RESUMO
BACKGROUND: The purpose of this study was to elucidate the relationship between the orientation of the osseous structure of the proximal femur encountered during total hip arthroplasty (THA) and preoperative femoral anteversion (FA). METHODS: Three-dimensional models were constructed using full-length lower extremity computed tomography images from a total of 80 participants. Femoral neck cutting was performed at heights of 5, 10, and 15 mm relative to the lesser trochanter. Following neck cutting, the angles formed by the anterior outer cortex and posterior outer cortex with the posterior condylar line (PCL) were defined as the anterior cortical angle (ACA) and posterior cortical angle (PCA), respectively. Univariate linear regression analysis was conducted using the remaining measurements with FA as the dependent variable. RESULTS: The mean age of the participants was 60.98 ± 10.82 years (males, 60.50 ± 11.36 years; females, 61.45 ± 10.37 years) (p = 0.697). All cortical angles and FA were larger in women compared to those in men. When comparing measurements by age groups, no statistically significant differences were observed. Univariate linear regression analysis with FA as the dependent variable showed statistical significance for all cortical angles. The adjusted R2 values were 0.711 (ACA5), 0.677 (ACA10), 0.572 (ACA15), 0.493 (PCA5), 0.574 (PCA10), and 0.446 (PCA15). CONCLUSION: Natural FA can be inferred from the anterior cortical angle (ACA) from femoral neck cutting plane observed during the THA procedure without preoperative images. TRIAL REGISTRATION: Retrospectively registered.
Assuntos
Artroplastia de Quadril , Fêmur , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Artroplastia de Quadril/métodos , Pessoa de Meia-Idade , Idoso , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Imageamento Tridimensional/métodos , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Anteversão Óssea/diagnóstico por imagem , Anteversão Óssea/etiologia , Anteversão Óssea/prevenção & controle , Estudos RetrospectivosRESUMO
The aim of this study was to investigate the biomechanical effects of stem extension with a medial tibial bone defect in primary total knee arthroplasty (TKA) on load distribution and stress in the proximal tibia using finite element (FE) analysis.FE simulations were performed on the tibia bone to evaluate the stress and strain on the tibia bone and bone cement. This was done to investigate the stress shielding effect, stability of the tibia plate, and the biomechanical effects in TKA models with various medial defects and different stem length models.The results demonstrated that in the bone defect model, the longer the stem, the lower the average von Mises stress on the cortical and trabecular bones. In particular, as the bone defect increased, the average von Mises stress on cortical and trabecular bones increased. The average increase in stress according to the size of the bone defect was smaller in the long stem than in the short stem. The maximal principal strain on the trabecular bone occurred mainly at the contact point on the distal end of the stem of the tibial implant. When a short stem was applied, the maximal principal strain on the trabecular bone was approximately 8% and 20% smaller than when a long stem was applied or when no stem was applied, respectively.The findings suggest that a short stem extension of the tibial component could help achieve excellent biomechanical results when performing TKA with a medial tibial bone defect.
Assuntos
Artroplastia do Joelho , Análise de Elementos Finitos , Prótese do Joelho , Tíbia , Humanos , Tíbia/cirurgia , Fenômenos Biomecânicos , Estresse Mecânico , Desenho de PróteseRESUMO
Background and objective With the steady advancement of computer-assisted surgical techniques, the importance of assessing and researching technology related to total knee arthroplasty (TKA) procedures has increased. Augmented reality (AR), a recently proposed next-generation technology, is expected to enhance the precision of orthopedic surgery by providing a more efficient and cost-effective approach. However, the accuracy of image-based AR in TKA surgery has not been established. Therefore, this study aimed to determine whether accurate bone resection can be achieved in TKA surgery using image-based AR. Methods In this study, we replaced traditional CT imaging and reconstructions for creating a bone 3D model by direct 3D scanning of the femur and tibia. The preoperative planning involved identifying anatomical landmarks and determining the surgical details. During surgery, markers were employed to create a local coordinate system for an AR-assisted surgical system using a Polaris camera. This approach helped minimize discrepancies between the 3D model and actual positioning, ensuring accurate alignment. Results The AR-assisted surgery using the image method resulted in fewer errors [average error: 0.32 mm; standard deviation (SD): 0.143] between the bone resection depth of the preoperative surgical plan and the bone model test results. Conclusions Our findings demonstrated the accuracy of bone resectioning by using image-based AR-assisted navigation for TKA surgery. Image-based AR-assisted navigation in TKA surgery is a valuable tool not only for enhancing accuracy by using smart glasses and sensors but also for improving the efficiency of the procedure. Therefore, we anticipate that image-based AR-assisted navigation in TKA surgery will gain wide acceptance in practice.
