Hypocholesterolaemic mechanism of bitter melon aqueous extracts via inhibition of pancreatic cholesterol esterase and reduction of cholesterol micellar solubility

This study investigated the hypocholesterolaemic effects of bitter melon aqueous extracts (BMAE) in vitro, the inhibitory effects of BMAE on pancreatic cholesterol esterase (CEase) and incorporation of cholesterol into micelles were investigated. BMAE decreased the in vitro micellar solubility of cholesterol in a dose-dependent manner. The conformation of CEase was investigated by means of circular dichroism (CD) and fluorescence. The result revealed the decrease of α-helix contents, increase of β-sheet and exposure of aromatic amino acid residuals. The incorporation of cholesterol into micelles was inhibited by BMAE. A complex was observed by transmission electron microscopy (TEM), which indicated interaction between cholesterol and BMAE. The result revealed that BMAE can play a role in decreased intestinal cholesterol absorption via inhibition of CEase, and of micelle formation.     

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.     

Acetylcholine Synthesis in a Primary Culture of Porcine Intermediate Lobe Cells

Previous pharmacological studies with the pituitary gland have suggested that acetylcholine (ACh) might be involved in the regulation of intermediate lobe (IL) function. Whether ACh is endogenous to the IL cells or provided from an extrinsic source is unclear. The present experiments tested the possibility that the endocrine cells of the IL may be a source of ACh by measuring certain cholinergic markers in a primary culture of dissociated porcine cells. The endogenous ACh content was readily measurable in both the freshly dissociated IL cells and in 2- or 4-day primary cultures. Choline acetyltransferase activity was also measurable in the freshly dissociated and cultured IL cells and was reduced by 53% in the presence of a specific inhibitor, napthylvinylpyridine (50 μM). IL cells incubated in the presence of [¹⁴C]choline (1 μM) were able to synthesize [¹⁴C]ACh and the accumulation of the new ACh was inhibited by hemicholinium-3 (30 μM), a competitive inhibitor of high affinity choline uptake at cholinergic nerve terminals. In conclusion, these results demonstrate that the endocrine cells of the IL are capable of synthesizing and storing ACh.     

Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility

Development of a disease screening biomarker involves several phases. In phase 2 its sensitivity and specificity is compared with established thresholds for minimally acceptable performance. Since we anticipate that most candidate markers will not prove to be useful and availability of specimens and funding is limited, early termination of a study is appropriate, if accumulating data indicate that the marker is inadequate. Yet, for markers that complete phase 2, we seek estimates of sensitivity and specificity to proceed with the design of subsequent phase 3 studies. We suggest early stopping criteria and estimation procedures that adjust for bias caused by the early termination option. An important aspect of our approach is to focus on properties of estimates conditional on reaching full study enrollment. We propose the conditional‐UMVUE and contrast it with other estimates, including naïve estimators, the well‐studied unconditional‐UMVUE and the mean and median Whitehead‐adjusted estimators. The conditional‐UMVUE appears to be a very good choice. Copyright © 2008 John Wiley & Sons, Ltd.     

Topography of cholinergic afferents from the nucleus basalis of meynert to representational areas of sensorimotor cortices in the rat

We investigated (1) the topography of projection neurons in the nucleus basalis of Meynert (NBM) with efferents to restricted regions of the primary somatosensory (SI), the second somatosensory (SII), and the primary motor (MI) cortices in the rat; (2) the percentage of these NBM projection neurons that were cholinergic; and (3) the collateralization, if any, of single NBM neurons to different subdivisions within SI, to homotopic areas of SI and SII, and to homotopic areas of SI and MI. Retrograde single-and double-labeling techniques were used to study NBM projections to electrophysiologically identified subdivisions of SI and to homotopic representational areas of SI and SII, and of SI and MI. Choline acetyltransferase immunocytochemistry was done to identify cholinergic NBM neurons. Of the retrogradely labeled NBM neurons that projected to selective subdivisions of SI, SII, and MI, 89%, 87%, and 88%, respectively, were cholinergic. We found a rostral-to-caudal progression of retrogradely labeled NBM neurons following a medial-to-lateral sequence of injections into subdivisions of SI. Overlapping groups of single-labeled NBM neurons were observed after injections of different tracers into adjacent subdivisions within SI or homotopic areas of SI and SII, and of SI and MI. We conclude that NBM innervation to SI, SII, and MI is mostly cholinergic in the rat, that each cortical area receives cholinergic afferents from neurons widely distributed within the NBM, and that each NBM neuron projects to a restricted cortical area without significant collateralization to adjacent subdivisions within SI or to homotopic areas of SI and SII, or SI and MI. © 1993 Wiley-Liss, Inc.     

谷氨酸脱氢酶,胆碱氧化酶和葡萄糖-6-磷酸酶对溶酶体中~(67)Ga积累的影响(英文)

目的:比较正常肝组织与肝癌AH 109A,吉田肉瘤中谷氨酸脱氢酶,胆碱氧化酶和葡萄糖-6-磷酸酶的活力对~(67)Ga摄取与积累的影响;方法:制备~(67)Ga枸橼酸溶液给大鼠静注后处死大鼠,制备亚细胞悬液,液闪计数器测定放射活度.结果:~(67)Ga的放射活性在正常肝组织溶酶体中(55％积聚)显著高于肝癌AH109A(32％积聚)和吉田肉瘤(18％)积聚.谷氨酸脱氢酶的活力在正常肝组织,肝癌和吉田肉瘤分别是1830±s 320 U·L~(-1),23±s 6 U·L~(-1)和7±s 2 U·L~(-1);胆碱氧化酶的活力分别是46±s 10 U·L~(-1),25.0±s 0.4 U·L~(-1),2.0±0.4 U·L~(-1);葡萄糖-6-磷酸酶活力分别是2550±s 180 U·L~(-1),84±s 14 U·L~(-1),78±s13 U·L~(-1).结论:正常肝组织中溶酶体酶活力很强,对~(67)Ga的积累起较大作用.癌变组织酶活力降低而作用减弱.吉田肉瘤细胞无肝细胞特点,其溶酶体对~(67)Ga积累作用不大.     

Prognostic significance of cytochemical analysis of leukemic M2 blasts

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.     

党参总碱对东莨菪碱引起小鼠记忆障碍和脑内乙酰胆碱及胆碱乙酰化酶的作用

用跳台法观察到党参总碱(DSA)能改善东莨菪碱(Scop)引起的记忆障碍,并能对抗Scop所致小鼠脑内乙酰胆碱(ACh)浓度下降及胆碱乙酰化酶(ChAT)活性的降低。体外实验发现当在反应液中加入DSA后,ChAT生成ACh的量增加。     

致倦库蚊有机磷抗性相关扩增酯酶B基因的多样性

本实验从佛山和成都两地的致倦库蚊群体中筛选出３个酯酶类型不同的有机磷（ＯＰ）抗性品系，ＦＳ－１、ＦＳ－２和ＣＤ－１品系。各品系的酯酶基因Ｂ扩增水平、酯酶活性和ＯＰ抗性水平三者一致。各品系酯酶Ｂ基因限制性酶切片段比较分析表明，我国的ＯＰ抗生库蚊群体中不仅有世界性分布的酯酶Ｂ１和Ｂ２，而且在佛山和成都地区各有一个新的独立扩增的酯酶Ｂ，分别命名为Ｂ６和Ｂ７。