Expert panel recommendations for topical hemostatic agent use in varied bleeding sites and situations during neuro-spine surgeries.

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.

Comparative Evaluation of Frictional Resistance Between Different Types of Ceramic Brackets and Stainless Steel Brackets With Teflon-Coated Stainless Steel and Stainless Steel Archwires: An In-Vitro Study.

Background Orthodontic tooth movement relies on sliding mechanics usually achieved by sliding the archwire through brackets. Sliding causes friction which is a force resisting the relative motion of two contacting objects. Frictional resistance is undesirable in orthodontic tooth movement because the archwire might bind with the bracket and prevent tooth movement. In addition, friction causes bending of the archwire leading to unwanted tooth movement or space loss through anchorage interference, prolonging the treatment time and root resorption. This study was performed to compare the frictional resistance produced by different types of ceramic brackets and stainless steel brackets with Teflon-coated stainless steel and stainless steel archwires. The surface texture of the wire before and after friction test was also evaluated using a scanning electron microscope (SEM). Methodology A total of 48 samples were tested. In total, 12 premolar brackets each of stainless steel (Ortho technology, Carlsbad, CA, USA), monocrystalline ceramic (Ortho technology, Carlsbad, CA, USA), polycrystalline ceramic (Ortho technology, Carlsbad, CA, USA), and ceramic bracket with a metal slot (Ortho technology, Carlsbad, CA, USA) having an 0.022-inch slot were coupled with 0.019 × 0.025-inch stainless steel and Teflon-coated stainless steel wires. Each bracket-wire assembly was vertically mounted and clamped to the jaws of the universal testing machine. The wire was pulled across the bracket with a cross head speed of 10 mm per minute. The readings obtained were recorded. To evaluate the surface roughness, wires were examined using an SEM (in four magnifications 250×, 500×, 1,000×, and 5,000×) before and after testing. Results Under the testing conditions, the stainless steel bracket-stainless steel wire combination produced the least frictional resistance, and the polycrystalline ceramic bracket-stainless steel wire combination produced the highest frictional resistance. Ceramic brackets with a metal slot generated lesser friction than other types of ceramic brackets but more friction than stainless steel brackets. Moreover, for all bracket-archwire combinations, Teflon-coated wires generated reduced frictional resistance compared to stainless steel wires. The surface examination of Teflon-coated stainless steel wire and conventional uncoated stainless steel wire revealed that Teflon-coated wire had a smoother surface compared to uncoated stainless steel wire. Conclusions Within the limitations of this study, it was concluded that the stainless steel bracket produced the lowest frictional resistance and the polycrystalline ceramic bracket produced the highest frictional resistance. Ceramic brackets with a metal slot showed a coefficient of friction that was more than but comparable to that of stainless steel brackets. Monocrystalline ceramic brackets generated lesser friction compared to polycrystalline ceramic brackets. Further, Teflon coating of stainless steel archwires can reduce frictional resistance compared to conventional uncoated stainless steel archwires. The surface of Teflon-coated stainless steel wires was found to be smoother than uncoated stainless steel wires.

Comparison of dexmedetomidine in two different doses on emergence agitation in children under sevoflurane anaesthesia: A double-blind randomised controlled trial.

BACKGROUND AND AIMS: Emergence agitation (EA) in children is one of the most common postoperative problems encountered in the recovery room. Sevoflurane has been strongly associated with EA owing to its lower solubility and rapid recovery. Dexmedetomidine has been found to reduce the incidence of EA. This study was designed to evaluate the effectiveness of dexmedetomidine in two doses in reducing EA in children. METHODS: This was a prospective double-blinded randomised study done on eighty children aged 5-14 years undergoing adenotonsillectomy/tonsillectomy under sevoflurane anaesthesia. Patients in Group A (n = 40) received 0.3 µg/kg/h and patients in group B (n = 40) received 0.5 µg/kg/h infusion after a bolus dose of 0.5 µg/kg of dexmedetomidine. The primary objective was to compare two different doses of dexmedetomidine on EA in the postoperative period. The secondary objectives were to assess the pain and perioperative haemodynamics in the recovery room. The anaesthesiologist blinded to the study charted the paediatric anaesthesia emergence delirium score (PAED), perioperative haemodynamic parameters, objective pain score and rescue medications if given. The data were analysed using Student's unpaired t-test, Chi-square test, repeated measures Analysis of Variance (ANOVA) and Mann-Whitney U test wherever appropriate. RESULTS: The incidence of EA was comparable between both groups (P = 0.960). The haemodynamic parameters (P > 0.05) and the objective pain score (P = 0.810) also did not show a statistically significant difference. CONCLUSION: A lower dose of dexmedetomidine (0.3 µg/kg/h) is equally effective as a higher dose (0.5 µg/kg/h) after a bolus dose of 0.5 µg/kg in decreasing EA.

