Multilocus Analyses Reveal Involvement of the ESR1, ESR2, and FSHR Genes in Migraine

Objective.— Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view. Methods.— We investigated 5 polymorphisms implicated in female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of 730 subjects matched for age and sex. The effect of gene–gene interaction was assessed using the set association approach, and the corresponding haplotypes were studied with PM Plus software. To corroborate initial results, we analyzed the selected markers using a cohort of 134 families in which 168 trios were suitable for transmission‐disequilibrium test (TDT) analysis under the migraine with aura (MA) phenotype. Results.— A total of 356 consecutive migraine patients (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and 374 matched controls [71% females]) were genotyped. In the 2‐point analyses, the ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and this association was higher with the FSHR polymorphism in MA females (P = .004, uncorrected). Using the SUMSTAT program, we observed ESR2‐ESR1‐FSHR significant gene–gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females). We corroborated that ESR2‐ESR1‐FSHR haplotypes interacted for migraine under a model‐free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e‐4, under the heterogeneity model; P = .001 for females). These results were corroborated using family‐based association approaches. We observed nominal association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study, and significant association for ESR1 using family‐based association test statistics. Haplotype‐TDT analyses showed further significant gene–gene interaction for ESR1‐ESR2 (global P = .009), ESR2‐FSHR (global P = .011), and nominally significant interaction for ESR2‐ESR1‐FSHR genes (global P = .037). Conclusion.— We found significant association of female hormone metabolism polymorphisms under the perspective of multigene approach.     

神经生长因子对局灶性脑缺血神经干细胞巢蛋白表达及细胞类型的影响

目的:实验于2006-02/07在锦州医学院科学实验中心完成。将72只健康SD大鼠按随机数字表法分为假手术组、模型组、神经生长因子治疗组,每组24只。采用Logna等改良法复制大脑中动脉血栓模型,动物清醒2h后进行功能评价,动物神经功能达到2级的纳入实验。假手术组除不进行大脑中动脉线栓外,其余同模型组。神经生长因子治疗组于缺血后立即腹腔注射神经生长因子1000μg/kg,1次/d。于缺血后1,3,7,14d处死动物,运用免疫组化和免疫荧光双标的方法观察神经生长因子对脑缺血后神经干细胞巢蛋白的表达及其细胞类型的影响。结果:72只大鼠均进入结果分析。①神经生长因子治疗组和模型组大脑皮质均可见巢蛋白阳性细胞,细胞呈圆形或椭圆形。与模型组相比,除缺血后1d外,神经生长因子治疗组其他时间点的巢蛋白阳性细胞数均明显高于模型组,两组缺血后各时间点的巢蛋白阳性细胞数均高于假手术组[模型组:(3.47±0.51),(5.13±1.14),(13.95±3.56),(8.97±2.08)个;神经生长因子治疗组:(3.81±0.66),(9.88±2.08),(19.87±3.86),(26.17±2.90)个,假手术组:0,P<0.05,P<0.01]。②模型组和神经生长因子治疗组3d时缺血皮质巢蛋白阳性突起主要与胶质纤维酸性蛋白共存,14d时巢蛋白与神经元特异性烯醇化酶共存明显增多。结论:神经生长因子能增加局灶性脑缺血后巢蛋白的阳性细胞的数目,并促进其分化为神经元和神经胶质细胞。     

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

A modified lightwand-guided nasotracheal intubation technique for oromaxillofacial surgical patients

