Solvatochromism, DNA binding, antitumor activity and molecular modeling study of mixed-ligand copper(II) complexes containing the bulky ligand: bis[N-(p-tolyl)imino]acenaphthene

Four mixed-ligand copper(II) complexes of the nitrogen ligand bis[N-(p-tolyl)imino]acenaphthene 1 (p-Tol-BIAN). These complexes, namely [Cu(p-Tol-BIAN)2](ClO4)2 2, [Cu(p-Tol-BIAN)(acac)](ClO4) 3, [Cu(p-Tol-BIAN)Cl2] 4 and [Cu(p-Tol-BIAN)(AcOH)(2)](ClO4)2 5, were prepared and characterized. Solvatochromism of the novel copper complexes in various solvents has been studied. Molecular mechanics (MM+) and molecular dynamic simulations have been performed to learn more about the solvatochromic behaviour and the DNA binding affinity of these complexes.     

Synthesis, characterization and antimicrobial activity of Fe(II), Zn(II), Cd(II) and Hg(II) complexes with 2,6-bis(benzimidazol-2-yl) pyridine ligand

2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.     

New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity

Metal complexes of 2-methyl-1H-benzimidazole-5-carboxylic acid hydrazide (4a; L(1)) and its Schiff base 2-methyl-N-(propan-2-ylidene)-1H-benzimidazole-5-carbohydrazide (5a; L(2)) with transition metal ions e.g., copper, silver, nickel, iron and manganese were prepared. The complexes formed were 1:1 or 1:2 M:L complexes and have the structural formulae [Cu(L(1))Cl(H(2)O)]Cl x 3 H(2)O (6), [Ag(L(1))NO(3)(H(2)O)] (7), [Ni(L(1))Cl(2)(H(2)O)(2)] x H(2)O (8), [Fe(L(1))Cl(3)(H(2)O)] x 3 H(2)O (9) and [Mn(L(1))(2)Cl(H(2)O)]Cl x 3 H(2)O (10) for ligand L(1), and [Cu(L(2))Cl(2)(H(2)O)(2)] x H(2)O (11), [Ag(L(2))(2)]NO(3) x H(2)O (12), [Ni(L(2))(2)Cl(2)] x 5 H(2)O (13), [Fe(L(2))(2)Cl(2)]Cl x 2 H(2)O (14) and [Mn(L(2))Cl(2)(H(2)O)(2)] x H(2)O (15) for ligand L(2). The antitumor activity of the synthesized compounds has been studied. The silver complex 7 was found to display cytotoxicity (IC(50)=2 microM) against both human lung cancer cell line A549 and human breast cancer cell line MCF-7.     

Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex

The ligand [C(16)H(10)O(2)N(4)S(2)] L has been synthesized by the condensation reaction of 2-mercaptobenzimidazole and diethyloxalate. The ligand L was allowed to react with bis(ethylenediamine)Cu(II)/Ni(II) complexes to yield [C(20)H(22)N(8)S(2)Cu]Cl(2)1 and [C(20)H(22)N(8)S(2)Ni]Cl(2)2 complexes. The Ni(II) complex was synthesized only to elucidate the structure of the complex. The complexes 1 and 2 were characterized by elemental analyses, IR, NMR, EPR, UV-vis spectroscopy and molar conductance measurements. Both the complexes are ionic in nature and possess square-planar geometry. The binding of the complex 1 to calf thymus DNA was investigated spectrophotometrically. The absorption spectra of complex 1 exhibits a slight red shift with "hyperchromic effect" in presence of CTDNA. Electrochemical analysis and viscosity measurements were also carried out to ascertain the mode of binding. The complex 1 in the absence and in presence of CT DNA in aqueous solution exhibits one quasi-reversible redox wave corresponding to Cu(II)/Cu(I) redox couple at a scan rate of 0.2 V s(-1). The shift in DeltaE(p), E(1/2) and I(pa)/I(pc) values ascertain the interaction of calf thymus DNA with copper(II) complex. There is decrease in viscosity of CTDNA which indicates that the complex 1 binds to CTDNA through a partial intercalative mode. The antibacterial and antifungal studies of the [C(7)H(6)N(2)S], [C(4)H(16)N(4)Cu]Cl(2,) [C(16)H(10)N(4)S(2)O(2)] and [C(20)H(22)N(8)S(2)Cu]Cl(2) were carried out against S. aureus, E. coli and A. niger. All the results reveal that the complex 1 is highly active against the bacterial strains and also inhibits fungal growth.     