Cauda Equina Syndrome: A Review of 15 Patients Who Underwent Percutaneous Transforaminal Endoscopic Lumbar Discectomy (PTELD) Under Local Anaesthesia.

INTRODUCTION: To analyse the results of Cauda Equina Syndrome (CES) operated by Percutaneous Transforaminal Endoscopic Lumbar Discectomy (PTELD). MATERIAL AND METHODS: The study is a retrospective series of 15 patients operated by PTELD. Bladder dysfunction was classified as incomplete CES (CESI) and complete CES retention (CESR). Bladder / motor recovery rate and its timing, Oswestry Disability Index (ODI), Visual Analogue Score (VAS), patient satisfaction index, and sexual dysfunction were used to measure the outcome objectively. Additionally, in CESR patients, post-void residual (PVR) urine was measured by sonography. Complications and technical problems were noted. RESULTS: There were ten patients of CESI and five patients of CESR. The average follow-up was 20.33(12.05) months. Bladder symptoms recovery was 100%, and motor recovery was 80%. VAS for back pain recovered to 0.53(0.52) from 8(2.39). VAS for leg pain recovered to 0.13(0.35) from 9.20(1.32). ODI improved to 6.07(2.85) from 77.52(13.20). The time to the recovery of bladder function was 1.47(1.55) days. All CESR patient's abnormal PVR urine was normalised at five weeks post-operative. No complications were reported. However, five technical executional problems occurred. CONCLUSION: PTELD can be considered for CES treatment due to its substantial and quick recovery advantages. However, more evidence support is needed to make it a practice recommendation.

Extending Horizon of Robotic Surgery to Bladder-Preserving Approach for Vesical Paraganglioma: Rare Case with Unusual Presentation.

Background: Vesical paraganglioma is rare and accounts for <0.1% of all urinary bladder tumors. They are mostly functional because of secretion of catecholamines and clinical presentation may mimic like a hyperfunctioning adrenal pheochromocytoma. They are easily misdiagnosed as urothelial malignancy and adequate perioperative attention is not provided. Case presentation: We hereby report a case of 55-year-old Indian lady with silent vesical paraganglioma at anatomically difficult location of bladder neck managed with robot-assisted excision of mass and bladder preservation. Conclusion: Surgery is the mainstay of the treatment that requires total excision of mass. However, minimally invasive bladder-preserving approach should be always kept as an option, if feasible. Robot assistance can help in bladder preservation even in difficult anatomic locations.

Cigarette smoking promotes cancer-related transformation of oral epithelial cells through activation of Wnt and MAPK pathway.

Aim: Study aims to investigate the effect of cigarette smoking on cancer-related transformation in oral epithelial cells of smokers through evaluating the alteration in Wnt/ß-catenin and MAPK pathways. Materials & methods: Exfoliated oral epithelial cells were collected from 138 subjects and categorized into nonsmokers, smokers and clinically diagnosed precancer and cancer patients. Real-time quantitative PCR was performed to detect the fold changes of related genes. Expressions of biomarkers were assessed using immunofluorescence and western blot. Results: Study shows significant (p < 0.001) alteration in mRNA level of TNF-α, NF-κß, FZD1, ß-catenin, PARD 3, MAPK1 and vimentin genes under cigarette smoking. Conclusion: Results suggested the progression of oral cancer under cigarette smoking occurs through multiple events and activation of canonical Wnt/MAPK pathways.

Fast Tract Anesthesia Using Isoflurane and Propofol During Off-pump Coronary Artery Bypass Graft Surgery.

This study aimed to evaluate myocardial protective effect of isoflurane and propofol as a fast tract anesthesia in off pump coronary artery bypass graft surgery by measuring postoperative cardiac enzyme Troponin-I, and liver enzyme. The study was conducted on 260 patients scheduled to undergo elective off pump coronary artery bypass graft surgery. Patients were randomly allocated to receive either isoflurane or propofol anesthesia and was aimed to extubated within 6 hours. Troponin-I levels were measured preoperatively, at arrival in postoperative intensive care unit, at 12, 24, 48, 72 hours and 4 weeks following surgery. Liver function was also assessed and compared between preoperative and postoperative values. There is no difference in Troponin-I levels between the two studies groups at observed pre and post-operative time intervals. Fast tract anesthesia using isoflurane and propofol provides same myocardial protection during and after OPCABG and overall outcome was excellent.

