Comparison of the efficacy of 0.9% normal saline with balanced crystalloid (Plasmalyte) in maintaining the metabolic profile in head injury patients undergoing evacuation of acute subdural haematoma - A randomised controlled trial.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Comparison of Dexmedetomidine Versus Fentanyl-Based Anesthetic Protocols Under Patient State Index Guidance in Patients Undergoing Elective Neurosurgical Procedures with Intraoperative Neurophysiological Monitoring.

Objectives The study was designed to elucidate the effects of dexmedetomidine as an anesthetic adjunct to propofol in total intravenous anesthesia (TIVA) on anesthetic dose reduction, the quality of intraoperative neurophysiological monitoring (IONM) recordings, analgesic requirements, and recovery parameters in patients undergoing neurosurgical procedures with neurophysiological monitoring. Methods A total of 54 patients for elective neurosurgical procedures with IONM were randomized to group D (dexmedetomidine) and group F (fentanyl). A loading dose of the study drug of 1µg/kg followed by 0.5 µg/kg/h infusion was used in two groups. Propofol-based TIVA with a Schneider target-controlled infusion model was used for induction and maintenance with effect site concentration of 4-5 and 2.5-4 µg/mL, respectively, titrated to a Patient State Index (PSI) of 25-40. Baseline IONM recordings were obtained after induction. The mean propofol consumption, number of patient movements, quality of IONM recordings, number of fentanyl boluses, hemodynamic characteristics, and recovery parameters were recorded. Results The mean propofol consumption was significantly lower in group D when compared to group F (101.4 ± 13.5 µg/kg/min vs 148.0 ± 29.8 µg/kg/min). Baseline IONM recordings were acquired in all patients without any difficulty. The two groups were comparable with respect to the number of additional boluses of fentanyl, patient movements, and recovery characteristics. Conclusion Dexmedetomidine as an adjuvant to propofol in TIVA reduces the requirement of the latter, without affecting the IONM recordings. The addition of dexmedetomidine also ensures stable hemodynamics and decreases the requirement of opioids with similar recovery characteristics.

Comparison of two techniques of goal directed fluid therapy in elective neurosurgical patients - a randomized controlled study.

BACKGROUND: Goal directed fluid therapy (GDFT) may be a rational approach to adopt in neurosurgical patients, in whom intravascular volume optimization is of utmost importance. Most of the parameters used to guide GDFT are derived invasively. We postulated that the total volume of intraoperative intravenous fluid administered during elective craniotomy for supratentorial brain tumours would be comparable between two groups receiving GDFT guided either by the non-invasively derived plethysmography variability index (PVI) or by stroke volume variation (SVV). METHODS: 60 ASA category 1, 2 and 3 patients between 18 and 70 years of age were randomized to receive intraoperative fluid guided either by SVV (SVV group; n = 31) or PVI (PVI group; n = 29). The total volume of fluid administered intraoperatively was recorded. Serum creatinine was measured before the surgery, at the end of the surgery, 24 h after surgery and on the fifth post-operative day. Arterial cannulation was performed before induction in all patients. Serum lactate was measured before induction, once in 2 h intraoperatively, at the end of the surgery and 24 h after the surgery. Brain relaxation score was assessed by the surgeon during dural opening and dural closure. Patients were followed up till discharge or death. The duration of mechanical ventilation and the duration of hospital stay was noted for all patients. RESULTS: The volume of fluid given intraoperatively was significantly higher in the SVV group (p = 0.005). The two groups were comparable with respect to serum lactate and serum creatinine measured at pre-determined time intervals. Brain relaxation score was also comparable between the groups. SVV and PVI displayed moderate to strong correlation intraoperatively. The duration of mechanical ventilation and the length of the hospital stay were comparable between the two groups. CONCLUSIONS: PVI and SVV are equally effective in guiding GDFT in adults undergoing elective craniotomy for supratentorial brain tumours.

Comparison of Postoperative Analgesic Efficacy of Ultrasound-Guided Bilateral Rectus Sheath Block With That of Local Anaesthetic Infiltration in Patients Undergoing Emergency Midline Laparotomy Surgeries: A Randomised Controlled Trial.

