RESUMEN
Rate coefficients of the gas-phase reactions of Cl atoms with a series of fluorinated diketones (FDKs): CF3C(O)CH2C(O)CH3 (TFP), CF3C(O)CH2C(O)CH2CH3 (TFH) and CF3C(O)CH2C(O)CH(CH3)2 (TFMH), have been measured at (298 ± 2) K and under atmospheric pressure. The experiments were performed using the relative-rate method with a GC-FID detection system. From different determinations and references used, the following rate coefficients were obtained (in cm3/(molecule·sec)): k4(TFP + Cl) = (1.75 ± 0.21) × 10-10, k5(TFH + Cl) = (2.05 ± 0.23) × 10-10, k6(TFMH + Cl) = (2.71 ± 0.34) × 10-10. Reactivity trends of FDKs were discussed and Free Energy Relationships analysis was developed. The expression lgkOH = 1.68 lgkCl + 5.71 was obtained for the reactivity of the studied FDKs together with similar unsaturated VOCs with Cl and OH radicals Additionally, acetic acid (CH3C(O)OH) and trifluoroacetic acid (CF3C(O)OH) were positively identified and quantified as degradation products using in situ FTIR spectroscopy. According to the identified products, atmospheric chemical mechanisms were proposed. The atmospheric implications of the studied reactions were assessed by the estimation of the tropospheric lifetimes of TFP, TFH, and TFMH concerning their reaction with Cl atoms to be 48, 41, and 31 hours, respectively. The relatively short residence in the atmosphere of the fluorocarbons studied will have a local/regional impact with restricted transport. Global warming potential (GWP(20yr)) calculated for the studied fluoro diketones were 0.014, 0.003 and 0.001 for TFP, TFH and TFMH, respectively with a negligible contribution to the greenhouse effect.
Asunto(s)
Contaminantes Atmosféricos , Atmósfera , Atmósfera/química , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/química , Modelos Químicos , Cetonas/química , Cloro/químicaRESUMEN
Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic ß-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic ß-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield).
Asunto(s)
Productos Biológicos , Floroglucinol , Productos Biológicos/síntesis química , Productos Biológicos/química , Catálisis , Cobre/química , Cetonas/química , Neopreno , Floroglucinol/química , Floroglucinol/síntesis química , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/química , Prenilación , Estereoisomerismo , Terpenos/síntesis química , Terpenos/químicaRESUMEN
Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.
Asunto(s)
Enfermedad de Alzheimer , Dieta Cetogénica , Enfermedad de Alzheimer/dietoterapia , Enfermedad de Alzheimer/metabolismo , Humanos , Dieta Cetogénica/métodos , Animales , Cetonas/metabolismoRESUMEN
BACKGROUND: Resecting the facet joint to relieve nerve pain can lead to spinal instability, deformity, and abnormal pressure on the anterior of the intravertebral disc. To mitigate these issues, surgeons often limit the amount of bone removed during facetectomy or stabilize the spine by fusion to maintain lumbar stability. This study aimed to assess how a M-PEEK rod system influenced the stability of the lumbar spine during graded facetectomy. METHODS: Facetectomy was performed on a validated L1-L5 finite element model which was then simulated both with and without the M-PEEK rod system. RESULTS: In extension, models implanted with M-PEEK in the interspinous space of L3/L4 experienced a 35.2% decrease in range of motion (ROM) at L3/L4, while others saw an 8.4-24.8% increase. For axial rotation, the ROM at L3/L4 increased by 2.2-5.4% in models with the M-Rod, and by 4.9-12.9% in models without the implant. In lateral flexion, the ROM at L3/L4 increased by 8.4-14.3% in models without a PEEK M-Rod (facetectomy only), with adjacent segments experiencing a 6.5% decrease in ROM in the implanted models. Overall, the difference in ROM between the intact and implanted models was minimal. CONCLUSIONS: Facetectomy involving the removal of 50% or more of the facet joint significantly increases range of motion and maximum intradiscal pressure, potentially accelerating disc degeneration, as shown in our finite element study. Stabilizing the segment with an M-PEEK rod may limit excessive motion, providing stability and maintaining intradiscal pressure closer to that of an intact model.
