13C-urea breath test during hospitalization for the diagnosis of Helicobacter pylori infection in peptic ulcer bleeding

Objective: To evaluate the accuracy of ¹³C‐urea breath test (UBT) to detect Helicobacter pylori infection in patients hospitalized with peptic ulcer bleeding and treated with proton pump inhibitors (PPIs). Methods: Patients hospitalized with peptic ulcer bleeding, and treated with omeprazole, had a first UBT performed the day after resuming oral feeding. Patients with a negative UBT during hospitalization underwent a repeated UBT 15 days after stopping PPIs. Results: The first UBT during hospitalization was positive in 86% of 131 patients. Time between admission and performance of the test was longer in patients with negative versus positive UBT (5.2 ± 0.7 versus 4.3 ± 0.5 days; p < .001). The repeated UBT became positive in 15 of 18 (83%) patients with a negative first UBT. In the multivariate analysis, the only variable associated with a negative first UBT was the time elapsed between admission and performance of the test (odds ratio = 6.6; 95%CI = 2.9–15.1). Conclusion: Most H. pylori‐positive patients with ulcer bleeding have a positive UBT (performed just after resuming oral feeding) despite previous treatment with high‐dose PPIs. Nevertheless, to preclude false‐negative results due to PPI therapy, the UBT should be performed as early as possible. If the infection cannot be demonstrated with this first UBT, H. pylori still needs to be definitively excluded with a second UBT performed after stopping PPIs.     

Isolation,identification, and quantification of Pentylcurcumene from Geophila repens: A new class of cholinesterase inhibitor for Alzheimer’s disease

The aerial part of Geophila repens (L.) I.M. Johnst (Rubiaceae) has been used in India to improve intelligence and memory for a long time. As part of our ongoing efforts in discovering potential bioactive compounds from G. repens, we have studied the isolation, identification, and quantification of a new class of cholinesterase inhibitor from G. repens for Alzheimer’s disease (AD). Terpene was isolated from hydroalcohol extract of G. repens (GRHA) and its structure was identified “Pentylcurcumene” by spectroscopic data. HPTLC fingerprint analysis was performed and good separation was achieved in mobile phase (benzene:methanol; 7.5:2.5, v/v, 254 and 366 nm; R_f 0.51). The method was validated using ICH guidelines in terms of linearity, specificity, sensitivity, accuracy, precision, robustness and stability. In cellular antioxidant studies e.g. DPPH, oxygen-radical-absorbance-capacity (ORAC) and cell-based-antioxidant-protection-in-erythrocytes (CAP-e) assays showed that, Pentylcurcumene showed remarkably different degrees of antioxidant activities in dose-dependent manner. Pentylcurcumene demonstrated anticholinesterase activities e.g. IC₅₀ of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition were 73.12 ± 0.56 and 97.65 ± 0.46 μg/ml, respectively. To better understand enzyme kinetics, Lineweaver-Burk plot of Pentylcurcumene displayed the highest affinity with competitive inhibition (reversible) towards both AChE (V_max 0.8) and BChE (V_max 0.6). An improved and advanced HPTLC tool of bioautography detection of Pentylcurcumene has been successfully demonstrated its anticholinesterase activities. Molecular docking simulations of Pentylcurcumene (ligand) and enzymes (proteins) exhibited the binding of ligand at active sites of AChE (human/rat) and BChE (human/homology) efficiently and also predicted the hydrophobic interaction of drug towards different amino acid residue within proteins. As per the results of antioxidant study and with the support of molecular docking analysis, it is concluded that Pentylcurcumene could be a potential first-line cholinesterase-inhibitor for AD.     

注射用丹参多酚酸盐联合丙戊酸钠治疗脑卒中后癫痫患者的疗效分析

目的:研究注射用丹参多酚酸盐联合丙戊酸钠对脑卒中后癫痫的临床疗效和安全性。方法:选择2016年1月～2019年4月东南大学附属中大医院江北院区神经内科住院的80例脑卒中后癫痫患者,将其随机分为两组。对照组的40例患者仅给予丙戊酸钠治疗,观察组的40例患者给予丹参多酚酸盐联合丙戊酸钠治疗。比较两组治疗后的脑电图检查结果、癫痫症状控制情况。结果:治疗后,观察组总有效率为明显高于对照组(97.50%vs. 80%,P0.05);两组的累及导联数、痫样放电、发作持续时间、发作次数较治疗前以及血清神经元特异性烯醇化酶(Neuron specific enolase,NSE)水平均较治疗前明显降低(P0.05),且观察组以上指标均明显低于对照组(P0.05)。两组的嗜睡、皮疹、头痛、感觉异常、恶心呕吐的发生率比较差异无明显统计学意义(P0.05)。结论:注射用丹参多酚酸盐联合丙戊酸钠治疗脑卒中后癫痫的疗效明显优于单用丙戊酸钠治疗,其可更有效控制癫痫症状,且安全性较高。     

