1.A novel KCNQ1 mutation in Chinese with congenital long QT syndrome.
Lu LIANG ; Zhong-dong DU ; Ling-ling CAI ; Jian-xin WU ; Tong ZHENG ; Tie-xiong QI
Chinese Journal of Pediatrics 2003;41(10):724-727
OBJECTIVECongenital long QT syndrome (LQTS) is an inherited disorder of cardiac repolarization characterized by prolongation of QT interval and polymorphic ventricular tachycardia torsade de pointes (TdP) in the electrocardiogram (ECG). Clinical symptoms include recurrent syncope, seizure or even sudden death. It is caused by mutations of at least seven genes, six of them encoding ion channels that determine the duration of ventricular action potentials. One of these genes, KCNQ1, encodes an alpha-subunit of cardiac slowly activated delayed rectifier potassium channel. Patients carrying mutations of KCNQ1 are named as LQT1, which accounts for 42% of patients with LQTS. This study sought to analyze the clinical data of Chinese with LQTS and to screen for the mutations of KCNQ1.
METHODSThe universally accepted phenotypic criteria of LQTS was used for identification of probands. There were six families with LQTS. They were enrolled in this study. Clinical and ECG data of each family member were recorded. Genomic DNA was prepared from peripheral blood lymphocytes. Polymerase chain reaction-single strand conformation polymorphism analysis was used to screen for mutations throughout the whole coding region of KCNQ1 and DNA sequencing was performed to determine the exact mutation site.
RESULTSThere were totally 13 patients in the six LQTS families. Five were male and eight female. One suffered from sudden death, 10 had syncope and 2 were asymptomatic. Eleven of the 13 patients had ECG data. Their QT and QTc (mean +/- SD) were (0.460 +/- 0.058) s and (0.516 +/- 0.058) s, respectively. TdP was observed in 3 patients (27%) during the syncope attack. By PCR-SSCP analysis, two novel KCNQ1 deletion mutations 356-357 Delta QQ and 626-631 Delta GSGGPP were identified in 7 patients of 2 families. None of 50 normal individuals carried these mutations, indicating these two mutations were likely to cause the disease. In addition, P448R was found in one affected and some unaffected members in other two families and in 7 of 50 (14%) normal individuals, indicating that this might be a polymorphism. All the three mutations located in C-terminal domain of KCNQ1 protein.
CONCLUSIONSTwo novel deletion mutations and one novel polymorphism of KCNQ1 gene were identified among 6 Chinese families with LQTS.
Adolescent ; Adult ; Base Sequence ; Child ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Electrocardiography ; Female ; Humans ; KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; Long QT Syndrome ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Single-Stranded Conformational ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated
2.Hypotriglyceridemic effects of apple polyphenols extract via up-regulation of lipoprotein lipase in triton WR-1339-induced mice.
Nan YAO ; Rong-rong HE ; Xiao-hui ZENG ; Xue-jun HUANG ; Tie-liang DU ; Jing-chao CUI ; Kurihara HIROSHI
Chinese journal of integrative medicine 2014;20(1):31-35
OBJECTIVETo investigate the anti-hyperlipidemic effects of apple polyphenols extract (APE) in Triton WR-1339-induced endogenous hyperlipidemic model.
METHODSFirstly, APE was isolated and purified from the pomace of Red Fuji Apple and contents of individual polyphenols in APE were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Secondly, forty male National Institude of Health (NIH) mice were randomly divided into 5 groups with 8 animals in each group. The Fenofibrate Capsules (FC) group and APE groups received oral administration of respective drugs for 7 consecutive days. All mice except those in the normal group were intravenously injected through tail vein with Triton WR-1339 on the 6th day. Serum and livers from all the mice were obtained 18 h after the injection. The changes in serum total cholesterol (TC), triglyceride (TG), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured by respective kits. Finally, expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) mRNA was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS SERUM TC AND TG LEVELS SIGNIFICANTLY INCREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY REDUCED THE SERUM LEVEL OF TG IN HYPERLIPIDEMIC MICE (P<0.01). SERUM LPL AND HTGL ACTIVITIES SIGNIFICANTLY DECREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE NORMAL GROUP (P<0.05). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE SERUM ACTIVITY OF LPL IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01). FURTHERMORE, COMPARED WITH THE NORMAL GROUP, HEPATIC MRNA LEVEL OF PPARα IN THE MODEL GROUP SIGNIFICANTLY DECREASED (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE EXPRESSION OF PPARα IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01):
CONCLUSIONAPE could reduce TG level via up-regulation of LPL activity, which provides new evidence to elucidate the anti-hyperlipidemic effects of APE.
