Sex-related differences in the efficacy of dexamethasone pretreatment for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: a randomized controlled study

Background/aim: Sex-related differences in response to pain have become a topic of increasing interest. However, sex-related differences in the efficacy of dexamethasone for postoperative analgesia have not been previously addressed. Materials and methods: The study included 196 men and 196 women, aged between 18 and 45 years, who were scheduled for laparoscopic cholecystectomy. The patients were randomly allocated into dexamethasone (M/F: 98/98) and control (normal saline; M/F: 98/98) groups. Patients in the study group received intravenous dexamethasone at 0.1 mg/kg (dexamethasone group) 1 h before induction of anesthesia. Patients in the control group received normal saline. Changes in cumulative morphine-containing, patient-controlled analgesia consumption in both sexes, pain intensity using a visual analog scale 24 h after surgery, mean morphine consumption adjusted for body weight, and incidence of postoperative nausea or vomiting were measured. Results: Women in both groups had significantly higher pain scores at 1 and 6 h postoperatively, higher levels of patient-controlled analgesia and mean morphine consumption, and more postoperative nausea and vomiting (P < 0.05). These effects were less severe in the dexamethasone group. Conclusion: The results suggest that women are less responsive than men to dexamethasone for postoperative analgesia and experience higher levels of postoperative pain.

Effectiveness of polydeoxyribonucleotide injection versus normal saline injection for treatment of chronic plantar fasciitis: a prospective randomised clinical trial.

PURPOSE: Polydeoxyribonucleotide (PDRN) has been used for the treatment of chronic tendinosis. This prospective randomised study was conducted to evaluate the efficacy and complications of PDRN injection for treatment of plantar fasciitis. METHODS: Forty patients with a clinical diagnosis of plantar fasciitis were randomly allocated to PDRN injection (PDRN group, n = 20) or normal saline injection (placebo group, n = 20). Injections were performed weekly for three weeks. Clinical evaluations were done at baseline and four and 12 weeks after treatment began using the visual analogue scale (VAS) for foot pain and Manchester-Oxford Foot Questionnaire (MOXFQ). We also monitored the complications in both groups at one, two, four and 12 weeks after initial treatment. RESULTS: The PDRN group achieved a significant improvement in VAS and MOXFQ scores at four weeks after treatment, and this improvement continued until 12 weeks after treatment. On the other hand, the placebo group did not achieve a significant improvement in the VAS or MOXFQ scores at four or 12 weeks. The initial VAS and MOXFQ scores of the PDRN group were not significantly different from those of the placebo group. At four weeks after treatment, the VAS and MOXFQ scores of the PDRN group were better than those of the placebo group, but the difference was not statistically significant. At 12 weeks after treatment, the VAS and MOXFQ scores of the PDRN group were significantly better than those of the placebo group. We noticed no injection-related complications, such as itching, urticaria, redness or infection signs around the injection site in either group. CONCLUSIONS: PDRN injection is an effective and safe treatment option and may be considered for plantar fasciitis.

Toe component excision in postaxial polydactyly of the foot.

BACKGROUND: Polydactyly of the fifth toe is the most common congenital malformation of the forefoot, and no consensus has been reached as to which toe component should be excised or by which surgical technique. The purpose of this study was to evaluate the results of the operative treatment of postaxial polydactyly and to offer treatment guidelines. METHOD: We retrospectively reviewed the details of 27 patients with postaxial polydactyly (36 feet) treated from September 2004 to March 2010. To select the dominant toe of postaxial polydactyly, we evaluated the morphological and radiological configurations. To excise the medial toe, we treated the polydactyly by dorsal rectangular flap and a full-thickness inguinal skin graft. To excise the lateral toe, we treated the polydactyly by racket-shape incision. Patient satisfaction indices were evaluated on the basis of responses to the PSQ-10 patient satisfaction questionnaire and clinical outcomes. RESULT: Overall surgical outcomes were satisfactory with the exception of 2 cases of skin graft problems. Eighteen of the 36 reconstructed toes were smaller than the normal toes, but valgus deformity was observed in only 3 cases. CONCLUSION: The described medial toe excision technique and the devised toe selection algorithm were able to satisfy functional and cosmetic requirements.

