Citations

Abstract Objectives Adults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon-like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates as disease-modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin (STZ)-induced rat model of AD. Methods Three months following the induction of AD by intracerebral injection of STZ, animals were orally administered with vildagliptin (2.5, 5 and 10 mg/kg) for 30 days. Dose-dependent and time-course effects of vildagliptin on memory retention were investigated during the course of treatment. Following treatment, the animals were sacrificed, and brain tissues were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP-1 levels, amyloid beta (Aβ) burden, tau phosphorylation and inflammatory markers. Key findings The results reveal a time-dependent improvement in memory retention and a dose-dependent attenuation of Aβ, tau phosphorylation and inflammatory markers and increased GLP-1 levels. Conclusions These robust therapeutic effects of vildagliptin demonstrate a unique mechanism for Aβ and tau clearance and reverse the cognitive deficits and pathology observed in AD.

Background: Medial elbow distraction during pitching as the primary mechanism contributing to adaptations in ulnar collateral ligament (UCL) appearance during magnetic resonance imaging (MRI) evaluation has not been established. Hypothesis: Uninjured high school–aged pitchers with unilateral adaptations of the UCL exhibit a higher peak internal elbow adduction moment than those without UCL adaptations. Study Design: Cohort study (Prevalence); Level of evidence, 2. Methods: Twenty uninjured, asymptomatic high school–aged pitchers underwent bilateral elbow MRI examinations. Three-dimensional motion analysis testing was performed to collect throwing arm biomechanics as participants pitched from an indoor mound. Nonparametric tests were performed to compare peak internal elbow adduction moment in uninjured participants with and without adaptations in UCL appearance and to determine the nature of the relationship between the peak internal adduction moment and UCL appearance. Results: Uninjured participants with UCL thickening exhibited a higher peak internal elbow adduction moment of 53.3 ± 6.8 N·m compared with uninjured participants without adaptations in UCL appearance, 38.8 ± 10.9 N·m ( P = .05), as higher moments were correlated with ligament thickening (correlation coefficient, 0.45) ( P = .02). Conclusion: This study establishes the association between medial elbow distraction captured by the internal adduction moment during pitching and UCL adaptations visible during MRI evaluation.

Background: Tissue adaptations in response to pitching are an expected finding during magnetic resonance imaging (MRI) evaluation of the throwing elbow of adult pitchers. These changes are considered normal in the absence of symptom complaints. It is unclear when during the playing career these tissue adaptations are initiated. Hypothesis: Abnormalities in the appearance of the throwing elbow compared with the nonthrowing elbow would be visible during MRI assessment of this asymptomatic population of high school–aged throwers. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Twenty-three uninjured, asymptomatic male high school–aged baseball pitchers (mean age, 16 years) with no history of elbow injury were recruited for the study. Participants had a minimum of 3 years’ experience with pitching as their primary position (mean experience, 6 years). Bilateral elbow MRI examinations were performed using a standardized protocol including fast spin-echo proton-density (axial and coronal), T1-weighted (sagittal), and T2-weighted fat-saturated (axial, sagittal, and coronal) sequences. Osteoarticular, ligamentous, musculotendinous, and neural structures were evaluated and compared bilaterally. The images were reviewed by a musculoskeletal radiologist who was blinded to all the gathered data on these athletes, including limb dominance. Results: Three participants (13%) had no abnormalities. Fifteen individuals (65%) had asymmetrical anterior band ulnar collateral ligament thickening, including 4 individuals who also had mild sublime tubercle/anteromedial facet edema. Fourteen participants (61%) had posteromedial subchondral sclerosis of the ulnotrochlear articulation, including 8 (35%) with a posteromedial ulnotrochlear osteophyte, and 4 (17%) with mild posteromedial ulnotrochlear chondromalacia. Ten individuals (43%) had multiple abnormal findings in the throwing elbow. Conclusion: Thickening of the anterior band of the ulnar collateral ligament and posteromedial subchondral sclerosis of the trochlea are common findings in the high school–aged pitcher and may be considered normal clinical findings in the absence of symptom complaints. Other changes in tissue appearance of the throwing elbow are uncommon in this age group and should be regarded with a higher level of caution when evaluating for the presence of injury. An understanding of the MRI appearance of the uninjured youth pitcher is necessary for clinicians to distinguish between normal adaptations and the presence of injury.