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1.
Eur Heart J ; 45(4): 287-305, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37992083

RESUMO

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Benzofenonas , Isoxazóis , Doenças Vasculares , Humanos , Fator de Transcrição AP-1 , Aminopropionitrilo , Estudos Transversais , Dissecção Aórtica/genética , Doenças da Aorta/patologia , Doenças Vasculares/patologia , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Fatores de Necrose Tumoral
2.
Small ; 20(10): e2306508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37919860

RESUMO

The design and fabrication of NO-evolving core-shell nanoparticles (denoted as NC@Fe), comprised of BNN6-laden COF@Fe3 O4 nanoparticles, are reported. This innovation extends to the modification of 3D printed polyetheretherketone scaffolds with NC@Fe, establishing a pioneering approach to multi-modal bone therapy tailored to address complications such as device-associated infections and osteomyelitis. This work stands out prominently from previous research, particularly those relying on the use of antibiotics, by introducing a bone implant capable of simultaneous NO gas therapy and photothermal therapy (PPT). Under NIR laser irradiation, the Fe3 O4 NP core (photothermal conversion agent) within NC@Fe absorbs photoenergy and initiates electron transfer to the loaded NO donor (BNN6), resulting in controlled NO release. The additional heat generated through photothermal conversion further propels the NC@Fe nanoparticles, amplifying the therapeutic reach. The combined effect of NO release and PPT enhances the efficacy in eradicating bacteria over a more extensive area around the implant, presenting a distinctive solution to conventional challenges. Thorough in vitro and in vivo investigations validate the robust potential of the scaffold in infection control, osteogenesis, and angiogenesis, emphasizing the timeliness of this unique solution in managing complicated bone related infectious diseases.


Assuntos
Estruturas Metalorgânicas , Polímeros , Benzofenonas , Polietilenoglicóis , Cetonas
3.
Toxicol Appl Pharmacol ; 484: 116868, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38382712

RESUMO

Pubertal mammary branching morphogenesis is a hormone-regulated process susceptible to exposure to chemicals with endocrine disruptive capacity, such as the UV-filter benzophenone-3 (BP3). Our aim was to assess whether intrauterine or in vitro exposure to BP3 modified the branching morphogenesis of the female mouse mammary gland. For this, pregnant mice were dermally exposed to BP3 (0.15 or 50 mg/kg/day) from gestation day (GD) 8.5 to GD18.5. Sesame oil treatment served as control. Changes of the mammary glands of the offspring were studied on postnatal day 45. Further, mammary organoids from untreated mice were cultured under branching induction conditions and exposed for 9 days to BP3 (1 × 10-6 M, 1 × 10-9 M, or 1 × 10-12 M with 0.01% ethanol as control) to evaluate the branching progression. Mice that were exposed to BP3 in utero showed decreased mRNA levels of progesterone receptor (PR) and WNT4. However, estradiol and progesterone serum levels, mammary histomorphology, proliferation, and protein expression of estrogen receptor alpha (ESR1) and PR were not significantly altered. Interestingly, direct exposure to BP3 in vitro also decreased the mRNA levels of PR, RANKL, and amphiregulin without affecting the branching progression. Most effects were found after exposure to 50 mg/kg/day or 1 × 10-6 M of BP3, both related to sunscreen application in humans. In conclusion, exposure to BP3 does not impair mammary branching morphogenesis in our models. However, BP3 affects PR transcriptional expression and its downstream mediators, suggesting that exposure to BP3 might affect other developmental stages of the mammary gland.