Pregnancy Outcome with Prosthetic Heart Valve in Bangladesh: A Retrospective Cohort Study.

The aim of this retrospective cohort study was to evaluate the occurrence of the maternal and fetal outcome during pregnancy and immediately after delivery in women with prosthetic heart valve, especially with oral anticoagulants therapy that must be weighed against the risk of intracardiac thrombosis. This study was undertaken at Department of Cardiac surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2012 to December 2017. A total of 82 pregnancies with heart valve prosthesis were evaluated in two groups: Group I (n=58) includes pregnancy with mechanical heart valve, while Group II (n=24) includes pregnancy with bioprosthetic valve. The mean age of patients was 25.7±2.5 years and 24.9±5.5 years in Group I and Group II respectively. Approximately 70% pregnancies ended in healthy live births, however about 75% of study population developed maternal complications in Group I, which is significantly higher than Group II. First trimester spontaneous miscarriage was statistically significant between two groups (p value <0.005). Mean birth weight and mean APGAR score was found normal in both study group. Majority of the patients were found in good health status during and after pregnancy. Proper antenatal care and early risk stratification are the fundamental measures to improve the maternal and fetal outcome in a patient with prosthetic heart valve.

Comparison of Effect of Airway Nebulization with Lignocaine 2% versus Ropivacaine 0.25% on Intubation and Extubation Response in Patients Undergoing Surgery under General Anesthesia: A Randomized Double-Blind Clinical Trial.

CONTEXT: Both intubation and extubation are associated with pressor response. AIMS: We aimed to evaluate if ropivacaine 0.25% nebulization would prevent hemodynamic and cough responses to intubation and extubation and compared it with lignocaine 2% and saline group. SETTINGS AND DESIGN: This was a randomized double-blind clinical trial. MATERIALS AND METHODS: A total of 75 patients classified as the American Society of Anaesthesiologists physical status Classes I and II belonging to 18-60 years were included in the randomized double-blind trial and divided into three groups; Group 1: received 5 ml of normal saline, Group 2: received 5 ml of 0.25% ropivacaine, Group 3: received 5 ml of 2% lignocaine through nebulization before the induction. Patients were then administered general anesthesia. Mean arterial pressure (MAP), heart rate (HR), and saturation were recorded at baseline (T1), at intubation (T2), upon anesthetic withdrawal (T3), upon eye opening (T4), upon extubation (T5), and 2 min after extubation (T6). Cough response was recorded at emergence and extubation. STATISTICAL ANALYSIS USED: Repeated measures analysis of variance were used to compare hemodynamic variables and Chi-square test to compare the grades of cough between the two groups. RESULTS: The drug ropivacaine was found to be effective in reducing the hemodynamic responses to both intubation and extubation when compared to saline (P < 0.05). At extubation, though the mean values of HR and MAP were lower in ropivacaine compared to lignocaine group, the difference did not achieve statistical significance (P = 0.103 and 0.153 respectively). Only 40% of patients who received ropivacaine had cough at extubation (P < 0.001). CONCLUSION: Ropivacaine when used through nebulization preinduction effectively reduced both intubation and extubation responses when compared to saline. However, there was no significant difference between the ropivacaine and lignocaine on extubation response.

A gland of diverse pathology and unpredictable behaviour: our experience of primary submandibular gland malignancies.

Submandibular gland tumours are relatively uncommon tumours and demonstrate diverse histological types and a variable prognosis. The aim of this study was to analyze our experience with submandibular malignancies over a period of 6 years (January 2009 to December 2015). Patient data from the 6-year period were reviewed retrospectively and 51 patients with submandibular malignancies were identified. Demographic data, clinicopathological details, treatment received, complications, and follow-up were recorded. The mean age of the 51 patients at presentation was 49.1 years. They were followed up for a mean 20.3 months. Nine of 47 patients (19.1%) developed distant metastasis during follow-up, while only three (6.4%) developed local recurrence. Disease-free survival at 2 years was 69.7% and overall survival at the end of 2 years was 77.8%. Actuarial 5-year survival was 57.8% when all subtypes were considered. The overall mean time to recurrence was 10 months (6-24 months). Nodal positivity was the only prognostic factor that was significant on multivariate analysis, while age, sex, perineural invasion, and grade were not. With advances in surgical and radiotherapy techniques, loco-regional control rates have improved greatly; however, effective adjuvant treatment to prevent systemic relapse is still lacking.