RESUMO
Pericapsular nerve group (PENG) block and periarticular injection (PAI) provide motor-sparing analgesia following hip surgery. We hypothesized that PAI offers non-inferior pain relief compared with PENG block in patients undergoing primary total hip arthroplasty (THA). In this randomized trial, 66 patients who underwent primary THA under spinal anesthesia were assigned to the PENG or PAI groups. The primary endpoint was the resting pain score 24 h postoperatively. The secondary endpoints included pain scores at rest and during movement at 6 and 48 h postoperatively, quadriceps strength at 24 h postoperatively, and opioid consumption at 24 and 48 h postoperatively. The mean difference in pain scores at rest between the two groups was 0.30 (95% confidence interval [CI], -0.78 to 1.39) at 24 h postoperatively. The upper 95% CI was lower than the non-inferiority margin, indicating non-inferior performance. No significant between-group differences were observed in the pain scores at 6 and 48 h postoperatively. Additionally, no significant differences in quadriceps strength and opioid consumption were observed between the two groups. The PAI and PENG blocks provided comparable postoperative analgesia during the first 48 h after primary THA. Further investigation is required to determine the optimal PAI technique and local anesthetic mixture.
RESUMO
INTRODUCTION: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness in postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). METHODS: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: the patient-controlled analgesia (PCA) group (n = 132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n = 99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 h postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin, length of hospital stay, and total morphine usage after surgery. RESULTS: Postoperative resting VAS at 6 h and 48 h was significantly lower in the PNB+PCA group compared with the PCA group (p = 0.075, p = 0.0318, respectively). However, there was no significant difference in either resting VAS at 24 h or active VAS. Complications of pneumonia and delirium until 1 month postoperative were significantly lower in the PNB + PCA group than the PCA group (p = 0.0022, p = 0.0055, respectively). CONCLUSION: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.
Assuntos
Analgesia Controlada pelo Paciente , Fraturas do Colo Femoral , Hemiartroplastia , Bloqueio Nervoso , Manejo da Dor , Medição da Dor , Dor Pós-Operatória , Humanos , Fraturas do Colo Femoral/cirurgia , Feminino , Idoso , Bloqueio Nervoso/métodos , Masculino , Estudos Retrospectivos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/tratamento farmacológico , Hemiartroplastia/métodos , Hemiartroplastia/efeitos adversos , Idoso de 80 Anos ou mais , Analgesia Controlada pelo Paciente/métodos , Manejo da Dor/métodos , Resultado do Tratamento , Tempo de InternaçãoRESUMO
Stimulating the brain in a precise location is crucial in ultrasound neuromodulation. However, improving the resolution proves a challenge owing to the characteristics of transcranial focused ultrasound. In this paper, we present a new neuromodulation system that overcomes the existing limitations based on an acoustic radiation force with a frequency-modulated waveform and standing waves. By using the frequency-modulated pattern interference radiation force (FM-PIRF), the axial spatial resolution can be reduced to a single wavelength level and the target location can be controlled in axial direction electronically. A linear frequency-modulated chirp waveform used in the experiment was designed based on the simulation results. The displacement of the polydimethylsiloxane (PDMS) cantilever was measured at intervals of 0.1 mm to visualize the distribution of radiation force. These results and methods experimentally show that FM-PIRF has improved spatial resolution and capability of electrical movement.
