To evaluate the analgesic activity of resveratrol in different doses in animal model

Background: Pain is a complex unpleasant phenomenon composed of sensory experiences originating from damaged tissue or abnormal physiological condition. The objective of this study was to evaluate the analgesic activity of resveratrol in different doses in animal model.Methods: Albino mice of either sex weighing 20-30 gms were selected for the study. Mice were divided into 4 groups of 6 animals each. The control group received 0.9% normal saline (10 ml/kg), standard group received indomethacin (10 mg/kg) and test groups received resveratrol (50 mg/kg and 100 mg/kg). The drugs were given orally 1 hour prior to the tests. The animals were tested for analgesia activity 30, 60, 90, 120 minutes after drug administration using tail flick method and 1% acetic acid was given intraperitoneally to induce writhing in the other method. Delay in the reaction time in tail flick method and decrease in total number of writhes in acetic acid induced writhing model denoted analgesic activity. Data analysis was done using one way ANOVA followed by Tukey’s HSD test. P<0.05 was considered as statistically significant.Results: Resveratrol showed significant increase in reaction time at various time periods in tail flick method and showed significant decrease in the number of writhes in acetic acid induced writhing method.Conclusions: In the study, resveratrol exhibited analgesic activity in both thermal and chemical pain models in both the doses, and analgesic activity in higher dose (100 mg/kg) was comparable to standard drug

Using different surgical techniques and ideas to reduce post-operative adhesion formation: a systematic review and meta-analysis

Adhesion development is the most common sequelae of intra-abdominal and pelvic surgery. Using a good surgical technique is advocated as a first step in preventing adhesions. However, the evidence for different surgical techniques to reduce adhesion formation needs confirmation. This review contributed to the growing knowledge pool by elucidating factors that potentially predispose to the development of adhesions. A literature search was performed using the PubMed database for all relevant English language articles and were reviewed with particular attention to predisposing factors to post-operative adhesion development. In addition, the reference lists of each article were reviewed to identify additional relevant articles. Various factors have been shown to directly increase the risk of post-operative adhesion development; namely, certain genetic polymorphisms in the interleukin-1 receptor antagonist, increased estrogen exposure, and endometriosis. There were 28 papers with 27 studies included for a systematic review. Of these, 17 studies were eligible for meta-analysis and 11 for qualitative assessment only. None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction. In a small low-quality trial, the pregnancy rate increased after subserous fixation of suture knots. However, the incidence of adhesions was lower after laparoscopic compared with open surgery (relative risk (RR): 0.14; 95% confidence interval (CI): 0.03-0.61) and when the peritoneum was not closed (RR: 0.36; 95% CI: 0.21-0.63). None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes, small bowel obstruction and infertility

Pharmacoeconomic analysis of brimonidine/timolol and travoprost 0.004% in the treatment of primary open angle glaucoma in Indian settings

Background: As we know primary open angle glaucoma need lifelong treatment. It possess financial burden to patient. We have done this study to compare the monthly cost and cost effectiveness of brimonidine /timolol fixed combi-nation and Travoprost 0.004% eye drops in patients of primary open angle glaucoma.Methods: Drops were dispensed at room temperature from 2.5-mL bottles of Travoprost, and 5ml of Brimonidine/Timolol. Two determinations of drop count were taken, each made from bottles held vertically and at a 45-degree angle. The total volumes of medication dispensed from each bottle were measured. Drops in five new bottles were counted and averaged for each drug. Drugs given to patients and asked them to come back with empty bottles for follow up after 2, 4, 8, 12 wks. IOP was measured and another bottle of drug is given. Average retail price was determined by survey of different brands available in market. Drop count, average retail price, and IOP reduction data were used to compute annual cost and cost effectiveness (annual cost per mmHg of IOP reduction) of both of the drugs.Results: Drops per 2.5ml bottle averaged 83 for Travoprost 0.004% and 100 drops per 5ml bottle for Brimonidine/Timolol. Average retail cost per bottle was 498 for Travoprost 0.004% and 204 for Brimonidine/Timolol. Annual re-tail cost was 3545 for Brimonidine/Timolol and 4910 for Travoprost 0.004%. Cost effectiveness ranges were 328 to 361 for Brimoni-dine/Timolol and 629 to 637 for Travoprost 0.004%.Conclusions: Brimonidine/Timolol had the lower monthly cost and annual cost and it is more cost effective than Travoprost 0.004%

Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: a pilot study

To assess the effect of vitamin D supplementation on parameters of Insulin Sensitivity/Resistance (IS/IR) and insulin secretion in subjects with Polycystic Ovarian Syndrome (PCOS). A prospective double-blind randomized control trial was conducted to assess the effect of vitamin D on insulin kinetics in women with PCOS. The trial was conducted in a tertiary care research hospital. A total of 36 subjects with PCOS, aged 18–35 years, were included in this study. Vitamin D3 4000  IU/day versus placebo was given once a month for 6 months and both groups received metformin. IS (by whole-body IS index or Matsuda index), IR (by homeostasis model assessment IR (HOMA-IR)) and insulin secretion (by insulinogenic index; II30) were the main outcome measures. Secondary outcome included Blood Pressure (BP), lipid profile, Disposition Index (DI) and vascular stiffness. Out of 36 subjects who consented, 32 completed the study. Subjects were randomized into two groups: group A (n = 15; metformin and vitamin D 4000  IU/day) or group B (n = 17; metformin and placebo). Oral glucose tolerance tests with 75 g glucose were carried out at baseline and 6 months after supplementation. Hypovitaminosis D was observed in 93.8% of all subjects with mean serum 25 hydroxy vitamin D level of 7.30 &#177; 4.45 ng/ml. After 6 months of vitamin D supplementation, there was no significant difference in any of the parameters of IS/IR (area under curve (AUC)–glucose, AUC–insulin, insulin:glucose ratio, HOMA-IR, Matsuda index, insulinogenic index and DI), II30 and cardiovascular risk factors between the two groups. Supplementation of vitamin D, at a dose of 4000  IU/day for 6 months, did not have any significant effect on parameters of IS/IR and insulin secretion in subjects with PCOS

Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatment in severe sepsis

INTRODUCTION: Several studies have indicated that early identification and treatment of patients with severe sepsis using standard supportive care improves outcomes. Earlier treatment with drotrecogin alfa (activated) (DrotAA) may also improve outcomes in severe sepsis. Using a recently constructed integrated severe sepsis database, our objectives in this study were to describe the influence of baseline clinical characteristics on timing of DrotAA treatment in patients with severe sepsis, to evaluate the efficacy of DrotAA with respect to timing of administration, and to examine the association between early intervention with DrotAA and patient outcomes, using adjustments for imbalances. METHODS: The database comprises data from 4,459 patients with severe sepsis (DrotAA, n = 3,228; placebo, n = 1,231) included in five clinical trials conducted in tertiary care institutions in 28 countries. Placebo data came only from randomized trials, whereas data for the DrotAA group came from randomized (PROWESS) and open-label/observational (ENHANCE) trials. RESULTS: Increased time-to-treatment with DrotAA was significantly associated with more organ dysfunction, greater need of mechanical ventilation, vasopressor use, or recent surgery. Earlier treatment was associated with higher baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Adjusted and unadjusted survival analyses suggested that compared with placebo, DrotAA treatment provided a potential survival benefit, regardless of time to treatment. Survival curves of DrotAA patients treated early compared with those treated late began to separate at 14 days. By 28 days, patients treated earlier had higher survival than those treated later (76.4% versus 73.5%, p = 0.03). Sepsis-induced multiorgan dysfunction was the most common cause of death followed by refractory shock and respiratory failure. Modeling of the treatment effect, as a function of time to treatment, suggested increased benefit with earlier treatment. CONCLUSION: Using an integrated database of five severe sepsis trials and appropriate statistical adjustments to reduce sources of potential bias, earlier treatment with DrotAA seemed to be associated with a lower risk-adjusted mortality than later treatment. These data suggest that earlier treatment with DrotAA may provide most benefit for appropriate patients

Effects of SNF472, a Novel Inhibitor of Hydroxyapatite Crystallization in Patients Receiving Hemodialysis - Subgroup Analyses of the CALIPSO Trial