Asunto(s)
Benzofenonas , Análisis de Elementos Finitos , Vértebras Lumbares , Polietilenglicoles , Polímeros , Rango del Movimiento Articular , Articulación Cigapofisaria , Humanos , Vértebras Lumbares/cirugía , Articulación Cigapofisaria/cirugía , Cetonas , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/fisiopatología , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Fenómenos Biomecánicos/fisiologíaRESUMEN
OBJECTIVE: For analyzing the mechanical properties of 2 cranio-orbital repair materials under distinct external impacts by finite element analysis and evaluating the stability of various repair materials. METHODS: Based on the computed tomography images of the patients with cranio-orbital fractures, three-dimensional models of the normal craniomaxillofacial models were established by segmenting them with Mimics 19.0, Geomagic Studio 12.0, and UG 12.0, respectively, to build the finite element models of titanium repair fixation and the poly-ether-ether-ketone repair fixation. The models were then simulated by Ansys 19.2, with divergent impact forces to analyze the stresses and displacements of the repair materials, as well as the internal fixation system, and to make a comparison on the stability of the distinct repair materials. RESULTS: The titanium mesh is stable at impact forces ≤1500 N. Furthermore, the poly-ether-ether-ketone mesh and the internal fixation system are resistant to fracture and displacement at impact forces of up to 3000 N. CONCLUSION: By simulating distinct mechanical environments, the biomechanical finite element analysis method can digitally assess the mechanical properties of cranio-orbital repair materials and objectively evaluate the stability of the repair materials and the internal fixation system.
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Benzofenonas , Análisis de Elementos Finitos , Fijación Interna de Fracturas , Cetonas , Fracturas Orbitales , Mallas Quirúrgicas , Titanio , Tomografía Computarizada por Rayos X , Humanos , Fracturas Orbitales/cirugía , Fracturas Orbitales/diagnóstico por imagen , Fenómenos Biomecánicos , Cetonas/química , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Polietilenglicoles/química , Polímeros , Ensayo de Materiales , Imagenología Tridimensional , Estrés Mecánico , Modelos Anatómicos , Simulación por ComputadorRESUMEN
A 7-year-old French Bulldog presented with an acanthomatous ameloblastoma affecting approximately 30% of the right mandibular body. We utilized a patient-specific 3D-printed surgical template to perform lateral fenestration of the mandible and elevation of the inferior alveolar nerve (IAN), facilitating nerve preservation during subsequent segmental mandibulectomy. The resulting critical-sized bone defect was anatomically stabilized using a patient-specific polyetheretherketone (PEEK) bridging plate. The recovery process was uneventful, with maintained occlusion and orofacial sensitivity.Similar to cases in humans with ameloblastoma, preserving orofacial sensitivity through the preservation of the inferior alveolar nerve seems feasible in dogs. Consequently, potential negative consequences of permanent regional denervation, which are unavoidable in traditional mandibulectomy, can be avoided. Bridging the ostectomy with a PEEK plate, offering advantages such as radiolucency, absence of imaging artifacts, and a modulus of elasticity similar to bone, proved to be functional in this canine patient, with no signs of complications observed up to the latest follow-up at 6 months.