Assuntos
Benzofenonas , Estradiol , Gravidez , Humanos , Camundongos , Feminino , Animais , Benzofenonas/toxicidade , Estradiol/metabolismo , Morfogênese , RNA Mensageiro/metabolismo , Glândulas Mamárias Animais
4.
Langmuir ; 40(20): 10648-10662, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712915

RESUMO

This study presents new insights into the potential role of polyelectrolyte interfaces in regulating low friction and interstitial fluid pressurization of cartilage. Polymer brushes composed of hydrophilic 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a PEEK substrate (SPMK-g-PEEK) are a compelling biomimetic solution for interfacing with cartilage, inspired by the natural lubricating biopolyelectrolyte constituents of synovial fluid. These SPMK-g-PEEK surfaces exhibit a hydrated compliant layer approximately 5 µm thick, demonstrating the ability to maintain low friction coefficients (µ ∼ 0.01) across a wide speed range (0.1-200 mm/s) under physiological loads (0.75-1.2 MPa). A novel polyelectrolyte-enhanced tribological rehydration mechanism is elucidated, capable of recovering up to ∼12% cartilage strain and subsequently facilitating cartilage interstitial fluid recovery, under loads ranging from 0.25 to 2.21 MPa. This is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behavior of polymer brushes. Contrary to conventional theories that emphasize interstitial fluid pressurization in regulating cartilage lubrication, this work demonstrates that SPMK-g-PEEK's frictional behavior with cartilage is independent of these factors and provides unabating aqueous lubrication. Polyelectrolyte-enhanced tribological rehydration can occur within a static contact area and operates independently of known mechanisms of cartilage interstitial fluid recovery established for converging or migrating cartilage contacts. These findings challenge existing paradigms, proposing a novel polyelectrolyte-cartilage tribological mechanism not exclusively reliant on interstitial fluid pressurization or cartilage contact geometry. The implications of this research extend to a broader understanding of synovial joint lubrication, offering insights into the development of joint replacement materials that more accurately replicate the natural functionality of cartilage.


Assuntos
Lubrificação , Polímeros , Polímeros/química , Animais , Polieletrólitos/química , Polietilenoglicóis/química , Cartilagem/química , Cartilagem/efeitos dos fármacos , Propriedades de Superfície , Benzofenonas/química , Cartilagem Articular/química , Cartilagem Articular/fisiologia , Cetonas/química
5.
Bioorg Med Chem Lett ; 109: 129841, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38838920

RESUMO

Protein phosphorylation is catalyzed by kinases to regulate cellular events and disease states. Identifying kinase-substrate relationships represents a powerful strategy to understand cell biology and disease yet remains challenging due to the rapid dynamics of phosphorylation. Over the last decade, several γ-phosphoryl modified ATP analogs containing crosslinkers were developed to covalently conjugate kinases, their substrates, and their associated proteins for subsequent characterization. Here, kinetics and crosslinking experiments demonstrated that the UV-activated analogs, ATP-aryl azide and ATP-benzophenone, offered the most robust crosslinking, whereas electrophilic ATP-aryl fluorosulfate promoted the most effective proximity-enabled crosslinking. The data will guide future applications of kinase-catalyzed crosslinking to study normal and disease biology.


Assuntos
Trifosfato de Adenosina , Reagentes de Ligações Cruzadas , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/química , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/síntese química , Benzofenonas/química , Benzofenonas/síntese química , Estrutura Molecular , Azidas/química , Humanos , Cinética , Fosforilação
6.
Environ Sci Technol ; 58(12): 5472-5482, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466321

RESUMO

The fate of selected UV filters (UVFs) was investigated in two soil aquifer treatment (SAT) systems, one supplemented with a reactive barrier containing clay and vegetable compost and the other as a traditional SAT reference system. We monitored benzophenone-3 (BP-3) and its transformation products (TPs), including benzophenone-1 (BP-1), 4,4'-dihydroxybenzophenone (4DHB), 4-hydroxybenzophenone (4HB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), along with benzophenone-4 (BP-4) and avobenzone (AVO) in all involved compartments (water, aquifer sediments, and biofilm). The reactive barrier, which enhances biochemical activity and biofilm development, improved the removal of all detected UVFs in water samples. Among monitored UVFs, only 4HB, BP-4, and AVO were detected in sediment and biofilm samples. But the overall retained amounts were several orders of magnitude larger than those dissolved. These amounts were quantitatively reproduced with a specifically developed simple analytical model that consists of a mobile compartment and an immobile compartment. Retention and degradation are restricted to the immobile water compartment, where biofilm absorption was simulated with well-known compound-specific Kow values. The fact that the model reproduced observations, including metabolites detected in the biofilm but not in the (mobile) water samples, supports its validity. The results imply that accumulation ensures significant biodegradation even if the degradation rates are very low and suggest that our experimental findings for UVFs and TPs can be extended to other hydrophobic compounds. Biofilms act as accumulators and biodegraders of hydrophobic compounds.


