A Randomised Controlled Trial Comparing Ketamine versus Fentanyl for Procedural Sedation in the Emergency Department for Adults with Isolated Extremity Injury.

Introduction: Alleviating pain and anxiety of patients during procedures is an essential skill for an Emergency Physician (EP). Several sedatives and dissociative agents are used for PSA (Procedural Sedation and Analgesia). In this study, we aimed to compare two drugs that is, ketamine and fentanyl for procedural sedation in adults with isolated limb injuries in the Emergency Department (ED). Materials and methods: In this prospective, randomised controlled interventional trial, patients aged between 18 to 65 years with isolated extremity injury requiring PSA in the ED were recruited. A total of 200 subjects were included in the study and randomly allocated to either the fentanyl (n=100) or the ketamine (n=100) group. Patients were blinded to the intervention and subsequently premedicated with Midazolam. Following this, they received either ketamine or fentanyl based on the group they were allocated to. Vital signs, including but not limited to the level of sedation, were measured at predetermined time intervals. A Modified Aldrete Score of >8 was used as a criterion for disposition from the ED. Data were collected in a pre-designed proforma. We aimed to compare the effectiveness as well as ascertain the safety profile of the two drugs for PSA in the ED. Results: There was no significant difference between the two groups when age, gender, mechanism of injury and comorbidities were compared. We found that there was no statistically significant difference between the two groups when blood pressure, respiratory rate and depth of sedation were compared. In both groups, there was a significant decrease in pain on the Numerical Rating Scale (NRS) following drug administration from 8 to 3 (p<0.001). Patients in the fentanyl group had an increased incidence of transient oxygen desaturation (p<0.001). Vomiting was more common in the ketamine group (p<0.001). Conclusion: PSA is a safe and efficacious procedure for patients undergoing painful procedures in ED. Patients in both the groups maintained hemodynamic stability throughout the procedure. From our study, we were able to conclude that both ketamine and fentanyl are similar in efficacy for PSA in the ED for adults with isolated limb injuries. In addition, no significant cardiovascular adverse events were noted in either group in our study.

Kaulath, a new fungal fermented food from horse gram.

Horse gram (Macrotyloma uniflorum) is used in the traditional method for treatmentof several health complications. It is also known that fermentation of such substrates yields a number of compounds that enhance the overall activities against several disease states. Solid state fermentation of horse gram using Penicillium camemberti showed an inhibition of pancreatic lipase and alpha glucosidase activities. The fermented material, termed Kaulath, showed 60 % increase in fat content. A reduction in sodium and increased levels of potassium and calcium was observed in Kaulath. In addition, a higher free radical scavenging activity was noted in this product compared to unfermented horse gram. Anti-nutritional factors, such as phytic acid and trypsin inhibitors showed a reduction in Kaulath. Furthermore, Kaulath, upto 1 g per kg body weight, did not exhibit any mortality or toxic effects in experimental rats after 14 days of administration. The hematological and clinical parameters were within safe limits between the groups, supported by the histopathology of liver and kidney. These results indicate potential food use of Kaulath in diets and as functional ingredients in formulated foods.

Sclerotiorin is non-mutagenic and inhibits human PMNL 5-lipoxygenase and platelet aggregation.

Sclerotiorin, isolated from the fermented broth of Penicillium frequentans, exhibited potent inhibition against human polymorphonuclear leukocytes 5-lipoxygenase and human platelet aggregation with a half maximal value 36 µM and 250 µM, respectively. Further, the Ames test has demonstrated the sclerotiorin to be non-mutagenic.

A tyrosinase inhibitor from Aspergillus niger.

Tyrosinase, in the presence of oxygen, is the main culprit in post harvest browning of food products, resulting in the drop in its commercial value. In an effort to seek natural tyrosinase inhibitors for food applications, a screening programme was undertaken. Of the 26 fungal cultures isolated from soil samples of Agumbe forest, India, one isolate S16, identified as Aspergillus niger, gave an inhibition of 84 % against the enzyme. The inhibitor was isolated by following an enzyme inhibition assay guided purification protocol. The structure of the inhibitor was elucidated and found to be kojic acid. The IC50 of the Competitive inhibitor was found to be 8.8 µg with a Ki of 0.085 mM.

Rapid screening of enzyme inhibitors using profiling of enzyme-metabolite assay by HPLC (PREMA-HPLC).

A number of isolates from different ecosystems were screened for their ability to inhibit tyrosinase resulting in the selection of isolate CFR 101, which showed an inhibition of 72%. The metabolites present in the crude extract of the selected isolate was profiled through high-performance liquid chromatography (HPLC) before the enzyme inhibition assay to reveal a 66% decrease in area of the peak at room temperature for 13.9 min, after the assay. Upon purification, this peak was identified as kojic acid, a known inhibitor of tyrosinase. This unique technique of combining a reaction assay mixture with HPLC profile wherein inhibitors can be rapidly pinpointed in crude extracts addresses the drawback of rapid chemical high-throughput screening (HTS) systems, which is limited to the chemical nature of metabolites without any evidence of their biological activities.

Familial hypophosphatemic rickets.

Rickets is the failure of mineralization of osteoid and newly formed bones in a child skeleton. It is commonly associated with vitamin D deficiency; however, it can be because of a decrease in the serum phosphate levels leading to inadequate mineralization of cartilage and bone, consequent skeletal deformities, and growth retardation. The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases. One of the hereditary types of hypophosphatemic rickets is the familial hypophosphatemic rickets. This rare variety was diagnosed in a 9-year-old patient who had come with a chief complaint of a missing tooth. In the present case, radiographic aspects of oral and systemic manifestations of familial hypophosphatemic rickets are highlighted.