Comparison of Nebulized Ketamine with Nebulized Magnesium Sulfate on the Incidence of Postoperative Sore Throat.

BACKGROUND: Postoperative sore throat (POST) is a known complication following general anesthesia requiring endotracheal intubation. Its incidence ranges from 21% to 65% and remains the eighth most undesirable postoperative event. Various measures have been tried to decrease the incidence of sore throat with various success rates. AIM: This study aimed at reducing the incidence of POST with ketamine and magnesium sulfate nebulization. SETTINGS AND DESIGN: This study is a prospective randomized, double-blinded study. MATERIALS AND METHODS: After Institutional Ethics Committee approval and written informed consent, 80 patients who fulfilled the inclusion and exclusion criteria were randomly divided into two groups to receive magnesium sulfate 250 mg in 5 ml saline in Group A and ketamine 50 mg in 5 ml saline nebulization in Group B before the start of general anesthesia. All patients received standard anesthesia protocol. After extubation, all patients were enquired about the incidence and severity of sore throat at 0, 2, 4, 6, and 24 h. STATISTICAL ANALYSIS USED: Paired t-test and Wilcoxon signed-rank test were used to compare hemodynamic variables and Chi-square test to compare the incidence and severity of sore throat. RESULTS: There were no differences in the demographic profile, duration of laryngoscopy, time taken to intubate, and duration of surgery between the two groups. The incidence and severity of sore throat were significantly decreased in ketamine group at 4 and 6 h when compared to magnesium sulfate group. CONCLUSION: Nebulization with ketamine 50 mg significantly decreases the incidence of POST when compared to magnesium sulfate 250 mg.

Transversus Abdominis Plane Block versus Ilioinguinal/Iliohypogastric Nerve Block with Wound Infiltration for Postoperative Analgesia in Inguinal Hernia Surgery: A Randomized Clinical Trial.

BACKGROUND: Various analgesic modalities have been used for postoperative analgesia in patients undergoing inguinal hernia surgery. In this randomized clinical trial, we have compared the analgesic efficacy of transversus abdominis plane (TAP) block with that of ilioinguinal/iliohypogastric (IIIH) nerve block with wound infiltration in patients undergoing unilateral open inguinal hernia repair. AIM: The primary objective of this study was to compare the efficacy of postoperative analgesia of ultrasound-guided TAP block and IIIH block with wound infiltration (WI) in patients undergoing open inguinal hernia surgery. SETTINGS AND DESIGN: This was a randomized clinical trial performed in a tertiary care hospital. MATERIALS AND METHODS: Sixty patients scheduled for hernia repair were randomized into two groups, Group T and Group I. Postoperatively, under ultrasound guidance, Group T received 20 ml of 0.25% ropivacaine - TAP block and Group I received 10 ml of 0.25% ropivacaine - IIIH block + WI with 10 ml of 0.25% ropivacaine. The primary outcome measure was the time to rescue analgesia in the first 24 h postoperatively. Fentanyl along with diclofenac was given as first rescue analgesic when the patient complained of pain. STATISTICAL ANALYSIS: Statistical comparisons were performed using Student's t-test and Chi-square test. RESULTS: Mean time to rescue analgesia was 5.900 ± 1.881 h and 3.766 ± 1.754 h (P < 0.001) and the mean pain scores were 5.73 ± 0.784 and 6.03 ± 0.850 for Group TAP and IIIH + WI, respectively. Hemodynamics were stable in both the groups. One-third of the patients received one dose of paracetamol in addition to the rescue analgesic in the first 24 h. There were no complications attributed to the block. CONCLUSION: As a multimodal analgesic regimen, definitely both TAP block and IIIH block with wound infiltration have a supporting role in providing analgesia in the postoperative period for adult inguinal hernia repair. In this study, ultrasound-guided TAP block provided longer pain control postoperatively than IIIH block with WI after inguinal hernia repair. There were no complications attributed to the blocks in either of the group.