Assuntos
Solo , Poluentes Químicos da Água , Porosidade , Protetores Solares/análise , Benzofenonas/química , Água/química , Poluentes Químicos da Água/análise
7.
Macromol Rapid Commun ; 45(4): e2300549, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37983912

RESUMO

This study focuses on developing surface coatings with excellent antifouling properties, crucial for applications in the medical, biological, and technical fields, for materials and devices in direct contact with living tissues and bodily fluids such as blood. This approach combines thermoresponsive poly(2-alkyl-2-oxazoline)s, known for their inherent protein-repellent characteristics, with established antifouling motifs based on betaines. The polymer framework is constructed from various monomer types, including a novel benzophenone-modified 2-oxazoline for photocrosslinking and an azide-functionalized 2-oxazoline, allowing subsequent modification with alkyne-substituted antifouling motifs through copper(I)-catalyzed azide-alkyne cycloaddition. From these polymers surface-attached networks are created on benzophenone-modified gold substrates via photocrosslinking, resulting in hydrogel coatings with several micrometers thickness when swollen with aqueous media. Given that poly(2-alkyl-2-oxazoline)s can exhibit a lower critical solution temperature in water, their temperature-dependent solubility is compared to the swelling behavior of the surface-attached hydrogels upon thermal stimulation. The antifouling performance of these hydrogel coatings in contact with human blood plasma is further evaluated by surface plasmon resonance and optical waveguide spectroscopy. All surfaces demonstrate extremely low retention of blood plasma components, even with undiluted plasma. Notably, hydrogel layers with sulfobetaine moieties allow efficient penetration by plasma components, which can then be easily removed by rinsing with buffer.


Assuntos
Azidas , Hidrogéis , Humanos , Hidrogéis/química , Polímeros/química , Plasma , Alcinos , Benzofenonas
8.
Epilepsy Behav ; 151: 109597, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181534

RESUMO

PURPOSE: To evaluate the quality of available information on Youtube videos about VNS as a "source of health information" for patients with drug resistant epilepsy. METHODS: Youtube videos were searched and screened using the terms "VNS for seizures," and "VNS surgery," "VNS epilepsy" in May 2023. The quality of the videos was evaluated the Quality Criteria for Consumer Health Information (DISCERN) and Global Quality Scale (GQS). The videos were analyzed in terms of content, accuracy, reliability, and quality. RESULTS: A total of 104 videos were searched. After excluding duplicate or inappropriate videos, 51 videos were analyzed. Youtube videos about vagal nerve stimulation are mostly on general information, surgical procedures, patient experiences and magnet use. When video sources are examined according to the quality, according to GQS, 75 % of high quality videos were narrated by physicians, all intermediate quality videos were narrated by physicians, and low quality ones narrated by physicians were 47.4 % and 28.9 % by the patients. All of the videos narrated by the patients were of low quality. There was a significant and strong correlation between GQS and Discern score (r = 0.807, p < 0.001). Only GQS scores of videos with different content were found to be statistically significant (p < 0.05). Two pediatric neurologists independently reviewed the videos and classified the videos as useful or misleading according to the GQS, DISCERN scala. The overall κ value for interobserver consistency according to Global Quality Scale was 0.781 (p < 0.001). (95 % confidence interval), indicating a very good level of agreement. CONCLUSION: Youtube videos may provide a worthful source for patients and parents seeking to find more information about VNS However incorrect information could easily be disseminated by high number of views of videos with low quality. High skilled and experienced professionals should create videos on Youtube to ensure that patients and parents can access more useful, high-quality, and accurate information on VNS.