Asunto(s)
Benzofenonas , Enfermedades de los Perros , Cetonas , Neoplasias Mandibulares , Osteotomía Mandibular , Polímeros , Perros , Animales , Osteotomía Mandibular/veterinaria , Osteotomía Mandibular/métodos , Enfermedades de los Perros/cirugía , Neoplasias Mandibulares/cirugía , Neoplasias Mandibulares/veterinaria , Ameloblastoma/cirugía , Ameloblastoma/veterinaria , Mandíbula/cirugía , Placas Óseas/veterinaria , Polietilenglicoles/uso terapéutico , Nervio Mandibular/cirugía , Reconstrucción Mandibular/veterinaria , Reconstrucción Mandibular/métodosRESUMEN
OBJECTIVE: Customized nonabsorbable membranes are widely used in severe alveolar bone defects and provide sufficient and precise regenerated bone tissue for subsequent dental implant placement. Although 3D-printed polyetheretherketone (PEEK) meshes have confirmed successful use in clinical cases, the performance of a PEEK mesh is not satisfactory. Compared with PEEK, polyetherketoneketone (PEKK) has better mechanical and processing properties. However, whether PEKK is suitable for making customized membranes remains unclear. The objectives of this study were (1) to evaluate the printing precision, surface characteristics, mechanical characteristics and biocompatibility of the PEKK mesh and (2) to compare the properties of the PEKK and PEEK meshes. MATERIALS AND METHODS: Both PEKK and PEEK meshes were designed and manufactured via additive manufacturing technology combined with computer-aided design (CAD). The printing precision was evaluated with a high-resolution extraoral scanner. The surface characteristics were evaluated with a contact angle system and three-dimensional optical microscopy. The mechanical characteristics were evaluated via three-point bending tests and tensile tests. The biocompatibility was evaluated with a CCK-8 assay, live/dead viability assay and qRT-PCT. RESULTS: Compared with the PEEK mesh, the PEKK mesh exhibited better control in terms of the thickness and aperture area. Both the PEKK mesh and the PEEK mesh had a hydrophobic surface, but the PEKK mesh had a smoother surface. Compared with the PEEK mesh, the PEKK mesh has better compression and tensile properties. Both the PEKK mesh and the PEEK mesh had good biocompatibility. The proliferation of cells on the PEKK mesh was slightly lower than that on the PEEK mesh. CONCLUSIONS: Compared with PEEK mesh, PEKK mesh has greater printing accuracy, smoother surfaces, better mechanical properties and similar biocompatibility and is expected to be used in the production of customized barrier membranes for the augmentation of severe bone defects. To ensure the stability of the mesh for clinical application, it is best to control the aperture diameter of the PEKK mesh to less than 2 mm with a thickness of 0.2 µm.
Asunto(s)
Benzofenonas , Materiales Biocompatibles , Diseño Asistido por Computadora , Cetonas , Ensayo de Materiales , Polietilenglicoles , Polímeros , Impresión Tridimensional , Mallas Quirúrgicas , Propiedades de Superficie , Aumento de la Cresta Alveolar/métodos , Animales , Humanos , Ratones , Resistencia a la TracciónRESUMEN
PURPOSE: To analyze the stress distribution of polyetheretherketone framework of implant-supported fixed maxillary prosthesis by three-dimensional finite element method. METHODS: Three dimensional finite element model of implant-supported fixed maxillary prosthesis was established. Polyetheretherketone as framework material, resin, zirconia, PEEK, baked plastic and lithium silicate were used to make crown prosthesis as experimental group, pure titanium and monolithic zirconia prosthesis model was used as control group. The feasibility of PEEK framework was analyzed by loading 150N axially and obliquely on the first molar, and the maximum compressive stress, minimum tensile stress and von Mises principal stress of the framework, crown, screw, implant, cortical and cancellous bone were measured and compared. RESULTS: Under axially loading, the von Mises stress in the monolithic zirconia and lithium silicate crowns were 361 MPa and 295 MPa, while the stress in resin and PEEK crowns were 35 MPa and 37 MPa, respectively. The screw von Mises stress of the experimental group was 694-724 MPa, which was much higher than 61 MPa of the control group.The maximum and minimum stresses of the screw appeared in the resin crown and PEEK crown group. Under oblique loading,von Mises stress of the framework in the experimental group was lower than that in the control group, but the maximum stress appeared in the resin crown and PEEK crown. von Mises stresses of monolic zirconia and lithium disilicate crowns in the experimental group were higher than that of resin and PEEK crowns. von Mises stress of the implant in the experimental group was twice that of the control group. von Mises stress in screw of the experimental group was much higher than that of the control group, and the maximum stress was 22 times that of the control group. The stresses of cancellous bone and cortical bone in the experimental group were twice that of the control group, and the differences were larger than that under vertical loading. CONCLUSIONS: In order to reduce the stress of crowns,resin or PEEK materials are preferred to be used as the crown prosthesis when PEEK was framework of implant-supported fixed maxillary prosthesis. Reducing the cantilever and lateral force may avoid excessive stress in screw.