Purpose Rectus sheath block (RSB) is increasingly utilised as a part of multimodal analgesia in laparotomy surgeries. We proposed this study to compare the analgesic efficacy of ultrasound-guided bilateral RSB with local anaesthetic (LA) infiltration. The primary outcome was the visual analogue scale (VAS) at rest and cough. The secondary outcomes were the postoperative morphine consumption, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV) and patient satisfaction score. Methods In our prospective, single-centre, randomised clinical trial, we enrolled a total of 100 patients undergoing emergency midline laparotomy surgeries. They were randomly allocated into two groups and were administered either LA infiltration (group L, n=50) or ultrasound-guided bilateral RSB (group R, n=50) with 15-20 ml of 0.25% bupivacaine end operatively. The categorical and ordinal variables were analysed using Chi-square/ Fisher's exact test. The continuous and discrete variables were analysed using Mann-Whitney/independent Student t-test. Results The median VAS scores in the postoperative period were significantly lower with RSB when compared with LA. Statistically significant differences in median VAS scores were noticed at one hour (P<0.001), four hours (P=0.001), eight hours (P<0.001), and 12 hours (P=0.014) at rest, and at one hour (P<0.001), four hours (P<0.001) and eight hours (P<0.001) during cough. The median morphine consumption was less with RSB (P<0.001). The time to first rescue analgesia was prolonged with RSB (P<0.001). The incidence of PONV was significantly lower with RSB (P=0.027). Conclusion Bilateral ultrasound-guided RSB provides extended postoperative analgesia at rest and cough for patients undergoing emergency laparotomy surgeries when compared with LA infiltration. There was a significant reduction in morphine consumption, incidence of PONV, and prolonged time to first rescue analgesia with RSB.

Comparison of the Analgesic Efficacy of Ultrasound-Guided Superficial Serratus Anterior Plane Block With Deep Serratus Anterior Plane Block in Patients Undergoing Modified Radical Mastectomy: A Randomized Clinical Trial.

Background Acute postoperative pain after breast cancer surgery adversely affects recovery and is an independent predictor of chronic postsurgical pain in these patients. Serratus plane blocks have been found to provide analgesia to the anterior hemithorax. However, trials comparing superficial serratus plane block and deep serratus block in breast cancer surgery patients are sparse. Methodology A total of 74 female patients with American Society of Anesthesiologists physical status I and II scheduled for elective modified radical mastectomy for breast cancer were randomized into two groups. Group A patients received a superficial serratus plane block with 30 mL of 0.25% bupivacaine, and group B patients received a deep serratus plane block with 30 mL of 0.25% bupivacaine. Postoperatively, the Numerical Rating Scale (NRS) score was measured during the immediate postoperative period, after 30 minutes and at one, four, eight, 16, and 24 hours, as well as on the second and third day. After discharge, the NRS scores were recorded in the second and third weeks and then monthly once for three months. All patients received patient-controlled analgesia with intravenous (IV) morphine. The duration of analgesia, pain scores, and 24-hour morphine consumption were also noted. Results In group A, the mean duration of analgesia (hours) was 5.51 ± 1.42, whereas in group B the mean duration of analgesia (hours) was 6.69 ± 1.18 (p < 0.01). NRS scores for pain during rest at 12 and 16 hours and NRS scores for pain during cough at eight, 12, and 16 hours, as well as at the third month were significantly lower in group B. However, morphine consumption was comparable between the groups. Conclusions Deep serratus plane block was associated with better NRS scores for pain on rest and coughing and prolonged duration of analgesia after a modified radical mastectomy. We conclude that the deep serratus plane block provides superior and extended analgesia than the superficial serratus plane block after a modified radical mastectomy.

Clinical utility of ultrasonography, pulse oximetry and arterial line derived hemodynamic parameters for predicting post-induction hypotension in patients undergoing elective craniotomy for excision of brain tumors - A prospective observational study.

