An Evaluation of Forearm Deformities in Hereditary Multiple Exostoses: Factors Associated With Radial Head Dislocation and Comprehensive Classification.

PURPOSE: This study attempted to evaluate a series of patients with hereditary multiple exostoses (HME) who could not be categorized according to the widely accepted Masada classification and to identify radiographic variables such as radial bowing, ulnar shortening, ulnar variance, radial articular angle, and carpal slip predictive of deformity. METHODS: We retrospectively reviewed data on 102 upper limbs of 53 pediatric patients with HME. Demographics, site of forearm involvement, and radiographic parameters were documented. Patients with exostoses of the forearms were categorized into 6 groups based on location of the exostoses and presence or absence of a dislocated radial head. Proportional ulnar shortening was calculated as the ratio of ulnar length to radial length. RESULTS: According to the Masada classification, 4 limbs were normal, 10 were type I, 2 were type II, and 24 were type III. Sixty-six limbs were unclassifiable. We classified those 66 limbs using a modification of the Masada classification. Of the 106 limbs, 11 (10.3%) had a dislocated radial head. Based on the radiographic analysis, patients with proportional ulnar shortening of less than 0.9 had a higher risk of radial head dislocation than did those with proportional ulnar shortening of 0.9 or greater. Patients with radial bowing greater than 8.1% showed a higher frequency of radial head dislocation than did those with radial bowing of 8.1% or less. Exostoses of both the distal radius and ulna tended to increase the rate of radial head dislocation. A greater amount of negative ulnar variance caused more radial bowing and a greater radioarticular angle. CONCLUSIONS: We propose a new comprehensive forearm classification for patients with HME. Proportional ulnar shortening less than 0.9 and radial bowing 8.1% or greater can be used to predict the risk of radial head dislocation. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Soluble epoxide hydrolase inhibitory components from Rheum undulatum and in silico approach.

Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50 values ranging from 2.5 ± 0.5 to 53.2 ± 4.4 µM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site. Compound 4 was identified as a competitive-type interaction in the active site. Molecular docking studies revealed the interacting residues and binding energy between sEH and inhibitors. Additionally, molecular dynamics provided detailed information on the interaction between the ligand and receptor.

Geranylgeranylacetone induces apoptosis via the intrinsic pathway in human melanoma cells.

The aim of this study was to test the anti-cancer effects of geranylgeranylacetone (GGA), an isoprenoid compound, on human melanoma cells. Human melanoma cell lines G361, SK-MEL-2, and SK-MEL-5 were treated with GGA at various doses (1-100µM). Cell viability was measured by crystal violet assay. Western blot analysis was adopted to detect marker proteins of apoptosis. GGA significantly reduced the viability of G361, SK-MEL-2, and SK-MEL-5 human melanoma cells at concentrations above 10µM. Western blot analysis showed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) after GGA treatment, as well as activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage. GGA also induced p53 and Bax expression, but did not affect expression of Bcl-2 and MITF. These findings suggest that GGA induces apoptosis through the intrinsic pathway. Accordingly, GGA should be considered for further development as a potential agent for melanoma.

Identification, characterization, kinetics, and molecular docking of flavonoid constituents from Archidendron clypearia (Jack.) Nielsen leaves and twigs.

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the leaves and twigs of Archidendron clypearia (Jack.) Nielsen (Fabaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of the water layer of A. clypearia, we isolated two new chalcones, clypesides A-B (1-2), 13 flavonoid derivatives (3-15) and established their structures based on an extensive 1D and 2D NMR, CD data, and MS analysis. All of the flavonoid derivatives inhibited sEH enzymatic activity in a dose-dependent manner, with IC50 values ranging from 10.0±0.4 to 30.1±2.1µM. A kinetic analysis of compounds 4, 8-10, 12, 13, and 15 revealed that the compounds 8-10 were non-competitive, 4, 13, and 15 were mixed-type, and 12 was competitive inhibitors. Additionally, molecular docking increased our understanding of their receptor-ligand binding. These results demonstrated that flavonoid derivatives from A. clypearia are potential sEH inhibitors.