Study ObjectiveTo investigate the efficiency of a double curve nasotracheal tube on lightwand-guided nasotracheal intubation.DesignProspective, randomized, controlled trial.SettingUniversity medical center hospital.Patients60 ASA physical status I and II patients undergoing oromaxillofacial surgery.Interventions and MeasurementsPatients undergoing surgery with nasotracheal intubation and general anesthesia were randomly enrolled in the laryngoscopy group or the lightwand group. The same type of double curve nasotracheal tube was used in both groups. In the laryngoscopy group, intubation was assisted with a Macintosh No. 3 standard curved blade and Magill forceps. In the lightwand group, intubation was aided with a flexible lightwand device (without the inner stiff stylet). Intubation time was divided into two parts: Part one, from selected naris to oropharynx; Part two, from oropharynx into trachea. Part one, Part two, and total intubation time, hemodynamic responses to nasotracheal intubation, and adverse events or complications were recorded.Main ResultsTotal intubation times in the lightwand group and the laryngoscopy group were 22.8 ± 8.0 sec vs 30.3 ± 8.2 sec (P < 0.001), respectively. The lightwand group had comparable hemodynamic responses to those of the laryngoscopy group. Adverse events and complications were all self-limited, with similar occurrence in both groups.ConclusionFor patients undergoing oromaxillofacial surgery, modified lightwand-guided nasotracheal intubation is feasible with a double curve nasotracheal tube and is an efficient alternative technique.     

Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells

Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 microM) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.     

A rare case of cardiogenic shock caused by takotsubo syndrome associated with SARS-CoV-2 infection: The value of echocardiography in the diagnosis and monitoring of the efficacy of extracorporeal membrane oxygenation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly invades the respiratory system, but may also cause various cardiovascular complications. We report a rare case of myocarditis associated with SARS-CoV-2 infection. A 61-year-old man was admitted to the hospital with a positive nucleic acid test for SARS-CoV-2. A sudden increase in troponin level (up to .144 ng/mL) was observed on the 8th day after admission. He developed symptoms of heart failure and progressed rapidly to cardiogenic shock. Echocardiography on the same day showed reduced left ventricular ejection fraction, reduced cardiac output, and segmental ventricular wall motion abnormalities. Takotsubo cardiomyopathy associated with SARS-CoV-2 infection was considered based on the typical echocardiography findings. We immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. The patient was successfully withdrawn from VA-ECMO after 8 days following recovery of ejection fraction to 65% and all indicators qualifying the withdrawal criteria. Echocardiography plays an important role in dynamic monitoring of cardiac changes in such cases and can help determine the timing of extracorporeal membrane oxygenation treatment and withdrawal.     

Gypenoside XLIX, a naturally occurring PPAR-alpha activator, inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells

Vascular cell adhesion molecule-1 (VCAM-1) is involved in several diseases, including chronic inflammation and atherosclerosis. Inhibition of the expression of this adhesion molecule is one of the key targets of anti-inflammatory, anti-cancer and anti-atherosclerotic drugs. Gynostemma pentaphyllum is a traditional medicine widely used in the treatment of respiratory inflammation, hyperlipidemia and atherosclerosis. However, its molecular mechanisms of action are still largely unknown. Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. pentaphyllum. We have recently demonstrated Gypenoside XLIX to be a selective peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gypenoside XLIX concentration-dependently (0-300 microM) inhibited VCAM-1 promoter activity after induction by cytokine tumor necrosis factor (TNF)-alpha in human umbilical vein endothelial cells (HUVECs) transfected with promoter-reporter construct pVCAM-1-LUC. Furthermore, Gypenoside XLIX inhibited TNF-alpha-induced VCAM-1 mRNA and protein overexpression in HUVECs. The result of the enzyme immunoassay demonstrated that Gypenoside XLIX inhibited TNF-alpha-induced increase in cell surface VCAM-1 protein levels in HUVECs. In the present study we show that activities of Gypenoside XLIX are similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, Gypenoside XLIX-induced inhibition on TNF-alpha-stimulated VCAM-1 promoter hyperactivity was completely abolished by a selective blocker of PPAR-alpha, MK-886. Thus, our findings suggest that Gypenoside XLIX inhibits cytokine-induced VCAM-1 overexpression and hyperactivity in human endothelial cells via a PPAR-alpha-dependent pathway. These data provide new insight into the rational basis of the use of the traditional Chinese herbal medicine G. pentaphyllum in the treatment of inflammatory and cardiovascular diseases, including atherosclerosis.