Background: Hypotension, which is a common adverse effect of induction of anesthesia, may be especially detrimental in neurosurgical patients. Hence, it is important to investigate hemodynamic parameters which may be useful in identifying patients at risk of hypotension, following induction. Our study was designed to assess the utility of parameters derived from ultrasonography, pulse oximeter and arterial line for predicting post-induction hypotension. Methods: The study was designed as a prospective, observational trial. Written informed consent was obtained from 100 American Society of Anesthesiologists (ASA) 1 and 2 patients, between 18-60 years of age, scheduled for elective craniotomy for brain tumors. Arterial cannula was inserted before induction of anesthesia and connected to Vigileo cardiac output monitor. Baseline stroke volume variation (SVV), stroke volume (SV), cardiac index (Ci), cardiac output (CO) and pulse pressure variation (PPV) were recorded. Plethysmography variability index (PVI) and perfusion index (PI) were obtained from the Masimo rainbow SET® Radical-7® pulse oximeter. Ultrasonographic assessment of the inferior vena cava (IVC) was performed before induction of anesthesia and again within 15 min after induction. Maximum and minimum IVC diameters (dIVCmax and dIVCmin) and collapsibility index (CI) were measured. All the other aforementioned parameters were recorded every minute starting at induction, until the 15th minute following induction. Results: PI, CI and dIVCmax were found to have the largest AUCROC for the prediction of post-induction hypotension (AUCROC 0.852, 0.823 and 0.781 respectively). Multiple logistic regression analysis revealed CI to be the most significant independent factor for the prediction of post-induction hypotension. Conclusion: Non-invasively derived hemodynamic parameters like dIVCmax, CI and PI were more accurate for the prediction of post-induction hypotension, compared to invasively derived parameters.

Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.

Nicotinamide N-methyltransferase (NNMT) is a metabolic regulator that catalyzes the methylation of nicotinamide (Nam) using the co-factor S-adenosyl-L-methionine to form 1-methyl-nicotinamide (MNA). Overexpression of NNMT and the presence of the active metabolite MNA is associated with a number of diseases including metabolic disorders. We conducted a high-throughput screening campaign that led to the identification of a tricyclic core as a potential NNMT small molecule inhibitor series. Elaborate medicinal chemistry efforts were undertaken and hundreds of analogs were synthesized to understand the structure activity relationship and structure property relationship of this tricyclic series. A lead molecule, JBSNF-000028, was identified that inhibits human and mouse NNMT activity, reduces MNA levels in mouse plasma, liver and adipose tissue, and drives insulin sensitization, glucose modulation and body weight reduction in a diet-induced obese mouse model of diabetes. The co-crystal structure showed that JBSNF-000028 binds below a hairpin structural motif at the nicotinamide pocket and stacks between Tyr-204 (from Hairpin) and Leu-164 (from central domain). JBSNF-000028 was inactive against a broad panel of targets related to metabolism and safety. Interestingly, the improvement in glucose tolerance upon treatment with JBSNF-000028 was also observed in NNMT knockout mice with diet-induced obesity, pointing towards the glucose-normalizing effect that may go beyond NNMT inhibition. JBSNF-000028 can be a potential therapeutic option for metabolic disorders and developmental studies are warranted.

Preoperative Vascular Function Assessment and Perioperative Vascular Events in Patients Posted for Elective Non-cardiac Surgeries.

Background Coronary atherosclerosis is usually asymptomatic until a major cardiac event occurs. Surgery is one of the major stress factors that play a role in hastening vascular deterioration in susceptible patients. Non-invasive tests to detect atherosclerosis and endothelial dysfunction have started gaining popularity nowadays, and of the several options, carotid artery intima-media thickness (IMT) and radial artery flow-mediated dilation (FMD) are two promising tests for detecting cardiovascular impairment. Methods This was a pilot study that was undertaken on 100 patients in a tertiary care medical center (Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry) between June 2015 and August 2016 with the aim of studying the prevalence of endothelial dysfunction and early atherosclerosis in the given population, and to find out the predictive power of preoperative vascular functional assessment in the prediction of perioperative cardiovascular events in the same population. We had selected patients who had at least two risk factors for endothelial dysfunction and were posted for elective non-cardiac surgical procedures via convenience sampling. Flow-mediated vasodilatation of the radial artery (FMD) and carotid intima-media thickness (CIMT) were measured on the previous day of surgery, while a fasting lipid profile was collected from the patients on the morning of the surgery. Endothelial dysfunction was defined as FMD<4.5%, while atherosclerosis was defined as CIMT>0.07 cm. Demographic details and baseline hemodynamic parameters of the patients were also noted preoperatively as well as intra-operatively, and patients were followed up for any major clinical adverse cardiovascular event post-operatively till they were discharged from the hospital. Results It was found that the prevalence of endothelial dysfunction was 23%, while the prevalence of early atherosclerosis was 33% in our study population. However, it was found that FMD and CIMT did not correlate with each other significantly, nor did they correlate significantly with perioperative cardiovascular events. The risk factors of the patients also did not correlate with the FMD and CIMT values of the patients in which they were impaired. Moreover, they did not have any significant correlation with the perioperative events that occurred. Conclusion The prevalence of endothelial dysfunction in our tertiary center was found to be 23%, and the prevalence of atherosclerosis was 33% in patients posted for elective non-cardiac surgery who had multiple risk factors. It was also found that non-invasive preoperative vascular assessment was not quite effective as hypothesized in predicting perioperative cardiovascular events.

