Pharmacokinetic aspects of meloxicam in koalas: including its hepatic microsomal metabolism compared with other selected species

Prior to this research, no disposition studies of meloxicam (nor any other non steroidal anti-inflammatory drugs) had been conducted in koalas (a specialist Eucalyptus spp. foliage feeder) despite being readily administered to this species, in the field. Thus, aspects of the in-vivo pharmacokinetic profile of meloxicam in the koala and the in-vitro metabolism of meloxicam in the koala and selected species were investigated. In the first stage of the research, a simple, sensitive and improved method using high performance liquid chromatography equipped with photo diode array detection was developed and validated to determine meloxicam concentrations in koala plasma, applicable for in-vivo pharmacokinetic study. Following intravenous injection, meloxicam exhibited a rapid plasma clearance of 0.44 ± 0.20 L/h/kg in koalas (n = 5). Median plasma terminal elimination t1/2 was 1.19 h (range 0.71 to 1.62 h). In koalas, bioavailability after the subcutaneous injection was approximately 56 to 70 % where oral bioavailability was negligible. Plasma protein binding of meloxicam was about 98%. Three hydroxylated metabolites of meloxicam (M1, M2 and M3) were detected in the koala plasma with one (M1) identified as the 5-hydroxy methyl metabolite. According to the in-vitro hepatic microsomal metabolism of meloxicam, it was demonstrated that biotransformation of meloxicam, likely mediated via cytochrome P450 enzymes, were much faster in koalas (and also in other Eucalyptus spp. foliage feeders: ringtail possums and brushtail possums) compared to rats or dogs. The rank order of apparent in-vitro intrinsic clearance was brushtail possums (n = 3) (mean: 394 μL/min/mg protein) > koalas (n = 6) (50 μL/min/mg protein) > ringtail possums (n = 2) (36 μL/min/mg protein) (with no significant difference between koalas and ringtail possums) > pooled rats (3.2 μL/min/mg protein) > pooled dogs (not determined as the rate of metabolism was too slow). According to the in-vitro study, single hydroxylated metabolite (M1) was determined as the major product of meloxicam in brushtail possums and the rat whereas multiple hydroxylated metabolites were observed in the koala (M1, M2, and M3) and the ringtail possum (M1 and M3). Using a well-stirred model, this research showed applicability of predicting in-vivo clearance of meloxicam in koalas and the rat from the apparent in-vitro intrinsic clearance data (average fold error for prediction was less than 2). While cytochrome P4502C9 is the major responsible enzymes for metabolism of meloxicam, the research also found that the stability of other cytochrome P4502C9 substrates, particularly non steroidal anti-inflammatory drugs were also generally not stable in hepatic microsomes of koala and other Eucalyptus.spp foliage feeders than the rat. Particularly, there was some similarity on the pattern of CYP2C9 substrates stabilities between koala and ringtail possum (Eucalyptus spp. foliage specialist feeders). This research demonstrated that koalas exhibited rapid plasma clearance and extremely poor oral bioavailability of meloxicam compared with other eutherian species. Due to differences in the rate of hepatic metabolism on meloxicam, other eutherians such as rats or dogs are inadequate model for dosage extrapolation of this drug in koalas. Furthermore, as catalytic activity of cytochrome P4502C-like enzymes appeared to be different in these Eucalyptus spp. foliage feeders, it is highly recommended to consider when extrapolating dosage of therapeutic drugs (cytochrome P4502C9 substrates), particularly non steroidal anti-inflammatory drugs, from other eutherians. On the other hand, as in-vivo clearance is one of the pharmacokinetic indexes for determining the dosage of drug, this study demonstrates the utility of in-vitro to in-vivo scaling as an alternative prediction method of drug clearance in koalas

Silver Ion Biocide Delivery System for Water Disinfection

U.S. space exploration missions have long considered returning to the Moon and exploration of Mars that challenge life support systems. For these long duration missions, there is interest in replacing the iodine water treatment system with ionic silver, a proven biocide. For long duration exploration missions, it is imperative that an effective biocide be used that prevents microbial growth, biofilm formation, and microbially induced corrosion in the water storage and distribution systems while minimizing logistical supply requirements associated with the biocide delivery system. Two biocide delivery systems have been developed that electrochemically produce silver ions for disinfecting water throughout the water storage and distribution system. One system uses a newly developed hybrid micro-filtration and ion-exchange membrane to produce an abundance of silver ions at the 1000 ppb level upstream in the water distribution system to prevent biofilm growth. This is followed by a downstream collection module that electrochemically removes these silver ions before the water is discharged. Another approach uses a membraneless reactor to produce a 1000 ppb silver ion concentration level that also has a mechanically driven electrode cleaning mechanism that removes oxide films ensuring long life operation. By maintaining a sufficiently high level of silver ions throughout the water storage and distribution system, biofilm formation is suppressed. This approach overcomes present concerns where spurious silver deposition occurs on the container and flow line surfaces thus lowering the silver ion concentration to unsatisfactory disinfection levels

Prospects for the cavity-assisted laser cooling of molecules

Cooling of molecules via free-space dissipative scattering of photons is thought not to be practicable due to the inherently large number of Raman loss channels available to molecules and the prohibitive expense of building multiple repumping laser systems. The use of an optical cavity to enhance coherent Rayleigh scattering into a decaying cavity mode has been suggested as a potential method to mitigate Raman loss, thereby enabling the laser cooling of molecules to ultracold temperatures. We discuss the possibility of cavity-assisted laser cooling particles without closed transitions, identify conditions necessary to achieve efficient cooling, and suggest solutions given experimental constraints. Specifically, it is shown that cooperativities much greater than unity are required for cooling without loss, and that this could be achieved via the superradiant scattering associated with intracavity self-localization of the molecules. Particular emphasis is given to the polar hydroxyl radical (OH), cold samples of which are readily obtained from Stark deceleration.Comment: 18 pages, 10 figure

