Therapeutic Effect of HDAC5 Binding and Cell Penetrating Peptide for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic anti-inflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-α and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION: These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with anti-inflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

Synthesis and neuroprotective effects of H2S-donor-peptide hybrids on hippocampal neuronal cells.

Hydrogen sulfide (H2S) has emerged as an endogenous signaling molecule that functions in many physiological and pathological processes of human cells in health and disease, including neuromodulation and neuroprotection, inflammation, angiogenesis, and vasorelaxation. The limited clinical applications of current H2S donors have led to the development of H2S donor hybrid compounds that combine current H2S donors with bioactive molecules. Finely tuned multi-targeting hybrid molecules have been shown to have complementary neuroprotective effects against reactive oxygen species (ROS)-induced oxidative stress. In this study, we developed hybrid molecules combining a dithiolethione-based slow-releasing H2S donor that exerts neuroprotective effects, with the tripeptides glycyl-L-histidyl-l-lysine (GHK) and L-alanyl-L-cystinyl-l-glutamine (ACQ), two natural products that exhibit powerful antioxidant effects. In particular, a hybrid combination of a dithiolethione-based slow-releasing H2S donor and ACQ exhibited significant neuroprotective effects against glutamate-induced oxidative damage in HT22 hippocampal neuronal cells. This hybrid remarkably suppressed Ca2+ accumulation and ROS production. Furthermore, it efficiently inhibited apoptotic neuronal cell death by blocking apoptosis-inducing factor release and its translocation to the nucleus. These results indicate that the hybrid efficiently inhibited apoptotic neuronal cell damage by complementary neuroprotective actions.

The effects of adjuvant intrathecal fentanyl on postoperative pain and rebound pain for anorectal surgery under saddle anesthesia.

BACKGROUND: Intrathecal opioid has been known to enhance the quality and prolong the duration of spinal anesthesia, as well as to reduce postoperative pain. The purpose of this study was to evaluate postoperative analgesic characteristics of intrathecal fentanyl for the first 48 hours after anorectal surgery under saddle anesthesia. METHODS: Eighty patients were recruited in our study. Forty patients were randomly allocated to group B that received 0.5% bupivacaine 5 mg with 0.3 ml normal saline. The other 40 patients were assigned to group BF which was given 0.5% bupivacaine 5 mg with fentanyl 15 µg. The primary outcome variable was a numeric rating scale (NRS) at six hours postoperatively. Secondary outcomes included changes in the NRS score between one and 48 hours postoperatively, consumption of rescue analgesics, and the frequency of rebound pain. RESULTS: Group BF exhibited a lower mean NRS score at postoperative six hours compared to group B (P < 0.001). However, the mean NRS score was not different after postoperative six hours between the two groups. The median consumption of rescue analgesics in group BF was less than that of group B (P = 0.028) and the frequency of rebound pain decreased in group BF when compared to group B (P = 0.021). The levels of sensory block were S1 dermatome and motor block scores were 0 for both groups. There was no significant difference in adverse effects between the groups. CONCLUSIONS: Intrathecal fentanyl 15 µg for anorectal surgery under saddle anesthesia led to an improved pain score for the first six hours after surgery and decreased postoperative analgesic use. Rebound pain diminished with intrathecal fentanyl and adverse effects did not increase.

Can an Anchored Cage be Substituted for an Anterior Cervical Plate and Screw for Single-Level Anterior Cervical Fusion Surgery?: Prediction of Poor Candidates Through a Review of Early Clinical and Radiologic Outcomes.

STUDY DESIGN: This is a case series of device failure patients. OBJECTIVE: To identify poor candidates for anterior cervical discectomy and fusion (ACDF) using an anchored cage. SUMMARY OF BACKGROUND DATA: An anchored cage has been used as an alternative implant for ACDF surgery because of ease of use, relatively acceptable fusion rate, and lower risk of plate-related complications, including dysphagia. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of 36 patients who underwent ACDF using an anchored cage between January 2012 and December 2013. The initial diagnoses included 8 traumatic soft disk herniations without posterior ligamentous complex injury, 25 degenerative soft disk herniations, 1 degenerative foraminal stenosis, 1 traumatic soft disk herniation after reducing a unilaterally dislocated facet joint, and 1 subluxation of a previously implanted cervical artificial disk. We encountered 5 cases with poor outcomes and performed 3 revisions on the index level. We reviewed the clinical and radiologic data for 31 patients with reasonable outcomes and reviewed the failed 5 cases separately. RESULTS: Among the 31 patients with reasonable outcomes, all the clinical parameters improved. For the radiologic outcomes, 10 cases of cage subsidence occurred and no patient experienced instability.Among the 5 patients with poor outcomes, 1 patient had traumatic soft disk herniation and a reduced unilaterally dislocated facet joint, 1 patient had subluxation of a previously implanted cervical artificial disk, and 3 patients had degenerative soft disk herniation and poor bone quality. Although 3 patients required revision surgeries, 2 patients showed only radiologic failures without revision. CONCLUSIONS: We analyzed the short-term outcomes of ACDF using an anchored cage and observed 5 patients with poor outcomes among 36 patients. We recommend the use of a single anchored cage for patients with definite evidence of posterior column stability and healthy bone. LEVEL OF EVIDENCE: Level 3.

Surgical Treatment of a Life-Threatening Large Retropharyngeal Hematoma after Minor Trauma : Two Case Reports and a Literature Review.