50Hz正弦磁场对肌质网钙释放通道Ryanodine受体的影响

目的 探讨正弦磁场对提取的骨骼肌肌质网(SR)囊泡钙释放通道(RyR1)的影响.方法 采用动态光谱法和同位素标记方法 ,分别检测了正弦磁场对SR囊泡Ca2+释放初速率、[3H]-Ryanodine平衡结合度、还原型辅酶(NADH)的氧化初速率和超氧(O·2-)产率的影响.结果 0.4 mT、50 Hz正弦磁场辐照SR囊泡30 min,由1 mmol/L NADH与1 mmol/L NAD调控的Ca2+释放初速率Con组为(10.82±0.89)pmol·mg-1 pro·s-1、MF组为(14.69±1.21)pmol·mg-1pro·s-1;上调了35%,[3H]-Ryan-odine平衡结合度上调15%,由(2.13±0.05)pmol/mg pro上升到(2.45±0.07)pmol/mg pro.另外,该磁场辐照SR囊泡30 min,导致NADH的氧化速率上调22%,由(0.88±0.11)×10-4FI/s上升到(1.07±0.13)×10-4FI/s;O·2-产率上调32%,由(0.99±0.09)×10-5FI/s上升到(1.31±0.06)×10-5FI/s. 结论 0.4 mT正弦磁场在低氧化还原电势环境下对RyR1有显著的激活,且该磁场促进了NADH氧化酶的活力和O·2-产率的增加.     

Synthesis and characterization of dinuclear macrocyclic cobalt(II), copper(II) and zinc(II) complexes derived from 2,2,2('),2(')-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]: DNA binding and cleavage studies

New homodinuclear macrocyclic complexes of cobalt(II), copper(II) and zinc(II) were isolated from the newly synthesized ligand 2,2,2',2'-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]. The structures of the complexes were elucidated by elemental analysis, molar conductance measurements, IR, 1H NMR, 13C NMR, electronic and ESI-MS spectroscopic techniques. In complex 1, Co(II) ions possess a tetrahedral coordination environment composed of O2S2 donor atoms while its Cu(II) and Zn(II) counterparts 2 and 3, respectively, reveal a six coordinate octahedral structure, defined by the O2S2 donors from the macrocyclic ring and two chloride ions. Molar conductance and spectroscopic data also support the proposed geometry of the complexes. DNA binding properties of complexes 1-3 were investigated using electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and cyclic voltammetry. The absorption spectra of complexes 2 and 3 with calf thymus DNA showed hypochromism, while complex 1 showed hyperchromism attributed to a partial intercalation and electrostatic binding modes, respectively. The intrinsic binding constant K(b) of complexes 1-3 were determined as 16.6 x 10(4) M(-1), 4.25 x 10(4) M(-1) and 3.0 x 10(4) M(-1), respectively. The decrease in the relative specific viscosity of calf thymus DNA with increasing concentration of the complexes authenticates the partial intercalation binding mode. Gel electrophoresis of complex 2 with plasmid DNA demonstrated that complex exhibits excellent "artificial" nuclease activity.     

Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: bis[N-(2,6-diisopropylphenyl)imino] acenaphthene

Two cobalt and two Nickel complexes of bis[N-(2,6-diisopropylphenyl)imino]acenaphthene (Pr-BIAN) ligand, have been synthesized. These complexes, namely [Co(Pr-BIAN)Cl2] 1, [Co(OAc)2 (Pr-BIAN)2](ClO4) 2, [Ni(Pr-BIAN)(NO3)2] 3 and [Ni(Pr-BIAN)2](ClO4)2 4, were characterized by elemental analyses, molar conductance, spectral (IR, UV-Visible and NMR) and magnetic moment measurements. In these complexes the geometries about the metal center are significantly different. While for complexes 2 and 3 an octahedral structure is proposed, in complex 4, square-planar coordination with an almost perfect planar arrangement of two Pr-BIAN ligands around the nickel center is suggested. In 1, two imine nitrogen atoms of Pr-BIAN and two chloride atoms are coordinating in a tetrahedral fashion around the cobalt center. Molecular mechanics (MM+) and semiempirical molecular orbital calculations have been performed for the most biologically active complex 1 and its free ligand Pr-BIAN and compared with inactive ligand bis[N-(p-tolylphenyl)imino]acenaphthene 6, to get insight into their molecular structures and to learn more about their stable molecular conformations.     