Assuntos
Desenho de Equipamento , Humanos , Terapia por Ultrassom/métodos , Terapia por Ultrassom/instrumentação , Dimetilpolisiloxanos/químicaRESUMO
BACKGROUND: The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose of this study was to determine the surgical outcomes and the risk factors for early septic failure after two-stage revision TKA for chronic PJI. METHODS: We identified a total of 246 adult patients who met the Musculoskeletal Infection Society (MSIS) diagnostic criteria for chronic PJI at two academic tertiary hospitals from March 2012 to December 2018. Finally, 151 patients who consecutively received two-stage exchange revision TKA for chronic PJI and who had a minimum 3-year follow-up were enrolled and retrospectively reviewed. Successful surgical treatment was evaluated for two-stage revision TKA and risk factors for early septic failure were identified. RESULTS: Early septic failures occurred within 3 years after reimplantation in 48 patients (31.8%). After accounting for potentially confounding variables, we found that male patient [odds ratio (OR): 2.753, 95% confidence interval (CI) 1.099-6.893, p = 0.031], fungus or mycobacterial infection (OR: 5.224, 95% CI 1.481-18.433, p = 0.01), and positive culture at reimplantation (OR: 4.407, 95% CI 1.255-15.480, p = 0.021) were independently associated with early septic failure after two-stage exchange revision TKA. CONCLUSION: Male patients, fungus or mycobacterial infection, and positive culture at reimplantation were independently associated with an increased risk of early septic failure after two-stage exchange revision TKA despite normal C-reactive protein values prior to reimplantation. Further prospective and high-quality studies are needed to determine the risk factors of two-stage exchange revision TKA for chronic PJI. LEVEL OF EVIDENCE: level IV; retrospective comparison; treatment study.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Infecções Relacionadas à Prótese , Adulto , Humanos , Masculino , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Antibacterianos/uso terapêutico , Fatores de Risco , Reoperação , Articulação do Joelho/cirurgiaRESUMO
Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatite , Neoplasias Hepáticas , Camundongos , Animais , Oligodesoxirribonucleotídeos/farmacologia , Oligodesoxirribonucleotídeos/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado , Fibrose , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Linhagem Celular , Oligonucleotídeos Antissenso/metabolismo , Hepatite/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismoRESUMO
Although the accuracy of other types of robotic systems for total knee arthroplasty (TKA) has been assessed in cadaveric studies, no investigations have been performed to evaluate this newly advanced active robotic system. Therefore, the authors aimed to analyze the accuracy of bone resection in terms of thickness and alignment in a cadaveric study. Three cadaveric specimens (six knees) and an active robotic system (CUVIS Joint, CUREXO) were used in the study. Three surgeons with different experiences in robotic TKAs performed this cadaveric study using the same robotic protocol with two different implant designs. The thickness and angle of bone resection planes obtained from the optical tracking system and the difference between resection planes and the planning data were assessed to determine accuracy. With respect to the overall resection accuracy compared to the plan, the cutting depth accuracy was within 1.0 mm mean of root mean square (RMS), and the resection angle accuracy in terms of sagittal, coronal, and axial planes was within 1.0 degree mean RMS. In contrast, no significant differences were observed between the planned and measured values in terms of the resection angles and cutting thickness. The hip-knee-ankle angle at postoperative evaluation was 0.7 degrees ± 0.7 degrees (RMS 1.0 degrees). This in vivo study suggests that the use of this newly advanced active robotic system for TKA demonstrates a high degree of accuracy in terms of resection thickness and alignment. This finding supports the clinical application of this advanced robotic system. LEVEL OF EVIDENCE: Cadaveric study, Level V.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Robótica , Humanos , Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Joelho/cirurgia , Cadáver , Osteoartrite do Joelho/cirurgiaRESUMO
BACKGROUND: A postoperative radiograph in total hip arthroplasty (THA) is usually obtained to evaluate the inclination and anteversion of the acetabular components. However, there is no gold-standard method for calculating the exact inclination and anteversion of the acetabular components on post-THA radiographs. We aimed to measure the actual anteversion of the acetabular component on postoperative radiographs by obtaining correlation data between the virtual and actual acetabular component positioning using virtual three-dimensional (3D) surgery. METHODS: A total of 64 hip scans of 32 patients who underwent lower-extremity computed tomography (CT) were retrospectively reviewed. We reconstructed 3D models of the 64 hips using customized computer software (Mimics). Furthermore, to identify the safe zone of acetabular component position in THA, we performed virtual 3D surgery simulations for five anteversion (-10°, 0°, 10°, 20°, and 30°) and five inclination (20°, 30°, 40°, 50°, and 60°) types. We analyzed the acetabular anatomy using 3D models to measure the radiographic, anatomical, and operative anteversion (RA, AA, OA) and inclination (RI, AI, OI) angles. Additionally, we used the Woo-Morrey (WM) method to calculate the anteversion angle in the reconstructed cross-table lateral (CL) radiographs and determined the correlation between these measurements. RESULTS: The safe zone of the acetabular component was visualized on post-THA CL radiographs using the WM method of anteversion measurement based on the different anteversions and inclinations of the acetabular component. The AA, RA, OA, OI, and WM differed significantly between males and females (p value < 0.05). As the anatomical inclination or anteversion increased, the WM anteversion measurements also increased. The radiographic anteversion measurement best matched the WM method of measurement, followed by anatomical and operative methods. CONCLUSIONS: The actual anteversion of the acetabular component after THA can be measured on CL radiographs with the WM method using a 3D virtual program, with good reproducibility.