Strain improvement of Aspergillus niger for the enhanced production of asperenone.

The enhancement of production of asperenone (Fig. 1), an inhibitor of lipoxygenase and human platelet aggregation from Aspergillus niger CFTRI 1105, was achieved by UV and nitrous acid mutagenesis. Nitrous acid mutants exhibited increased inhibitor production when compared with UV irradiated mutants. I N 41 a first-generation nitrous acid mutant produced 5.1 fold increased asperenone over parent strain. Mutant II N 31 obtained by second-generation nitrous acid treatment produced 60.3 mg asperenone/g biomass, which was 131 fold increase when compared to first generated mutant I N 41 and 670 fold increase over the parent strain. This mutant was stable for several generations on production medium.

Sclerotiorin, a novel inhibitor of lipoxygenase from Penicillium frequentans.

Foods rich with unsaturated fatty acids are prone to enzymatic and nonenzymatic lipid peroxidation; lipoxygenase, a metalloenzyme and a free radical former, oxidizes polyunsaturated fatty acids and is one of the key enzymes in lipid oxidation. Here, we report sclerotiorin, purified from the fermented broth of Penicillium frequentans, as a potent reversible, uncompetitive inhibitor against soybean lipoxygenase-1 (LOX-1) with a half-maximal value (IC50) of 4.2 microM. The inhibitor also showed an antioxidant property by scavenging free radical with an ED50 of 0.12 microM; in addition, nonenzymatic lipid peroxidation was inhibited with a PD50 value of 64 microM and did not show metal chelation. The observations made in this study suggest that sclerotiorin possibly inhibits LOX in two ways: one, by interacting with the enzyme-substrate complex, and two, as an antioxidant by quenching or trapping the free radical intermediates formed in the enzyme reaction. Sclerotiorin compares well with other known natural and synthetic lipoxygenase inhibitors.

Sclerotiorin, from Penicillium frequentans, a potent inhibitor of aldose reductase.

Aldose reductase, the first key enzyme in the polyol pathway, is involved in complications of diabetes. Sclerotiorin, isolated and purified from the fermented broth of Penicillium frequentans, inhibited aldose reductase with an IC(50 )0.4 microM. The inhibitor also showed antibacterial activity against Bacillus spp.

A spectroscopic study of the interaction of nigerloxin, a fungal metabolite, with serum albumin.

Nigerloxin [2-amido-3-hydroxy-6-methoxy-5-methyl-4-(prop-1'-enyl) benzoic acid], a fungal metabolite, is an inhibitor of lipoxygenase and aldose reductase with free radical-scavenging properties. The interaction of nigerloxin with bovine serum albumin (BSA) was investigated using fluorescence spectroscopy and circular dichroic measurements. The fluorescence of BSA was quenched following interaction with nigerloxin, and this property was used to generate a binding constant. The estimated association constant was 1.01 +/- 0.2 x 10(6) M(-1). Job's method of continuous variation indicated that nigerloxin formed a 1:1 +/- 0.1 complex with BSA. To understand the nature of the interaction, the variance in the association constant as a function of temperature in the range of 14-45 degrees C was used to calculate the thermodynamic parameters. The thermodynamic parameters at 27 degrees C derived from the mass action plot and van't Hoff's plot were as follows: deltaG = -8.2 +/- 0.1 kcal/mol, deltaH approximately equal to 0 kcal/mol, and deltaS = 27.5 +/- 0.4 cal/mol/K (where deltaG is free energy, deltaH is enthalpy, and deltaS is entropy). Increasing ionic strength did not favor interaction. Circular dichroic measurements revealed that the interaction of nigerloxin with BSA did not lead to changes in the secondary structure of the protein. The reversibility of the interaction verified by the dilution method was found to be reversible. These measurements suggest that partial hydrophobic and partial ionic bonding play a role in the interaction of nigerloxin with BSA.

Nigerloxin, a novel inhibitor of aldose reductase and lipoxygenase with Free radical scavenging activity from Aspergillus niger CFR-W-105.

An enzyme inhibitor, nigerloxin, with inhibition against soy bean lipoxygenase-I (LOX-1), rat lens aldose reductase (RLAR) as well as free radical scavenging activity was isolated from the fermented wheat bran using Aspergillus niger CFR-W-105. Its chemical structure was identified as 2-amido-3-hydroxy-6-methoxy-5-methyl-4-(prop-1'-enyl) benzoic acid by NMR and GCEIMS data. The IC50 values against LOX-1 and RLAR were found to be 79 microM and 69 microM and ED50 against 1,1-diphenyl-2-picrylhydrazyl (DPPH) was 66 microM.

A lipoxygenase inhibitor from Aspergillus niger.

A lipoxygenase-1 (LOX-1) inhibitor was isolated from the fermented broth of Aspergillus niger CFTRI 1105. It was purified, using column and preparative thin layer chromatography. 1H NMR and GC-MS examination revealed the structure of the inhibitor to be 2-(2'-methyl, 4'-hydroxyphenyl), 2-(4"hydroxyphenyl)-propane with a molecular weight of 242 and the molecular formula C,6H18O2. This bisphenol-derivative inhibitor shows 50% inhibition of soybean LOX-I at 0.98 mM concentration. The activity of this inhibitor was compared with commercial bisphenol A and its structural analogues, butylhydroxyanisole and butylhydroxytoluene in an attempt to understand the role of functional groups affecting lipoxygenase activity.