RESUMO
OBJECTIVE To determine the contents of N-nitroso impurities in raw materials/formulations of propranolol， metoprolol， atenolol， esmolol and bisoprolol， and clarify the attention threshold. METHODS Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q/Orbitrap HRMS）was adopted. An ACE Excel 3 C18-AR column was used for the separation and a mixture of 0.2% formic acid solution with 0.01 mol/L ammonium acetate and methanol was employed as the mobile phase by gradient elution， at a flow rate of 0.60 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The heated electrospray ionization source was employed in the positive full mass spectra-selected ion monitoring mode. The contents of N-nitroso impurities in raw materials/formulations of 15 batches of β-blockers from 10 manufacturers were determined by this method. Discovery Studio software was applied to predict the toxicity of the impurities and estimate the attention threshold. RESULTS Among 5 kinds of β-blockers， the linear ranges of N-nitroso propranolol， N-nitroso metoprolol， N-nitroso atenolol， N-nitroso esmolol and N-nitroso bisoprolol were 1.01-503.38， 1.02-508.38， 0.97-483.63， 1.11-554.27 and 1.05-523.92 ng/mL， respectively （r＞0.999）. The limits of quantitation were 1.04， 0.25， 0.05， 0.55 and 1.05 ng/mL， and the limits of detection were 0.52， 0.08， 0.02， 0.17 and 0.52 ng/mL， respectively. RSDs of precision， reproducibility， recovery， stability and durability tests were all lower than 7.5% （n＝6 or n＝5）. Among the 15 batches of samples， except for 1 batch， N-nitroso propranolol （1.07-8.91 ng/mg）， N-nitroso metoprolol （1.43-3.37 ng/mg）， N-nitroso atenolol （1.33 ng/mg）， N-nitroso esmolol （0.19 ng/mg） and N-nitroso bisoprolol （1.27 ng/mg） were detected in all other batches. According to predictions， the above 5 impurities had varying degrees of reproductive toxicity， mutagenicity and carcinogenicity， with attention thresholds of 1.0， 0.4， 4.3， 0.2 and 46.7 ng/mg， respectively. CONCLUSIONS The established method is simple， rapid， sensitive and specific， the estimated attention thresholds are clear， which can be used for the control of N-nitroso impurities in various β-blockers.
RESUMO
Objective To explore the application of subdermal vascular network skin graft in severed finger reunion with small area skin defects.Methods Modified subdermal vascular network,which was inversion thin and middle thick,was used to repair defect of severed finger reunion without exposure of blood vessel.There were 10 patients and 14 fingers,including 7 patients and 10 fingers injured in the dorsal sid with 5 fingers' extensor tendon exposed,and 3 patients and 4 fingers injured in the palmar side with 2 patients' flexor tendon exposed.The defect area was ranged from 1.0 cm × 0.8 cm to 3.0 cm × 1.5 cm.Results In 6 larger subdermal vascular network,skin's edge became blue and blister appeared in the middle.The others was good with skin texture and aspect.Conclusions Modified subdermal vascular network skin graft is safe and effective choose to solve severed finger reunion with smnall area skin defects.
RESUMO
Our study aimed to profile the effect of fasting during the Ramadan month on cognitive function in a group of healthy Muslim athletes. Eighteen male athletes underwent computerized neuropsychological testing during [fasting] and after [non-fasting] Ramadan. Diet was standardized, and tests were performed at 0900h and 1600h to characterize potential time-of-day [TOD] interactions. Psychomotor function [processing speed], vigilance [visual attention], visual learning and memory, working memory [executive function], verbal learning and memory were examined. Capillary glucose, body temperature, urine specific gravity, and sleep volume were also recorded. Fasting effects were observed for psychomotor function [Cohen's d=1.3, P=0.01] and vigilance [d=0.6, P=0.004], with improved performance at 0900h during fasting; verbal learning and memory was poorer at 1600h [d=-0.8, P=0.03]. A TOD effect was present for psychomotor function [d=-0.4, P<0.001], visual learning [d=-0.5, P=0.04], verbal learning and memory [d=-1.3, P=0.001], with poorer performances at 1600h. There was no significant fasting effect on visual learning and working memory. Our results show that the effect of fasting on cognition is heterogeneous and domain-specific. Performance in functions requiring sustained rapid responses was better in the morning, declining in the late afternoon, whereas performance in non-speed dependent accuracy measures was more resilient