RESUMO
The effect of peripheral nerve block (PNB) according to leg lengthening following total hip arthroplasty (THA) has not been studied yet. The purpose of this study was to investigate the effect of PNB according to the change in leg length after THA. From January 2016 to August 2021, 353 patients who underwent unilateral THA for osteonecrosis of the femoral head or osteoarthritis of the hip joint were retrospectively reviewed. The patients were divided into two groups for comparison: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). We further divided the patients into two groups (leg lengthening after surgery < 10 mm and >10 mm) and compared them. After propensity score matching, the PCA and PCA + PNB groups, with 134 patients each, were compared and analyzed. The pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 6, 24, and 48 h (p = 0.0001, 0.0009, and <0.0001, respectively). In the subgroup analysis, for patients whose limb lengthening was less than 10 mm after THA, the pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 24 and 48 h (p = 0.0165 and 0.0015, respectively). However, in patients whose limb lengthening was more than 10 mm after THA, there was no significant difference between the pain intensity at activity and rest in the two groups at postoperative 6, 24, and 48 h (p > 0.05). PNB did not show superiority in terms of pain reduction in patients whose limb lengthening was more than 10 mm after THA. Further investigations on methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.
RESUMO
Objective. Although recent studies have shown that mechanical stress plays an important role in ultrasound neuromodulation, the magnitude and distribution of the mechanical stress generated in tissues by focused ultrasound transducers have not been adequately examined. Various acoustic radiation force (ARF) equations used in previous studies have been evaluated based on the tissue displacement results and are suitable for estimating the displacement. However, it is unclear whether mechanical stress can be accurately determined. This study evaluates the mechanical stress predicted by various AFR equations and suggests the optimal equation for estimating the mechanical stress in the brain tissue.Approach. In this paper, brain tissue responses are compared through numerical finite element simulations by applying the three most used ARF equations-Reynolds stress force ((RSF)), momentum flux density tensor force, and attenuation force. Three ARF fields obtained from the same pressure field were applied to the linear elastic model to calculate the displacement, mechanical stress, and mean pressure generated inside the tissue. Both the simple pressure field using a single transducer and the complex standing wave pressure field using two transducers were simulated.Main results. For the case using a single transducer, all three ARFs showed similar displacement. However, when comparing the mechanical stress results, only the results using the RSF showed a strong stress tensor at the focal point. For the case of using two transducers, the displacement and stress tensor field of the pattern related to the standing wave were calculated only from the results using the RSF.Significance. The model using RSF equation allows accurate analysis on stress tensor inside the tissue for ultrasound neuromodulation.
Assuntos
Acústica , Encéfalo , Estresse Mecânico , Ultrassonografia , Encéfalo/diagnóstico por imagem , Movimento (Física) , TransdutoresRESUMO
BACKGROUND: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. PURPOSE: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. RESULTS: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. CONCLUSION: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. REGISTRATION: NCT03990805 (ClinicalTrials.gov identifier).