Only a few cases of anterior longitudinal ligament (ALL) injury related with retropharyngeal hematoma without fracture have previously been reported. The treatment of choice for retropharyngeal hematoma is generally considered to be conservative care, but we believe that early surgery of this pathology would be better in certain situations. Here, we describe two cases with life-threatening large retropharyngeal hematomas related with ALL injuries and operated on at an early stage. Two previously healthy patients visited the emergency room with neck pain and dyspnea after falling. Serious neck swelling was observed and lateral neck X-ray showed severe widening of the prevertebral space. Due to dyspnea progression, emergency endotracheal intubation was performed. Although there was no primary cause of the retropharyngeal hematoma on preoperative examination, ALL tearing was intraoperatively confirmed during early surgery. The in-hospital evolutions of the patients were favorable after surgery. We should bear in mind the possibility of ALL injury and perform early surgery where possible given the earlier convalescence and good prognosis.

Protective effect of artemisia asiatica extract against renal ischemia-reperfusion injury in mice.

OBJECTIVES: An extract of Artemisia asiatica was reported to possess antioxidative and cytoprotective actions in various experiments. Ischemia-reperfusion injury remains a major problem in kidney transplant, and the inflammatory response to ischemia-reperfusion injury exacerbates the resultant renal injury. In the present study, we investigated whether an extract of Artemisia asiatica exhibits renoprotective effects against ischemia-reperfusion-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. An extract of Artemisia asiatica (100 mg/kg oral) was administered 4 days before ischemia-reperfusion injury. Sham operation and phosphate-buffered saline were used as controls. Blood and renal tissues were evaluated at 48 hours after ischemiareperfusion injury. RESULTS: Treatment with an extract of Artemisia asiatica significantly decreased blood urea nitrogen, serum creatinine levels, and kidney tubular injury (P ≤ .05). Western blot showed that an extract of Artemisia asiatica significantly increased the level of heme oxygenase-1 and B-cell lymphoma 2 at 48 hours after ischemia-reperfusion injury and attenuated the level of inducible nitric oxide synthase. CONCLUSIONS: An extract of Artemisia asiatica improves acute renal ischemia-reperfusion injury by reducing inflammation and apoptosis. These findings suggest that an extract of Artemisia asiatica is a potential therapeutic agent against acute ischemia-induced renal damage.

A unilateral open door laminoplasty technique: prospective analysis of the relationship between midline extensor muscle preservation and postoperative neck pain.

Since laminoplasty was first introduced, several techniques have been developed to reduce postoperative neck pain and progressive kyphosis following this procedure. We describe the importance of deep muscle preservation to prevent postoperative neck pain following cervical posterior surgery, using the inter-muscular plane. We performed cervical laminoplasty on 10 patients from March to July 2012. The mean follow-up duration was 14.6 (range 12-18) months, and the mean age was 58.8 (48-68) years. There were eight men and two women in the study cohort, which consisted of eight cases of cervical spondylotic myelopathy and two cases of ossification of the posterior longitudinal ligament. The Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) score were assessed before and at 6 and 12 months after surgery. The numeric rating scale (NRS) for neck pain was evaluated at 1, 3, 6, and 12 months after surgery. CT scan was performed immediately after the operation, and a radiograph was performed preoperatively and during the follow-up evaluation at 1, 3, 6, and 12 months after surgery. The preoperative JOA and NDI scores improved in all patients. Although there were two patients who complained of moderate postoperative neck pain (NRS 4 and 5), their condition gradually improved. Seven patients had mild or no neck pain (below NRS 3) at the 12 month follow-up. In addition, the cervical alignment was well maintained in all but one patient. Although larger prospective cohorts, longer follow-up periods, and comparative analyses are still needed, the clinical and radiological outcomes observed in the short 12 month period in this small cohort are promising.

Systemic capillary leak syndrome under general anesthesia: a case report.

Systemic capillary leak syndrome (SCLS) is very rare and lethal disease and only 150 cases have been reported after the first publication of its report in 1960 by Clarkson. SCLS is characterized by hemoconcentation and hypoalbuminemia caused by reversible plasma extravasation. Its mechanism is unknown, but transient dysfunction of the endothelium is the most suspected cause and trigger of this event may cause immunologic disarrangement. After recovery of endothelial function, fluid injected during the shock period is redistributed and can cause severe pulmonary edema. SCLS should be considered in patients with acute and severe hypotension with hemoconcentration and hypoalbuminemia without obvious cardiac dysfunction. Especially we should take into account the possibility of SCLS if fluid replacement does not work or the shock state is aggravated despite aggressive fluid resuscitation and vasopressor administration. SCLS itself is a very rare disease; furthermore, SCLS that develops during well-controlled surgery is even more rare. So we report this case with review of the literature.

Lumbar plexopathy after radical nephrectomy -A case report-.

Lumbar plexopathy is characterized by an abrupt onset of sensory disturbances, weakness, and loss of deep tendon reflexes of lower extremities. The various causes of lumbar plexopathy include trauma, infections, space-occupying lesion, vascular diseases, metabolic diseases, and the use of drugs such as heroin. Postoperative rhabdomyolysis occurs secondary to prolonged muscle compression due to surgical positioning. Herein, we report a case of lumbar plexopathy, complicating an injury to the paraspinal muscle and iliopsoas muscle that occurred in the flexed lateral decubitus position following radical nephrectomy.