Complementary functions of ATM and H2AX in development and suppression of genomic instability

Upon DNA damage, histone H2AX is phosphorylated by ataxia-telangiectasia mutated (ATM) and other phosphoinositide 3-kinase-related protein kinases. To elucidate further the potential overlapping and unique functions of ATM and H2AX, we asked whether they have synergistic functions in the development and maintenance of genomic stability by inactivating both genes in mouse germ line. Combined ATM/H2AX deficiency caused embryonic lethality and dramatic cellular genomic instability. Mechanistically, severe genomic instability in the double-deficient cells is associated with a requirement for H2AX to repair oxidative DNA damage resulting from ATM deficiency. We discuss these findings in the context of synergies between ATM and other repair factors.     

Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period

BACKGROUND: the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited. AIMS: it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1-year follow-up. METHODS AND RESULTS: in all patients who were referred for cardiac transplant evaluation within a 12-month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ-preserving intervention or surgery, either PTCA (n=11), CABG (n=4), valve repair (n=7), multisite pacing (n=7), or partial ventricular resection (n=5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n=17) or received a ventricular assist device (n=3). CONCLUSIONS: within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.     

Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial hypertrophic cardiomyopathy affects actomyosin interaction in different ways

cAMP-dependent protein kinase (PKA)-dependent phosphorylation of the two serine residues in the amino terminal region unique to cardiac troponin I (cTnI) is known to cause two effects: (i) decrease of the maximum Ca2+-controlled thin filament-activated myosin S1-ATPase (actoS1-ATPase) activity and mean sliding velocity of reconstituted thin filaments; (ii) rightward shift of the Ca2+ activation curves of actoS1-ATPase activity, filament sliding velocity, and force generation. We have studied the influence of phosphorylation of human wild-type cTnI and of two mutant cTnI (G203S and K206Q) causing familial hypertrophic cardiomyopathy (fHCM) on the secondary structure by circular dichroism spectroscopy and on the Ca2+ regulation of actin-myosin interaction using actoS1-ATPase activity and in vitro motility assays. Both mutations slightly influence the backbone structure of cTnI but only the secondary structure of cTnI-G203S is also affected by bis-phosphorylation of cTnI. In functional studies, cTnI-G203S behaves similarly to wild-type cTnI, i.e. the mutation itself has no measurable effect and bis-phosphorylation alters the actoS1-ATPase activity and the in vitro thin filament motility in the same way as does bis-phosphorylation of wild-type cTnI. In contrast, the mutation K206Q leads to a considerable increase in the maximum actoS1-ATPase activity as well as filament motility compared to wild-type cTnI. Bis-phosphorylation of this mutant cTnI still suppresses the maximum actoS1-ATPase activity and filament sliding velocity but does no longer affect the Ca2+ sensitivity of these processes. Thus, these two fHCM-linked cTnI mutations, although reflecting similar pathological situations, exert different effects on the actomyosin system per se and in response to bis-phosphorylation of cTnI.     

Circadian 5-HT production regulated by adrenergic signaling

Using on-line microdialysis, we have characterized in vivo dynamics of pineal 5-hydroxytryptamine (5-HT; serotonin) release. Daily pineal 5-HT output is triphasic: (i) 5-HT levels are constant and high during the day; (ii) early in the night, there is a novel sharp rise in 5-HT synthesis and release, which precedes the nocturnal rise in melatonin synthesis; and (iii) late in the night, levels are low. This triphasic 5-HT production persists in constant darkness and is influenced strongly by intrusion of light at night. We demonstrate that both diurnal 5-HT synthesis and 5-HT release are activated by sympathetic innervation from the superior cervical ganglion and show that these processes are controlled by distinct receptors. The increase in 5-HT synthesis is controlled by beta-adrenergic receptors, whereas the increase in 5-HT release is mediated by alpha-adrenergic signaling. On the other hand, the marked decrease in 5-HT content and release late at night is a passive process, influenced by the extent of melatonin synthesis. In the absence of melatonin synthesis, the late-night decline in 5-HT release is prevented, reaching levels roughly twice as high as that of the day value. In summary, our results demonstrate that 5-HT levels display marked circadian rhythms that depend on adrenergic signaling.     

CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis

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The effects of combined hyperbaric oxygen therapy on patients with post-stroke depression

[Purpose] To observe the effect of combined hyperbaric oxygen therapy on patients with post-stroke depression. [Subjects] Ninety patients with post-stroke depression were randomly divided into 3 groups: fluoxetine treatment group (n = 30), hyperbaric oxygen therapy group (n = 30), and hyperbaric oxygen combined treatment group (n = 30). [Methods] Fluoxetine treatment group received anti-depression drugs (fluoxetine, 20 mg/day), hyperbaric oxygen therapy group received hyperbaric oxygen (once a day, 5 days/week), hyperbaric oxygen combined treatment group received fluoxetine and hyperbaric oxygen treatments as described above. All patients received routine rehabilitation therapy. Hamilton Depression Scale (HAMD), and Scandinavian Stroke Scale (SSS) scores were evaluated before and at the end of 4th week. The total effective rate of depression release between the 3 groups was also compared at the end of study. [Results] The end scores of HAMD and SSS in the 3 groups were significantly lower than those before treatment. The total effective rate of combined hyperbaric oxygen therapy group after treatment was higher than the other two groups. [Conclusions] Combined hyperbaric oxygen therapy plays an important role in the treatment of patients with post-stroke depression. The total effective rate of combined hyperbaric oxygen therapy was higher than other routine anti post-stroke depression treatments.Key words: Hyperbaric oxygen therapy, Post-stroke depression, Fluoxetine     

神经外科病房多重耐药菌感染的临床特点和护理对策

[目的]分析神经外科病房多重耐药菌(MDRO)感染的特点,探讨相应的护理对策。[方法]将2012年1月—2014年8月神经外科病房的56例培养标本作为研究对象,分析 MDRO 的数量、种类和感染部位。[结果]56份培养标本细菌耐甲氧西林金黄色葡萄球菌占37.50%、铜绿假单胞菌占25.00%、肺炎克雷伯菌占17.86%、大肠埃希菌占12.50%、鲍曼不动杆菌占7.14%,主要感染部位呼吸道占50.00%、泌尿道占25.00%、血液占1 9.64%、切口占5.36%。[结论]加强对各类人员的培训和宣教,积极实施护理干预可降低神经外科病房 MDRO 发生几率。     

正常孕11~16周孕妇子宫动脉血流多普勒特征的研究

目的分析正常孕11~16周孕妇子宫动脉血流多普勒超声特征。方法选取广州市妇女儿童医疗中心297名正常孕11~16周的单胎孕妇,根据每一孕周为一组共分为6组(11~11+6周、12~12+6周、13~13+6周、14~14+6周、15~15+6周、16~16+6周);按胎盘位置分为居中组、右侧组、左侧组;按子宫动脉阻力指数(RI)分为<0.60组、0.60~0.69组、0.70~0.79组、0.80~0.85组及≥0.85组;分析不同孕周、不同胎盘位置的子宫动脉的多普勒参数特征,及子宫动脉不同RI值舒张早期α切迹的出现频率。结果 (1)子宫动脉的平均双侧子宫动脉收缩期最大血流速度(S)与舒张末期血流速度(D)比值(S/D)、搏动指数(PI)、阻力指数(RI)随孕周增加而下降,但RIm、S/Dm值在各孕周之间差异无统计学意义;孕15、16周PIm值与11、12、13、14周相比,差异有统计学意义(P值<0.05)。各孕周PIm平均值为:11周1.96±0.39、12周1.94±0.45、13周1.79±0.43、14周1.79±0.36、15周1.51±0.43、16周1.50±0.30。(2)胎盘附着侧的子宫动脉RI、PI、S/D值均低于对侧,其中左侧胎盘组双侧RI差值为-0.04(t=-3.095,P=0.005)、双侧PI差值为-0.24(t=-3.232,P=0.004)、双侧S/D差值为-1.00(t=-2.965,P=0.007);右侧胎盘组双侧RI差值为0.04(t=6.159,P=0.000)、双侧PI差值为0.43(t=6.614,P=0.000)、双侧S/D差值为2.05(t=6.378,P=0.000);居中胎盘组双侧RI差值为0.02(t=4.150,P=0.000)、双侧PI差值为0.14(t=4.475,P=0.000)、双侧S/D差值为0.54(t=4.376,P=0.000)。(3)子宫动脉按RI分组的α切迹发生率:<0.60组,双侧均为0;0.60~0.69组,左侧为0.08、右侧为0.08;0.70~0.79组中,左侧为0.34、右侧为0.31;0.80~0.85组中,左侧为0.65、右侧为0.72;≥0.85组中,右侧为0.81,左侧为0.87。结论孕11~16周子宫动脉多普勒参数有可能作为检测子宫胎盘灌注的可靠方法之一。