Pharmacokinetic profile of enrofloxacin and its metabolite ciprofloxacin in Asian house geckos (Hemidactylus frenatus) after single-dose oral administration of enrofloxacin

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were determined following oral administration in 21 Asian house geckos (Hemidactylus frenatus) at a dose of 10 mg/kg. Changes in enrofloxacin and ciprofloxacin plasma concentrations were quantified at regular intervals over 72 h (1, 2, 6, 12, 24, 48, and 72 h). Samples were analysed by high-pressure liquid chromatography (HPLC) and the enrofloxacin pharmacokinetic data underwent a two-compartment analysis. Due to the limited ciprofloxacin plasma concentrations above the lower limit of quantification (LLOQ), the ciprofloxacin data underwent non-compartment analysis and the half-life was determined by the Lineweaver-Burke plot and analysis. The enrofloxacin and ciprofloxacin mean half-lives (t½) were 0.95 h (α) / 24.36 h (β), and 11.06 h respectively, area under the curve (AUC0-24h) were 60.56 and 3.14 µg/mL*h, respectively, maximum concentrations (Cmax) were 12.31 and 0.24 µg/mL, respectively, and time required to reach the Cmax (Tmax) were 1 and 2 h respectively. Enrofloxacin was minimally converted to the active metabolite ciprofloxacin, with ciprofloxacin concentrations contributing only 4.91% of the total fluoroquinolone concentrations (AUC0-24h). Based on the pharmacokinetic indices when using susceptibility breakpoints when determined at mammalian body temperature it is predicted that single oral administration of enrofloxacin (10 mg/kg) would result in plasma concentrations effective against susceptible bacterial species inhibited by an enrofloxacin MIC ≤ 0.5 µg/mL in vitro, but additional studies will be required to determine its efficacy in vivo

Polysaccharide peptide extract from Coriolus versicolor increased Tmax of tamoxifen and maintained biochemical serum parameters, with no change in the metabolism of tamoxifen in the rat

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10–100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (Tmax) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician’s knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy

Recursive quantum repeater networks

Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layering, and virtualizes the addresses of resources to improve information hiding and resource management. Our architecture is useful for building arbitrary distributed states, including fundamental distributed states such as Bell pairs and GHZ, W, and cluster states.Comment: 14 page

Insights Gained into Marginalized Students Access Challenges During the COVID-19 Academic Response

The American Chemical Society (ACS) Committee on Minority Affairs (CMA) endeavors to support all chemistry faculty and staff as they educate all of our students during this pandemic. While the chemistry education community and the ACS have both provided resources as most institutions transitioned to virtual platforms, this pandemic disproportionally affects our students of color, lower socio-economic and rural backgrounds, and students with disabilities. Specifically, these students must overcome hurdles of technology access, environmental disruptions, and cultural pressures in order to be successful. Therefore, CMA has formulated partnerships with both academic and industrial institutions to highlight some best practices to improve future virtual learning experiences of these oftentimes marginalized students. Specifically, the work presented here examines programs and policies at three academic institutions with very different student body demographics and surrounding learning environments (Indiana University Purdue University Indianapolis (IUPUI), The College of New Jersey (TCNJ), and Los Angeles Community College District (LACCD)) with an attempt to identify variables that enhance marginalized student success in chemistry courses. The combination of their results suggests elements such as access to technology, home responsibility, and impostor syndrome, that other learning programs should consider to increase virtual learning success. Furthermore, other stopgap measures implemented at industrial partners give insight as to how these considerations can be implemented during virtual internship programs to meet their learning objectives associated with entering their institutional pipeline

Using the Bullet Cluster as a Gravitational Telescope to Study z~7 Lyman Break Galaxies

We use imaging obtained with the Hubble Space Telescope Wide Field Camera 3 to search for z_850 dropouts at z~7 and J_110 dropouts at z~9 lensed by the Bullet Cluster. In total we find 10 z_850 dropouts in our 8.27 arcmin^2 field. Using magnification maps from a combined weak and strong lensing mass reconstruction of the Bullet Cluster and correcting for estimated completeness levels, we calculate the surface density and luminosity function of our z_850 dropouts as a function of intrinsic (accounting for magnification) magnitude. We find results consistent with published blank field surveys, despite using much shallower data, and demonstrate the effectiveness of cluster surveys in the search for z~7 galaxies.Comment: 12 pages, 2 tables, 9 figures. Accepted for publication in ApJ. V3: two new figures, improved calculation of intrinsic counts, better organization, added references; main results did not change significantl

Feasibility of detecting single atoms using photonic bandgap cavities

We propose an atom-cavity chip that combines laser cooling and trapping of neutral atoms with magnetic microtraps and waveguides to deliver a cold atom to the mode of a fiber taper coupled photonic bandgap (PBG) cavity. The feasibility of this device for detecting single atoms is analyzed using both a semi-classical treatment and an unconditional master equation approach. Single-atom detection seems achievable in an initial experiment involving the non-deterministic delivery of weakly trapped atoms into the mode of the PBG cavity.Comment: 11 pages, 5 figure