4-nitroacetophenone-derived thiosemicarbazones and their copper(II) complexes with significant in vitro anti-trypanosomal activity

N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M, 1), N(4),N(4)-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4DM, 2) and N(4)-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4Pip, 3) and their copper(II) complexes [Cu(4NO(2)Ac4M)(2)] (4), [Cu(4NO(2)Ac4DM)(2)] (5) and [Cu(4NO(2)Ac4Pip)(2)] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO(2)Ac4DM (2), [Cu(4NO(2)Ac4M)(2)] (4) and [Cu(4NO(2)Ac4DM)(2)] (5) proved to be as active as the clinical reference drugs nifurtimox and benznidazol. Taking into consideration the serious side effects and the poor efficacy of the reference drugs, as well as the appearance of resistance during treatment, the studied compounds could constitute a new class of anti-trypanosomal drug candidates.     

Bioactivity of novel transition metal complexes of N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide

Cu(II), Fe(III), and Mn(II) complexes of a novel ligand N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide (H(2)mtbh) have been synthesized and characterized by elemental analyses, IR, UV-vis, NMR, mass, EPR and M?ssbauer spectroscopy. The results suggest a square planar structure for [Cu(Hmtbh)Cl] and [Cu(mtbh)] whereas an octahedral structure for [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)]. Mn(II) and Fe(III) complexes were found to inhibit proliferation of HT29 cells. [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)] inhibited proliferation of HT29 cells with half maximal inhibition (IC(50)) of 8.15+/-0.87 and 68.1+/-4.8 microM, respectively, whereas H(2)mtbh showed growth inhibition with IC(50) of 90.9+/-7.8 microM and were able to inhibit NMT activity in vitro. Mn(II) and Fe(III) complexes inhibited NMT activity in a dose dependent manner with IC(50) values of 20+/-2.2 and 60+/-7.2 microM, respectively, whereas ligand (H(2)mtbh) displayed IC(50) of 3.2+/-0.5 mM.     

Synthesis, crystal structure and pharmacological evaluation of two new Cu(II) complexes of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone: a comparative investigation

Two new copper(II) complexes have been synthesized by reacting 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone (H(2)L) with CuCl(2)·2H(2)O or Cu(NO(3))(2)·3H(2)O. The structures of the complexes have been determined by single crystal X-ray diffraction studies. Results obtained using spectroscopic methods strongly suggested that the ligand and its Cu(II) complexes could interact with calf thymus DNA through intercalation. In the case of protein binding, the obtained results indicated that all the three compounds could quench the intrinsic fluorescence of bovine serum albumin through static quenching process. In addition, antioxidant activity tests showed that H(2)L and its copper(II) complexes possess significant scavenging effect against free radicals. Further, the two copper(II) complexes exhibited effective cytotoxic activity against a panel of human cancer cell lines.     

Biological evaluation of a novel water soluble sulphur bridged binuclear copper(II) thiosemicarbazone complex

The reaction of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4(N,N)-dimethylthiosemicarbazone (HL) with copper(II) nitrate in methanol yielded water soluble [{Cu(L)(CH(3)OH)}(2)](NO(3))(2) · H(2)O. Structural analysis revealed that the complex consists of centrosymmetric binuclear entities containing square-pyramidal copper(II) ions bridged through the sulfur atoms. The spectroscopic experimental evidences strongly suggested that the ligand and complex could interact with calf thymus DNA (CT-DNA) through intercalation. A gel electrophoresis assay demonstrated the ability of the complex to cleave the pBR322 plasmid DNA. The complex also exhibited a strong binding to bovine serum albumin (BSA) over the ligand. Investigations of antioxidative properties showed that the complex has strong radical scavenging properties. Further, the cytotoxic effect of the complex was examined on HeLa, Hep G2, and HEp-2, which showed that the complex exhibited substantial cytotoxic specificity on HeLa over the other two.     