Assuntos
Mídias Sociais , Estimulação do Nervo Vago , Humanos , Criança , Reprodutibilidade dos Testes , Benzofenonas , Disseminação de Informação , Gravação em Vídeo
9.
CNS Spectr ; 29(3): 166-175, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38487834

RESUMO

OBJECTIVE: The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies. METHODS: The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria. RESULTS: Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val-Val participants). There were insufficient nature and number of studies for meta-analysis. CONCLUSION: The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).


Assuntos
Inibidores de Catecol O-Metiltransferase , Catecol O-Metiltransferase , Cognição , Tolcapona , Humanos , Inibidores de Catecol O-Metiltransferase/farmacologia , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Cognição/efeitos dos fármacos , Catecol O-Metiltransferase/genética , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Adulto , Memória de Curto Prazo/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Phytopathology ; 114(2): 464-473, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37565813

RESUMO

Frequent fungicide applications are required to manage grapevine powdery mildew (Erysiphe necator). However, this practice is costly and has led to widespread fungicide resistance. A method of monitoring in-field fungicide efficacy could help growers maximize spray-interval length, thereby reducing costs and the rate of fungicide resistance emergence. The goal of this study was to evaluate if hyperspectral sensing in the visible to shortwave infrared range (400 to 2,400 nm) can quantify foliar fungicide efficacy on grape leaves. Commercial formulations of metrafenone, Bacillus mycoides isolate J (BmJ), and sulfur were applied on Chardonnay grapevines in vineyard or greenhouse settings. Foliar reflectance was measured with handheld hyperspectral spectroradiometers at multiple days post-application. Fungicide efficacy was estimated as a proxy for fungicide residue and disease control measured with the Blackbird microscopy imaging robot. Treatments could be differentiated from the untreated control with an accuracy of 73.06% for metrafenone, 67.76% for BmJ, and 94.10% for sulfur. The change in spectral reflectance was moderately correlated with the cube root of the area under the disease progress curve for metrafenone- and sulfur-treated samples (R2 = 0.38 and 0.36, respectively) and with sulfur residue (R2 = 0.42). BmJ treatment impacted foliar physiology by enhancing the leaf mass/area and reducing the nitrogen and total phenolic content as estimated from spectral reflectance. The results suggest that hyperspectral sensing can be used to monitor in-situ fungicide efficacy, and the prediction accuracy depends on the fungicide and the time point measured. The ability to monitor in-situ fungicide efficacy could facilitate more strategic fungicide applications and promote sustainable grapevine protection. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Bacillus , Benzofenonas , Fungicidas Industriais , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , Enxofre
11.
Arch Toxicol ; 98(6): 1909-1918, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553590

RESUMO

Previously, we found that the ultraviolet filter benzophenone-3 (BP3) causes fetal growth restriction in mice when is applied when implantation occurs (first week of gestation). However, whether BP3 can affect gestation and fertility after implantation period is unknown. We aimed to study the effects on reproductive physiology of the offspring caused by perinatal exposure to BP3. C57BL/6 pregnant mice were dermally exposed to 50 mg BP3/kg bw.day or olive oil (vehicle) from gestation day 9 (gd9) to postnatal day 21 (pnd1). We observed no differences in mother's weights, duration of gestation, number of pups per mother, onset of puberty or sex ratio. The weights of the pups exposed to benzophenone-3 were transiently lower than those of the control. Estrous cycle was not affected by perinatal exposure to BP3. Besides, we performed a fertility assessment by continuous breeding protocol: at 10 weeks of age, one F1 female and one F1 male mouse from each group was randomly chosen from each litter and housed together for a period of 6 months. We noticed a reduction in the number of deliveries per mother among dams exposed to BP3 during the perinatal period. To see if this decreased fertility could be associated to an early onset of oocytes depletion, we estimated the ovarian reserve of germ cells. We found reduced number of oocytes and primordial follicles in BP3. In conclusion, perinatal exposure to BP3 leads to a decline in the reproductive capacity of female mice in a continuous breeding protocol linked to oocyte depletion.