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Resultado do Tratamento , Injeções Intra-Articulares , Dor/etiologia , Método Duplo-CegoRESUMO
PURPOSE: The aim of this study was to compare the anatomical structures of the acetabular rim around the anterior inferior iliac spine (AIIS) ridge that indicate anterior focal coverage of acetabulum between the sexes using a three-dimensional (3D) model. METHODS: 3D models of 71 adults (38 men and 33 women) with normal hip joints were used. Based on the location of the inflection point (IP) of the acetabular rim around the AIIS ridge, the patients were classified into anterior and posterior types, and the ratios thereof for each sex were compared. Coordinates for the IP, the most anterior point (MAP), and the most lateral point (MLP) were obtained and compared between the sexes and between anterior and posterior types. RESULTS: Coordinates for IPs in men were located anterior and inferior to those in women. MAP coordinates for men were located inferior to those for women, and MLP coordinates for men were located lateral and inferior to those for women. Comparing AIIS ridge types, we noted that coordinates for IPs of the anterior type were located medial, anterior, and inferior to those of the posterior type. Meanwhile, MAP coordinates of the anterior type were located inferior to those of the posterior type, and MLP coordinates of the anterior type were located lateral and inferior to those of the posterior type. CONCLUSION: Anterior focal coverage of the acetabulum appears to differ between the sexes, and this difference may affect the development of pincer-type femoroacetabular impingement (FAI). Additionally, we found that anterior focal coverage differs according to anterior or posterior positioning of the bony prominence around the AIIS ridge, which may affect development of FAI.
Assuntos
Impacto Femoroacetabular , Caracteres Sexuais , Adulto , Humanos , Feminino , Masculino , Acetábulo/diagnóstico por imagem , Impacto Femoroacetabular/diagnóstico por imagem , População do Leste Asiático , Articulação do Quadril/diagnóstico por imagemRESUMO
Parkinson's disease (PD), a neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons. The pathogenesis of PD is associated with several factors including oxidative stress, inflammation, and mitochondrial dysfunction. Ca2+ signaling plays a vital role in neuronal signaling and altered Ca2+ homeostasis has been implicated in many neuronal diseases including PD. Recently, we reported that apamin (APM), a selective antagonist of the small-conductivity Ca2+-activated K+ (SK) channel, suppresses neuroinflammatory response. However, the mechanism(s) underlying the vulnerability of DA neurons were not fully understood. In this study, we investigated whether APM affected 1-methyl-4-phenyl pyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells and rat embryo primary mesencephalic neurons. We found that APM decreased Ca2+ overload arising from MPP+-induced neurotoxicity response through downregulating the level of CaMKII, phosphorylation of ERK, and translocation of nuclear factor NFκB/signal transducer and activator of transcription (STAT)3. Furthermore, we showed that the correlation of MPP+-mediated Ca2+ overload and ERK/NFκB/STAT3 in the neurotoxicity responses, and dopaminergic neuronal cells loss, was verified through inhibitors. Our findings showed that APM might prevent loss of DA neurons via inhibition of Ca2+-overload-mediated signaling pathway and provide insights regarding the potential use of APM in treating neurodegenerative diseases.
Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Doença de Parkinson , Humanos , Ratos , Animais , Cálcio/metabolismo , Apamina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Fármacos Neuroprotetores/farmacologia , Neuroblastoma/metabolismo , 1-Metil-4-fenilpiridínio/toxicidade , Neurônios Dopaminérgicos/metabolismo , Transdução de Sinais , Estresse Oxidativo , Doença de Parkinson/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/patologia , Apoptose , Linhagem Celular TumoralRESUMO
The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.
Assuntos
Insuficiência Renal Crônica , Obstrução Ureteral , Actinas/metabolismo , Animais , Autofagia/genética , Proteína Beclina-1/metabolismo , Modelos Animais de Doenças , Fibronectinas/metabolismo , Fibrose , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Rim/metabolismo , Mamíferos/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Oligonucleotídeos/farmacologia , RNA não Traduzido/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/genética , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismoRESUMO
Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.
