Effects of the anesthetic agent propofol on neural populations

The neuronal mechanisms of general anesthesia are still poorly understood. Besides several characteristic features of anesthesia observed in experiments, a prominent effect is the bi-phasic change of power in the observed electroencephalogram (EEG), i.e. the initial increase and subsequent decrease of the EEG-power in several frequency bands while increasing the concentration of the anaesthetic agent. The present work aims to derive analytical conditions for this bi-phasic spectral behavior by the study of a neural population model. This model describes mathematically the effective membrane potential and involves excitatory and inhibitory synapses, excitatory and inhibitory cells, nonlocal spatial interactions and a finite axonal conduction speed. The work derives conditions for synaptic time constants based on experimental results and gives conditions on the resting state stability. Further the power spectrum of Local Field Potentials and EEG generated by the neural activity is derived analytically and allow for the detailed study of bi-spectral power changes. We find bi-phasic power changes both in monostable and bistable system regime, affirming the omnipresence of bi-spectral power changes in anesthesia. Further the work gives conditions for the strong increase of power in the δ-frequency band for large propofol concentrations as observed in experiments.     

新型可降解PEI衍生物的表征及其在Brl-3A细胞中的毒性和转染研究

目的:对新型可降解高分子进行表征,研究其在Brl-3A细胞中的毒性和转染效率,以及连接剂比例对以上方面的影响。方法:通过化学方法合成不同比例PEI-Tr高分子,考察其包裹质粒DNA形成纳米颗粒的粒径和电位,以CCK-8方法考察Brl-3A细胞中的细胞毒性,以荧光素酶质粒为报告基因考察Brl-3A细胞中的转染效率。结果:PEI-Tr材料能形成200 nm以下带20 mV左右正电荷的纳米颗粒,具有较好的细胞内吞能力和溶液稳定性,细胞毒性实验证明,随着浓度增加PEI-Tr材料显示了远低于PEI-25kDa的细胞毒性,细胞转染实验表明其拥有高效输送质粒的能力。结论:PEI-Tr是一种高效低毒的可降解聚阳离子载体,在基因输送领域有很大的潜力;连接剂的比例在聚阳离子功能中起到重要作用。     

全麻下颈动脉内膜剥脱术的麻醉体会

目的:评价颈动脉内膜剥脱术(CEA)麻醉疗效,以及经颅多普勒超声(TCD)、微血管多普勒超声(MVD)应用的价值,以及适合颈动脉内膜剥脱术的适合麻醉方法。方法:回顾性分析苏州大学附属一医院脑卒中中心2012年5月至2013年5月所进行的颈动脉内膜剥脱术治疗的19名颅外颈动脉狭窄患者的资料。患者临床症状均伴有不同程度的脑缺血症状。颈动脉狭窄程度2例中度狭窄,17例重度狭窄。所有手术操作均全麻下在显微镜下操作。1例采用补片成形。18例术中采用TCD及MVD监测下完成,1例未采用超声监测。结果:手术成功率为100%,无死亡率。术前脑缺血症状术后患者均有恢复。未发现过度灌注的并发症。麻醉效果达到预期目的。结论:颈动脉内膜剥脱术在多普勒超声MVD及TCD监测下治疗颅外颈动脉狭窄是一种安全、有效的措施;全身麻醉下行CEA手术安全可靠。     

Multiple Propofol-binding Sites in a γ-Aminobutyric Acid Type A Receptor (GABAAR) Identified Using a Photoreactive Propofol Analog

Propofol acts as a positive allosteric modulator of γ-aminobutyric acid type A receptors (GABA_ARs), an interaction necessary for its anesthetic potency in vivo as a general anesthetic. Identifying the location of propofol-binding sites is necessary to understand its mechanism of GABA_AR modulation. [³H]2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (azietomidate) and R-[³H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), photoreactive analogs of 2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (etomidate) and mephobarbital, respectively, have identified two homologous but pharmacologically distinct classes of intersubunit-binding sites for general anesthetics in the GABA_AR transmembrane domain. Here, we use a photoreactive analog of propofol (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol ([³H]AziPm)) to identify propofol-binding sites in heterologously expressed human α1β3 GABA_ARs. Propofol, AziPm, etomidate, and R-mTFD-MPAB each inhibited [³H]AziPm photoincorporation into GABA_AR subunits maximally by ∼50%. When the amino acids photolabeled by [³H]AziPm were identified by protein microsequencing, we found propofol-inhibitable photolabeling of amino acids in the β3-α1 subunit interface (β3Met-286 in β3M3 and α1Met-236 in α1M1), previously photolabeled by [³H]azietomidate, and α1Ile-239, located one helical turn below α1Met-236. There was also propofol-inhibitable [³H]AziPm photolabeling of β3Met-227 in βM1, the amino acid in the α1-β3 subunit interface photolabeled by R-[³H]mTFD-MPAB. The propofol-inhibitable [³H]AziPm photolabeling in the GABA_AR β3 subunit in conjunction with the concentration dependence of inhibition of that photolabeling by etomidate or R-mTFD-MPAB also establish that each anesthetic binds to the homologous site at the β3-β3 subunit interface. These results establish that AziPm as well as propofol bind to the homologous intersubunit sites in the GABA_AR transmembrane domain that binds etomidate or R-mTFD-MPAB with high affinity.     