Synthesis, characterization, and study on HeLa cells activity of a dinuclear complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O

The complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O(where phen=1,10-phenanthroline and pyri=3,5-pyridine dicarboxylic acid)has been synthesized and characterized. IR spectra, elemental analysis and X-ray single-crystal diffraction were carried out to determine the composition and crystal structure of the complex. The binding of the complex with HC-DNA (HeLa cells DNA, which was extracted by ourselves) was investigated by fluorescence spectrum. Gel electrophoresis assay demonstrates the ability of the complex to cleave the extracted HC-DNA. Additionally, the complex exhibited a significant cytotoxic specificity and cancer cell inhibitory rate. The apoptotic tests indicate that the complex have an apoptotic effect on HeLa cells.     

Anomalous behavior of pentacoordinate copper complexes of dimethylphenanthroline and derivatives of terpyridine ligands: Studies on DNA binding, cleavage and apoptotic activity

Copper(II) complexes with substituted terpyridine ligands, namely [Cu(itpy)(dmp)](NO₃)₂ (1) and [Cu(ptpy)(dmp)](NO₃)₂ (2) have been synthesized and characterized. The interaction of the complexes with CT-DNA has been explored using spectroscopic techniques and viscosity. Complexes 1 and 2 bind in the grooves of DNA, interestingly 1 in the minor and 2 in the major groove. Both the complexes have been found to promote DNA cleavage; complex 1 through hydrolytic and 2 oxidative. Complexes 1 and 2 have been found to be cytotoxic and bring about apoptosis of human lung cancer cell line A549.     

高容量血液滤过对多器官功能障碍综合征患者呼吸力学和血流动力学的影响

目的 探讨高容量血液滤过对多器官功能障碍综合征(MODS)患者呼吸力学和血流动力学的影响.方法 选择各种病因的MODS患者41例,按照信封法随机分为高容量血液滤过(HVHF)组21例和连续性静脉-静脉血液滤过(CVVH)组20例.观察两组治疗前及治疗24 h气道峰压(Ppeak)、肺动态顺应性(Cdyn)、心排血量(CO)、外周循环阻力(SVR)、肺循环阻力(PVR)和血气分析.结果 HVHF组治疗24 h,Ppeak、Cdyn、CO、PVR、SVR、氧合指数分别为(31.32±2.23)cm H2O(1 cm H2O=0.098 kPa)、(26.18±3.54)ml/cm H2O、(6.18±0.91)L/min、(194.95±11.51)dyn·s·cm-5、(1071.55±66.50)dyn·s·cm-5、(220.41±21.41)mm Hg(1 mm Hg=0.133 kPa),与治疗前的(42.00±3.34)cm H2O、(17.91±4.31)ml/cm H2O、(8.68±1.17)L/min、(267.27±16.29)dyn·s·cm-5、(805.32±18.82)dyn·s·cm-5、(119.41±17.10)mm Hg比较,差异均有统计学意义(P＜0.01),且与CVVH组治疗24 h比较差异亦有统计学意义(P＜0.01).结论 HVHF可明显改善MODS患者的呼吸力学和血流动力学指标.

Abstract：

Objective To investigate the effect of continuous high volume hemofiltration (HVHF)on respiratory mechanics and hemodynamics in multiple organ dysfunction syndrome (MODS). MethodsForty-one adult patients with MODS who received mechanical ventilation were divided into HVHF group(21 cases) and continuous vein-vein hemofiltration (CVVH) group (20 cases) by envelople. The peak airway pressure (Ppeak), dynamic pulmonary compliance(Cdyn), cardiac output(CO ), systemic vascular resistance(SVR), pulmonary vascular resistance (PVR) and blood gas analysis before treatment and 24 hours after treatment were measured. Results Twenty-four hours after treatment, the levels of Ppeak, Cdyn, CO, PVR,SVR and oxygenation index were (31.32 ±2.23) cm H2O (1 cm H2O =0.098 kPa), (26.18 ±3.54)(220.41 ±21.41) mm Hg (1 mm Hg =0.133 kPa) respectively in HVHF group,significantly higher than those before treatment [(42.00 ±3.34) cm H2O, (17.91 ±4.31) ml/cm H2O, (8.68 ±1.17) L/min,(267.27 ± 16.29) dyn·s·cm-5, (805.32 ± 18.82)dyn ·s·cm-5, ( 119.41 ± 17.10) mm Hg] (P ＜ 0.01 ),as well as higher than those in CVVH group after 24 hours' treatment (P ＜ 0.01 ). Conclusion HVHF shows significant beneficial effects on respiratory mechanics and hemodynamics of MODS.     

Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for S(I) did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10?? pmol?1 · L?1 × min?1) and 30 g/d HAM-RS2 (7.13 × 10?? pmol?1 · L?1 × min?1), but both were higher than after the control treatment (4.66 × 10?? pmol?1 · L?1 × min?1) (P < 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean ± pooled SEM = 1.80 ± 0.08; geometric mean = 6.05 × 10?? pmol?1 · L?1 × min?1). These results suggest that consumption of 15-30 g/d of HAM-RS2 improves S(I) in men. Additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed.     

Efficient hydrolysis of 4-nitrophenylphosphate catalyzed by copper bipyridyl in microemulsions

The hydrolysis of 4-nitrophenylphosphate (NPP) in the presence of copper bipyridyl [Cu(bpy)(H(2)O)(2)](2+) in oil in water microemulsion media was investigated. The reaction was monitored by measuring the absorbance of the nitrophenolate ion produced in the reaction aliquots with time. The order of effectiveness of the microemulsion system towards the hydrolysis of NPP in the presence of the copper dipyridyl complex was found to be cationic>anionic>aqueous at neutral pH. The result of the present investigation exhibits catalytic turnovers for metal to NPP ratio of 1:20. Catalysis in the microemulsion mediated reaction solutions was evident even in low concentrations of the metal ions in 1:2000 metal to NPP ratio. An explanation for the enhanced catalytic activity of the [Cu(bpy)(H(2)O)(2)](2+) complex for the hydrolysis of NPP is afforded. The application of the above systems for possible environmental decontamination of aryl organophosphates is anticipated.     

辛伐他汀和非诺贝特对小鼠肝脏载脂蛋白M表达的影响及调控机制

目的 探讨辛伐他汀和非诺贝特及两者联合对小鼠肝脏载脂蛋白M（apoM）表达的影响及其机制,为防治动脉粥样硬化提供依据.方法 32只C57BL/6N小鼠按数字表法分为四组,对照组：普通饮食喂养;他汀组：辛伐他汀[10 mg/（kg·d）]干预;贝特组：非诺贝特[100 mg/（kg·d）]干预;联合组：辛伐他汀[10 mg/（kg·d）]和非诺贝特[100 mg/（kg·d）]干预,4周后分别检测小鼠肝脏apoM mRNA和蛋白、肝细胞核因子-1α（HNF-1α）mRNA、肝X受体-α（LXRα）mRNA的表达.结果 辛伐他汀和非诺贝特均上调apoM mRNA（1.97±0.04;2.02±0.02）和蛋白、HNF-1α mRNA（1.74±0.05;1.71±0.04）的表达,联合组（3.07±0.03;2.57±0.03）升高程度高于他汀组（1.97±0.04;1.74±0.05）和贝特组（2.02±0.02;1.71±0.04）（P＜0.05）.辛伐他汀下调LXRα mRNA（1.00±0.02）表达（P＜0.05）,非诺贝特上调LXRα mRNA（2.80±0.04）表达（P＜0.05）,联合组LXRα mRNA表达（1.56±0.03）与对照组（1.53±0.03）比较差异无统计学意义（P＞0.05）.结论 辛伐他汀和非诺贝特可上调apoM表达,两者联合疗效更显著;其机制可能与两者调控HNF-1α和LXRα有关.     

毛蚶中甲肝病毒净化实验研究

[目的 ]　研究被甲肝病毒污染的毛蚶净化方法。　 [方法 ]　采用二氧化氯 (ClO2 )、臭氧 (O3)和紫外线等物理和化学联合方法 ,通过循环水系统 ,净化被人工染毒的毛蚶。　 [结果 ]　应用ClO2 、O3和紫外线不同组合方法净化 4d能有效灭活甲肝病毒浓度 (TCID50 )为 1 0 4 的人工染毒毛蚶中的甲肝病毒 (HAV)。　 [结论 ]　ClO2 、O3和紫外线联合净化方法具有灭活毛蚶体内HAV的作用 ,但其效果与净化时间和毛蚶体内HAV浓度密切相关。     

Effects of prior heavy-intensity exercise on oxygen uptake and muscle deoxygenation kinetics of a subsequent heavy-intensity cycling and knee-extension exercise

