Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Comparative study on hearing status of preeclampsia infants with different degrees of hypertensive disorder complicating pregnancy and preeclampsia infants without hypertensive disorder complicating pregnancy / 中国实用妇科与产科杂志

OBJECTIVE: To explore the influence and significance of preeclampsia with different degrees of gestational hypertension on infant hearing.METHODS: Totally 1046 newborns whose mothers had a history of pre-eclampsia with hypertensive disorder complicating pregnancy were divided into groups according to the severity of pre-eclampsia and whether they were premature or not from Jan. 2015 to Dec. 2017 in the Forth Hospital of Shijiazhuang.Hearing tests were conducted and compared with newborns whose mothers had no history of pre-eclampsia with hypertensive disorder complicating pregnancy.RESULTS: Of the 14 741 infants studied,57 were finally diagnosed with sensorineural hearing loss,with a total abnormality rate of 0.39%(57/14 741).Among them,34 infants with pre-eclampsia without hypertensive disorder complicating pregnancy had an abnormality rate of 0.25%.There were 12 infants with mild preeclampsia in their mothers,with an abnormality rate of 1.47%.There were 11 infants whose mothers had severe preeclampsia,with an abnormality rate of 4.76%.There were significant differences between mild group and control group,severe group and control group,and severe group and mild group(P0.05),but there was significant difference between the severe group and the control group,and between the severe group and the mild group(P<0.01 and P<0.05,respectively).CONCLUSION: Premature infants with severe hypertensive disorder complicating pregnancy and preeclampsia are at high risk of hearing impairment.The higher the degree of hypertension,the higher the rate of hearing impairment.The emphasis should be put on strengthening the hearing monitoring and follow-up of such children.

Comparison of hemogram changes under chronic intermittent hypoxia in Lasiopodomys mandarinus and Kunming Mus musculus / 生理学报

Mandarin vole (Lasiopodomys mandarinus) spends almost all of its life underground and must have evolved remarkable adaptations to cope with the subterranean hypoxic stress. The aim of present study is to explore the adaptation mechanism through the comparison of hemogram changes under chronic intermittent hypoxia in Mandarin vole and Kunming (KM) mouse (Mus musculus). Mandarin vole and KM mouse were treated with chronic intermittent hypoxia (10.0% oxygen), which was maintained by an oxygen cabin, for 4 h per day during four weeks. Then blood samples from the animals with and without hypoxia treatment were analyzed by a hematology analyzer. The results showed that under normoxic condition mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell count (WBC) and platelet (PLT) in Mandarin vole were significantly lower than those in KM mouse. On the contrast, red blood cell count (RBC) and mean corpuscular hemoglobin concentration (MCHC) in Mandarin vole were higher than that in KM mouse. After four-week chronic intermittent hypoxia treatment, the hemogram changes were as following. MCV and HCT were elevated in Mandarin vole, not affected in KM mouse. Both hemoglobin (HGB) content and MCH in KM mouse increased, while only MCH increased in Mandarin vole. No obvious changes of WBC and PLT were found in two species. These results suggest that the adaptive mechanism of blood system in Mandarin vole responding to hypoxic conditions is different from that of KM mouse. As a subterranean vole, the Mandarin vole has a better tolerance to hypoxia.

Factors affecting proprioceptive recovery after anterior cruciate ligament reconstruction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Proprioception plays an important role in knee movements. Since there are controversies surrounding the overall recovery time of proprioception following surgery, it is necessary to define the factors affecting proprioceptive recovery after anterior cruciate ligament (ACL) reconstruction and to investigate the relationship between proprioception and muscle strength.</p><p><b>METHODS</b>A total of 36 patients who had their ACL reconstructed with a semitendinosus/gracilis graft (reconstructed group: 6 months post-surgery) and 13 healthy adults without any knee injury (control group) were included in the study. Knee proprioception was evaluated with a passive reproduction test. Isokinetic strength was measured using the Biodex System. Statistical analysis was used to compare proprioception of the reconstructed group versus the control group, and to define causal factors, including sex, hamstring/quadriceps ratio, and the course of injury before reconstruction. We also investigated the correlation between the passive reproduction error and quadriceps index.</p><p><b>RESULTS</b>There was a significant difference in proprioception between the reconstructed and control groups (P < 0.05). When the course of injury before reconstruction was less than 4 months, there was a linear correlation with proprioception 6 months after the operation (r = 0.713, P < 0.05). There was a positive correlation between post-surgery proprioception and the quadriceps index at 6 months post-surgery.</p><p><b>CONCLUSIONS</b>Impaired knee proprioception is observed 6 months after ACL reconstruction. Within 4 months of injury, early undertaking of reconstruction is associated with better proprioception outcome. Patients with enhanced proprioception have a better quadriceps index.</p>

Effects of tetramethylpyrazine on large-conductance Ca²⁺-activated potassium channels in porcine coronary artery smooth muscle cells / 生理学报

The aim of the present study was to examine the effects of tetramethylpyrazine (TMP) on large-conductance Ca(2+)-activated potassium channels (BK(Ca) channels) in porcine coronary artery smooth muscle cells, in order to provide the experimental evidence for expounding the mechanism of TMP in dilating coronary artery. Cell-attached and inside-out single channel recording techniques were used to observe the effects of TMP on BK(Ca) channels as well as the effects after the cells were treated by protein kinase A (PKA) inhibitor or protein kinase G (PKG) inhibitor. In inside-out patch, TMP activated BK(Ca) channels by increasing open-state probability (N(Po)) and decreasing close time (Tc) in a concentration-dependent manner. TMP (0.73~8.07 mmol/L) in the bath solution increased N(Po) from (0.01+/-0.003) to (0.03+/-0.01)~(1.21+/-0.18) (P<0.01, n=10), and decreased Tc from (732.33+/-90.67) ms to (359.67+/-41.30) ~ (2.96+/-0.52) ms (P<0.01, n=10). These actions of TMP occurred even when the free Ca(2+) concentration in the bath was reduced to ~ 0 mmol/L. The specific inhibitors of PKA (H-89, 3 mumol/L) and PKG (KT-5823, 1 mumol/L) had no influence on the activation of TMP on BK(Ca) channels. These findings suggest that TMP can directly activate BK(Ca) channels in coronary artery smooth muscle, which probably is an important mechanism in dilating coronary artery.

Mornitoring of the enantiomers of (?) -trans tramadol andits active metabolite in the serum of postoperative patients afterdifferent intravenous doses of (?)-trans tramadol hydrochloride injection / 中国临床药理学与治疗学

Aim To investigate the relationship between the clinical actions and the serum concentrations of the enantiomers of (?)-trans tramadol and its active metabolite. Methods 20 postoperative patients were divided into two groups and given multiple intravenous doses of (?)-trans tramadol hydrochloride injection, 400 mg?d-1 (group A) or 300 mg?d-1 (group B). The blood samples were taken at 38 h after the initial dose. The concentrations of the enantiomers of (?)-trans tramadol and its active metabolite, (?)-trans O-demethyltramadal were determined with high performance capillary electrophoresis(HPCE). Results The concentrations of the enantiomers of (?)-trans tramadol, the frequency and serious level of adverse reactions were higher in group A than in group B. The concentrations of the enantiomers of (?)-trans O-demethyltramadal, the analgesic effect were similar between group A and group B. Conclusion There is much closer relation between the analgesic effect and the concentration of (+)-O-demethyltramadal. The frequency and serious level of adverse reactions may be attributed to the higher concentrations of the enantiomers of (?)-trans tramadol, which are caused by the saturated metabolism.