As 95% of all prescriptions are for orally administered drugs, the issue of oral absorption is central to the development of pharmaceuticals. Oral absorption is limited by a high molecular weight (>500 Da), a high log P value (>2.0) and low gastrointestinal permeability. We have designed a triple action nanomedicine from a chitosan amphiphile: quaternary ammonium palmitoyl glycol chitosan (GCPQ), which significantly enhances the oral absorption of hydrophobic drugs (e.g., griseofulvin and cyclosporin A) and, to a lesser extent, the absorption of hydrophilic drugs (e.g., ranitidine). The griseofulvin and cyclosporin A C(max) was increased 6- and 5-fold respectively with this new nanomedicine. Hydrophobic drug absorption is facilitated by the nanomedicine: (a) increasing the dissolution rate of hydrophobic molecules, (b) adhering to and penetrating the mucus layer and thus enabling intimate contact between the drug and the gastrointestinal epithelium absorptive cells, and (c) enhancing the transcellular transport of hydrophobic compounds. Although the C(max) of ranitidine was enhanced by 80% with the nanomedicine, there was no appreciable opening of tight junctions by the polymer particles.

Electrode materials with three-dimensional (3D) mesoporous structures possess superior features, such as shortened solid-phase lithium diffusion distance, large pore volume, full lithium ion accessibility, and a high specific area, which can facilitate fast lithium ion transport and electron transfer between solid/electrolyte interfaces. In this work, we introduce a facile synthesis route for the preparation of a 3D nanoarchitecture of Ge coated with carbon (3D-Ge/C) via a carbothermal reduction method in an inert atmosphere. The 3D-Ge/C showed excellent cyclability: almost 86.8% capacity retention, corresponding to a charge capacity of 1216 mAh g -1 even after 1000 cycles at a 2 C-rate. Surprisingly, the high average reversible capacity of 1122 mAh g -1 was maintained at a high charge rate of 100 C (160 A g -1 ). Even at an ultrahigh charge rate of 400 C (640 A g -1 ), an average capacity of 429 mAh g -1 was attained. Further, the full cell composed of 3D-Ge/C anode and LiCoO2 cathode exhibited excellent rate capability and cyclability with 94.7% capacity retention over 50 cycles. 3D-Ge/C, which offers a high energy density like batteries as well as a high power density like supercapacitors, is expected to be used in a wide range of electrochemical devices.A novel, facile synthetic route has been proposed to prepare a 3D nanoarchitecture Ge coated with carbon (3D-Ge/C) via a carbothermal reduction. The GeO 2 /PVP composite was carbonized in an argon atmosphere at 775 °C for 1 h to carbonize the PVP. During carbonization, the carbothermal reduction of GeO 2 occurred and simultaneously formed Ge within a 3D structure.

Germanium (Ge) possesses a great potential as a high‐capacity anode material for lithium ion batteries but suffers from its poor capacity retention and rate capability due to significant volume expansion by lithiation. Here, a facile synthetic route is introduced for producing nanometer‐sized Ge crystallites interconnected by carbon (GEC) via thermal decomposition of a Ge‐citrate complex followed by a calcination process in an inert atmosphere. The GEC electrode shows outstanding electrochemical performance, i.e., an almost 98.8% capacity retention of 1232 mAh g−1, even after 1000 cycles at the rate of C/2. Importantly, a high discharge capacity of 880 mAh g−1 is maintained at the very high rate of 10 C. The excellent anode performance of GEC stems from both effective buffering of carbon anchored to the Ge nanocrystals and the high open porosity of the GEC aggregated powder with an average pore diameter of 32 nm. Furthermore, the interfacial layer formed between Ge and carbon plays an essential role in prolonging the cycle life. The GEC electrode can be successfully employed as an anode for next generation lithium ion batteries.

The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.

ObjectivesThe penetration of hydrocortisone (HC) from six topical over-the-counter products along with one prescription cream through cultured normal human-derived epidermal keratinocytes (Epiderm™), mouse skin and synthetic nylon membrane was performed as well as the effect hydrating the skin by pre-washing was explored using the Upright Franz Cell.Method and ResultsPermeation of HC through EpiDerm™, mouse skin and synthetic membrane was highest with the topical HC gel formulation with prewash treatment of the membranes among seven products evaluated, 198 ± 32 µg/cm2, 746.32 ± 12.43 µg/cm2, and 1882 ± 395.18 µg/cm2, respectively. Pre-washing to hydrate the skin enhanced HC penetration through EpiDerm™ and mouse skin. The 24-hour HC released from topical gel with prewash treatment was 198.495 ± 32 µg/cm2 and 746.32 ± 12.43 µg/cm2 while without prewash, the 24-h HC released from topical gel was 67.2 ± 7.41 µg/cm2 and 653.43 ± 85.62 µg/cm2 though EpiDerm™ and mouse skin, respectively. HC penetration through synthetic membrane was ten times greater than through mouse skin and EpiDerm™. Generally, the shape, pattern, and rank order of HC diffusion from each commercial product was similar through each membrane.

No abstract

No abstract

IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5′-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50–90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function.