自体血清联合玻璃酸钠治疗白内障术后干眼症患者的效果

目的:研究自体血清联合玻璃酸钠治疗白内障术后干眼症患者的临床效果。方法:选择2015年1月～2018年12月我院收治的186例白内障术后干眼症患者,随机分为观察组以及对照组,每组各83例。对照组采用玻璃酸钠滴眼液治疗,观察组联合采用自体血清滴眼液治疗。连续给药4 w后,比较两组的治疗有效率,治疗前后的泪膜破裂试验和泪液分泌试验结果,泪液坏死因子(TNF)-α、白介素(IL)-6以及高敏C-反应蛋白(hs-CRP)水平的改变情况。结果:治疗后,观察组的有效率为95.18%(79/83),明显高于对照组[79.52%(66/83)](P0.05)。两组治疗后的泪膜破裂试验和泪液分泌试验结果均较治疗前明显改善(P0.05),且观察组的泪膜破裂试验和泪液分泌试验的改善程度明显优于对照组(P0.05);两组治疗后的泪液hs-CRP、TNF-α和IL-6水平均较治疗前明显降低,且观察组更少指标明显低于对照组(P0.05)。结论:自体血清联合玻璃酸钠对白内障术后干眼症患者的临床效果明显优于单用玻璃酸钠滴眼液,其可更有效增加泪膜的稳定性,减轻角膜损伤,减少泪液分泌,这可能与下调患者泪液中hs-CRP、TNF-α和IL-6水平有关。     

Effect of salinity on germination characters and seedlings parameters of Egyptian flax cultivars growing in Nyiregyhaza

In the recent years using non-traditional sources, i.e. saline water in irrigation becomes essential. Overcoming the toxic effects of salinity stress and improving salt tolerance is consider one of the challenges for enhancing germination, seedling characters and biochemical analysis. Therefore, a laboratory experiment was conducted to study the response of seven Egyptian flax cultivars i.e. (Giza 9, Giza 10, Giza 11, Giza 12, Sakha 2, Sakha 5 and Sakha 6) germinated under five salinity stress i.e. (control, 3, 6, 9 and 12?dS?m^?1) at Research Institute of Nyiregyhaza using Factorial Experimental in Randomized Complete Block Design (RCBD) with four replications. The following results were recorded: Tested Egyptian flax cultivars significantly varied for germination characters, seedling properties and chemical analysis. Giza 11 exceeded recorded the maximum values of germination and seedling characters, potassium and proline content compared with the other studied cultivars. Increasing salinity stress up to 12?dS?m^?1 significantly affected germination characters, seedlings parameters and chemical analysis. In general, Giza 11 cultivar substantiated best at high level of salinity stress compared with other studied cultivars. Furthermore, produced the lowest values of Na⁺ content.     

Intracellular Na+ Regulates Epithelial Na+ Channel Maturation

Epithelial Na⁺ channel (ENaC) function is regulated by the intracellular Na⁺ concentration ([Na⁺]_i) through a process known as Na⁺ feedback inhibition. Although this process is known to decrease the expression of proteolytically processed active channels on the cell surface, it is unknown how [Na⁺]_i alters ENaC cleavage. We show here that [Na⁺]_i regulates the posttranslational processing of ENaC subunits during channel biogenesis. At times when [Na⁺]_i is low, ENaC subunits develop mature N-glycans and are processed by proteases. Conversely, glycan maturation and sensitivity to proteolysis are reduced when [Na⁺]_i is relatively high. Surface channels with immature N-glycans were not processed by endogenous channel activating proteases, nor were they sensitive to cleavage by exogenous trypsin. Biotin chase experiments revealed that the immature surface channels were not converted into mature cleaved channels following a reduction in [Na⁺]_i. The hypothesis that [Na⁺]_i regulates ENaC maturation within the biosynthetic pathways is further supported by the finding that Brefeldin A prevented the accumulation of processed surface channels following a reduction in [Na⁺]_i. Therefore, increased [Na⁺]_i interferes with ENaC N-glycan maturation and prevents the channel from entering a state that allows proteolytic processing.     

Cell Polarity Kinase MST4 Cooperates with cAMP-dependent Kinase to Orchestrate Histamine-stimulated Acid Secretion in Gastric Parietal Cells

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show that PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser-66 and Thr-567. Histamine stimulation activates PKA, which phosphorylates MST4 at Thr-178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin prephosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells.     

Rescue of Na+ Affinity in Aspartate 928 Mutants of Na+,K+-ATPase by Secondary Mutation of Glutamate 314

The Na⁺,K⁺-ATPase binds Na⁺ at three transport sites denoted I, II, and III, of which site III is Na⁺-specific and suggested to be the first occupied in the cooperative binding process activating phosphorylation from ATP. Here we demonstrate that the asparagine substitution of the aspartate associated with site III found in patients with rapid-onset dystonia parkinsonism or alternating hemiplegia of childhood causes a dramatic reduction of Na⁺ affinity in the α1-, α2-, and α3-isoforms of Na⁺,K⁺-ATPase, whereas other substitutions of this aspartate are much less disruptive. This is likely due to interference by the amide function of the asparagine side chain with Na⁺-coordinating residues in site III. Remarkably, the Na⁺ affinity of site III aspartate to asparagine and alanine mutants is rescued by second-site mutation of a glutamate in the extracellular part of the fourth transmembrane helix, distant to site III. This gain-of-function mutation works without recovery of the lost cooperativity and selectivity of Na⁺ binding and does not affect the E₁-E₂ conformational equilibrium or the maximum phosphorylation rate. Hence, the rescue of Na⁺ affinity is likely intrinsic to the Na⁺ binding pocket, and the underlying mechanism could be a tightening of Na⁺ binding at Na⁺ site II, possibly via movement of transmembrane helix four. The second-site mutation also improves Na⁺,K⁺ pump function in intact cells. Rescue of Na⁺ affinity and Na⁺ and K⁺ transport by second-site mutation is unique in the history of Na⁺,K⁺-ATPase and points to new possibilities for treatment of neurological patients carrying Na⁺,K⁺-ATPase mutations.