New posterior column reconstruction using titanium lamina mesh after total en bloc spondylectomy of spinal tumour.

PURPOSE: To investigate the usefulness of titanium lamina mesh for posterior column reconstruction after total en bloc spondylectomy in patients with spinal tumour and evaluate the radiographic outcomes of this method. METHOD: Eight patients who underwent total en bloc spondylectomy with posterior column reconstruction using titanium lamina mesh and bone graft to treat a spinal tumour were included in this study. The mean age at the time of surgery was 50.6 years (range, 16.5-70.9 years) and the mean follow-up duration was 50.2 months (range, 28.1-68.7 months). The pathological lesions were located from the T2 to L1 vertebrae. There were four patients in each primary and metastatic tumour group. For the posterior column reconstruction, titanium lamina mesh was used and bone graft was applied over the lamina mesh. Radiographic evaluation was used to investigate the displacement of lamina mesh and union of the grafted bone above lamina mesh. RESULTS: At the postoperative six month follow-up, a bony bridge on the titanium mesh between upper and lower adjacent lamina was observed in all cases, except for one with infection. On the last follow-up, there was no collapse or displacement of titanium lamina mesh, and there was no instability or malalignment of the spinal column. CONCLUSIONS: Posterior column reconstruction using titanium lamina mesh during total en bloc spondylectomy for spinal tumour was a useful surgical option that provided new lamina reconstruction for stability of spinal column and protection of the neural elements.

Abies holophylla Leaf Essential Oil Alleviates Allergic Rhinitis Based on Network Pharmacology.

Abies holophylla is an evergreen coniferous species that has been widely used for treating pulmonary diseases and colds. Previous research has demonstrated the anti-inflammatory effect of Abies species and the anti-asthmatic activities of Abies holophylla leaf essential oil (AEO). As asthma and allergic rhinitis (AR) share pathophysiology and pharmacotherapeutic interventions, AEO inhalation can also ameliorate upper respiratory allergic diseases. This study explored the protective effects of AEO on AR with network pharmacological pathway prediction. The potential target pathways of AEO were analyzed by a network pharmacological approach. The BALB/c mice were sensitized by ovalbumin (OVA) and 10 µm particular matter (PM10) to induce allergic rhinitis. Aerosolized AEO 0.0003% and 0.03% were delivered by nebulizer for 5 min a day, 3 times a week for 7 weeks. Nasal symptoms (sneezing and rubbing), histopathological changes in nasal tissues, serum IgE, and zonula occludens-1 (ZO-1) expressions on nasal tissues were analyzed. After AR induction with OVA+PM10 and inhalation of AEO 0.0003% and 0.03% treatment, AEO significantly decreased allergic symptoms (sneezing and rubbing), hyperplasia of nasal epithelial thickness, goblet cell counts, and serum IgE level. The network analysis demonstrated that the possible molecular mechanism of AEO is highly associated with the IL-17 signaling pathway and tight junction. The target pathway of AEO was investigated in RPMI 2650 nasal epithelial cells. Treatment of AEO on PM10-treated nasal epithelial cells significantly reduced the production of inflammatory mediators related to the IL-17 signaling pathway, NF-κB, and the MAPK signaling pathway and prevented the reduction in TJ-related factors. When taken together, AEO inhalation may be considered as a potential treatment for AR by alleviating nasal inflammation and recovering the tight junction.

Effect and mechanism of Magnolia officinalis pharmacopuncture for treating localized fat via network pharmacology and experimental study.

