腹腔镜直肠癌切除术与开腹根治术的远期疗效对比

目的:比较腹腔镜直肠癌切除术与开腹根治术的远期疗效。方法:选取在我院治疗的直肠癌患者84例,随机分为观察组(腹腔镜切除术)和对照组(开腹根治术)各42例。对比两组患者的术后临床效果及1年、3年的局部复发率、远处转移率及生存率。结果:观察组术后出血量、肠功能恢复时间、保肛率、下床活动时间、术后住院天数及术后并发症均优于观察组,两组比较差异具有统计学意义(P0.05)。两组手术时间比较,差异无统计学意义(P0.05)。两组患者淋巴结清扫个数、标本长度及远切端距离比较,差异均无统计学意义(P0.05)。观察组手术1年和3年后局部复发率、远处转移率及生存率比较,差异无统计学意义(P0.05)。结论:直肠癌采取腹腔镜切除术与开腹根治术有同样的远期治疗效果,临床上可根据患者情况优先选用。     

Radical-induced purine lesion formation is dependent on DNA helical topology

Abstract

Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO^?) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5′,8-cyclo-2′-deoxyguanosine (5′,8-cdG) and 5′,8-cyclo-2′-deoxyadenosine (5′,8-cdA). SC, OC, and L dsDNA conformers together with folded and non-folded G-quadruplexes d[TGGGGT]₄ (TG4T), d[AGGG(TTAGGG)₃] (Tel22), and the mutated tel24 d[TTGGG(TTAGGG)₃A] (mutTel24) were exposed to HO^? radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L?>?OC???SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 (～50% solution folded) and mutTel24 (～90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33?Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage.     

Superoxide,amine buffers and tetranitromethane: A novel free radical chain reaction

The amine buffer Tris slowly reduces tetranitromethane (TNM) to the nitroform anion in a non-accelerating reaction. The amine buffers HEPES and MOPS also (slowly) react with TNM but the dialkylaminoalkyl radicals formed from these two buffers undergo further reactions resulting in a rapid, accelerating, free radical chain process whereby the amine is oxidized and TNM reduced. The chemical functionality in any reaction component, not necessarily the buffer, required for this radical chain mechanism is >N-CH<. In the presence of such groups, the quantification of superoxide by TNM is impossible.     

Direct Detection of Radical Production in the Ischaemic and Reperfused Myocardium: Current Status

Electron spin resonance (em.) spectroscopy, which is a specific method for directly detecting free radicals in biological systems, has now been used in a number of studies to examine free radical generation in both ischaemic and reperfused myocardial tissue. This review critically assesses the information which has been obtained to date with particular reference to the elucidation of the nature and source of the radicals observed in these studies.     

Kinetic Analysis of the Effect of (−)-Epigallocatechin Gallate on the DNA Scission Induced by Fe(II)

The DNA strand scission induced by Fe(II) in a citrate buffer solution and the effect of (?)-epigallocatechin gallate (EGCg) were kinetically analyzed. The rate of consumption of dissolved oxygen by Fe(II) in each of these solutions was measured and paralleled that DNA scission. Coordinated EGCg accelerated these reactions. Curves of the time-course characteristics of DNA scission were simulated by using the rate constant of oxygen consumption and by assuming that scission with the hydroxyl radical (OH), which was formed from the dissolved oxygen, proceeded competitively with the scavenging of OH by citrate, Cl^? ions and EGCg added. Free EGCg acted as a DNA scission inhibitor to scavenge OH, in contrast to the case of the coordinated one. This analysis is useful for estimating the rate constant of the reaction between an antioxidant and OH, and might provide a new method for measuring the OH-scavenging activity.     

Metabolic stability of superoxide adducts derived from newly developed cyclic nitrone spin traps

Reactive oxygen species are by-products of aerobic metabolism involved in the onset and evolution of various pathological conditions. Among them, the superoxide radical is of special interest as the origin of several damaging species such as H₂O₂, hydroxyl radical, or peroxynitrite (ONOO⁻). Spin trapping coupled with ESR is a method of choice to characterize these species in chemical and biological systems and the metabolic stability of the spin adducts derived from reaction of superoxide and hydroxyl radicals with nitrones is the main limit to the in vivo application of the method. Recently, new cyclic nitrones bearing a triphenylphosphonium or permethylated β-cyclodextrin moiety have been synthesized and their spin adducts demonstrated increased stability in buffer. In this article, we studied the stability of the superoxide adducts of four new cyclic nitrones in the presence of liver subcellular fractions and biologically relevant reductants using an original setup combining a stopped-flow device and an ESR spectrometer. The kinetics of disappearance of the spin adducts were analyzed using an appropriate simulation program. Our results highlight the interest of the new spin trapping agents CD-DEPMPO and CD-DIPPMPO for specific detection of superoxide with high stability of the superoxide adducts in the presence of liver microsomes.     

The biosynthesis and biological function of diphthamide

Abstract

Eukaryotic and archaeal elongation factor 2 contains a unique post-translationally modified histidine residue, named diphthamide. Genetic and biochemical studies have revealed that diphthamide biosynthesis involves a multi-step pathway that is evolutionally conserved among lower and higher eukaryotes. During certain bacterial infections, diphthamide is specifically recognized by bacterial toxins, including diphtheria toxin, Pseudomonas exotoxin A and cholix toxin. Although the pathological relevance is well studied, the physiological function of diphthamide is still poorly understood. Recently, many new interesting developments in understanding the biosynthesis have been reported. Here, we review the current understanding of the biosynthesis and biological function of diphthamide.     

Oxidative radical cyclizations of diketopiperazines bearing an amidomalonate unit. Heterointermediate reaction sequences toward the asperparalines and stephacidins

Abstract

A novel approach to the diazabicyclo[2.2.2]octane core of prenylated bridged diketopiperazine alkaloids is described by direct oxidative cyclizations of functionalized diketopiperazines mediated by ferrocenium hexafluorophosphate or the Mn(OAc)₃?2H₂O/Cu(OTf)₂ system. Divergent reaction pathways take place depending on the substitution pattern of the substrates and the oxidation conditions such as temperature or the presence or absence of persistent radical TEMPO. For ester-substituted diketopiperazines, the ester group exerts a significant influence on the reaction outcome and stereochemistry of the radical cyclizations.     

Dimeric cinnamoylamide analogues for regulation of tyrosinase activity in melanoma cells: A role of diamide-link chain length

Dimeric cynnamoyl analogues (DCAs) with depigmenting activity have been developed. In this study, a role of diamide linkage chain length of DCAs as a tyrosinase inhibitor was investigated on tyrosinase inhibitory activity, antioxidative activity, hydrophobicity and anti-melanogenesis as well as structural characteristics and dipole moments based on density functional theory. DCAs with different diamide-link chain lengths (n?=?2, 3, and 4) and various functional groups (m-coumaroyl, p-coumaroyl, isoferuloyl and feruloyl groups) were synthesized. DCAs with a diamide-link chain length of three indicated high inhibitory effect of melanin production on α-melanocyte stimulating hormone (α-MSH) stimulated B16F1 cells. Approach of p-hydroxyl group of DCAs to active site of tyrosinase, an important melanogenic enzyme, is interfered by addition of m-methoxy group. In structural modeling based on density functional theory, DCAs with a diamide-link chain length of three showed folded shapes, and they had lower dipole moment than with a diamide-link chain length of two or four. Thus, for the enhancement of the depigmenting activities of dimeric compounds, the diamide-link chain length is important. Our results provide an important index for the design of dimeric compounds with physiological activities.