Asunto(s)
Benzofenonas , Análisis de Elementos Finitos , Cetonas , Polietilenglicoles , Polímeros , Cetonas/química , Polímeros/química , Polietilenglicoles/química , Prótesis Dental de Soporte Implantado/métodos , Coronas , Análisis del Estrés Dental/métodos , Maxilar/cirugía , Circonio/química , Ensayo de Materiales , Estrés Mecánico , Titanio/química , HumanosRESUMEN
BACKGROUND: In connection with the war in Ukraine and the use of modern high-energy weapons by the enemy, the nature of injuries have changed. These changes require improvement of approaches to the treatment of patients with gunshot and mine-explosive bone defects. CASE PRESENTATION: We present the case of treatment of a 28-year-old Ukranian man with a gunshot multifragmentary fracture of the proximal humerus with a bone defect using three-dimensional printing of a polyetheretherketone frame (scaffold) for alloplastic material. The analysis of this case expands the possibilities of using three-dimensional printing technologies of polyetheretherketone scaffolds in the treatment of significant bone defects. CONCLUSION: Modern military trauma requires individualized treatment for each patient. The use of individual polyetheretherketone scaffolds in the treatment of a gunshot multifragmentary fracture with a bone defect has a positive clinical effect.
Asunto(s)
Benzofenonas , Cetonas , Polietilenglicoles , Polímeros , Fracturas del Hombro , Andamios del Tejido , Heridas por Arma de Fuego , Humanos , Heridas por Arma de Fuego/cirugía , Masculino , Adulto , Fracturas del Hombro/cirugía , Impresión Tridimensional , Resultado del Tratamiento , Materiales BiocompatiblesRESUMEN
We report the case of a 46-year-old Japanese woman diagnosed with Stage â £ right breast cancer, cT1cN1M1(ovarian and peritoneal metastases). We administered bevacizumab+paclitaxel as the first-line treatment. In the 13th course, the peritoneal dissemination progressed, and the regimen was changed to eribulin(1.4 mg/m2)as the second-line treatment. During the second course, abdominal distension developed and was resolved during follow-up. However, abdominal distension and pain were observed from day 9 of the fourth course. Based on the results of blood chemistry and CT scans, she was diagnosed with acute pancreatitis(CT Grade 1)and was admitted to the hospital. After fasting and fluid replacement therapy, her clinical symptoms and laboratory data improved, and was discharged from the hospital 8 days later. She had no history of excessive alcohol consumption and no evidence of biliary disease, and was considered having eribulin-induced pancreatitis.
Asunto(s)
Neoplasias de la Mama , Furanos , Cetonas , Pancreatitis , Humanos , Femenino , Furanos/uso terapéutico , Furanos/efectos adversos , Persona de Mediana Edad , Cetonas/uso terapéutico , Pancreatitis/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Enfermedad Aguda , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Policétidos PoliéteresRESUMEN
BACKGROUND: Titanium has been the conventional implant material of choice for fixation in both primary and metastatic spine tumour surgeries (MSTS). However, these implants result in artefact generation during post-operative computed tomography (CT) or magnetic resonance imaging (MRI), resulting in poor planning of radiotherapy (RT) and suboptimal tumour surveillance. Carbon fibre-reinforced polyetheretherketone (CFR-PEEK) implants have gained momentum for instrumentation in MSTS due to their radiolucent properties. This in turn does not sacrifice the biomechanical strength of the implants. In this study, we compared the peri-operative outcomes, post operative imaging artefacts and dosimetricdata of CFR-PEEK implants to titanium implants to asses for potential benefits in post-operative RT planning in patients who underwent MSTS. METHODS: This is a retrospective study involving 42 patients operated for MSTS. Patient-related data including demographics, tumour pathology, intra-operative data, functional outcome, and RT-related data were collected for both groups. All patients were followed-up post-operatively for a minimum of 2 years or until demise, whichever was earlier. RESULTS: In our study, 20 (47.6%) patients had CFR-PEEK implants, while 22 (52.4%) of patients had titanium implants used for MSTS. Both groups of patients had similar clinical outcomes for pain and overall survival predictability pre-operatively (P>0.05). Mean number of levels instrumented by titanium screws were 6.8±2.93, while for the CFR-PEEK screws were 4.07±1.05. Mean volume of artefact generated during post operative CT was 75.1±43.4 mm3 in titanium group and 13.3±14.2 mm3 in CFR-PEEK group (P=0.005). The mean time taken to contour the artefacts was 17.3±5.84 minutes in the titanium group, while the CFR-PEEK group took 9.60±7.17 minutes (P=0.049). CONCLUSIONS: Our study suggests that carbon fibre reinforced PEEK screws significantly reduce artefact generation and the time taken to contour them during post-operative RT planning, while delivering equivalent clinical and functional outcomes as compared to standard titanium implants.
