Nucleic acid-induced potentiation of matrix metalloproteinase-9 enzymatic activity.

Matrix metalloproteinases (MMPs) play varied roles in normal biology and diseases where, depending on the context, both inhibition and enhancement of the enzymatic activity may be beneficial. However, there are very few reports of positive modulators of MMP activity. We report that polynucleotides, including single-stranded DNA, RNA, and even double-stranded DNA, bind to and enhance the enzymatic activity of MMP9. This enhancement of MMP9 catalytic activity is not shared by biologically active polycationic molecules suggesting nonspecific charge screening as an unlikely mechanism. Deletion construct and MMP1, 2, and 3 studies suggest that the type-II fibronectin repeat domains of the enzyme appear to play a role in mediating the nucleotide potentiation of MMP9 activity. Single-stranded DNA enhances nerve growth factor-induced MMP9-dependent neurite extension in pheochromocytoma 12 cells providing evidence for potential biological significance of the nucleotide-mediated allosteric enhancement of the catalytic activity.

[The Effect of Dexamethasone on Postoperative Nausea and Vomiting in Posterior Correction and Fusion Surgery for Adolescent Idiopathic Scoliosis].

BACKGROUND: Although dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in both adults and children, the evidence in children is mainly from minor, short surgical proce- dures such as tonsillectomy and strabismus surgery. METHODS: In this study, we reviewed medical re- cords of patients who had undergone posterior correc- tion and fusion surgery for adolescent idiopathic scoio- sis at our institution and evaluated the effect of dexa- methasone on PONV prophylaxis. RESULTS: Four of 11(36%) patients who had received prophylactic dexamethasone and 26 of 33 (79%) pa- tients who had not received dexamethasone developed PONV during the first 72 hours of surgery (OR 0.15 [95% CI : 0.04-0.681, P=0.02). Without dexametha- sone, 76% patients developed PONV within 24 hr of surgery. Although the incidence gradually declined, 24% of patients still developed PONV even later than 48 hr after surgery. In contrast the incidence of PONV during the first 24 hr in patients who had received dexamethasone was 36%, and none of them experi- enced PONV after 24 hr. CONCLUSIONS: The results of this study suggest that dexamethasone is effective in reducing PONV in chil- dren and adolescents undergoing posterior correction and fusion surgery for scoliosis. A randomized con- trolled trial is needed to confirm the findings of this study.

[Management of Pulmonary Blood Flow for a Patient with Congenital Pulmonary Vein Stenosis Undergoing Pulmonary Venous Obstruction Release and Pulmonary Artery Banding].

Congenital pulmonary vein stenosis (CPVS) is a rare fetal congenital heart disease with a prevalence of 1.7 per 100,000 children younger than two years of age. Because of the difficulty of maintaining the pulmonary blood flow, CPVS is associated with a 50% survival rate within five years of diagnosis. We describe a successful management of pulmonary blood flow for a 4-month-old-girl with CPVS, combined with atrial septal defect and ventricular septal defect, undergoing pulmonary vein obstruction release (PVOR). In this case, CPVS was the only cause for pulmonary hypertension because there was no significant pressure gradient between each pulmonary capillary wedge pressure and the paired pulmonary vein pressure, indicating the normal pulmonary vascular structure prior to pulmonary vein stenosis. As pulmonary blood flow was estimated to be high after PVOR, pulmonary artery banding was also performed. Management of pulmonary blood flow is the most important issue for anesthesia of this surgery, especially in postcardiopulmonary bypass period, when the pulmonary vasoconstriction is induced by endothelial dysfuncion.

[Anesthetic management of a patient with severe subcutaneous and mediastinal emphysema due to pertussis infection].

A 20-month-old girl, with respiratory failure due to severe subcutaneous and mediastinal emphysema, was scheduled to undergo percutaneous drainage of emphysema and induction of extracorporeal membrane oxygenation. Paroxysm, a symptom of the infection of Bordetella pertussis, was the cause of emphysema. In patients with severe neck subcutaneous emphysema, management of difficult airway is the most important safety issue in the practice of anesthesia. Following the American Society of Anesthesiologist (ASA) guidelines for management of difficult airway, we prepared various types of equipment to facilitate intubation and surgeons were beside the patient during induction of anesthesia for emergency invasive airway access. To prevent the progression of emphysema, preservation of spontaneous breathing during the perioperative period was also important. Combined with propofol and midazolam, pethidine was an effective agent for safe anesthetic induction because it produces less respiratory depression compared to other opiate analgesics. In conclusion, this case demonstrates the importance of prediction of and preparation for difficult airway. Furthermore, anesthesiologists should consider the optimization of anesthesia to avoid progression of emphysema.

Effects of prophylactic dexamethasone on postoperative nausea and vomiting in scoliosis correction surgery: a double-blind, randomized, placebo-controlled clinical trial.

Dexamethasone is widely used for postoperative nausea and vomiting (PONV) prophylaxis, but its effect on PONV prevention in paediatric patients is validated only in short minor surgical procedures. In this study, we aimed to determine whether a single dose of dexamethasone reduces PONV in highly invasive surgeries that require opioid-based postoperative analgesia. One hundred adolescents undergoing scoliosis correction surgery were randomized to receive intravenous dexamethasone 0.15 mg/kg (dexamethasone group) or saline (control group) at induction of anaesthesia. The primary outcome was the incidence of PONV in the 72 h postoperatively. Data for 98 patients were available for analysis. The 72-h incidence of PONV was significantly lower in the dexamethasone group than in the control group (62.5% vs 84.0%; RR 0.74, 95% CI 0.58-0.96, P = 0.02). During the first and second 24-h postoperative intervals, fewer patients in the dexamethasone group received rescue antiemetics. Visual analogue scale scores for nausea and pain were lower in the dexamethasone group than in the control group during the first 24 h postoperatively. Dexamethasone did not increase the number of adverse events. The results of this study showed that a single dose of dexamethasone was effective for reducing PONV after paediatric scoliosis correction surgery.

dCas9-mediated transcriptional activation of tissue inhibitor of metalloproteinases.

Selective gene activation with the dCas9 (deactivated clustered regularly interspaced short palindromic repeats [CRISPR] associated protein 9)/CRISPR targeting of a transcriptional activator effector is now well established. However, the optimal targeting of guide RNA (gRNA) for a given gene is largely a matter of trial and error. We explored the optimal targeting site for tissue inhibitor of metalloproteinases (TIMPs) by first screening multiple gRNA target sites using a luciferase-based promoter-reporter system and next confirmed the effective TIMP induction in the mouse motor neuron-like neuron-enriched spinal cord 34 (NSC34) cells. Screening of many gRNAs targeting the 1-1.9 kB promoter regions of TIMP1-3 identified several hot-spots for optimal gene induction, however, no general pattern defining the optimal target site with respect to the proximity of known transcription factor binding sites or distance from the start ATG was apparent. TIMP2 with a larger basal transcriptional activity showed a greater fold-induction with gRNA compared with TIMP1 or 3 supporting the importance of an open-chromatin for best gRNA-mediated transcriptional induction. The rank order of induction potency for different gRNA identified in the promoter-reporter screening held true for the NSC34 cells. Co-activation with multiple gRNAs greatly increased the gene induction.