Background: Recently, for various reasons, the need for non-invasive treatment for localized fat has emerged. This study confirmed whether Magnolia officinalis (MO) pharmacopuncture reduces localized fat by promoting lipolysis and inhibiting adipogenesis. Methods: The network was built using genes related to the active compound of MO and the mode of action of MO was predicted by the functional enrichment analysis. Based on the result from network analysis, 100 µL of 2 mg/mL MO pharmacopuncture was injected into the inguinal fat pad for 6 weeks in obese C57BL/6J mice. Normal saline was injected into the right-side inguinal fat pad as a self-control. Results: It was expected that the 'AMP-activated protein kinase (AMPK) signaling pathway' would be affected by the MO Network. MO pharmacopuncture reduced the weight and size of inguinal fat in HFD-induced obese mice. The phosphorylation of AMPK along with the increases of lipases was significantly increased by MO injection. Also, the expression levels of fatty acid synthesize-related mediators were suppressed by MO injection. Conclusion: Our results demonstrated that MO pharmacopuncture promoted the expression of AMPK, which has beneficial effects on activation of lipolysis and inhibition of lipogenesis. Pharmacopuncture of MO can be a non-surgical alternative therapy in the treatment of local fat tissue.

In silico binding free energy predictability with π-π interaction energy-augmented scoring function: benzimidazole Raf inhibitors as a case study.

The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding π-π interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure π-π interaction energies between ring groups. The result of this simple addition shows possibility of π-π interaction generalization in scoring functions.

Protective effects of inhalation of essential oils from Mentha piperita leaf on tight junctions and inflammation in allergic rhinitis.

Allergic rhinitis is one of the most common diseases, which is caused by IgE-mediated reactions to inhaled allergens. Essential oils from the Mentha piperita leaf (EOM) are known to be effective for various diseases, such as respiratory diseases. However, the effect of inhalation of EOM on tight junctions and inflammation related to allergic rhinitis is not yet known. The purpose of this research was to explain the effects of the inhalation of EOM on tight junctions and inflammation of allergic rhinitis through network pharmacology and an experimental study. For that purpose, a pharmacology network analysis was conducted comprising major components of EOM. Based on the network pharmacology prediction results, we evaluated the effect of EOM on histological changes in mice with ovalbumin and PM10-induced allergic rhinitis. Allergic symptoms, infiltration of inflammatory cells, and regulation of ZO-1 were investigated in mice with allergic rhinitis. Other allergic parameters were also analyzed by reverse transcription polymerase chain reaction and western blot in nasal epithelial cells. In the network analysis, the effects of EOM were closely related to tight junctions and inflammation in allergic rhinitis. Consistent with the results from the network analysis, EOM significantly decreased epithelial thickness, mast cell degranulation, goblet cell secretion, and the infiltration of inflammatory cells in nasal tissue. EOM also regulated the MAPK-NF-κB signaling pathway, which was related to tight junctions in nasal epithelial cells. This research confirmed that inhalation of EOM effectively restores tight junctions and suppresses inflammation in the allergic rhinitis model. These results reveal that EOM has a therapeutic mechanism to treat allergic rhinitis.

Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping.

The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q(2) value of 0.867, r(2) value of 0.991 in CoMFA and q(2) value of 0.628, r(2) value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide.

Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines.

The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC(50)=0.62 and 4.49muM, respectively) and turned out to be a selective and potent CRAF inhibitor.

QM/MM based 3D QSAR models for potent B-Raf inhibitors.

Three dimensional (3D) quantitative structure-activity relationship studies of 37 B-Raf inhibitors, pyrazole-based derivatives, were performed. Based on the co-crystallized compound (PDB ID: 3D4Q), several alignment methods were utilized to derive reliable comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. Receptor-guided alignment with quantum mechanics/molecular mechanics (QM/MM) minimization led to the best CoMFA model (q (2) = 0.624, r (2) = 0.959). With the same alignment, a statistically reliable CoMSIA model with steric, H-bond acceptor, and hydrophobic fields was also derived (q (2) = 0.590, r (2) = 0.922). Both models were validated with an external test set, which gave satisfactory predictive r (2) values of 0.926 and 0.878, respectively. Contour maps from CoMFA and CoMSIA models revealed important structural features responsible for increasing biological activity within the active site and explained the correlation between biological activity and receptor-ligand interactions. New fragments were identified as building blocks which can replace R1-3 groups through combinatorial screening methods. By combining these fragments a compound with a high bioactivity level prediction was found. These results can offer useful information for the design of new B-Raf inhibitors.

Arthroscopic microfracture for osteochondral lesions of the talus.

