IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a ...breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcε receptor I complex.
The recent breakthrough in all-atom, protein structure prediction opens new avenues for a range of computational approaches in enzyme design. These new approaches could become instrumental for the ...development of technical biocatalysts, and hence our transition toward more sustainable industries. Here, we discuss one approach, which is well-known within inorganic catalysis, but essentially unexploited in biotechnology. Specifically, we review examples of linear free-energy relationships (LFERs) for enzyme reactions and discuss how LFERs and the associated Sabatier Principle may be implemented in algorithms that estimate kinetic parameters and enzyme performance based on model structures.
•Linear scaling between binding- and activation energies occurs for some enzyme reactions.•This is particularly seen for heterogeneous biocatalysis involving insoluble substrate.•Linear free-energy relationships simplify computational prediction of kinetic parameters.•It is proposed that this can be exploited in future enzyme discovery and -engineering.
The aims of this study were: To evaluate the surface hardness of simulated dentin caries lesions treated with either silver nanoclusters (AgNCls) synthesized in polymethacrylic acid (PMAA) or 38% ...silver diammine fluoride (SDF), as well as observe the penetration of the treatment solutions into the simulated caries lesions. Dentin blocks 4 mm thick obtained from caries-free third molars were sectioned and then simulated caries lesions on the occlusal dentin surfaces were created. Each specimen (n = 8) was divided into four sections: (A) treated with 20% AgNCls/PMAA; (B) treated with SDF 38% (FAgamin, Tedequim, Cordoba, Argentina); (C) sound tooth protected by nail-varnish during artificial caries generation (positive control); and (D) artificial caries lesion without surface treatment (negative control). AgNCls/PMAA or SDF were applied on the simulated lesions with a microbrush for 10 s, then excess removed. The surface hardness was measured by means of Vickers indentation test. To trace the depth of penetration, up to 400 μm, of silver ions, elemental composition of the samples was observed using EDX, coupled with SEM, and measured every 50 μm from the surface towards the pulp chamber. Laser Induced Breakdown Spectroscopy (LIBS) was also employed to trace silver ion penetration; the atomic silver line 328.06 nm was used with a 60 μm laser spot size to a depth of 240 μm. Student's-t test identified significant differences between treatment groups for each depth and the Bonferroni test was used for statistical analysis of all groups (p < 0.05). Mean surface hardness values obtained were 111.2 MPa, 72.3 MPa, 103.3 MPa and 50.5 MPa for groups A, B, C and D respectively. There was a significant difference between groups A and C compared with groups B and D, the group treated with AgNCls/PMAA achieved the highest surface hardness, similar or higher than the sound dentin control. A constant presence of silver was observed throughout the depth of the sample for group A, while group B showed a peak concentration of silver at the surface with a significant drop beyond 50 μm. The 20% AgNCls/PMAA solution applied to simulated dentin caries lesions achieved the recovery of surface hardness equivalent to sound dentin with the penetration of silver ions throughout the depth of the lesion.
The present work shows the synthesis of ZnO nanoparticles through a green method, using
extracts, which provide the reducing and stabilizing compounds. The conditions of the medium in which the ...reaction was carried out was evaluated, that is, magnetic stirring, ultrasound assisted, and resting condition. UV-Vis, FTIR spectroscopy, and X-ray diffraction results confirmed the synthesis of ZnO with nanometric crystal size. The scanning electron microscopy analysis showed that the morphology and size of the particles depends on the synthesis condition used. It obtained particles between 20 and 200 nm in the sample without agitation, while the samples with stirring and ultrasound were 80 nm and 100 nm, respectively. ZnO nanoparticles showed antibacterial activity against Gram-positive
and Gram-negative
. A quantitative analysis was performed by varying the concentration of ZnO nanoparticles. In all cases, the antibacterial activity against Gram-positives was greater than against Gram-negatives. Ultrasound-assisted ZnO nanoparticles showed the highest activity, around 99% and 80% for
and
, respectively. Similar results were obtained in the study of the anti-inflammatory activity of ZnO nanoparticles; the ultrasound-assisted sample exhibited the highest percentage (93%), even above that shown by diclofenac, which was used as a reference. Therefore, the ZnO nanoparticles synthesized with
extracts have properties that can be used safely and efficiently in the field of biomedicine.
