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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).
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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.
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Objective To evaluate the role of magnetic resonance spectroscopy (MRS) and diffusion-weighted MRI (DWI) in detecting regional cerebral metabolic changes and changes of water molecular motion in rabbits after explosive brain injury at different time points of injury after being treated with hyperbaric oxygen therapy. Methods Ninety New Zealand white rabbits were divided into control group, trauma group and hyperbaric oxygen treatment group. The injured models in the later 2 groups were established using 600 mg TNT equivalent of paper detonators in the rabbit brain at the top of 6.5 cm vertical distance. Rabbits in the trauma group and hyperbaric oxygen treatment group were sub-divided into 1, 3, 7, 14 and 21 d treatment groups, respectively. The survival of these rabbits was observed at these time points. Hyperbaric oxygen treatments lasting for 1, 3, 7, 14 and 21 d were given to each hyperbaric oxygen treatment sub-groups, respectively. Performance under MRS was detected and dynamic changes of N-acetylaspartate (NAA)/creatine (Cr) ratio and NAA/choline(Cho)+Cr value were observed with MRS. DWI was employed to detect the dynamic changes of apparent diffusion coefficient (ADC) values. Results The NAA/Cr ratio in the trauma group markedly decreased right after the injury and slightly rose 7 d after the injury. Compared with that in the trauma group, the NAA/Cr ratio in the hyperbaric oxygen treatment group was significantly increased (P＜0.05). The NAA/Cho+Cr value in the trauma group was markedly decreased right after the injury, while that in the hyperbaric oxygen treatment group was obviously increased as compared with that in the trauma group (P＜0.05). ADC values in the region of interest of the trauma group was decreased after 1 d of treatment and gradually increased after 3 d of treatment; the ADC values in the hyperbaric oxygen treatment group was obviously higher than those in the trauma group (P＜0.05). Conclusion Hyperbaric oxygen might improve the prognosis by improving local metabolism of neurons, inhibiting brain edema, and enhancing local gliosis repair;, ultra-early intervention (within one week of injury) may be much favorable for animals/patients after explosive brain injury.
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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.
Subject(s)
Animals , Mice , Adaptation, Physiological , Physiology , Arvicolinae , Blood , Chronic Disease , Erythrocytes , Hemoglobins , Hypoxia , Blood , Blood , Species SpecificityABSTRACT
Objective To explore the effect of blocking of gap junction communication on neuronal apoptosis in rabbit hypothalamus after explosive brain injury. Methods Forty-eight rabbits were equally randomized into control group and experimental group. Octanol, a gap junction blocker, was injected through the left ventricle to block the gap junction communication in the experimental group and physiological saline in the control group instead. Rabbit models with explosive brain injury were induced by paper detonators 2 h after that. One, 3 and 7 d after the inducement, these rabbit models were sacrificed and thus, they were subdivided into 3 groups (n=8). The protein expression of gap junctional connexins 43 (Cx43) was observed by Western blotting and caspase-3 protein expressions in the hypothalamus were detected by immunohistochemical staining and RT-PCR. Results The protein expression of Cx43 in the experimental group was significantly lower than that in the control group at all time points (P<0.05), and that in the experimental group reached the peak level 3 d after the brain injury.The expressions of caspase-3 in the experimental group were significantly lower than those in the control group after the injury (P<0.05). Conclusion Blocking of gap junction communication can reduce the incidence rate of neuronal apoptosis in the hypothalamus after brain injury, and Cx43 might play an important regulation role in this process.
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Objective To observe the changes of autophagy and apoptosis in the cerebral cortex in rats with brain explosive injury and received hyperbaric oxygen (HBO) treatment, and investigate the effect and significance of HBO on them. Methods Fifty-four SD rats were randomly divided into control group (n=6), explosive injury group (n=24) and explosive injury treated with HBO group (n=24).The control group was not injured and 600 mg TNT electric detonators were exploded over the brain of rats at a 12 cm distance in the explosive injury group and explosive injury treated with HBO group. HBO management was given to the explosive injury treated with HBO group 3 and 22 h after explosive injury and at the same time of the other 6 d. RT-PCR and Western blotting were used to detect the changes of Beclin-1 and caspase-3 in the cerebral cortex on the 6th and 24th h, 3rd and 7th d of injury. Results The expression levels of Beclin-1 and caspase-3 in the explosive injury group and explosive injury treated with HBO group were obviously higher than those in the control group (P＜0.05). The levels of Beclin-1and caspase-3 in the explosive injury treated with HBO group were significantly lower than those in the explosive injury group at the same time points (P＜0.05). Conclusion The decreased expressions of autophagy and apoptosis in brain cells by HBO treatment might be one of the possible mechanisms of treating craniocerebral injury.
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<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>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Anterior Cruciate Ligament , Pathology , General Surgery , Knee Injuries , Pathology , General Surgery , Proprioception , Physiology , Plastic Surgery Procedures , Methods , Recovery of FunctionABSTRACT
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.
Subject(s)
Animals , Coronary Vessels , Cell Biology , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Patch-Clamp Techniques , Potassium Channels, Calcium-Activated , Physiology , Pyrazines , Pharmacology , Swine , Vasodilator Agents , PharmacologyABSTRACT
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.