Assuntos
Benzofenonas , Camundongos Endogâmicos C57BL , Oócitos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Benzofenonas/toxicidade , Benzofenonas/administração & dosagem , Gravidez , Masculino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Oócitos/efeitos dos fármacos , Camundongos , Fertilidade/efeitos dos fármacos , Protetores Solares/toxicidade , Exposição Materna/efeitos adversos
12.
Retina ; 44(7): 1196-1202, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437826

RESUMO

PURPOSE: To compare topical nonsteroidal anti-inflammatory drug (NSAID) efficacy on intravitreal injection-induced pain reduction and determine the most efficient topical NSAID. METHODS: This randomized-controlled study included 662 eyes of 662 patients. Based on the types of NSAID administered before intravitreal injection, eight subgroups were formed. In the control group, a sterile saline solution was applied instead of NSAIDs. The visual analog scale was used to assess pain scores after intravitreal injection. The visual analog scale scores were noted immediately and 6 hours following injection (sixth hour). RESULTS: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% had the lowest scores, immediately after and after 6 hours, with no significant differences. Diclofenac and ketorolac had higher visual analog scale scores than the first trio but lower scores than the control group. Flurbiprofen, pranoprofen, and indomethacin did not significantly affect immediate pain; however, at the sixth hour, the visual analog scale scores were significantly reduced. CONCLUSION: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% were the most effective NSAIDs for pain reduction. Although some NSAIDs did not have a significant effect on immediate pain, they all provided significant benefits at the sixth hour.


Assuntos
Anti-Inflamatórios não Esteroides , Benzenoacetamidas , Dor Ocular , Injeções Intravítreas , Fenilacetatos , Anti-Inflamatórios não Esteroides/administração & dosagem , Humanos , Masculino , Feminino , Dor Ocular/prevenção & controle , Dor Ocular/diagnóstico , Dor Ocular/tratamento farmacológico , Idoso , Fenilacetatos/administração & dosagem , Pessoa de Meia-Idade , Benzenoacetamidas/administração & dosagem , Benzofenonas/administração & dosagem , Bromobenzenos/administração & dosagem , Administração Tópica , Medição da Dor , Soluções Oftálmicas , Cetorolaco/administração & dosagem , Idoso de 80 Anos ou mais
13.
J Toxicol Environ Health A ; 87(17): 687-700, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38836411

RESUMO

The increasing use of UV filters, such as benzophenone-3 (BP-3) and titanium dioxide nanoparticles (TiO2 NPs), has raised concerns regarding their ecotoxicological effects on the aquatic environment. The aim of the present study was to examine the embryo-larval toxicity attributed to BP-3 or TiO2 NPs, either alone or in a mixture, utilizing zebrafish (Danio rerio) as a model after exposure to environmentally relevant concentrations of these compounds. Zebrafish embryos were exposed to BP-3 (10, 100, or 1000 ng/L) or TiO2 NPs (1000 ng/L) alone or in a mixture (BP-3 10, 100, or 1000 ng/L plus 1000 ng/L of TiO2 NPs) under static conditions for 144 hr. After exposure, BP-3 levels were determined by high-performance liquid chromatography (HPLC). BP-3 levels increased in the presence of TiO2 NPs, indicating that the BP-3 degradation decreased in the presence of the NPs. In addition, in the presence of zebrafish, BP-3 levels in water decreased, indicating that zebrafish embryos and larvae might absorb BP-3. Data demonstrated that, in general, environmentally relevant concentrations of BP-3 and TiO2 NPs, either alone or in a mixture, did not significantly induce changes in heart and spontaneous contractions frequencies, levels of reactive oxygen species (ROS), morphological and morphometric parameters as well as mortality rates during 144 hr exposure. However, the groups exposed to TiO2 NPs alone and in a mixture with BP-3 at 10 ng/L exhibited an earlier significant hatching rate than the controls. Altogether, the data indicates that a potential ecotoxicological impact on the aquatic environment exists.


