Experimental research on individual-specific rapid potassium supplementation strategy for fatal severe hypokalemia / 中华危重病急救医学

Objective To explore the effectiveness and safety of the individual-specific rapid potassium supplementation strategy, and to provide experimental basis for treating fatal severe hypokalemia. Methods An acute fatal severe hypokalemia model was reproduced in 20 healthy adult Japanese big ear white rabbits with half lethal dose (LD50) of barium chloride (BaCl2) solution 168 mg·5 mL-1·kg-1. The rabbits were divided into conventional potassium supplementation group and individual-specific rapid potassium supplementation group according to random number table method with 10 rabbits in each group. All the animals were injected with 3% KCl through the auricular marginal veins by a micro-injection pump, and the target plasma potassium concentration was 4 mmol/L. The rabbits in conventional potassium supplementation group were administered continuously potassium infusion at the standard infusion rate of 0.4 mmol·kg-1·h-1. And those in the individual-specific rapid potassium supplementation group were treated in two steps: first, a loading dose of potassium was rapidly injected within 5 minutes, and this step was repeated until the plasma potassium concentration increased to 3.5 mmol/L; second, a sustaining dose of potassium infusion was continued at the rate of 0.4 mmol·kg-1·h-1 after the increase in plasma potassium concentration. The changes in electrocardiogram, blood pressure, respiratory rate (RR), plasma potassium concentration, urine potassium concentration, urine volume, potassium content in extracellular fluid (ECF) and other parameters were monitored. The potassium supplementation, potassium excretion and potassium cross cell status were recorded. Adverse reactions and 7-day death were observed. Results Since the BaCl2 administration, the plasma potassium concentration of all experimental rabbits were significantly lower than baseline at 0.5 hour, which was decreased below 2.5 mmol/L at 2.0 hours when the ventricular arrhythmias appeared, indicating the reproduction of fatal severe hypokalemia model was successful. There was no significant difference in gender, weight, baseline heart rate (HR), RR, mean arterial pressure (MAP), blood gas analysis or K+, Na+, Cl- levels between the two groups. Compared with baseline levels, MAP was significantly decreased and RR was significantly increased before potassium supplementation in both groups, but the parameters were improved significantly and restored to the baseline after potassium supplementation. There was no significant difference in MAP or RR during potassium supplementation between the two groups. The amount of potassium supplementation in two groups showed no significant differences. However, compared with the conventional potassium supplementation group, in the individual-specific rapid potassium supplementation group, the increase in plasma potassium concentration, urine potassium concentration, and the increase in potassium content in ECF were significantly increased [the increase in plasma potassium concentration (mmol/L): 2.40±0.33 vs. 1.51±0.75, urine potassium concentration (mmol/L):164.94±18.07 vs. 108.35±19.67, the increase in potassium content in ECF (mmol): 1.17±0.16 vs. 0.73±0.35], the duration of potassium infusion was shortened (hours: 2.1±0.7 vs. 4.7±1.4), the total urine volume, renal excretion of potassium, and the amount of transcellular potassium shift were significantly decreased [total urine volume (mL):6.40±1.78 vs. 13.60±4.69, renal excretion of potassium (mmol): 1.04±0.26 vs. 1.46±0.51, amount of transcellular potassium shift (mmol): 1.39±0.21 vs. 1.84±0.62], the duration of arrhythmia was shortened (minutes: 19.60±8.92 vs. 71.80±9.84), with statistically significant differences (all P < 0.05). Hyperkalemia did not occur in both groups. The rabbits of the individual-specific rapid potassium supplementation group were all alive, while 4 died in the conventional potassium supplementation group, and statistically significant difference was found between the two groups (P < 0.01). Conclusions These data demonstrate that the individual-specific rapid potassium supplementation strategy can shorten the time for correcting hypokalemia, which is a better option to reverse life-threatening arrhythmia caused by severe hypokalemia, with a high rescue success rate. The process of potassium supplement is safe and effective.

Interactions of uranyl ion with cytochrome b5 and its His39Ser variant as revealed by molecular simulation in combination with experimental methods.

The biological toxicity of uranyl ion (UO (2) (2+) ) lies in interacting with proteins and disrupting their native functions. The structural and functional consequences of UO (2) (2+) interacting with cytochrome b (5) (cyt b (5)), a small membrane heme protein, and its heme axial ligand His39Ser variant, cyt b (5) H39S, were investigated both experimentally and theoretically. In experiments, although cyt b (5) was only slightly affected, UO (2) (2+) binding to cyt b (5) H39S with a K (D) of 2.5 µM resulted in obvious alteration of the heme active site, and led to a decrease in peroxidase activity. Theoretically, molecular simulation proposed a uranyl ion binding site for cyt b (5) at surface residues of Glu37 and Glu43, revealing both coordination and hydrogen bonding interactions. The information gained in this study provides insights into the mechanism of uranyl toxicity toward membrane protein at an atomic level.

Drug-resistant gene based genotyping for Acinetobacter baumannii in tracing epidemiological events and for clinical treatment within nosocomial settings / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acinetobacter baumannii has emerged as an important pathogen related to serious infections and nosocomial outbreaks around the world. However, of the frequently used methods, pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) in Acinetobacter baumannii genotyping lack the direct molecular proof of drug resistance. This study was conducted to establish a typing method based on drug resistant gene identification in contrast to traditional PFGE and AFLP in the period of nosocomial epidemic or outbreak.</p><p><b>METHODS</b>From January 2005 to October 2005, twenty-seven strains of Acinetobacter species from Intensive Care Units, the Second Affiliated Hospital in Ningbo were isolated, including both epidemic and sporadic events. Susceptibility test, PFGE, AFLP and drug resistance gene typing (DRGT) were carried out to confirm the drug resistance and analyze the genotyping, respectively. PFGE was used as a reference to evaluate the typeability of DRGT and AFLP.</p><p><b>RESULTS</b>Twenty-seven strains of Acinetobacter displayed multiple antibiotic resistance and drug resistant genes, and beta-lactamase genes were detected in 85.2% strains. The result of DRGT was comparable to PFGE in Acinetobacter strains with different drug resistance though a little difference existed, and even suggested a molecular evolution course of different drug-resistant strains. AFLP showed great polymorphism between strains and had weak ability in distinguishing the drug resistance.</p><p><b>CONCLUSION</b>Compared to AFLP and PFGE, DRGT is useful to analyze localized molecular epidemiology of nosocomial infections and outbreaks, which would benefit clinical diagnosis and therapy.</p>

[Textual research on the hypothesis of Zhang Zhong-jing "being the governor of Changsha"].

It was always a historical disputed case on the hypothesis of Zhang Zhong-jing, a famous doctor in the Eastern Han Dynasty (25 - 220 A.D.), was once the governor of Changsha. Based on large amount of studies on archival materials combining with unearthed relics, it can be fully ascertained that Zhang Zhongjing had been the governor of Changsha with his tenure in the year of Jian'an 7th to 10th or 12th year, ie, from 202 A.D. to 205 or 207. During this period, Zhang insisted to have clinical practice and wrote his Shang Han Za Bing Lun (Treatise on Exogenous Cold and Miscellaneous Diseases), exerting profound influence on later generations. The Zhang-gong ci (memorial ancestral temple for Mr. Zhang) was built in Changsha city in the Qing dynasty to commemorate him and the medical sage Zhang Zhong-jing is recalled and venerated deeply by the people in the city even today.