Abstract Objectives Ischemic preconditioning (IP) affords resistance to liver ischemia–reperfusion (IR) injury, providing an early phase of protection. Development of delayed IP against IR injury was ...assessed using partial IR in rat liver. Methods The IP manuver (10 minutes of ischemia and up to 72 hours of reperfusion) was induced before 1 hour of ischemia and 20 hours of reperfusion. At the end of the reperfusion period, blood and liver samples were analyzed for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), haptoglobin and tumor necrosis factor-α (TNF-α) levels, hepatic histology, protein carbonyl and glutathione (GSH) contents as well as nuclear factor-κB (NF-κB), and activating protein-1 (AP-1) DNA binding. Results The IP manuver significantly increased protein carbonyl/GSH ratios (275%), serum ALT (42%), and AST (58%); these changes normalized after 12 hours. Serum AST, ALT, and LDH levels were significantly increased by IR (4-, 5.6-, and 7.0-fold, respectively), with significant changes in liver histology, protein carbonyl/GSH ratio (481% enhancement), and serum TNF-α (6.1-fold increase). Delayed IP in IR animals reduced serum AST (66%), ALT (57%), and LDH (90%) and liver GSH depletion (89%), with normalization of protein carbonyl content, serum TNF-α levels, and liver histology. Enhanced AP-1/NF-κB DNA binding ratios and diminished haptoglobin expression induced by IR were normalized by IP. Conclusion These data support that delayed IP suppresses IR-induced liver injury, oxidative stress, and TNF-α response, which coincide with recovery of IR-altered signaling functions represented by normal AP-1/NF-κB DNA binding ratios and acute phase responses.
To evaluate the biocompatibility of a glass-ionomer (GIC) and a resin-modified glass-ionomer cement (RM-GIC), cell viability was examined in a model of human gingival fibroblasts using morphological, ...biochemical, and ionic patterns by means of phase contrast microscopy, lactate dehydrogenase (LDH) release, and quantitative x-ray microanalysis (EPXMA).
The GIC Ketac-Molar Easymix (3M ESPE) and the RM-GIC Vitrebond (3M ESPE) were compared in human gingival fibroblasts exposed to the cements for 72 h. As controls, fibroblasts cultured with DMEM culture medium (negative control) and with 1% triton × (positive control) were used.
Light microscopic findings showed greater morphological alterations in cells exposed to RM-GIC than to GIC. The relative percentage of LDH released from the cells to the supernatant was significantly higher in RMGIC cultures than in the control. Quantitative x-ray microanalysis showed that cultures exposed to RM-GIC were characterized by an increase in intracellular Na and a decrease in intracellular Cl and K. These changes in ion composition were significant compared to control and GIC cultures.
The three indicators of cellular biocompatibility after 72 h of exposure showed that RM-GIC led to more marked alterations than GIC in human gingival fibroblasts.
The purpose of this study was to evaluate clinical and radiologic outcomes of arthroscopic superior capsular reconstruction (ASCR) with fascia lata autograft in patients with irreparable rotator cuff ...tears (IRCTs) performed using a single lateral-row fixation technique.
We studied a retrospective case series of patients with large or massive IRCTs for ASCR with fascia lata autograft. Clinical outcomes were evaluated using the Visual Analog Scale (VAS) and the Constant score. Healing of the graft was assessed by magntic resonance imaging or ultrasound. Acromiohumeral distance was evaluated by radiographs.
Thirty-one patients with an average age of 61 years and an average follow-up of 35 months (24-51 months) underwent ASCR with fascia lata autograft. There was a significant improvement in VAS (7.7-0.7), Constant score (36.0-78.7), forward elevation (115°-171°), external rotation (33°-50°), strength (0.3 kg-2.3 kg), and acromiohumeral distance (6.1 mm-8.6 mm) (P < 0.001). Graft failure was present in 13.8% of patients, as shown by magnetic resonance imaging (26 patients) or ultrasound (3 patients). Patients with failed ASCR showed worse Constant scores (68.5.8 vs 80.2, P = 0.007), worse VAS (2.5 vs 0.4, P = 0.00002), worse external rotation (20° vs 54°, P = 0.004), lower acromiohumeral distance (5mm vs 9mm, P = 0.007), and a high association with the presence of os acromiale (χ2P = 0.003). No revision or subsequent surgical procedures were required.