Assuntos
Benzofenonas , Embrião não Mamífero , Protetores Solares , Titânio , Poluentes Químicos da Água , Peixe-Zebra , Animais , Titânio/toxicidade , Titânio/química , Benzofenonas/toxicidade , Protetores Solares/toxicidade , Protetores Solares/química , Embrião não Mamífero/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Nanopartículas/toxicidade , Nanopartículas Metálicas/toxicidade , Ecotoxicologia , Larva/efeitos dos fármacos
14.
J Toxicol Environ Health A ; 87(6): 266-273, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38166509

RESUMO

Benzophenone-3 (BP-3, 2-hydroxy-4-methoxybenzophenone, oxybenzone) is one of the most widely used types of benzophenone organic sunscreen. However, this compound is a potentially harmful toxicant. The aim of this study was 2-fold to: (1) utilize a Hershberger bioassay in vivo in castrated male Sprague-Dawley rats to investigate the anti-androgenic activities of BP-3, and (2) use in vitro a methyl tetrazolium assay to compare the toxicity between Leydig cells (TM3 cells) and mouse fibroblast (NIH-3T3) cell lines. In the Hershberger assay, rats were divided into 6 groups (each of n = 7): a vehicle control, negative control, positive control, PB-3 low (40 mg/kg), BP-3 intermediate (200 mg/kg), and BP-3 high (1000 mg/kg)-dose. The weight of the ventral prostate was significantly decreased at BP-3 doses of 200 or 1,000 mg/kg/day. In addition, the levator anibulbocavernosus muscle weights were also significantly reduced at BP-3 doses of 40, 200, or 1,000 mg/kg/day. In the MTT assay, the viability of NIH-3T3 mouse fibroblast cells was within the normal range. However, the TM3 mouse testis Leydig cell viability was significantly lowered in a concentration-dependent manner. Therefore, data indicate that BP-3 might exert in vivo anti-androgenic and in vitro cytotoxic effects in cells associated with the male reproductive system compared to normal non-reproductive cells.Abbreviation: BP-3: benzophenone-3; CG: Cowper's gland; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; GP: glans penis; LABC: levator anibulbocavernosus muscle; MTT: methyl tetrazolium; NC: negative control; PC: positive control; SV: seminal vesicle; TP: testosterone propionate; VC: vehicle control; VP: ventral prostate.


Assuntos
Antineoplásicos , Orquiectomia , Camundongos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Antagonistas de Androgênios/farmacologia , Benzofenonas/toxicidade , Antineoplásicos/farmacologia , Tamanho do Órgão , Genitália Masculina
15.
Planta Med ; 90(7-08): 631-640, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843801

RESUMO

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.


Assuntos
Garcinia , Espectroscopia de Ressonância Magnética , Garcinia/química , Estrutura Molecular , Frutas/química , Benzofenonas/química , Benzofenonas/isolamento & purificação , Benzofenonas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Floroglucinol/química , Floroglucinol/isolamento & purificação , Humanos
16.
BMC Ophthalmol ; 24(1): 120, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491368

RESUMO

PURPOSE: To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS: This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS: One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION: When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.


Assuntos
Benzofenonas , Bromobenzenos , Catarata , Membrana Epirretiniana , Edema Macular , Humanos , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/patologia , Edema Macular/patologia , Tomografia de Coerência Óptica , Anti-Inflamatórios não Esteroides , Estudos Retrospectivos , Vitrectomia/métodos
17.
Skin Res Technol ; 30(5): e13744, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38771547