The purpose of the present study was to evaluate the outcomes of arthroscopic microfracture for isolated osteochondral lesions of the talus without combined lesions, in patients of less than 50 years old with lesions of <1.5 cm(2). Thirty-five patients (35 ankles) with isolated osteochondral lesions of the talus were treated by arthroscopic microfracture. There were 27 men and 8 women of average age 35 years (range 17-50) and mean body mass index (BMI) 25 kg/m(2) (range 20-34) at the time of surgery. Clinical outcome evaluations were performed at a mean follow-up of 33 months. Overall results, as determined using American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot scores, were excellent in 16 (46%), good in 15 (43%), and fair in 4 (11%). Mean AOFAS scores improved from 63 points (range 52-77) preoperatively to 90 points (range 73-100) at final follow-up, median Ankle Activity Score (AAS) from 3 points (range 1-5) to 6 points (range 3-8), mean Visual Analogue Scale (VAS) scores from 7 points (range 5-8) to 2 points (range 0-5), and mean Short Form-36 scores showed improvements in physical function, role limitation, bodily pain, social function, and general health (P < 0.05). In terms of prognostic factors, a longer symptom duration was found to negatively affect outcome, as determined by AOFAS scores, AAS, and VAS scores. Arthroscopic microfracture for isolated osteochondral lesions of the talus is a safe and effective procedure, which provides good clinical outcomes in the majority of patients.

Anterior Cervical Debridement and Fusion for Cervical Pyogenic Spondylodiscitis: Use of Anterior Cervical Plating or Not?

STUDY DESIGN: Retrospective multicenter case series. OBJECTIVE: We sought to evaluate the safety and efficacy of anterior cervical plating in anterior cervical debridement and fusion (ACDF) for patients with cervical pyogenic spondylodiscitis (CPS). SUMMARY OF BACKGROUND DATA: Due to concerns about bacterial seeding on the foreign material after instrumentations in pyogenic infections, the safety and efficacy of anterior cervical plating for CPS are still undetermined and controversial. Little information is available about the safety and efficacy of anterior cervical plating to manage CPS. METHODS: Twenty-three patients who underwent ACDF with (n = 12) or without (n = 11) plating for CPS were included. The mean age was 62.6 years. Medical records were reviewed and radiological parameters including segmental height, segmental angle, C2-C7 angle, and fusion status were analyzed. The mean follow-up period after surgery was 21.3 months. RESULTS: After ACDF with plating, segmental height, segmental angle, and C2-C7 angle were significantly improved compared with preoperative conditions and remained well-maintained at the last follow-up. After ACDF without plating, three radiological parameters were also initially improved compared with preoperative condition, but significantly deteriorated to preoperative levels at the time of the last follow-up. The fusion rate was higher in the ACDF with plating group compared with the ACDF without plating group (90.9% vs. 63.6%; P < 0.01). One patient who received ACDF with plating and four patients who received ACDF without plating underwent revision surgery due to nonunion or bone graft dislodgement. No recurrence of pyogenic spondylodiscitis occurred in either group. CONCLUSION: ACDF with plating showed better surgical outcomes compared with ACDF without plating for CPS. We recommend the use of anterior cervical plating, which can provide biomechanical stability, for better healing of CPS. To our knowledge, this is the largest surgical case series of CPS. LEVEL OF EVIDENCE: 4.

Effects of Processed Polygonum multiflorum with KIOM Patent on Bone Remodeling-Related Protein Expression in Human Osteoblast-Like SaOS-2 Cells.

This present study evaluated the effects of processed P. multiflorum on osteogenesis using Sarcoma osteogenic (SaOS-2) cell lines and osteoclastogenesis of bone marrow-derived macrophage cells (BMM) and to elucidate differences in effect on the expression of bone-related proteins between commercially sold P. multiflorum and patented, in vitro-propagated Korea Institute of Oriental Medicine (KIOM) P. multiflorum. Raw P. multiflorum and P. multiflorum that were stir-baked and steamed in black bean juice were compared, and western blotting analysis was performed to investigate the expression of bone remodeling-related proteins in SaOS-2 cells. In the cells treated with P. multiflorum steamed in black bean juice, the expression of RANKL was decreased, whereas that of osteoprotegerin, alkaline phosphatase, Runx2, and osterix was increased. Owing to these results, we conclude that processed P. multiflorum can be used as an alternative treatment for bone diseases such as osteoporosis, osteopenia, periodontitis, and Paget's disease.

