The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

Biosynthesis and secretion of the third component of complement by human endothelial cells in vitro.

The third component of complement (C3) is synthesized and released by cultured human capillary endothelial cells. After the incubation of cells in a methionine-free medium containing 35S-methionine for 48 hr, culture supernatants were immunoprecipitated with anti-human C3 serum. SDS solubilization and 2-ME reduction of the immunoprecipitates, followed by separation with SDS-polyacrylamide gel electrophoresis and autoradiography, revealed two major bands comparable to those of the alpha and beta chains of human C3. The content of C3 in the culture medium harvested at different time-intervals was determined by ELISA. The C3 secretion rate was about 250 ng/10(6) cells/5 days in the primary culture medium and 75 ng/10(6) cells/5 days after seven passages. The capillary endothelial cells described here have factor VIIIRAg specific for endothelial cells, and exhibit ring formation resembling capillary lumina, but they lack Weibel-Palade bodies.     

Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS) — an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with ^113mIn. Ten patients with ARDS exhibiting increased PPA indices (>1.0x10^-3/min) were given an intravenous infusion of terbutaline (7 g/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0x10^-3/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n=5) and non-survivor (n=5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p<0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implication for beta-2-agonists in ARDS.     

急性颅内血肿清除后继发对侧迟发性血肿

目的：急性外伤性颅内血肿清除的术中及术后，如及时发现对侧迟发性血肿并治疗可提高疗效。方法：在术中发生急性脑肿胀时应在对侧钻颅探查或术后病人恶化时行ＣＴ检查。结果：治疗３０例对侧迟发血肿病人其中１０例死亡，手术死亡率为３３．３％。结论：在清除急性外伤性颅内血肿时发生急性脑肿胀或术后病情恶化应想到对侧可能是迟发性血肿形成，宜尽早钻颅探查或复查ＣＴ，早诊早治可改善预后。     

The effect of mental countermeasures on a novel brain‐based feedback concealed information test

The feedback concealed information test (fCIT) is a novel form of the CIT, providing participants with feedback regarding their memory concealment performance. The fCIT utilizes event‐related potentials (recognition‐P300 and feedback‐related event‐related potentials) and has been shown to provide high efficiency in detecting information concealment. However, it is unclear how well the fCIT performs in the presence of mental countermeasures. To address this question, participants were trained to use countermeasures during fCIT. Results showed that the recognition‐P300 efficiency decreased when participants used countermeasures. However, the efficiencies of feedback‐related negativity and feedback‐P300 were unchanged, with feedback‐P300 still showing a high detection efficiency (AUC = 0.86) during countermeasures. These findings demonstrate the potential of fCIT for subverting countermeasures.     

从DNA转录角度探讨喜树碱类药物的神经毒性

喜树碱类药物作为公认抗肿瘤药,其机制与抑制肿瘤细胞DNA复制过程中拓扑异构酶I(topoisomerase I,Topo-I)的活性有关。因此,分裂增殖活跃的肿瘤细胞对该类药物更为敏感。近年来,实验及临床研究均有报道,喜树碱对不具有分裂增生特性的神经元也显示出较明显的毒性作用,可引起神经元凋亡,但其机制目前并不明确。在深入分析喜树碱类药物药理作用的基础上,结合目前其神经毒性的研究进展,提出喜树碱对神经元的毒性机制可能依然与抑制Topo-I活性有关,可能是通过干扰DNA转录过程中Topo-I的活性,导致DNA转录障碍,最终引发神经元凋亡。并在该研究思路的基础上,初步提出下一步的工作设想。     

维甲酸对新生大鼠高氧肺损伤的干预作用

目的探讨高氧暴露新生大鼠肺组织结构的变化和连接蛋白Connexin26(Cx26)的表达情况及维甲酸对其影响。方法24只3日龄SD大鼠随机分为3组:高氧暴露维甲酸组(维甲酸组)、高氧暴露安慰组(高氧组)、空气暴露对照组(对照组);采用950mL/L氧体积分数条件下制作新生大鼠高氧肺损伤模型;观察大鼠一般情况,用HE染色法观察肺组织结构变化及辐射状肺泡计数(RAC),免疫组织化学检测Cx26的表达。结果体质量、RAC等方面与空气组相比,高氧组、维甲酸组均有显著差异[(13.53±1.27)、(13.38±1.29)、(17.37±0.89)g,F=30.19P=0;(11.15±1.33)、(12.49±1.47)、(13.94±0.98),F=9.59P=0];Cx26蛋白在空气组表达比较局限,高氧组弥散表达,而维甲酸组更多表达;阳性细胞分别为(13.68±1.28)%、(17.82±1.72)%、(19.69±1.77)%,F=29.36P=0。结论维甲酸对新生大鼠高氧肺损伤具有保护作用,可能与间隙连接蛋白Cx26表达的改变有密切的关系。     

Poly(N-vinylcaprolactam) containing solid lipid polymer hybrid nanoparticles for controlled delivery of a hydrophilic drug gemcitabine hydrochloride

Folic acid tagged and hydrophilic polymer containing solid lipid nanoparticles (SLNs) were formulated for the controlled and targeted delivery of gemcitabine, a hydrophilic drug. Drug loaded SLNs were prepared by double emulsion method and optimized by 3² level factorial design. Then, a hydrophilic polymer, namely, poly(N-vinylcaprolactam) (PVCL) was incorporated in the optimized SLN batch in the first aqueous phase (W1) to obtain solid lipid polymer hybrid nanoparticles (SLPHNs) that were further decorated with folic acid (F-SLPHNs). TEM analysis of SLNs and SLPHNs revealed the spherical shape with no aggregation while SLPHNs showed higher % EE. SLPHNs exhibited limited burst release of gemcitabine compared to SLNs as well as lower overall % release. All the formulations showed good cytocompatibility against MDA-MB-231 cell lines and folic acid-tagged hybrid particles (F-SLPHNs) showed remarkably higher cellular uptake.

A hydrophilic polymer, poly(N-vinylcaprolactam), incorporated into solid lipid nanoparticles (SLNs) imparts better encapsulation and controlled release of gemcitabine.     

Successful Surgical and Endovascular Multidisciplinary Therapy for Mid-aortic Syndrome with Complicated Atherosclerotic Comorbidities in an Older Patient

Mid-aortic syndrome (MAS) is a rare vascular disorder that causes refractory hypertension. A 76-year-old woman was hospitalized for acute heart failure (HF) with drug-resistant hypertension; other comorbidities included epigastric artery rupture, old myocardial infarction, an intraventricular thrombus, and a cerebral artery aneurysm. Angiography revealed severe narrowing of the descending aorta, which led to the diagnosis of MAS. Although intensive medical treatment improved her HF, optimal blood pressure (BP) could not be achieved. Percutaneous coronary intervention and surgical bypass for diseased aorta was then performed in two stages, resulting in the achievement of optimal BP and alleviation of HF.