Comparison of i-gel™ and laryngeal mask airway Classic™ in terms of ease of insertion and hemodynamic response: A randomized observational study.

CONTEXT: Laryngeal mask airway (LMA) Classic™ has an inflatable cuff while i-gel™ has a noninflatable cuff made of thermoplastic elastomer. AIMS: To compare ease of insertion, number, and duration of insertion attempts among the two device. Secondary objectives were to evaluate the hemodynamic response and SpO2 during device insertion and during maintenance of general anesthesia. SETTINGS AND DESIGN: This study was conducted as randomized observational study in a teaching hospital. SUBJECTS AND METHODS: One hundred American Society of Anesthesiologists I and II, patients posted for surgery under general anesthesia were divided in two groups of fifty each. LMA Classic™ and i-gel™. Ease of insertion, duration of insertion, hemodynamic data, and episodes of hypoxia during insertion, 1, 3 and 5 min for 30 min, during removal and 1 min after removal. STATISTICAL ANALYSIS USED: Descriptive analyses were expressed as a mean ± standard deviation. Independent t-test used for parametric data, Chi-square test for nonparametric data and hemodynamic data were analyzed using repeated measures ANOVA to find statistical difference within the groups. RESULTS: Devices were easy to insert, the mean duration of insertion attempts was 15.92 ± 1.62 s in the i-gel™ group, while it was 26.06 ± 5.12 s in the LMA Classic™ group, was statistically significant (P = 0.0001). CONCLUSIONS: Successful and shorter duration of insertion, with less hemodynamic response makes i-gel™ a suitable alternative to LMA Classic™ during general anesthesia.

Left Atrial Myxoma in a Late Case of Lung Carcinoma.

Concomitant occurrence of lung carcinoma and an atrial myxoma is rare. We are reporting such a case, a 55 year old male, farmer, smoker for 30 years was under evaluation for his recent episode of stroke with hemiparesis during which an echocardiography showed presence of a left atrial myxoma and chest x-ray showed a lesion in the midzone of right lung. Fine needle aspiration cytology (FNAC) from enlarged right supraclavicular lymphnode revealed metastatic adenocarcinoma. Patient was referred to a tertiary cancer care hospital thereafter.

A Randomized Controlled Study of 0.5% Bupivacaine, 0.5% Ropivacaine and 0.75% Ropivacaine for Supraclavicular Brachial Plexus Block.

INTRODUCTION: For any surgery in the upper extremity that does not involve the shoulder, a supraclavicular block is preferred, as it is a safe procedure associated with rapid onset and reliable anaesthesia. Although ropivacaine has been extensively studied for epidural anaesthesia, very few reports exist on its use in supraclavicular brachial plexus block. AIM: This study was conducted to investigate and compare the effectiveness of supraclavicular brachial plexus anaesthesia with two different concentrations of ropivacaine (0.5% and 0.75%) and to compare them with the standard 0.5% bupivacaine. MATERIALS AND METHODS: Ninety patients of age 18 to 60 years belonging to American Society of Anaesthesiologists (ASA) status 1 or 2, admitted to Pondicherry Institute of Medical Sciences were chosen for the study and were divided into three groups. Group A received 30 ml of 0.5% bupivacaine, group B received 30 ml of 0.5% ropivacaine and group C received 30 ml of 0.75% ropivacaine into the supraclavicular region, by a nerve-stimulator technique. Onset time of each of the drug was recorded both for the sensory and motor block. Duration of sensory and motor block was recorded along with peri-operative haemodynamic monitoring. RESULTS: The onset of complete sensory and motor block observed with both ropivacaine groups and bupivacaine was similar (16.85±6.67 min in group A, 17.79±5.03 min in group B and 18.48±6.14 in group C, p>0.05); onset of motor block (21.45±4.45 min in group A, 22.23±4.05 min in group B and 22.33±5.17 in group C, p < 0.05). The duration of sensory block with 0.5% bupivacaine was 11.58 hours, with 0.5% ropivacaine was 9.02 hours with 0.75% ropivacaine was 8.87 hours (p<0.001). The duration of motor block with 0.5% bupivacaine was 12.94 hours, with 0.5% ropivacaine was 8.29 hours with 0.75% ropivacaine was 7.89 hours (p<0.001). Multiple comparison test with Bonferroni correction showed there was statistically significant difference in mean duration of sensory block between Group A (0.5% bupivacaine) and Group B (0.5% ropivacaine) and also between Group A (0.5% bupivacaine) and Group C (0.75% ropivacaine). However, there were no statistically significant difference in mean duration of sensory block between Group B (0.5% ropivacaine) and Group C (0.75% ropivacaine). The preoperative, intra operative and postoperative heart rate, systolic & diastolic blood pressure and oxygen saturation were comparable among the three study groups (p>0.05). No side effects were recorded in the study. CONCLUSION: The onset of sensory and motor block was similar in all the three groups. However, when compared to bupivacaine group, recovery of motor functions was faster in both the ropivacaine groups. Patients in all the 3 groups did not experience any adverse effects.

