Determination of Therapeutic Equivalence of Generic Products of Gentamicin in the Neutropenic Mouse Thigh Infection Model

Background: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. Methodology/Principal Findings: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P,0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (E max = 4.81 to 5.32 vs. 5.99 log 10 CFU/g, P#0.043). Although the design lacked power to detect differences in survival after thigh infection with P. aeruginosa, dissemination to vital organs was significantly higher in animals treated with generic gentamicin despite 4 days of maximally effective treatment. Conclusion: Pharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteri

Measuring oxytocin and vasopressin:bioassays, immunoassays and random numbers

In this review, we consider the ways in which vasopressin and oxytocin have been measured since their first discovery. Two different ways of measuring oxytocin in widespread use currently give values in human plasma that differ by two orders of magnitude, and the values measured by these two methods in the same samples show no correlation. The notion that we should accept this seems absurd. Either one (or both) methods is not measuring oxytocin, or, by ‘oxytocin’, the scientists that use these different methods mean something very different. If these communities are to talk to each other, it is important to validate one method and invalidate the other, or else to establish exactly what each community understands by ‘oxytocin’. A similar issue concerns vasopressin: again, different ways of measuring vasopressin give values in human plasma that differ by two orders of magnitude, and it appears that the same explanation for discrepant oxytocin measurements applies to discrepant vasopressin measurements. The first assays for oxytocin and vasopressin measured biological activity directly. When immunoassays were introduced, they encountered problems: high molecular weight factors in raw plasma interfered with the binding of antibodies to the hormones, leading to high and erroneous readings. When these interfering factors were removed by extraction of plasma samples, immunoassays gave measurements consistent with bioassays, with measures of turnover and with the sensitivity of target tissues to exogenous hormone. However, many recent papers use an enzyme‐linked immunoassay to measure plasma levels without extracting the samples. Like the first radioimmunassays of unextracted plasma, this generates impossibly high and wholly erroneous measurements

Photodecomposition of Metal Nitrate and Chloride Compounds Yields Amorphous Metal Oxide Films

UV light is found to trigger the decomposition of MCl_<i>x</i> or M­(NO₃)_<i>x</i> (where M = Fe, Co, Ni, Cu, or Zn) to form uniform, amorphous films of metal oxides. This process does not elevate the temperature of the substrate and thus conformal films can be coated on a range of substrates, including rigid glass and flexible plastic. The formation of the oxide films were confirmed by a combination of powder X-ray diffraction, X-ray photoelectron spectroscopy, X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy techniques. Amorphous oxide films of iron, nickel and a combination of iron and nickel demonstrated oxygen evolution reaction electrocatalytic activities commensurate with films of the same compositions prepared by widely used electrodeposition and sputtering methods. These results illuminate a potential route to amorphous oxides at scale using simple metal precursors without vacuum or heat

Electrolysis of Gaseous CO₂ to CO in a Flow Cell with a Bipolar Membrane

The conversion of CO₂ to CO is demonstrated in an electrolyzer flow cell containing a bipolar membrane at current densities of 200 mA/cm² with a Faradaic efficiency of 50%. Electrolysis was carried out by delivering gaseous CO₂ at the cathode with a silver catalyst integrated in a carbon-based gas diffusion layer. Nonprecious nickel foam in a strongly alkaline electrolyte (1 M NaOH) was used to mediate the anode reaction. While a configuration where the anode and cathode were separated by only a bipolar membrane was found to be unfavorable for robust CO₂ reduction, a modified configuration with a solid-supported aqueous layer inserted between the silver-based catalyst layer and the bipolar membrane enhanced the cathode selectivity for CO₂ reduction to CO. We report higher current densities (200 mA/cm²) than previously reported for gas-phase CO₂ to CO electrolysis and demonstrate the dependence of long-term stability on adequate hydration of the CO₂ inlet stream