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Benzofenonas , Fibra de Carbono , Cetonas , Polietilenglicoles , Polímeros , Prótesis e Implantes , Neoplasias de la Columna Vertebral , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/secundario , Adulto , Anciano , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: The purpose of this study was to evaluate the effect of using different types of metallic and non-metallic telescopic crown attachment materials on wear resistance and surface tomography changes in implant-retained mandibular overdentures. MATERIALS AND METHODS: Completely edentulous mandibular epoxy models were fabricated, in which two implants were placed in the canine region and retained to the implants with three different material combinations used for the construction of telescopic attachments. Thirty-three identical mandibular overdentures were fabricated using the conventional standardized technique. The study groups were divided into three categories according to the material used for the construction of the secondary copings. The primary copings in all the study groups were constructed of PEEK, while the secondary coping in group I was PEEK, group II was ZrO2 and CoCr for group III. Primary copings were cemented on a ready-made abutment. Secondary copings were placed over the primary copings in the desired path of insertion, then picked up into the intaglio surface of the overdentures. A cyclic loading machine was used to apply repeated insertion-removal cycles simulating nearly 10 years of clinical use. Stereomicroscope with a built-in camera was used to monitor the reduction in width of the primary copings to evaluate the wear resistance of each material combination. RESULTS: There was highly statistically significant difference between the study groups after the application of 1.000, 5.000 and 10.000 cycles. The highest level of wear resistance was recorded for the PEEK/PEEK combination, whereas PEEK/ZrO2 and PEEK/CoCr showed no significant differences. CONCLUSIONS: Implant retained overdenture with PEEK-PEEK telescopic crown attachment is associated with the highest wear resistance among all the study groups. PEEK-PEEK combination may be the treatment of choice for fabrication of telescopic attachment in implant retained overdenture as it provides better resistance to wear. It offers the advantages for geriatric patients as it decreases the possibility for repeated repair and replacement of attachment, increase long-term patient satisfaction and shelf life of prosthesis.
Asunto(s)
Benzofenonas , Prótesis Dental de Soporte Implantado , Prótesis de Recubrimiento , Cetonas , Propiedades de Superficie , Circonio , Humanos , Aleaciones de Cromo/química , Coronas , Estudios Prospectivos , Materiales Dentales , Polímeros , Polietilenglicoles , Técnicas In Vitro , Ensayo de Materiales , Alisadura de la Restauración Dental , Análisis del Estrés Dental , Diseño de Prótesis Dental , Retención de DentaduraRESUMEN
Although difluoromethyl ketones are used as tools in chemical biology and leads in drug discovery, the metabolic stability of these compounds is generally uncharacterized and must be inferred from in vivo pharmacological assays. In order to address this gap which impedes their wider use, we have synthesized and performed metabolic stability studies for thirty-nine ß-amino and ß-hydroxy difluoromethyl ketones. These investigations provide structure-stability relationships of the difluoromethyl ketones following incubation with rodent serum and liver microsomes.
Asunto(s)
Cetonas , Microsomas Hepáticos , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/química , Animales , Cetonas/química , Cetonas/síntesis química , Cetonas/farmacología , Ratas , Relación Estructura-Actividad , Estructura MolecularRESUMEN
BACKGROUND: Polyetheretherketone (PEEK) is well known for its excellent physical-chemical properties and biosafety. The study aimed to open up a new method for clinical application of PEEK to reconstruct large-scale bone defects. METHODS: A bilayer scaffold for bone regeneration was prepared by combining a sulfonated PEEK barrier framework (SPEEK) with a hydrogel layer loaded with aspirin (ASA) and nano-hydroxyapatite (nHAP) by the wet-bonding of Polydopamine (PDA). RESULTS: The hydrogel was successfully adhered to the surface of SPEEK, resulting in significant changes including the introduction of bioactive groups, improved hydrophilicity, and altered surface morphology. Subsequent tests confirmed that the bilayer scaffold exhibited enhanced compression resistance and mechanical compatibility with bone compared to a single hydrogel scaffold. Additionally, the bilayer scaffold showed stable and reliable bonding properties, as well as excellent biosafety verified by cell proliferation and viability experiments using mouse embryo osteoblast precursor (MC3T3-E1) cells. CONCLUSION: The bilayer bone regeneration scaffold prepared in this study showed promising potential in clinical application for bone regeneration.