Caries is the most prevalent chronic noncommunicable disease. Strategies to prevent its onset and early interventions to arrest the progression of early lesions have been emphasised throughout recent ...decades to avoid or delay the restorative spiral of the tooth. More individuals are retaining their natural teeth into old age, thereby necessitating ongoing restorative dentistry intervention for their maintenance. The aim of this systematic review was to update the state of the art regarding clinical studies reporting the effectiveness of different nonrestorative caries treatment options in the 5-year period from 2017 to 2022. Relevant articles were retrieved from 2 electronic databases, including randomised clinical trials (RCTs) published from January 2017 until April 2022, assessing effectiveness and secondary effects of at least one nonrestorative caries treatment option, carried out with adults and/or children with noncavitated or cavitated carious lesions on either primary or permanent teeth and diagnosed by radiographs or visual/tactile assessment. All 35 included articles presented the results of RCTs with a follow-up period ranging from 6 to 84 months. Most of these studies were considered high-quality articles with a low risk of bias. Sealants and fluoride gels and varnishes were mentioned in 12 studies as effective strategies to prevent the onset of caries lesions and to arrest them in the early stages. Resin infiltration reported high caries arresting rates in noncavitated proximal lesions in 10 publications. Silver diammine fluoride presented high caries-arresting rates in open dentin lesions, both in primary and permanent dentitions as well as in root caries lesions that were accessible for cleansing. New evidence has been published between 2017 and 2022 as the result of numerous clinical studies providing further evidence of the effectiveness of nonrestorative caries treatment options.
Abstract
The aims of the study were: (1) To compare the staining effect on demineralized dentin simulating caries between silver nanoclusters (AgNCls) synthesized using polymethacrylic acid (PMAA) ...and silver diammine fluoride (SDF), and (2) to measure the shear bond strength (SBS) of a glass ionomer cement (GIC) to simulated caries lesions with and without the application of AgNCls/PMAA or SDF. Dentine blocks 4 mm thick from twenty-four non-carious third molars were sectioned and coated with nail varnish (Revlon, New York, USA). Simulated caries lesions on occlusal dentin surfaces were created (66 h in 0.05 M acetate buffer 2.2 mM calcium/phosphate pH 5.0). Specimens were divided into groups and treated with (n = 8): (A) 20% AgNCls/PMAA; (B) SDF 38% (Fagamin, Tedequim, Córdoba, Argentina); or (C) without treatment. AgNCls/PMAA or SDF were applied on the exposed surfaces with a microbrush for 10 s. Samples were incubated for 24 h at 37 °C at 100% relative humidity. Surface color was measured according to the CIE-L*a*b* system before and after demineralization (R0 and R1), 24 h and one week after treatment (R2 and R3), using a spectrophotometer (CM-600D Konica Minolta Sesing Inc., Japan). Groups A and B received an extra application of AgNCls/PMAA or SDF before a conventional GIC (Fuji IX-Gold Label, GC Corp, Tokyo, Japan) was bonded using a mold, 4 mm diameter × 3 mm high. For SBS, a Universal Testing Machine (Digimess RS-8000-5, China)—crosshead speed of 1 mm/min—was used. Statistical analysis was performed using ANOVA, Student-
t
and Scheffe-test at a significance of p < 0.05. Group A presented a stable color p = 0.24 between R1-R2 and R1-R3 in contrast to significant color changes in Group B (p = 0.02). SBS was higher (p < 0.01) in Group A (10.4 ± 2.7 MPa) compared to Groups B (3.3 ± 1.3 MPa) and C (4.0 ± 0.4 MPa), where no differences between the latter groups were observed (p = 0.77). Results of this preliminary study demonstrated that 20% AgNCls/PMAA did not stain simulated carious dentin and improved SBS of the GIC. The relevance of this study relies on the development of a therapeutic system to potentially arrest caries lesions without staining.
Objectives
To assess the 3-year cumulative survival rate of atraumatic restorative treatment (ART) and conventional resin composite restorations (CRT) placed in persons with disability.
Materials and ...methods
Patients referred for restorative care to the Haemophilia Foundation special care service were treated by one of two specialists. Patients and/or caregivers were provided with written and verbal information regarding treatment options and selected the alternative they preferred. Treatment was provided as selected unless this option proved clinically unfeasible when an alternative technique was proposed. The treatment protocols were ART (hand instruments/high-viscosity glass-ionomer) in the clinic or CRT (rotary instrumentation/resin composite) in the clinic or under general anaesthesia (GA). After 6, 12, 24 and 36 months, two independent, trained and calibrated examiners evaluated restoration survival using established ART codes. The proportional hazard model with frailty corrections gave survival estimates over 3 years.
