An investigation into the effects of extracorporeal membrane oxygenation on pharmacokinetics

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Degradation mechanism and toxicity reduction of methyl orange dye by a newly isolated bacterium Pseudomonas aeruginosa MZ520730

Methyl orange (MO) dye is recalcitrant in nature, hard to degrade and if released into the soil and aquatic resources could cause serious threats on environment and human health. MO is toxic to plant growth. Bacterial treatment may be a sustainable solution for its degradation and decolourization. In this work, a bacterium (RKS6) was isolated from textile industry wastewater and sludge samples and identified as Pseudomonas aeruginosa based on the 16S rRNA gene sequencing analysis. RKS6 showed more than 99% decolorization of MO dye (100 mg/l) and 96% reduction of total organic carbon (TOC) within 12 h, at 30 °C, pH 7 at static conditions. RKS6 also produced MnP enzyme of molecular weight ∼53 kDa as characterized by the SDS-PAGE analysis. Further, LC-MS analysis showed that MO dye was degraded into 4-[(4-aminophenyl) diazenyl] benzene sulfonate, 4, 2-((dihydroxymethyl) hyrazono-4) 5-benzene sulfonate, 4-(triazan-2-yl) benzene sulfonic, water and carbon dioxide by RKS6. Toxicity assessment showed that the solution treated by the bacterium allowed 90% seed germination indicating that RKS6 was effective in mineralization and detoxification of MO dye and can be effectively used in industrial wastewater treatment

Dried blood spot sampling with LC-MS analysis for routine therapeutic caffeine monitoring in neonates

A liquid chromatography–mass spectrometry (LC-MS) method was developed and validated for the determination of therapeutic levels of caffeine in dried blood spot (DBS) samples. Caffeine is used in the treatment of Apnoea of Prematurity (AoP) in newborn children. Calibration DBS samples were prepared by spotting 15l of whole blood spiked with the analyte onto specimen collection cards. 5mm disks cut from the centre of the DBS were extracted in methanol containing the internal standard. The extract was separated using a Zorbax Eclipse Plus C18 column and the MS, operated in electrospray positive ion mode, used single ion monitoring at m/z 195 for caffeine and 198 for the IS. The overall extraction recovery of caffeine from spiked blood spots was demonstrated to be 44-47%. Validation of the micro-analytical method showed good precision (coefficient of variation) and accuracy (relative error) and specificity and was linear within the tested calibration range 500-25000ng/ml for caffeine. Investigation of different specimen collection papers revealed different matrix effects with significant ion suppression from the FTA Elute paper itself. Requiring only a micro volume (15µl) blood sample for analysis, the developed DBS based micro-analytical method has the potential to facilitate the routine monitoring of caffeine in neonates

Heat release rate estimation in laminar premixed flames using laser-induced fluorescence of CH2O and H-atom

The present work demonstrates the feasibility of heat release rate imaging using the laser-induced fluorescence (LIF) of atomic hydrogen (H-atom) and formaldehyde (CH2O) in laminar premixed flames. The product of H-atom LIF and CH2O LIF signals is evaluated on a pixel-by-pixel basis and is compared with that of the OH × CH2O technique. These results for equivalence ratio ranging from 0.8 to 1.1 are compared with computations of one-dimensional freely-propagating flames. The performance of these markers is studied based on the following two aspects: the spatial accuracy of the local heat release rate and the trend in the total heat release rate with equivalence ratio. The measured trend in the spatial distribution of radicals and the deduced heat release rate agree well with the computational values. The variation in the spatially integrated heat release rate as a function of equivalence ratio is also investigated. The results suggest that the trend in the variation of the integrated heat release rate and the spatial location of heat release rate can be evaluated by either of these markers. The OH-based marker showed certain sensitivity to the chemical mechanism as compared to the H-atom based marker. Both the OH-based and H-atom based techniques provide close estimates of heat release rate. The OH based technique has practical advantage when compared to the H-atom based method, primarily due to the fact that the H-atom LIF is a two-photon process

A novel PKD1 variant demonstrates a disease-modifying role in trans with a truncating PKD1 mutation in patients with Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common form of Polycystic Kidney Disease (PKD) and occurs at a frequency of 1/800 to 1/1000 affecting all ethnic groups worldwide. ADPKD shows significant intrafamilial phenotypic variability in the rate of disease progression and extra-renal manifestations, which suggests the involvement of heritable modifier genes. Here we show that the PKD1 gene can act as a disease causing and a disease modifier gene in ADPKD patients