Effect of perineural bupivacaine infiltration on reducing inguinodynia in patients undergoing inguinal meshplasty - a randomized controlled trial.

INTRODUCTION: Inguinodynia after inguinal meshplasty is a notable complication with an incidence of 13-37%. We wanted to determine if a perineural infiltration of bupivacaine given intraoperatively would reduce the incidence of immediate postoperative pain and inguinodynia. METHODOLOGY: We have conducted a single-blinded randomized controlled trial including 100 patients with inguinal hernia. Patients in the control group received only spinal anaesthesia. The intervention group received perineural bupivacaine infiltration in addition to spinal anaesthesia. Intraoperatively Ilioinguinal, iliohypogastric, and genital branch of the genitofemoral nerve was identified and 2 mL of 0.5% bupivacaine was given perineurally along these identified nerves. Presence of inguinodynia, immediate post-operative pain scores using the Wong-Baker faces pain scale, duration of analgesics use, use of additional analgesics along with Paracetamol 500 mg tablet, and the length of hospital stay between the groups were recorded. RESULTS: 100 patients were randomized in the study, 49 in control and 51 in the intervention group. Both the group was comparable in terms of demographic characteristics. The intervention group had significantly lower median pain score at 3 h [4 ± 1.662 vs. 6 ± 1.55; p = .0001] and 6 h [4 ± 1.33 vs. 6 ± 1.307; p = .0001]. The incidence of inguinodynia did not significantly differ between the two groups (p-value = .12). CONCLUSION: Intraoperative Perineural bupivacaine infiltration significantly reduces the immediate postoperative pain. However, there was no significant reduction in the incidence of inguinodynia or additional analgesic requirement.

Ease of lumbar epidural catheter insertion with prepuncture ultrasound as guidance compared with conventional palpatory technique when performed by anesthesiology residents: A randomized controlled trial.

BACKGROUND AND AIMS: Lumbar epidural catheter insertion is conventionally performed by anesthesia residents by palpation of anatomical landmarks with relatively blind localization of epidural space which may lead to an increase in failure rate. We aim to compare the ease of lumbar epidural catheterization using prepuncture ultrasound as guidance with that of conventional palpatory technique. Comparisons were made with reference to number of insertion attempts, total time taken for the procedure, frequency of dural puncture, and overall satisfaction score as assessed by Likert's scale. MATERIAL AND METHODS: Eighty, ASA 1-3, patients undergoing elective surgeries requiring lumbar epidural catheterization were recruited for the study. Study participants were randomized into two groups. In group P, epidural catheterization was performed using the conventional palpatory method and in group U, it was performed with the help of ultrasound determined parameters. Number of insertion attempts, total time taken for successful insertion of epidural catheter, frequency of dural puncture, and overall satisfaction of ease of insertion as determined by Likert's scale were compared between both the groups. Data were analyzed using SPSS statistical software version 17 and P value <0.05 was considered statistically significant. RESULTS: The number of insertion attempts was significantly lesser in Group U (P = 0.019). The total procedure time was significantly higher in group U (P < .001). There was no significant difference in ease of insertion score, as measured by Likert's scale between both the groups (P = 0.45). CONCLUSION: Prepuncture ultrasound guidance improves the first attempt success rate of lumbar epidural catheterization with reduced incidence of dural puncture with similar overall satisfaction score but increases the total time taken for the procedure when compared to conventional palpatory technique.