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Benzofenonas , Materiales Biocompatibles , Regeneración Ósea , Proliferación Celular , Durapatita , Indoles , Cetonas , Osteoblastos , Polietilenglicoles , Polímeros , Andamios del Tejido , Regeneración Ósea/efectos de los fármacos , Ratones , Animales , Durapatita/uso terapéutico , Cetonas/química , Proliferación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Indoles/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Aspirina/farmacología , Aspirina/uso terapéutico , Ensayo de Materiales , Propiedades de Superficie , Hidrogeles/uso terapéutico , Células 3T3 , Regeneración Tisular Dirigida/métodosRESUMEN
Approximately 30% of patients with epilepsy are drug-refractory. There is an urgent need to elucidate the exact pathophysiology of different types of epilepsies and the mechanisms of action of both antiseizure medication and metabolic therapies to treat patients more effectively and safely. For example, it has been demonstrated that exogenous ketone supplement (EKS)-generated therapeutic ketosis, as a metabolic therapy, may decrease epileptic activity in both animal models and humans, but its exact mechanism of action is unknown. However, it was demonstrated that therapeutic ketosis, among others, can increase adenosine level, which may enhance activity of A1 adenosine receptors (A1Rs) in the brain. It has also been demonstrated previously that adenosine has anti-epileptic effect through A1Rs in different models of epilepsies. Thus, it is possible that (i) therapeutic ketosis generated by the administration of EKSs may exert its anti-epileptic effect through, among other mechanisms, increased adenosine level and A1R activity and that (ii) the enhanced activity of A1Rs may be a necessary anti-epileptic mechanism evoked by EKS administration-generated ketosis. Moreover, EKSs can evoke and maintain ketosis without severe side effects. These results also suggest that the therapeutic application of EKS-generated ketosis may be a promising opportunity to treat different types of epilepsies. In this literature review, we specifically focus on the putative role of A1Rs in the anti-epileptic effect of EKS-induced ketosis.
Asunto(s)
Anticonvulsivantes , Epilepsia , Cetonas , Receptor de Adenosina A1 , Humanos , Receptor de Adenosina A1/metabolismo , Animales , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Cetonas/farmacología , Suplementos Dietéticos , Adenosina/metabolismo , Adenosina/farmacología , Cetosis/metabolismo , Cetosis/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVES: 3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital. METHODS: A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed. RESULTS: Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient. CONCLUSION: This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.
Asunto(s)
Benzofenonas , Cetonas , Sistemas de Atención de Punto , Polietilenglicoles , Polímeros , Impresión Tridimensional , Cráneo , Humanos , Cráneo/cirugía , Prótesis e Implantes , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/instrumentación , Diseño de PrótesisRESUMEN
BACKGROUND: Frailty is a geriatric syndrome characterized by chronic inflammation and metabolic insufficiency that creates vulnerability to poor outcomes with aging. We hypothesize that interventions which target common underlying mechanism of aging could ameliorate frailty. Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on inflammatory and metabolic aging pathways in laboratory animal models. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. OBJECTIVES: The primary objective of this randomized, placebo-controlled, double-blinded, parallel-group, pilot trial is to determine tolerability of 12-weeks of KE ingestion in a broad population of older adults (≥ 65 years). Secondary outcomes include safety and acute blood ketone kinetics. Exploratory outcomes include physical function, cognitive function, quality of life, aging biomarkers and inflammatory measures. METHODS: Community-dwelling adults who are independent in activities of daily living, with no unstable acute medical conditions (n = 30) will be recruited. The study intervention is a KE or a taste, appearance, and calorie matched placebo beverage. Initially, acute 4-hour ketone kinetics after 12.5g or 25g of KE consumption will be assessed. After collection of baseline safety, functional, and biological measurements, subjects will randomly be allocated to consume KE 25g or placebo once daily for 12-weeks. Questionnaires will assess tolerability daily for 2-weeks, and then via phone interview at bi-monthly intervals. Safety assessments will be repeated at week 4. All measures will be repeated at week 12. CONCLUSION: This study will evaluate feasibility, tolerability, and safety of KE consumption in older adults and provide exploratory data across a range of aging-related endpoints. This data will inform design of larger trials to rigorously test KE effects on aging mechanisms and clinical outcomes relevant to frailty.