A novel PKD1 variant demonstrates a disease-modifying role in trans with a truncating PKD1 mutation in patients with Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common form of Polycystic Kidney Disease (PKD) and occurs at a frequency of 1/800 to 1/1000 affecting all ethnic groups worldwide. ADPKD shows significant intrafamilial phenotypic variability in the rate of disease progression and extra-renal manifestations, which suggests the involvement of heritable modifier genes. Here we show that the PKD1 gene can act as a disease causing and a disease modifier gene in ADPKD patients

Quantitative analysis of methyl and propyl parabens in neonatal DBS using LC-MS/MS

AIM: Excipients are used to overcome the chemical, physical and microbiological challenges posed by developing formulated medicines. Both methyl and propyl paraben are commonly used in pediatric liquid formulations. There is no data on systemic exposure to parabens in neonates. The European Study of Neonatal Exposure to Excipients project has investigated this. Results & methodology: DBS sampling was used to collect opportunistic blood samples. Parabens were extracted from the DBS and analyzed using a validated LC-MS/MS assay. DISCUSSION & CONCLUSION: The above assay was applied to analyze neonatal DBS samples. The blood concentrations of parabens in neonates confirm systemic exposure to parabens following administration of routine medicines

Conjugation of enrofloxacin with amine functionalized zinc oxide nanoparticle enhances antibacterial activity in vitro

233-240Increased resistance to a large number of antibacterial drugs poses a serious challenge in chemotheraphy of infectious diseases. Here, we have made and attempt to redesign the existing chemotherapeutic agent enrofloxacin (EN) to treat resistant bacteria. Precisely, we synthezied EN conjugated zinc oxide nanoparticles (EN-ZNP) and explored enhancing the antibacterial activity of enrofloxacin. Zinc oxide nanoparticles (ZNP) were synthesized by microwave irradiation and amine functionalization by co-condensation with APTES and then by utilizing EPC/NHS chemistry, enrofoxacin was conjugated. Conjugation and their stability were confirmed by FT-IR spectra and Zeta potential. EN fraction in EN-ZNP was determined indirectly using UV-Vis spectroscopy. The MIC values obtained for EN-ZNP against MTCC cultures and clinical isolates of Escherichia coli, Salmonella typhimurium, Staphylococcus aureus were significantly (P <0.05) lower than ZNP and, when compared to native EN it is significantly higher. However, the concentration of conjugated EN in EN-ZNP was significantly lower than the MIC of native EN. The results suggest that enrofloxacin can be successfully conjugated with amine functionalized zinc oxide nanoparticles. The antibacterial efficacy was significantly improved when ZNP conjugated with EN against standard MTCC cultures and clinical isolates

Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13-cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial.

(1) Background: 13-cis-retinoic acid (13-CRA) is a key component of neuroblastoma treatment protocols. This randomized crossover study compares the pharmacokinetics (PK), safety and palatability of a novel oral liquid formulation to the current method of extracting 13-CRA from capsules. (2) Methods: Pharmacokinetics was evaluated in two consecutive treatment cycles. Patients were randomized to receive either liquid or capsule formulation on cycle 1 and then crossed over to the alternative formulation on cycle 2. The daily dose was 200 mg/m2, reduced to 160 mg/m2 in patients with weight ≤ 12 kg. (3) Results: A total of 20 children, median (range) age 4.3 (1-11.6) y were recruited. Pharmacokinetic data were pooled and a population model describing the disposition of 13-CRA and 4-oxo-13-CRA was developed. Bioavailability of the liquid formulation was estimated to be 65% higher (95% CI; 51-79%) than the extracted capsule. CmaxSS and AUC(0-12)SS estimates were also significantly higher; mean (95% CI) differences were 489 (144-835) ng/mL and 3933 (2020-5846) ng/mL·h, respectively (p < 0.01). There were no significant differences in reported adverse effects. Parents found dosing considerably easier with liquid formulation. (4) Conclusions: The pharmacokinetics, safety and palatability of a new liquid formulation of 13-CRA compares favorably to 13-CRA extracted from capsules. Clinical Trial Registration: clinicaltrial.gov NCT03291080