Results
Sixty-six patients (13.6 ± 7.8 years) with 16 different disability profiles participated. CRT in the clinic proved feasible for five patients (13%), and 14 patients received CRT under GA (21%). ART was used for 47 patients (71.2%). Altogether, 298 dentine carious lesions were restored in primary and permanent teeth (182 ART; 116 CRT). The 3-year cumulative survival rates and jackknife standard errors for the 182 ART and 116 CRT restorations were 94.8 ± 2.1 and 82.8 ± 5.3%, respectively (
p
= 0.01).
Conclusions
The 3-year follow-up results confirm that ART is an effective treatment protocol.
Clinical relevance
Patients with disability, many of whom have difficulty coping with CRT, may benefit from the ART approach.
Drug provocation tests (DPT) are considered the gold standard procedure to ascertain the diagnosis of beta-lactam (BL) allergy. Regarding route of administration, current recommendations prioritize ...oral challenges, considering them safer, and reserving the intravenous route for drugs for which this is the only formulation.
To compare in terms of tolerance and safety two protocols of BL DPT, using an oral protocol (OR-DPT) and an intravenous protocol (IV-DPT).
A descriptive, retrospective study was performed, including adult patients who underwent IV-DPT or OR-DPT for suspected immediate or delayed hypersensitivity to BL antibiotics, over a period of 4 years (between January 2018 and December 2021). Demographical data, index hypersensivity reactions’ characteristics and tolerance to DPT were reviewed.
A total of 1036 patients underwent DPT, mean age of 56.8 (standard deviation, SD, 17.8) years, 655 were women (63.2%). Immediate drug hypersensitivity reactions (DHR) had occurred in 564 of patients (54.4%). OR-DPT were performed in 439 (42.4%) and IV-DPT in 597 (57.6%). The frequency of reactions during DPT, regardless of the route used, was low (3.6%): only 16 (3.6%) in OR-DPT and 21 (3.5%) in IV-DPT. From IV-DPT, 16 out 21 DHR during DPT were immediate compared with 4 out of 16 in OR-DPT. Adjusted relative risk of developing a hypersensitivity reaction during IV-DPT versus OR-DPT was 1.13 (95% confidence interval (CI)0.57–2.22).
The results suggest that OR-DPT and IV-DPT are both safe procedures when adequately performed. However, IV-DPT protocols showed a higher rate of immediate DHR during DPT probably due to the selection of basal high-risk patients to undergo IV-DPT. In conclusion, IV-DPT may be considered as an option for challenges in drug-allergy studies, entailing a precise administration.
For the first time, this study shows the nanoarchitectonic process to obtain an acetogenin-enriched nanosystem (AuNPs-Ac) using an aqueous extract from
Mill (ACM) composed of gold nanoparticles ...embedded in an organic matrix that acts as stabilizing agent and presents anti-inflammatory activity and cytotoxical effect against HepG2 cell line, promoting apoptosis. The synthesis of AuNPs-Ac was confirmed by x-ray diffraction analysis, showing metallic gold as the only phase, and the scanning transmission microscope showed an organic cap covering the AuNPs-Ac. Fourier-transformed infrared suggests that the organic cap comprises a combination of different annonaceous acetogenins, alkaloids, and phenols by the presence of bands corresponding to aromatic rings and hydroxyl groups. High-Performance Liquid Chromatography has demonstrated the presence of annonacin, a potent acetogenin, in the extract of ACM. An
anti-inflammatory activity of the extract of ACM and the AuNPs-Ac was performed using the albumin denaturation method, showing a nonlinear response, which is better than sodium diclofenac salt in a wide range of concentrations that goes from 200 to 400
g ml
with both samples. The viability assay was studied using trypan blue, treating IMR90 and HepG2 at different concentrations of AuNPs-Ac. The results defined a median lethal dose of 800
g ml
against HepG2 through apoptosis according to the ratio of caspase-cleaved 9/alpha-tubulin evaluated. It was also demonstrated that the nanosystem presents a higher cytotoxic effect on the HepG2 cell line than in IMR90, suggesting a targeted mechanism. In addition, the nanosystem performs better than using only the extract of ACM in the anti-inflammatory or antiproliferative test, attributed to their higher surface area.
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