Clinical Outcomes of Percutaneous Plantar Fasciotomy Using Microdebrider Coblation Wand.

BACKGROUND: Plantar fasciitis is the most common cause of heel pain in adults. Multiple conservative treatment plans exist; however, some cases do not obtain significant clinical improvement with conservative treatment and require further intervention. This retrospective case study evaluated the success rate of percutaneous plantar fasciotomy and confounding comorbidities that negatively affect outcomes. METHODS: A series of 41 patients treated with percutaneous plantar fasciotomy using the Topaz EZ microdebrider coblation wand were invited to participate in this retrospective follow-up study, and 88% (N = 36) participated. A limited chart review was completed and the patients answered a survey with the visual analog scale (VAS) for pain and the Foot and Ankle Ability Measure (FAAM) questionnaire. Average outcomes were calculated and 45 variables were analyzed to determine if they were statistically significant confounders. Patients had symptoms for an average of 3 years before the procedure and were contacted for follow-up at an average of 14 months after the procedure. RESULTS: The average VAS for pain score was 1.3 ± 1.8 and the average FAAM score was 92 ± 15. Eighty-nine percent of patients had a successful outcome, defined as FAAM greater than 75. In addition, patients at 18 months postprocedure reported complete or near-complete resolution of symptoms with an FAAM score greater than 97. Concurrent foot pathologies (eg, tarsal tunnel syndrome), oral steroid treatment prior to the procedure, and immobilization with a boot prior to the procedure were statistically significant negative confounders (P < .05). Being an athlete was a positive confounder (P = .02). CONCLUSION: Percutaneous plantar fasciotomy using a microdebrider coblation was an effective treatment for plantar fasciitis, particularly without concurrent foot pathology, with a low risk of complications. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Stimulatory Toll-like receptor 2 suppresses restraint stress-induced immune suppression.

Stress can enhance or suppress immune functions depending on a variety of factors. Our previous studies observed that Toll-like receptor 2 (TLR2) participates in chronic restraint stress-induced immune dysfunction. However, the mechanism by which TLR2 prevents immune suppression remains elusive. Our investigation found that stimulation of TLR2 by peptidoglycan (PGN) significantly attenuates splenocyte apoptosis and markedly blocks alterations of anti-apoptotic and apoptotic proteins. Activation of TLR2 inhibits chronic stress-reduced phosphorylation of c-Jun N-terminal kinase (JNK) and diminishes chronic stress-induced up-regulation of corticosterone production. Additionally, our data show that chronic stress causes a dramatic decrease of cytokine IL-2 level but an increase of IL-4 and IL-17 in CD4(+) T cells. Interestingly, PGN could block these alterations of cytokine levels. Collectively, our studies demonstrate that stimulation of TLR2 attenuates chronic stress-induced immune suppression by modulating apoptosis-related proteins and immunoregulatory agents.

ß-arrestin 2-mediated immune suppression induced by chronic stress.

OBJECTIVE: Stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced immune suppression remain to be elucidated. ß-Arrestin 2 serves as adaptor, scaffold, and/or signal transducer. The role of ß-arrestin 2 in stress-induced immune suppression is not known yet. METHODS/RESULTS: Here, we demonstrate that ß-arrestin 2 deficiency in mice increases the sensitivity to the chronic stress-induced reduction in the number of splenocytes. Interestingly, the stress-induced suppression of T helper-type (Th) 1 cytokines and the increased production of Th2 cytokines were greatly enhanced in ß-arrestin 2-deficient mice compared with wild-type mice. Moreover, inhibition of PI3K in ß-arrestin 2-deficient mice exerts an additive effect on the stress-induced reduction in the number of splenocytes. CONCLUSION: Our study demonstrates that a deficiency in ß-arrestin 2 augments stress-induced immune suppression.

Selective recognition of uracil and its derivatives using a DNA repair enzyme structural mimic.

During DNA repair, uracil DNA glycosylase (UDG) pulls unwanted uracil into its active site through hydrogen bonding and pi-pi stacking interactions. The reason why UDG binds only uracil tightly--and not its derivatives, such as thymine--remains unclear. In this study, we synthesized the stable, water-soluble receptor 1a as a structural mimic of the active site in UDG. Compound 1a contains a 2,6-bis(glycylamino)pyridine group, which mimics the amino acid residues of UDG that interact with uracil through a hydrogen-bonding network; it also possesses a pyrene moiety as a pi-pi stacking interaction element and fluorescent probe that mimics the aromatic groups (phenyl and fluorescent indolyl units) found in the active site of UDG. Receptor 1a binds selectively to uracil and derivatives (including thymine, 5-formyluracil, 5-fluorouracil, and 5-nitrouracil) and some DNA and RNA nucleosides (including thymidine and uridine) through hydrogen bonding and pi-pi stacking interactions. Interestingly, a plot of log K(b) with respect to the values of pK(a) of the N(3)H units of uracil and its derivatives was linear, with a negative slope (beta) of -0.24 +/- 0.03. Thus, compounds featuring lower values of pK(a) for their N(3)H units provided greater apparent binding constants for their complexes with receptor 1a, suggesting acidity-dependent binding of uracil and its derivatives to this receptor; notably, uracil bound more tightly than did thymine. Our study provides some insight into how uracil and its derivatives in DNA are bound by DNA repair enzymes through hydrogen bonding and pi-pi stacking interactions.

Synthetic resveratrol aliphatic acid inhibits TLR2-mediated apoptosis and an involvement of Akt/GSK3beta pathway.

As resveratrol derivatives, resveratrol aliphatic acids were synthesized in our laboratory. Previously, we reported the improved pharmaceutical properties of the compounds compared to resveratrol, including better solubility in water and much tighter binding with human serum albumin. Here, we investigate the role of resveratrol aliphatic acids in Toll-like receptor 2 (TLR2)-mediated apoptosis. We showed that resveratrol aliphatic acid (R6A) significantly inhibits the expression of TLR2. In addition, overexpression of TLR2 in HEK293 cells caused a significant decrease in apoptosis after R6A treatment. Moreover, inhibition of TLR2 by R6A decreases serum deprivation-reduced the levels of phosphorylated Akt and phosphorylated glycogen synthase kinase 3beta (GSK3beta). Our study thus demonstrates that the resveratrol aliphatic acid inhibits cell apoptosis through TLR2 by the involvement of Akt/GSK3beta pathway.