This study examined the effects of prior heavy-intensity exercise on the adjustment of pulmonary oxygen uptake (VO(2p)) and muscle deoxygenation Δ[HHb] during the transition to subsequent heavy-intensity cycling (CE) or knee-extension (KE) exercise. Nine young adults (aged 24 ± 5 years) performed 4 repetitions of repeated bouts of heavy-intensity exercise separated by light-intensity CE and KE, which included 6 min of baseline exercise, a 6-min step of heavy-intensity exercise (H1), 6-min recovery, and a 6-min step of heavy-intensity exercise (H2). Exercise was performed at 50 r·min(-1) or contractions per minute per leg. Oxygen uptake (VO(2)) mean response time was ～20% faster (p < 0.05) during H2 compared with H1 in both modalities. Phase 2 time constants (τ) were not different between heavy bouts of CE (H1, 29.6 ± 6.5 s; H2, 28.0 ± 4.6 s) or KE exercise (H1, 31.6 ± 6.7 s; H2, 29.8 ± 5.6 s). The VO(2) slow component amplitude was lower (p < 0.05) in H2 in both modalities (CE, 0.19 ± 0.06 L·min(-1); KE, 0.12 ± 0.07 L·min(-1)) compared with H1 (CE, 0.29 ± 0.09 L·min(-1); KE, 0.18 ± 0.07 L·min(-1)), with the contribution of the slow component to the total VO(2) response reduced (p < 0.05) in H2 during both exercise modes. The effective τHHb was similar between bouts for CE (H1, 18.2 ± 3.0 s; H2, 18.0 ± 3.6 s) and KE exercise (H1, 26.0 ± 7.0 s; H2, 24.0 ± 5.8 s). The ΔHHb slow component was reduced during H2 in both CE and KE (p < 0.05). In conclusion, phase 2 VO(2p) was unchanged with priming exercise; however, a faster mean response time of VO(2p) during the heavy-intensity exercise preceded by a priming heavy-intensity exercise was attributed to a smaller slow component and reduced muscle deoxygenation indicative of improved muscle O(2) delivery during the second bout of exercise.     

大鼠气管内注入纳米二氧化钛后的血浆代谢组学研究

目的 运用一维磁共振氢谱(1H MR)结合模式识别的代谢组学技术探讨大鼠气管内注入纳米二氧化钛(nano-TiO2)的毒效应,并寻找毒效应的靶器官及生物标志物.方法 将24只SD大鼠按数字表法随机分为4组,分别为高剂量组(40.0 mg/kg nano-TiO2)、中剂量组(4.0 mg/kg nano-riO2)、低剂量组(0.4 mg/kg nano-TiO2)和对照组(生理盐水),每组各6只大鼠.按0.1 ml/100 g采用非暴露式气管内注入方式,染毒1次.观察1周后,进行血浆1H MR检测,并对代谢图谱进行主成分分析(PCA).同时摘取心、肺、肝、肾等器官作组织病理学检查.结果 血浆代谢组学分析表明:高剂量组乳酸相对含量[(37.86±2.58)×10-3]、柠檬酸相对含量[(2.21±0.45)×10-3]、胆碱相对含量[(7.74±0.76)×10-3]和肌酸相对含量[(4.17 d-1.15)×10-3]低于对照组[(52.07±5.12)×10-3、(3.01±0.21)×10-3、(9.28±0.78)×10-3、(8.59±2.64)×10-3](t值分别为-6.024、-3.177、-3.374、-4.215,P值均<0.05);而葡萄糖相对含量[(19.41±1.72)×10-3]高于对照组[(14.45±2.45)×10-3](t=2.802,P<0.05);中剂量组乳酸相对含量[(44.39±5.09)×10-3]和肌酸相对含量[(3.67±0.76)×10-3]低于对照组[(52.07±5.12)×10-3、(8.59±2.64)×10-3](t值分别为-3.254、-4.694,P值均<0.05);低剂量组丙酮酸相对含量[(3.84±0.70)×10-3]高于对照组[(3.13×±0.46)×10-3](t=2.787,P<0.05),胆碱相对含量[(8.10±0.72)×10-3]低于对照组[(9.28±0.78)×10-3](t=-2.602,P<0.05).各剂最组大鼠各个组织脏器均未见明显的病理变化.结论 大鼠肺脏、肝脏、肾脏和心脏是nano-TiO2气管注入染毒的靶器官;乳酸、丙酮酸、匍萄糖、柠檬酸、胆碱和肌酸可作为寻找nano-TiO2致机体毒作用靶器官的参考生物标志物.