Perioperative management of poly-trauma in a postmitral valve replacement patient with severe left ventricular systolic dysfunction.

The anesthetic management of a patient with severe left ventricular (LV) dysfunction undergoing noncardiac surgery poses a challenge to the anesthesiologist as LV dysfunction is commonly complicated by progressive congestive heart failure and malignant arrhythmias. When the cause for LV dysfunction is postvalve replacement, additional complications such as intraoperative thrombosis, bleeding, and infective endocarditis need to be addressed perioperatively. In such situations, the anesthesiologist must have the knowledge hemodynamics, diagnostic evaluations, and treatment modalities, more so regarding various drugs used during anesthesia. We report a case of postmitral valve replaced patient with severe LV dysfunction posted for surgery of fracture of the femur and facial fractures managed successfully during anesthesia.

Cardiac Tamponade following Mitral Valve Replacement for Active Infective Endocarditis with Ring Abscess.

Periannular extension and abscess formation are rare but deadly complications of infective endocarditis (IE) with high mortality. Multimodality cardiac imaging, invasive and noninvasive, is needed to accurately define the extent of the disease. Debridement, reconstruction, and valve replacement, often performed in an emergent setting, remain the treatment of choice. Here we present a case of severe IE in a 29-year-old intravenous drug user who after undergoing debridement of the abscess, annular reconstruction, and mitral valve replacement (MVR) presented with recurrence of shortness of breath and pedal edema. Transthoracic echocardiogram (TTE) showed a 6.2 × 5.5 cm cavity, posterior to and communicating with the left ventricle through a 3 cm wide fistulous opening, in proximity of the reconstructed mitral annulus. The patient underwent a redo MVR with patch closure of the fistulous opening, with good clinical outcome. This case highlights the classic TTE findings and the necessity for close follow-up in the perioperative period in patients undergoing surgery for periannular extension of infection. A cardiac magnetic resonance imaging can be considered, preoperatively, in such cases to identify the extent of myocardial involvement and surgical planning.

p47phox and reactive oxygen species production modulate expression of microRNA-451 in macrophages.

The production of microRNAs (miRNA) is influenced by various stimuli, including environmental stresses. We hypothesized that reactive oxygen species (ROS)-associated stress could regulate macrophage miRNA synthesis. miRNAs undergo unique steps of maturation processing through either one of two pathways of cytoplasmic processing. Unlike the canonical pathway, the regulation of alternative cytoplasmic processing of miRNA has not been fully elucidated yet. We cultured bone marrow derived macrophages (BMDM) from wild type (WT) and p47(phox-/-) mice and profiled miRNA expression using microarrays. We analyzed 375 miRNAs including four endogenous controls to normalize the data. At resting state, p47(phox-/-) BMDM has the markedly reduced expression of miR-451 compared to WT BMDM, without other significant differences. Unlike majority of miRNAs, miR-451 goes through the unique alternative processing pathway, in which Ago2 plays a key role. In spite of significant reduction of mature miR-451, however, its precursor form, pre-mir-451, was similar in both BMDMs, suggesting that the processing of pre-mir-451 is impaired in p47(phox-/-) BMDM. Moreover, p47(phox-/-) BMDM expressed significantly reduced level of Ago2. In contrast, Ago2 mRNA levels were similar in WT and p47(phox-/-) BMDM, suggesting a post-transcriptional defect of Ago2 production in p47(phox-/-) macrophages, which resulted in impaired processing of pre-miR-451. In order to examine the functional significance of miR-451 in macrophages, we cultured BMDMs from miR-451 knock-out mice. Of interest, miR-451-deficient BMDM exhibited reduced ROS generation upon zymosan stimulation, compared to WT BMDM. Our studies suggest functional crosstalk between ROS and miR-451 in the regulation of macrophage oxidant stress.