Assuntos
Insuficiência Renal Crônica , Obstrução Ureteral , Animais , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Modelos Animais de Doenças , Fibrose , Rim/metabolismo , Camundongos , Oligonucleotídeos/farmacologia , Insuficiência Renal Crônica/metabolismo , Obstrução Ureteral/metabolismoRESUMO
Peripheral nerve block (PNB) for patients with total knee arthroplasty (TKA) is one of the recommended interventions in ERAS protocols. However, most existing studies involved unilateral TKA (UTKA). As such, this study aimed to evaluate the effectiveness of PNB in terms of immediate postoperative analgesia, length of hospital stays (LOS), and early functional outcomes in both UTKA and simultaneous bilateral TKAs (BTKAs). We reviewed 236 patients who underwent primary TKA with PNB, with 138 and 98 being UTKA and BTKAs, respectively; those in the PNB group underwent femoral nerve and adductor canal block. The matched control and PNB groups-who received intravenous/epidural patient-controlled analgesia (IVPCA/PCEA) alone or IVPCA in addition to PNB after surgery, respectively-were compared. The VAS scores at rest until 48 h after surgery were significantly lower in PNB groups compared to those in the IVPCA groups. At 0- 6 h of activity, VAS scores of the UTKA with PNB group were also lower than the IVPCA group. Compared to PCEA groups, VAS scores at 0-6 h of activity were higher in both the UTKA and BTKAs with PNB groups. However, at 24-48 h at rest, the scores of those in the UTKA with PNB group were lower than those in the PCEA group. The control and experimental UTKA and BTKAs groups had similar LOS and functional outcomes at 90 days postoperatively. In primary TKA, PNB has great analgesic effects for immediate postoperative pain control, and represents a similar analgesic effect to epidural PCA.
RESUMO
INTRODUCTION: Preoperative carbohydrate drinks are recommended to reduce fasting time before surgery. Older adults are at risk of pulmonary aspiration and hyperglycemia after consuming carbohydrate drinks because of increased insulin resistance and delayed gastric emptying. We investigated the effects of oral carbohydrate drinks on perioperative insulin resistance, metabolic responses, and gastric volume in older adults. METHODS: Fifty-six patients (aged more than 65 years) were randomly assigned to the control or carbohydrate (CHO) group. The CHO group received 400 mL of a carbohydrate drink 2 to 3 hours before anesthesia. The control group was allowed clear fluid intake 2 hours before anesthesia. Blood glucose and insulin levels were measured before intake of the carbohydrate drink and 1 hour postoperatively. Gastric volume was measured before spinal anesthesia. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance. RESULTS: Homeostasis model assessment for insulin resistance was not different between the control and CHO groups preoperatively (2.5 versus 3.3, P = 0.156) or postoperatively (2.6 versus 2.4, P = 0.817). Preoperative gastric volume was comparable between the control and CHO groups (35.5 versus 30.8 mL, P = 0.696). DISCUSSION: Preoperative oral consumption of carbohydrates did not affect insulin resistance or gastric volume in older adults undergoing total knee or hip arthroplasty. Preoperative carbohydrate loading is safe in older adults undergoing total knee or hip arthroplasty. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author on reasonable request. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT04206189).
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Resistência à Insulina , Administração Oral , Idoso , Glicemia , Humanos , Insulina , Cuidados Pré-Operatórios , Estudos ProspectivosRESUMO
Transcranial focused ultrasound (FUS) is a noninvasive treatment for brain tumors and neuromodulation. Based on normal incidence, conventional FUS techniques use a focused or an array of ultrasonic transducers to overcome the attenuation and absorption of ultrasound in the skull; however, this remains the main limitation of using FUS. A dual-mode conversion technique based on Lamb waves is proposed to achieve high transmission efficiency. This concept was validated using the finite element analysis (FEA) and experiments based on changes in the incident angle. Aluminum, plexiglass, and a human skull were used as materials with different attenuations. The transmission loss was calculated for each material, and the results were compared with the reflectance function of the Lamb waves. Oblique incidence based on dual-mode conversion exhibited a better transmission efficiency than that of a normal incidence for all of the specimens. The total transmission losses for the materials were 13.7, 15.46, and 3.91 dB less than those associated with the normal incidence. A wedge transducer was designed and fabricated to implement the proposed method. The results demonstrated the potential applicability of the dual-mode conversion technique for the human skull.