Association between prehypertension and psychological distress among adults in Saudi Arabia: A population-based survey

BackgroundPrehypertension is a precursor to hypertension status. Psychological distress has been identified earlier among hypertensives; however, there is little evidence for the presumptive relationship between prehypertension and psychological distress.ObjectiveThe study aimed to assess the psychological wellbeing of the Al-Kharj, Saudi Arabia population, using the General Health Questionnaire (GHQ-12) and correlating it with prehypertensive patients in the same population.MethodsA cross-sectional analysis of the population of Al-Kharj, Saudi Arabia, was carried out between January and June of 2016. With an 85 percent response rate, a total of 1016 participants participated in the study. A multiple linear regression analysis was performed to assess the relationship between prehypertension and psychological distress.ResultsThe findings of the adjusted analysis demonstrated that, on average prehypertensive patients were more distressed psychologically than non-hypertensive patients (unstandardized Beta regression coefficient = 3.600; P-value 0.025). Similarly, on average women were found to be more psychologically distressed than men (unstandardized Beta = 1.511, P-value 0.002). Civil workers and unemployed individuals were more psychologically distressed than employed individuals (unstandardized Beta = 1.326, P-value 0.041) while adjusting for the sociodemographic and other variables such as BMI, diabetes status, cholesterol, and smoking status.ConclusionThe current study shows that as compared to normotensive patients, self-rated mental wellbeing and psychological wellbeing are all considerably poorer among prehypertensive patients. To prevent individuals from having negative psychological outcomes and their long-term complications, the Government of Saudi Arabia needs to concentrate on prehypertensive, female, and unemployed individuals. Well-designed longitudinal studies, primarily in Saudi Arabia, are needed in the future to research the cause and impact of poor mental health and prehypertension.     

Hydrologic and geologic factors that influenced spatial variations in loess deposition in China during the last interglacial-glacial cycle: results from proxy climate and GCM analyses

Results from climate proxy and General Circulation Model (GCM) analyses suggest that variations in soil moisture and desert expansion are key hydrologic and geologic factors, respectively, influencing temporal and spatial variations in loess texture and distribution in the Loess Plateau of China. During the last glacial period a reduction in soil moisture led to dune destabilization and a southward expansion of the desert (the source of loess) toward the Loess Plateau. Changes in soil moisture in East Asia may have been influenced by the size and extent of the Fennoscandian ice sheet, and the atmospheric circulation pattern that it induced downstream. These results suggest that both regional factors (i.e. changes in soil moisture and the position of the desert margin) and hemispherical factors (i.e. changes in the size and extent of the Eurasian ice sheets) have influenced loess deposition on the Loess Plateau of China.     

Simultaneous Electrophysiological Recording and Calcium Imaging of Suprachiasmatic Nucleus Neurons

Simultaneous electrophysiological and fluorescent imaging recording methods were used to study the role of changes of membrane potential or current in regulating the intracellular calcium concentration. Changing environmental conditions, such as the light-dark cycle, can modify neuronal and neural network activity and the expression of a family of circadian clock genes within the suprachiasmatic nucleus (SCN), the location of the master circadian clock in the mammalian brain. Excitatory synaptic transmission leads to an increase in the postsynaptic Ca²⁺ concentration that is believed to activate the signaling pathways that shifts the rhythmic expression of circadian clock genes. Hypothalamic slices containing the SCN were patch clamped using microelectrodes filled with an internal solution containing the calcium indicator bis-fura-2. After a seal was formed between the microelectrode and the SCN neuronal membrane, the membrane was ruptured using gentle suction and the calcium probe diffused into the neuron filling both the soma and dendrites. Quantitative ratiometric measurements of the intracellular calcium concentration were recorded simultaneously with membrane potential or current. Using these methods it is possible to study the role of changes of the intracellular calcium concentration produced by synaptic activity and action potential firing of individual neurons. In this presentation we demonstrate the methods to simultaneously record electrophysiological activity along with intracellular calcium from individual SCN neurons maintained in brain slices.     

Mixing ability analysis of wheat cultivar mixtures under diseased and nondiseased conditions

Summary Mixing ability analyses, adapted from combining ability analyses used in plant breeding, were performed on yield and stripe rust (Puccinia striiformis) severity data for two-way mixtures among either four or five club wheat (Triticum aesitivum) cultivars grown in five environments. Initially, two statistics were calculated for each trait: general mixing ability (GMA), the average performance of a cultivar over all of the mixtures, and specific mixing ability (SMA), the deviation of a mixture from the estimated performance of the pair based on its average performance in mixtures. General mixing ability was further divided into two components: genotype performing ability (GPA), the innate ability of a cultivar to yield and resist disease in pure stand, and true general mixing ability (TGMA), the average ability of a cultivar to influence yield and disease when mixed with other cultivars. Significant mean squares for genotypes, GMA, SMA, and TGMA were found for all of the traits in most environments. Examination of TGMA and SMA revealed cultivars and cultivar combinations that were statistically better mixers than the others. Some of the significant effects were probably due to the use of cultivars that differed in height and stripe rust resistance, but for other combinations there was no apparent explanation for enhanced mixing ability.Paper No. 9132 of the Oregon Agricultural Experiment Station. Supported in part by USDA Grants 88-34106-3631 and 88-37151-3662