Thermoplastic polyethersulfone (PES) modified multifunctional tetraglycidyl-4,4 0 -diaminodiphenylmethane (TGDDM) and triglycidyl para-aminophenol (TGAP) epoxy prepolymers cured with 4,4 0 -diaminodiphenylsulfone (44DDS) were prepared using a continuous reactor method and their reaction-induced phase separated morphologies and mechanical properties were measured and correlated with chemical compositions. 1 H nuclear magnetic resonance ( 1 H NMR) and near-infrared spectroscopy (NIR) were used to quantify the chemical network formation. Atomic force microscopy (AFM) with nanomechanical mapping was employed to resolve the nanoscale phase-separated morphologies. The extent of phase separation in cured networks and resultant domain sizes were determined to be controllable depending upon the multifunctional epoxy compositions. The results obtained from mechanical studies further indicated that tensile modulus was not largely affected by multifunctional epoxy compositions while fracture toughness increased with increase of TGAP content.

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The aim of this study was to formulate and systematically evaluate in vitro and in vivo Helicobacter pylori (Hp) efficacy of chitosan (CS) nanoparticles (NPs). CS NPs were prepared by the polymerid dispersion method. The in vitro anti-Hp effect of concentration, pH and deacetylation degree of CS NP solutions was detected. Then, 60 BALB/c mice were randomly divided into 3 groups and Hp-infected mice were established by inoculating with Hp strain. Thereafter that, mice in different groups received PBS, CS solution of CS NP solution intragastrically, twice daily for 14 consecutive days. Four weeks after the last administration, the mice were killed and part of the gastric mucosa was embedded in paraffin, cut into sections and assayed with Giemsa staining. Part of the gastric mucosa was used to quantitatively culture Hp. At pH 4-6, the anti-Hp effect of CS NP solution had a negative correlation with pH value (P < 0.01), and the optimal pH value was 4; there was a significant difference in anti-Hp effect between 88.5% deacelytation degree (DD88.5) CS NP and 95% deacelytation degree (DD95) CS NP (P < 0.05-0.01). The anti-Hp effect ranked from high to low, i.e., from DD95 CS NP to DD88.5 CS NP; the anti-Hp effect of DD88.5 CS NP and DD95 CS NP showed no difference within between 5 and 20 g/l (P> 0.05). The Hp eradication rate was 0, 55 and 75%, respectively, among the three groups (P < 0.01) and the Hp colonized density in the control group and CS group was significantly higher than that in the CS NP group (P < 0.01, 0.05). These results suggest that CS NP improves the anti-Hp efficacy of CS in vitro or in vivo and has the potential to kill Hp directly.

We developed a panel of multiplex quantitative real-time reverse transcription polymerase chain reaction (mqRT-PCR) assay consisting of seven internally controlled qRT-PCR assays to detect 16 different respiratory viruses. We compared the new mqRT-PCR with a previously reported two-tube mRT-PCR assay using 363 clinical sputum specimens. The mqRT-PCR assay performed comparably with the two-tube assay for most viruses, offering the advantages of quantitative analysis, easier performance, lower susceptibility to contamination, and shorter turnaround time in laboratories equipped with conventional real-time PCR instrumentation, and it could therefore be a valuable tool for routine surveillance of respiratory virus infections in China.

INTRODUCTION: PTG-200 (JNJ-67864238) is an oral peptide that acts locally in intestinal tissues to block IL-23 signaling by selectively binding the IL-23 receptor (IL-23R). The gastrointestinal (GI)-restriction of PTG-200 is demonstrated in vivo by marked drug concentrations in GI tissues and feces and limited systemic blood exposure. PTG-200 therapeutic potential was established in a rat model of TNBS-induced colitis, where its threshold concentration in colonic tissue and luminal feces associated with efficacy was determined to inform the human efficacious dose. 1 The objectives of this Phase 1 study were to assess safety, tolerability, and pharmacokinetics (PK) of PTG-200. METHODS: This first-in-human (FIH) Phase 1 study was a single-center, randomized, double-blind, placebo-controlled trial comprising single and 14-day multiple ascending dose (SAD and MAD) arms in 82 healthy male volunteers. Oral doses ranged from 150 mg to 900 mg once daily (QD, fasted or fed) or twice daily (BID, fed). Subjects were monitored for safety and tolerability. PK in plasma, urine and feces was evaluated. RESULTS: Oral administration of PTG-200 was well-tolerated. There were no serious adverse events, dose-limiting toxicities, or clinically significant adverse events. PTG-200 plasma exposure was low (Table 1), below that expected to result in systemic biological activity. Following single-dose oral administration under fasted conditions, plasma PTG-200 concentrations exhibited dose-related increases with a median time to maximal concentration (Tmax) at 2 h. Administration of a high-fat meal prolonged the median Tmax to 4 h and had a modest effect on peak concentration (Cmax) and estimated overall exposure. Repeat dosing led to dose-related increases in plasma exposure. Consistent with a terminal half-life of ∼1.5 h in plasma, PTG-200 showed no evidence of accumulation except for the 900 mg BID group. Fecal concentrations in several cohorts met or exceeded the targeted threshold concentration associated with efficacy as established using the preclinical colitis model. CONCLUSION: Orally administered PTG-200 was well-tolerated in this FIH study. Systemic PK was consistent with the GI-restricted design of PTG-200. These safety and PK characteristics, combined with fulfillment of fecal drug threshold concentrations, support further clinical development of PTG-200 for the treatment of IBD. A Phase 2 study in patients with moderate-to-severe Crohn's disease is planned.