RESUMEN
BACKGROUND: High tibial osteotomy (HTO) aims to realign the varus knee to alleviate stress in the medial compartment. However, detailed information on the impact of HTO on stress distribution across the tibiofemoral joint surface still needs to be completely elucidated. PURPOSE/HYPOTHESIS: The present study aimed to analyze the subchondral bone density distribution to validate the alignment threshold causing paradoxical changes. We hypothesized that there would be a paradoxical stress change in the medial compartment beyond a specific threshold for lower limb realignment after HTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective clinical study of 32 knees from 30 patients who underwent medial opening-wedge HTO between 2015 and 2019 was conducted at Hokkaido University Hospital. The subchondral bone density across the tibiofemoral joint was analyzed using computed tomography-osteoabsorptiometry before and after HTO. The high-density area (HDA) within the medial and lateral compartments and their subregions, which were quartered in the coronal plane, was specifically examined. RESULTS: The hip-knee-ankle angle, medial proximal tibial angle (MPTA), joint line obliquity (JLO), and joint line convergence angle significantly changed after HTO (P < .01). The HDA of the medial compartment to the total HDA ratio decreased from 83% to 77%. Paradoxically, the HDA in the most central subregion of the medial compartment increased from 24% to 30%. There were significant differences between MPTA and JLO in patients with and without paradoxical changes in the HDA. MPTA and JLO cutoff values causing paradoxical changes in the HDA were 94° and 4°, respectively. CONCLUSION: There was a paradoxical stress increase in the M4 region at the medial compartment associated with the MPTA and JLO beyond specific thresholds. Therefore, surgical planning should be cautiously performed to prevent overcorrection, which can lead to adverse stress distribution changes.
RESUMEN
γ-Aminobutyric acid receptors (GABARs) mediate fast inhibitory neurotransmission and are targets for insecticides. GABARs are composed of five subunits, the composition of which dictates the pharmacological characteristics of GABARs. Both competitive and noncompetitive GABAR antagonists can be used as insecticides. Gabazine is a potent competitive antagonist of mammalian α1ß2γ2 GABARs; however, it is less potent against insect GABARs. To explore how gabazine interacts with GABARs, we examined whether the sensitivity of the small brown planthopper (Laodelphax striatellus) RDL GABAR (LsRDLR) to gabazine is increased when its amino acid residues are substituted with α1ß2γ2 GABAR residues. In the results, two of the generated mutants showed enhanced gabazine sensitivity. Docking simulations of gabazine using LsRDLR homology models and an α1ß2γ2 GABAR cryo-EM structure revealed that the accommodation of gabazine into the "aromatic box" in the orthosteric site lowered the binding energy. This information may help in designing GABAR-targeting insecticides with novel modes of action.