Evaluation of Cognitive and Psychomotor Functional Changes in Anesthesiology Residents after 12 hours of Continuous Work in Operation Theater: An Observational Study.

Background: Prolonged working hours in operation theater may impair cognitive and psychomotor function. Aims: This study was done to evaluate the changes in cognitive and psychomotor changes in the anesthesia residents after 6 and 12 h of continuous work in operation theater. Settings and Design: Sixty anesthesia residents whose working hours were expected to be longer than 12 h were recruited for this prospective, observational study. Methods: The study consisted of a set of five tests used for assessing the cognitive and psychomotor functions. The tests were conducted for the participants at 0, 6, and 12 h of work and the total scores at the respective time period were noted. The tests were manual dexterity test using purdue peg board, finger tapping test, visual spatial capacity memory test, digit symbol substitution test (DSST), and frontal assessment battery. Statistical Analysis: The observations of the purdue peg board test, finger tapping test, and digit symbol substitution test at 0, 6, and 12 h were tested using the repeated measures analysis of variance and paired t-test. The observations of visual spatial capacity memory test and frontal assessment battery were tested using the Chi-square test. Results: In the purdue peg board test, there was significant reduction in the mean number of pins assembled by the participants over 12 h of work. There was a significant difference in the number of finger taps by the dominant hand between 0 and 12 h and also between 6 and 12 h. In the visual spatial memory test, there was no significant difference in the performance of the participants with incorrect response at 0 and 12 h of duration. There was a significant decrease in the number of correct response among the participants in the digit symbol substitution test at 0 and 12 h of work. There was no significant difference in the scores obtained in frontal assessment battery test which was used to assess the cognitive function. Conclusion: There was a significant reduction in the psychomotor functions of the anesthesiology residents after 12 continuous hours of work in the operation theater and there was no significant reduction in cognitive function observed during that period.

Evaluation of Neuromuscular Blockade with Vecuronium during General Anesthesia with Oxygen, Nitrous Oxide, Isoflurane versus Oxygen, Air, Isoflurane: A Randomized Controlled Study.

BACKGROUND: The use of air oxygen mixture with isoflurane has become more common in the place of nitrous oxide, especially in laparoscopic and abdominal surgeries. With a varied mixture of gases and isoflurane used in general anesthesia, the exact dosing requirement and time duration of action have not been precisely studied with vecuronium when given as a bolus, as is given routinely. PURPOSE: This study was undertaken to evaluate and compare the neuromuscular effect of vecuronium during anesthesia with oxygen, nitrous oxide and isoflurane versus oxygen, air and isoflurane. METHODOLOGY: The study was a prospective, randomized controlled trial on 70 patients allocated into two groups as follows: Group N (nitrous oxide group) and Group A (medical air group). The primary objective was to measure and compare the posttetanic count (PTC1) - train of four (TOF1) interval, to evaluate the time taken for recovery from the intense blockade in both groups. The secondary objectives were to compare time duration for twitch height depression to be 30% of baseline after administering vecuronium, time duration from vecuronium administration to appearance of the first PTC1, PTC (n) at the reappearance of the 1st twitch, time interval between TOF1 and TOF3 and time from vecuronium administration to appearance of TOF3 in both the groups. RESULTS: There is no significant difference between both the groups with reference to the block onset time using 30% depression of single twitch and recovery time from neuromuscular blockade using PTC, PTC1-TOF1 and TOF1-TOF3 time intervals. CONCLUSION: Measuring and comparing neuromuscular transmission monitoring parameters such as the onset time(ST depression to 30%), and recovery using PTC, PTC1-TOF1 and TOF1-TOF3 time intervals, it is concluded that the character of neuromuscular block with vecuronium is unaffected and not prolonged with or without nitrous oxide when used with isoflurane.