Coronary artery calcium (CAC) is highly prevalent and linked with poor outcomes in patients receiving maintenance hemodialysis, and its reduction may improve patient prognosis. SNF472, a selective inhibitor of hydroxyapatite crystallization, slows CAC progression in patients receiving maintenance hemodialysis. In this analysis, we assessed the efficacy of SNF472 in prespecified patient subgroups. In a randomized clinical trial SNF472 300 mg, SNF472 600 mg, or placebo were infused thrice weekly in 91, 92, and 91 patients receiving maintenance hemodialysis and with CAC at baseline, respectively. In prespecified subanalyses, the percent change in CAC volume score (CACvs) from baseline to week 52 in modified intention-to-treat (mITT) and per-protocol (PP) populations was calculated in the following subgroups: age, sex, diabetes mellitus, dialysis vintage, prior atherosclerotic cardiovascular disease, baseline use of non-calcium and calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, and statins. In the main trial, SNF472 significantly reduced CACvs progression compared with placebo (11% versus 20% mITT analyses; P = 0.016; 8% vs. 24% PP analyses; P < 0.001). Treatment differences for CACvs progression were similar across all subgroups, and all interaction P values were non-significant in mITT and PP analyses. SNF472 treatment for 52 weeks reduced CACvs progression compared with placebo in a broad range of patients receiving maintenance hemodialysis. Future studies will determine the impact of SNF472 on cardiovascular events in this population

Trial design and baseline characteristics of CaLIPSO : a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification

The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants. Adult patients on maintenance haemodialysis (≥6 months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100-3500 U were enrolled. Patients were stratified by Agatston score (100-1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300 mg or SNF472 600 mg administered intravenously three times weekly during each haemodialysis session. Overall, 274 patients were randomized. The mean age of trial participants was 63.6 (standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315-1435), 1728 U (625-4978) and 103 U (31-262), respectively, and the median (25th-75th percentile) calcium volume scores at baseline were 666 (310-1234), 1418 (536-4052) and 107 (38-278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline. The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve

High-Pressure Properties of Wolframite-Type ScNbO4

In this work, we used Raman spectroscopic and optical absorption measurements and first-principles calculations to unravel the properties of wolframite-type ScNbO4 at ambient pressure and under high pressure. We found that monoclinic wolframite-type ScNbO4 is less compressible than most wolframites and that under high pressure it undergoes two phase transitions at ∼5 and ∼11 GPa, respectively. The first transition induces a 9% collapse of volume and a 1.5 eV decrease of the band gap energy, changing the direct band gap to an indirect one. According to calculations, pressure induces symmetry changes (P2/c–Pnna–P2/c). The structural sequence is validated by the agreement between phonon calculations and Raman experiments and between band structure calculations and optical absorption experiments. We also obtained the pressure dependence of Raman modes and proposed a mode assignment based upon calculations. They also provided information on infrared modes and elastic constants. Finally, noncovalent and charge analyses were employed to analyze the bonding evolution of ScNbO4 under pressure. They show that the bonding nature of ScNbO4 does not change significantly under pressure. In particular, the ionicity of the wolframite phase is 61% and changes to 63.5% at the phase transition taking place at ∼5 GPa

Title: Ultrasound (US) Imaging Use in the Management of the Difficult Tracheal Intubation

The ultrasound has been in clinical use since the early 1900s, but its use in the airway has not been published extensively so far. Combining the skills of USG with thorough knowledge of regional anatomy can prove to be a boon to improving the quality of care being delivered to patients. Preoperative use of USG at different levels of the neck combined with the risk assessment methods can help to organize predictors of difficult airway and difficult laryngoscopy. Basic comprehension of USG physics, transducer selection, and probe orientation and a better understanding of airway anatomy contribute to the accuracy of ultrasound interpretation. In day-to-day practice, there is a potential for failed tracheal intubations followed by failure of gaining adequate access to the airway, thus posing challenges to anesthesiologists. Besides predicting difficult airway, USG provides an incentive to properly place an endotracheal tube (ETT) to an adequate depth, estimation of the size of ETT particularly helpful in children and obese, laryngeal mask airway (LMA) confirmation, surgical airways, and post-extubation stridor assessment and thus prevents the risk of reintubation. With the promising and increasing number of evidence exists, there is potential for incorporation of upper airway USG into further standard of care assessment, monitoring, and imaging modalities