Animals ; Chlorogenic Acid ; pharmacology ; therapeutic use ; Cholesterol ; blood ; Flavonoids ; pharmacology ; therapeutic use ; Hyperlipidemias ; blood ; drug therapy ; enzymology ; pathology ; Hypolipidemic Agents ; pharmacology ; Lipoprotein Lipase ; blood ; genetics ; Male ; Mice ; PPAR alpha ; genetics ; metabolism ; Phytotherapy ; Polyethylene Glycols ; RNA, Messenger ; genetics ; metabolism ; Tannins ; pharmacology ; therapeutic use ; Triglycerides ; blood ; Up-Regulation ; drug effects
3. Edaravone intervening the proliferation and differentiation of neural stem cells in rats with permanent cerebral ischemia
Xiao-Van LIANG ; Meng ZHAO ; Xin DU ; Hong-Wei LIU ; Yang ZHOU ; Yu GU ; Tie-Jun ZHANG
Acta Anatomica Sinica 2021;52(3):370-376
Objective To observe the effect of edaravone on endogenous neural stem cells in rats with permanent cerebral ischemia. Methods The rat model of permanent cerebral ischemia was established by electrocoagulation. Thirty SD rats were randomly divided into three groups; sham operation group, brain injury group and edaravone group. Six hours after the establishment of the model, the edaravone group was intraperitoneally injected with 1.5 g/L edaravone (10 ml/kg) once a day. The sham operation group and the cerebral ischemia group were intraperitoneally injected with saline of equal volume for 7 days. 24 hours after the last administration, BrdU positive cells, Nestin/BrdU positive cells, neuronal class III β-tubulin (Tuj1)/BrdU positive cells and glial fibrillary acidic protein (GFAP)/BrdU positive cells were observed by immunofluorescent staining, Tuj1 and GFAP protein expressions were detected by Western blotting. Results Compared with the cerebral ischemia group, the BrdU positive cells, Nestin/BrdU positive cells, Tuj1/BrdU positive cells and GFAP/BrdU positive cells increased significantly in the infraventricular area and the cortex area around the ischemia in the edaravone group (P<0.05). Compared with the cerebral ischemia group, the expression of Tuj1 and GFAP protein in the cerebral cortex of edaravone group increased ( P<0.05). Conclusion Edaravone can promote the proliferation of endogenous neural stem cells and astrocytes in the subventricular area and the cortex around ischemia, and promote the differentiation of endogenous neural stem cells into neurons.
4.Effect of Paroxysmal Atrial Fibrillation on Parameters Monitored by Transpulmonary Thermodilution Method.
Hua-dong ZHU ; Liang-liang ZHENG ; Chen LI ; Dong-qi YAO ; Ji-hai LIU ; Tie-kuan DU ; Xue-zhong YU ; Jun XU
Acta Academiae Medicinae Sinicae 2016;38(2):140-143
OBJECTIVETo investigate the effect of atrial fibrillation on the accuracy of parameters monitored by transpulmonary thermodilution method.
METHODSTotally 12 patients from emergency intensive care unit with paroxysmal atrial fibrillation were enrolled. The hemodynamic parameters such as heart rate, mean arterial pressure, cardiac index, systemic vascular resistance index, intrathoracic blood volume index, and extravascular lung water index were monitored by transpulmonary thermodilution method before paroxysmal atrial fibrillation and during atrial fibrillation, the number of B-lines was detected by lung ultrasonography before and during paroxysmal atrial fibrillation. The changes of all the parameters were analyzed.
RESULTSWhen the paroxysmal atrial fibrillation happened, the heart rate increased significantly [(123.3±20.0) beat/min vs. (98.9±12.3) beat/min, P=0.006]; the mean arterial pressure [(86.9±10.2) mmHg vs. (93.0±12.5) mmHg, P=0.058], cardiac index [(2.82±0.62) L/(min·m(2)) vs. (3.31±1.02) L/(min·m(2)), P=0.058] and systemic vascular resistance index [(2254±947) dyn·s·cm(-5)·m(2) vs. (2302±828) dyn·s·cm(-5)·m(2), P=0.351] had no obvious change; however, the intrathoracic blood volume index significantly increased [(1333±90) ml/m(2) vs. (937±111) ml/m(2), P<0.001]; extravascular lung water index also increased significantly [(16.1±1.1) ml/kg vs. (6.5±1.9) ml/kg, P<0.001]. No significant difference was found in the number of B-lines detected by lung ultrasonography before and during atrial fibrillation (10.0±4.2 vs. 9.4±4.4, P=0.180).
CONCLUSIONBoth intrathoracic blood volume and extravascular lung water monitored by transpulmonary thermodilution method were overvalued during paroxysmal atrial fibrillation, which may mislead the clinical judgment and decision-making.
Atrial Fibrillation ; physiopathology ; Blood Pressure ; Blood Volume ; Cardiac Output ; Extravascular Lung Water ; Heart Rate ; Hemodynamics ; Humans ; Intensive Care Units ; Thermodilution ; Vascular Resistance