ASCR, with autologous fascia lata and single lateral row configuration, is an effective option in irreparable rotator cuff tears and results in clinical and radiologic improvement.
Level IV, retrospective case series.
Background:
Outcomes following meniscal allograft transplantation (MAT) are an evolving topic.
Purpose:
To review clinical outcomes in younger, previously active patients who underwent an isolated ...MAT or MAT plus any osteotomy. Concurrent surgeries, complications, and graft survivorship are presented.
Study Design:
Case series; Level of evidence, 4.
Methods:
Inclusion criteria included having undergone MAT with a minimum of 1 year of follow-up with at least 1 of the following patient-reported outcome (PRO) measures collected pre- and postoperatively: visual analog scale for pain, Knee injury and Osteoarthritis Outcome Score (KOOS), the Western Ontario and McMaster Universities Arthritis Index, the 36-Item Short Form Health Survey, and overall satisfaction. From patient records, we recorded descriptive data, side (medial/lateral), previous or concurrent procedures, perioperative complications, revisions, and conversion to arthroplasty. Two-factor analysis of variance (ANOVA) was used to test for differences in age and body mass index (BMI). A 2 × 2 chi-square test was used to determine if the spectrum of procedures performed on our study’s patient group was representative of the entire population. PRO results were analyzed using a multivariate ANOVA.
Results:
From a total of 91 eligible patients, 61 (63 knees) met our inclusion criteria. Mean presurgery age was 25.5 ± 9.2 years, and mean BMI was 26.7 (range, 18.5-38.4). At follow-up (mean, 4.8 years; range, 1.0-13.6 years) overall PROs were statistically and clinically improved at final follow-up (P ≤ .003); effect sizes were moderate and large. KOOS Pain and KOOS Activities of Daily Living showed some main or interaction effects that were trivial or small. Patient satisfaction with the treatment was ≥7 out of 10 in 85% of patients. A minimum of 1 subsequent surgery for various concerns was necessary in 23% of the 93 knees. Graft survival in the included patients was 100%.
Conclusion:
Complications (conditions requiring at least 1 subsequent surgery) affected about one-quarter of the patients who underwent MAT. Nevertheless, MAT seemed to provide our patients with adequate pain relief and improved function.
Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited ...therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. We investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence. TERT silencing or treatment of NRAS-mutant melanoma with the telomerase-dependent telomere uncapping agent, 6-thio-2'-deoxyguanosine (6-thio-dG), led to rapid cell death, along with evidence of both telomeric and non-telomeric DNA damage, increased ROS levels, and upregulation of a mitochondrial antioxidant adaptive response. Combining 6-thio-dG with the mitochondrial inhibitor Gamitrinib attenuated this adaptive response and more effectively suppressed NRAS-mutant melanoma. Our study uncovers a robust dependency of NRAS-mutant melanoma on TERT, and provides proof-of-principle for a new combination strategy to combat this class of tumors, which could be expanded to other tumor types.
Las enfermedades broncopulmonares se asocian a diversos mecanismos inflamatorios de las vías aéreas. Evaluar y comprender el perfil inflamatorio de estos pacientes podría contribuir a conocer la ...etiología y así optimizar el tratamiento. El esputo inducido es una técnica mínimamente invasiva, por lo que su implementación resulta de interés en la práctica habitual. Aunque el estudio del esputo inducido ha demostrado utilidad y seguridad, los centros que desarrollan esta técnica en la Argentina son escasos. Con el objetivo de estandarizar el procedimiento de recolección y análisis de muestras de esputo inducido en pacientes con enfermedades inflamatorias broncopulmonares, se desarrolló esta guía consensuada por los centros con experiencia en esta técnica en nuestro país. Es nuestra intención difundir esta técnica, mínimamente invasiva, para su aplicación en servicios especializados. Esta guía de procedimientos detalla los materiales que son requeridos, los métodos y los estándares de calidad y seguridad tanto para los pacientes como para los operadores.
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