ASNA could increase the soil pH and cation exchange capacity (CEC) and decrease the bioavailability of Pb and Zn. When the ASNA addition increased from 0 to 2%, the bioavailability (extracted by CaCl) of Pb and Zn decreased by 47% and 72%, respectively. Moreover, the addition of the ASNA facilitated the transformation of Pb from a reducible fraction to oxidizable and residual fractions and Zn from an exchangeable fraction to a residual fraction. The correlation analysis and cluster analysis verify that the ASNA modulates the chemical speciation of heavy metals by increasing the soil's CEC and pH, thereby immobilizing heavy metals. It is expected that this study can provide a new method for the remediation of Pb- and Zn-contaminated soil.
Topics: Coal Ash; Coal; Soil Pollutants; Aluminum Oxide; Silicon Dioxide; Metals, Heavy; Soil; Zinc
PubMed: 36498279
DOI: 10.3390/ijerph192316204 -
Biosensors & Bioelectronics Aug 2022Chronic wounds represent an important healthcare challenge in developed countries, being wound infection a serious complication with significant impact on patients' life...
Chronic wounds represent an important healthcare challenge in developed countries, being wound infection a serious complication with significant impact on patients' life conditions. However, there is a lack of methods allowing an early diagnosis of infection and a right decision making for a correct treatment. In this context, we propose a novel methodology for the electrical monitoring of infection biomarkers in chronic wound exudates, using nanoporous alumina membranes. Lysozyme, an enzyme produced by the human immune system indicating wound infection, is selected as a model compound to prove the concept. Peptidoglycan, a component of the bacterial layer and the native substrate of lysozyme, is immobilized on the inner walls of the nanochannels, blocking them both sterically and electrostatically. The steric blocking is dependent on the pore size (20-100 nm) and the peptidoglycan concentration, whereas the electrostatic blocking depends on the pH. The proposed analytical method is based on the electrical monitoring of the steric/electrostatic nanochannels unblocking upon the specific degradation of peptidoglycan by lysozyme, allowing to detect the infection biomarker at 280 ng/mL levels, which are below those expected in wounds. The low protein adsorption rate and thus outstanding filtering properties of the nanoporous alumina membranes allowed us to discriminate wound exudates from patients with both sterile and infected ulcers without any sample pre-treatment usually indispensable in most diagnostic devices for analysis of physiological fluids. Although size and charge effects in nanochannels have been previously approached for biosensing purposes, as far as we know, the use of nanoporous membranes for monitoring enzymatic cleavage processes, leading to analytical systems for the specific detection of the enzymes has not been deeply explored so far. Compared with previously reported methods, our methodology presents the advantages of no need of neither bioreceptors (antibodies or aptamers) nor competitive assays, low matrix effects and quantitative and rapid analysis at the point-of-care, being also of potential application for the determination of other protease biomarkers.
Topics: Aluminum Oxide; Biomarkers; Biosensing Techniques; Humans; Muramidase; Peptidoglycan; Wound Infection
PubMed: 35421671
DOI: 10.1016/j.bios.2022.114243 -
Molecules (Basel, Switzerland) Apr 2022The development of green and sustainable materials for use as heterogeneous catalysts is a growing area of research in chemistry. In this paper, mesoporous SiO-AlO mixed...
The development of green and sustainable materials for use as heterogeneous catalysts is a growing area of research in chemistry. In this paper, mesoporous SiO-AlO mixed oxide catalysts with different Si/Al ratios were prepared via hydrolytic (HSG) and nonhydrolytic sol-gel (NHSG) processes. The HSG route was explored in acidic and basic media, while NHSG was investigated in the presence of diisopropylether as an oxygen donor. The obtained materials were characterized using EDX, N-physisorption, powder XRD, Si, Al MAS-NMR, and NH-TPD. This approach offered good control of composition and the Si/Al ratio was found to influence both the texture and the acidity of the mesoporous materials. According to Al and Si MAS NMR analyses, silicon and aluminum were more regularly distributed in NHSG samples that were also more acidic. Silica-alumina catalysts prepared via NHSG were more active in esterification of acetic acid with n-BuOH.
Topics: Aluminum Oxide; Catalysis; Esterification; Gels; Oxides; Silicon Dioxide
PubMed: 35458732
DOI: 10.3390/molecules27082534