Correlation between performance of QM/MM docking and simple classification of binding sites.

Use of SiteMap for binding site classification and its connection to QM/MM (quantum mechanics/ molecular mechanics) docking performance were investigated. Using the hydrophilic/hydrophobic character values along with balance between them which SiteMap calculates, we sorted 455 cocrystal complexes available from protein data bank into three groups and tested how Glide, a conventional docking program, and QPLD, a QM/MM docking program, perform on them. QPLD showed improvements on all three groups over Glide but with varying degrees. Analysis of the results was carried out, and establishment of correlations between the classification of binding sites and QM/MM docking performance was attempted. It was found that QM/MM docking delivers the most improvements for primarily hydrophobic binding sites with substantial hydrophilic interactions. Based on our findings, we make suggestions for use of QM/MM docking and directions for further developments.

Quantum mechanical scoring for protein docking.

We develop a docking protocol based on quantum mechanical/molecular mechanical calculations in which quantum mechanical energy is used as scoring. We test the protocol with three groups of examples with various binding site characteristics. The new docking method performs as well as or better than conventional docking methods in all three groups. In particular, for proteins with primarily hydrophobic binding sites, structural motifs with possible pi-pi interactions are often found and it is shown that these can be better modeled with quantum mechanical scoring docking than force field based methods. It seems that the new method performs in such cases to a great accuracy.

Pharmacophore-based 3D-QSAR of HIF-1 inhibitors.

(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of hypoxia-inducible factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q(2) = 0.564, r(2)=0.945; CoMSIA: q(2) = 0.575, r(2)=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors.

Reconstruction of neglected Achilles tendon rupture using the flexor hallucis tendon.

Neglected ruptures of the Achilles tendon (AT) are not common and have a greater tendency to cause complications and to produce poorer functional results than fresh ruptures. Numerous surgical procedures have been described for the reconstruction of neglected AT ruptures. However, no report has been issued about an AT rupture neglected for more than 2 years. The authors reported about three patients (four tendons) with a neglected AT rupture of mean duration of 5 years, who were treated by interposed scar tissue repair combined with flexor hallucis longus tendon transfer. All patients experienced good clinical results and were satisfied with surgery.

Outcome of unilateral versus simultaneous correction for hallux valgus.

BACKGROUND: Hallux valgus surgery has been performed on only one side, even though patients may have bilateral hallux valgus. This study evaluated the results of simultaneous surgical correction for bilateral hallux valgus compared with unilateral correction. MATERIALS AND METHODS: A retrospective review of 52 patients (69 feet) that underwent proximal metatarsal chevron osteotomy and distal soft tissue procedure for moderate to severe hallux valgus was conducted. Minimum followup was at least 12 months. Patients were divided into two groups, simultaneous bilateral surgical group (Group A) and a unilateral surgical group (Group B). Group A comprised 34 feet in 17 women and Group B comprised 35 feet in 35 women. RESULTS: Average AOFAS scores were 57.0 points in group A and 52.8 points in group B preoperatively and at the last follow-up improved to 93.4 points and 92.2 points, respectively. Very satisfied or satisfied levels of patient satisfaction were 94.1% in Group A and 91.4% in Group B. Average hallux valgus angles in Groups A and B changed from 34.8 degrees and 37.9 degrees preoperatively to 12.5 degrees and 12.4 degrees postoperatively, respectively. Intermetatarsal 1-2 angles in Groups A and B changed from an average of 15.7 degrees and 18.4 degrees preoperatively to 7.4 degrees and 7.1 degrees postoperatively, respectively. No significant inter-group differences were observed in clinical and radiographic outcomes. CONCLUSIONS: Based on our results, the results of simultaneous bilateral correction for hallux valgus deformity was not worse than a unilateral correction. We advocate simultaneous correction for bilateral hallux valgus requiring surgical correction.