Alkylphloroglucinol derivatives and triterpenoids with soluble epoxide hydrolase inhibitory activity from Callistemon citrinus.

Phytochemical analysis of the leaves and stems of Callistemon citrinus (Curtis) Skeels led to the isolation of two new alkylphloroglucinols, gallomyrtucommulone E and F (1 and 2), along with four other known alkylphloroglucinol derivatives, gallomyrtucommulone A (3), endoperoxide G3 (4), myrtucommulone B (5), callistenone B (6) and five known triterpenoids, including betulinic acid (7), 3ß-acetylmorolic acid (8), 3ß-hydroxy-urs-11-en-13(28)-olide (9), diospyrolide (10) and ursolic acid (11). The structures of the natural compounds were determined from the spectroscopic evidences including 1D-/2D-NMR and HR-MS spectrometry. All the isolated compounds were assessed for the effects on the sEH inhibitory activity. The acylphloroglucinols myrtucommulone B (5)/callistenone B (6) (in mixture), and two triterpenoids, ursolic acid (11) and 3ß-hydroxy-urs-11-en-13(28)-olide (9) displayed strong inhibition of sEH activity, with IC50 values of 0.7, 11.2 and 24.8 µM, respectively.

Baicalin-induced Akt activation decreases melanogenesis through downregulation of microphthalmia-associated transcription factor and tyrosinase.

Scutellaria baicalensis has been used topically to treat inflammatory skin diseases in traditional East Asian medicine. Because post-inflammatory hyperpigmentation of the skin is difficult to manage, we investigated the effects of baicalin, a major component of S. baicalensis, on melanin synthesis in Mel-Ab cells. Our data showed that baicalin significantly inhibited melanin production and tyrosinase activity in a dose-dependent fashion, but it did not directly influence tyrosinase activity. Moreover, baicalin treatment triggered decreases in both mRNA and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase. Although AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) activation were induced in baicalin-treated Mel-Ab cells, they were not responsible for baicalin-induced hypopigmentation. Because the Akt pathway is also known to be involved in regulation of melanogenic protein expression and melanin synthesis, we examined the effects of baicalin on the Akt pathway. Our results showed that baicalin treatment stimulated Akt activation. Treatment with LY294002, a specific Akt inhibitor, restored baicalin-induced melanogenesis inhibition and abolished MITF and tyrosinase downregulation by baicalin. Taken together, our data suggest that Akt activation by baicalin inhibits melanin production via downregulation of MITF and tyrosinase in Mel-Ab cells.

A comparison of stability and clinical outcomes in single-radius versus multi-radius femoral design for total knee arthroplasty.

We compared the intraoperative varus-valgus stability from 0° to 90° of flexion and postoperative clinical outcomes in patients receiving TKA via either a single-radius femoral design (50 TKA, SR group) or multi-radius femoral design (50 TKA, MR group). We measured stabilities at 0°, 30°, 60° and 90° of flexion using a navigation system. The clinical outcomes including HSS scores, WOMAC scores and VAS score during stair climbing were compared after a minimum of 2-year follow-up. The single-radius femoral designs in TKA showed better intra-operative stability at 30° of flexion (7.6 vs. 8.3) compared with the multi-radius femoral design, but not at other angles. However, the clinical outcomes revealed no other significant differences in terms of HSS scores, WOMAC scores and VAS score between two groups.

Current trends in anterior cruciate ligament reconstruction.

The advances in the knowledge of anatomy, surgical techniques, and fixation devices have led to the improvement of anterior cruciate ligament (ACL) reconstruction over the past 10 years. Nowadays, double bundle and anatomical single bundle ACL reconstruction that more closely restores the normal anatomy of the ACL are becoming popular. Although there is still no definite conclusion whether double bundle ACL reconstruction provides better clinical results than single bundle reconstruction, the trend has shifted to anatomic reconstruction regardless of single bundle or double bundle techniques. We could not find any significant differences in the clinical outcomes and stability after ACL reconstruction according to the type of graft or fixation device. Therefore, surgeons should select an ideal ACL reconstruction according to the patient's condition and surgeon's experience.