A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease. In mice with high fat diet (HFD)-induced obesity, JBSNF-000088 treatment caused a reduction in body weight, improved insulin sensitivity and normalized glucose tolerance to the level of lean control mice. These effects were not seen in NNMT knockout mice on HFD, confirming specificity of JBSNF-000088. The compound also improved glucose handling in ob/ob and db/db mice albeit to a lesser extent and in the absence of weight loss. Co-crystal structure analysis revealed the presence of the N-methylated product of JBSNF-000088 bound to the NNMT protein. The N-methylated product was also detected in the plasma of mice treated with JBSNF-000088. Hence, JBSNF-000088 may act as a slow-turnover substrate analog, driving the observed metabolic benefits.

Anaesthetic Implications of Severe Hyperthyroidism Secondary to Molar Pregnancy: A Case Report and Review of Literature.

Pregnant women with gestational trophoblastic disease have an increased likelihood to develop hyperthyroidism secondary to increased secretion of human chorionic gonadotropin. Most of these cases of hyperthyroidism remain undiagnosed and may present as a thyrotoxic crisis during the perioperative period. Pregnant patients with gestational trophoblastic disease should be always evaluated for hyperthyroidism, and in cases of severe hyperthyroidism, antithyroid treatment should be initiated before evacuation of the mole. Anesthetic management of these cases is challenging in view of the emergency nature of the surgery and potential for thyroid crisis. Spinal anesthesia can be safely administered and has a protective role in preventing thyroid crisis.

Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide.

Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-l-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT.

Comparison of ease of administration of intranasal midazolam spray and oral midazolam syrup by parents as premedication to children undergoing elective surgery.

BACKGROUND: The efficacy of midazolam as premedication in children for providing pre-operative sedation and reducing parental separation anxiety has been well established. Many studies have compared the effectiveness and medication acceptance of midazolam via oral and intranasal routes. In this study, we have compared the ease of administration of oral midazolam syrup and intranasal midazolam spray as premedication, administered by parents to children. METHODS: Ninety children were randomly allocated into one of the two groups: group N received nasal midazolam spray 0.2 mg/kg and group O received oral midazolam syrup 0.5 mg/kg administered by the parent. The parent recorded ease of administration score and facial hedonic score. The observer recorded modified medication acceptance score. Vitals and sedation scores were assessed at specific intervals. Thirty minutes after drug administration the child was separated from the parent, and parental separation anxiety score was recorded. Mask acceptance score was recorded after application of mask upon arrival in the OT. RESULTS: Oral midazolam syrup was found to have better ease of administration than intranasal midazolam spray as felt by the parent. Medication acceptance was better for oral midazolam. Both the groups had similar sedation scores at 15 and 30 min. Children in the oral group had a better reduction in parental separation anxiety at 30 min after drug administration and better mask acceptance than the nasal group. CONCLUSION: Oral midazolam syrup is easier for parents to administer and has better medication acceptance in children when compared to intranasal midazolam spray.

Co-crystal structures of PTK6: With Dasatinib at 2.24 Å, with novel imidazo[1,2-a]pyrazin-8-amine derivative inhibitor at 1.70 Å resolution.

Human Protein tyrosine kinase 6 (PTK6)(EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed five-fold or more in human breast tumors and breast cancer cell lines but its expression being low or completely absent from normal mammary gland. There is a recent interest in targeting PTK6-positive breast cancer by developing small molecule inhibitor against PTK6. Novel imidazo[1,2-a]pyrazin-8-amines (IPA) derivative compounds and FDA approved drug, Dasatinib are reported to inhibit PTK6 kinase activity with IC50 in nM range. To understand binding mode of these compounds and key interactions that drive the potency against PTK6, one of the IPA compounds and Dasatinib were chosen to study through X-ray crystallography. The recombinant PTK6 kinase domain was purified and co-crystallized at room temperature by the sitting-drop vapor diffusion method, collected X-ray diffraction data at in-house and resolved co-crystal structure of PTK6-KD with Dasatinib at 2.24 Å and with IPA compound at 1.70 Å resolution. Both these structures are in DFG-in & αC-helix-out conformation with unambiguous electron density for Dasatinib or IPA compound bound at the ATP-binding pocket. Relative difference in potency between Dasatinib and IPA compound is delineated through the additional interactions derived from the occupation of additional pocket by Dasatinib at gatekeeper area. Refined crystallographic coordinates for the kinase domain of PTK6 in complex with IPA compound and Dasatinib have been submitted to Protein Data Bank under the accession number 5DA3 and 5H2U respectively.