RESUMO

BACKGROUND: Evidence from animal models suggests a role for the organic ultraviolet filter benzophenone-3's (BP-3) on white blood cells (WBCs). However, BP-3's effect on WBCs in humans is unknown. MATERIALS AND METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. We included participants >6 years with data on urinary BP-3, urinary creatinine, and WBC count. Quintiles of urinary creatinine-normalized BP-3 (CnBP-3) levels were used in linear regression models adjusting for age, gender, race, body mass index (BMI), smoking status, education level, family income to poverty threshold ratio, survey cycle, and season. RESULTS: Of the 16 959 participants, 8564 (50.5%) were females, 6602 (38.9%) were White, and 3870 (22.8%) were Black. The mean (standard deviation) age was 37.6 (22.7) years, BMI was 26.8 (7.40) kg/m2, WBC count was 7.22 (2.53) × 109/L, neutrophil count was 4.15 (1.86) × 109/L, and lymphocyte count was 2.25 (1.33) × 109/L and median (interquartile range) of CnBP-3 was 12.1 (44.9) µg/gm. The highest quintile of CnBP-3 was associated with significantly lower WBC and neutrophil counts compared to the lowest quintile of CnBP-3 (Δ quintiles = -137 × 106/L, 95% CI: -249 to -24, p = 0.02 and = -177 × 106/L, 95% CI: -323 to -30, p = 0.02, respectively). In contrast, we did not observe a difference in lymphocyte count between the lowest and highest quintiles of CnBP-3 in unadjusted or adjusted analyses. CONCLUSION: We found an inverse relationship between BP-3 levels and WBC and neutrophil counts, and not with lymphocyte count. Further research is needed to confirm our findings.


Assuntos
Benzofenonas , Inquéritos Nutricionais , Protetores Solares , Humanos , Feminino , Masculino , Contagem de Leucócitos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Creatinina/sangue , Creatinina/urina , Adolescente
18.
Neurosurg Rev ; 47(1): 72, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285230

RESUMO

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.


Assuntos
Benzofenonas , Polímeros , Polimetil Metacrilato , Crânio , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Crânio/cirurgia
19.
Eur Spine J ; 33(1): 332-338, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37737497

RESUMO

BACKGROUND: A comparison of fusion rates and clinical outcomes of instrumented transforaminal interbody fusion (TLIF) between polyetheretherketone (PEEK) and titanium-coated PEEK (Ti-PEEK) cages is not well documented. METHODS: A single-centre, prospective, randomised study included patients who underwent one-level TLIF between L3-S1 segments. Patients were randomised into one of two groups: TLIF surgery with the PEEK cage and TLIF surgery with the Ti-PEEK cage. Clinical results were measured. All patients were assessed by repeated X-rays and 3D CT scans. Cage integration was assessed using a modified Bridwell classification. The impact of obesity and smoking on fusion quality was also analysed. Patients in both groups were followed up for 2 years. RESULTS: Altogether 87 patients were included in the study: of these 87 patients, 81 (93.1%) completed the 2-year follow-up. A significant improvement in clinical outcome was found in the two measurements scales in both groups (RM: p = 0.257, VAS: p = 0.229). There was an increase in CobbS and CobbL angle in both groups (p = 0.172 for CobbS and p = 0.403for CobbL). Bony fusion was achieved in 37 of 40 (92.5%) patients in the TiPEEK group and 35 of 41 (85.4%) in the PEEK group (p = 0.157). Cage subsided in 2 of 40 patients (5%) in the TiPEEK group and 11 of 41 (26.8%) in the PEEK group (p = 0.007). Body mass index > 30 and smoking were not predictive factors of bony fusion achievement. CONCLUSION: There is no significant advantage of TiPEEK cages over PEEK cages in clinical outcome and fusion rate 2 years after surgery.


Assuntos
Benzofenonas , Polímeros , Fusão Vertebral , Titânio , Humanos , Vértebras Lombares/cirurgia , Estudos Prospectivos , Fusão Vertebral/métodos , Polietilenoglicóis , Cetonas , Resultado do Tratamento
20.
BMC Musculoskelet Disord ; 25(1): 488, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909212

RESUMO

PURPOSE: To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties. METHOD: Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct. RESULTS: All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure. CONCLUSION: PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.


Assuntos
Benzofenonas , Cetonas , Parafusos Pediculares , Polímeros , Humanos , Cetonas/química , Feminino , Masculino , Polietilenoglicóis/química , Pessoa de Meia-Idade , Remoção de Dispositivo , Teste de Materiais , Idoso , Materiais Biocompatíveis , Falha de Prótese , Reoperação
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