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Ésteres , Fragilidad , Cetonas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Envejecimiento/efectos de los fármacos , Método Doble Ciego , Ésteres/administración & dosificación , Estudios de Factibilidad , Proyectos Piloto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Many people convicted for drunken driving suffer from an alcohol use disorder and some traffic offenders consume denatured alcohol for intoxication purposes. Venous blood samples from people arrested for driving under the influence of alcohol were analyzed in triplicate by headspace gas chromatography (HS-GC) using three different stationary phases. The gas chromatograms from this analysis sometimes showed peaks with retention times corresponding to acetone, ethyl methyl ketone (2-butanone), 2-propanol, and 2-butanol in addition to ethanol and the internal standard (1-propanol). Further investigations showed that these drink-driving suspects had consumed an industrial alcohol (T-Red) for intoxication purposes, which contained > 90% w/v ethanol, acetone (~ 2% w/v), 2-butanone (~ 5% w/v) as well as Bitrex to impart a bitter taste. In n = 75 blood samples from drinkers of T-Red, median concentrations of ethanol, acetone, 2-butanone, 2-propanol and 2-butanol were 2050 mg/L (2.05 g/L), 97 mg/L, 48 mg/L, 26 mg/L and 20 mg/L, respectively. In a separate GC analysis, 2,3-butanediol (median concentration 87 mg/L) was identified in blood samples containing 2-butanone. When the redox state of the liver is shifted to a more reduced potential (excess NADH), which occurs during metabolism of ethanol, this favors the reduction of low molecular ketones into secondary alcohols via the alcohol dehydrogenase (ADH) pathway. Routine toxicological analysis of blood samples from apprehended drivers gave the opportunity to study metabolism of acetone and 2-butanone without having to administer these substances to human volunteers.
Asunto(s)
Acetona , Butanonas , Etanol , Oxidación-Reducción , Humanos , Etanol/sangre , Cetonas/sangre , Cromatografía de Gases , Masculino , Adulto , Femenino , Intoxicación Alcohólica , Conducción de Automóvil , 2-Propanol , Nivel de Alcohol en Sangre , Consumo de Bebidas Alcohólicas , Alcoholes , Persona de Mediana EdadRESUMEN
To expand the selection of raw material for fabricating extracorporeal membrane oxygenation (ECMO) and promote its application in lung disease therapy, polyether ether ketone hollow fiber membrane (PEEK-HFM) with designable pore characteristics, desired mechanical performances, and excellent biocompatibility was selected as the potential substitute for existing poly (4-methyl-1-pentene) hollow fiber membrane (PMP-HFM). To address the platelet adhesion and plasma leakage issues with PEEK-HFM, a natural anticoagulant heparin was grafted onto the surface using ultraviolet irradiation. Additionally, to explore the substitutability of the heparin layer while considering cost and scalability, a heparin-like layer composed of copolymers of acrylic acid and sodium p-styrenesulfonate was also constructed on the surface of PEEK-HFM Even though the successful grafting of heparin and heparin-like layers on the PEEK-HFM surface reduced the pore parameters, improvements in surface hydrophilicity also prevented the platelet-adhesion phenomenon and improved the anticoagulant behaviour, making it a viable alternative for commercial PMP-HFMs in ECMO production. Furthermore heparin-modified and heparin-like modified PEEK-HFMs demonstrated similar performance, indicating that synthetic layers can effectively replace natural heparin. This study holds practical and instructive significance for future research and the application of membranes in the development of oxygenators.
Asunto(s)
Benzofenonas , Oxigenación por Membrana Extracorpórea , Heparina , Membranas Artificiales , Polietilenglicoles , Polímeros , Heparina/química , Oxigenación por Membrana Extracorpórea/métodos , Polímeros/química , Polietilenglicoles/química , Humanos , Adhesividad Plaquetaria/efectos de los fármacos , Cetonas/química , Materiales Biocompatibles/química , Permeabilidad , Ensayo de Materiales , Aire , AnimalesRESUMEN
Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3ß/ß-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.