2′-OH Protection by the p-Nitrophenylethylsulfonyl (NPES) Group in Oligoribonucleotide Synthesis

Abstract

The NPES group has been sucessfully applied for protection of the 2′-hydroxyl function in synthesizing the adenylate dimer ApA.     

Recent Progress in Oligoribonucleotide Synthesis

Abstract

The usefulness of the p-nitrophenylethylsulfonyl (NPES) group for 2′-OH protection in oligoribonucleotide synthesis is further investigated. The difficulties of uridine protection are discussed and the p-cyanophenylethyl (CPE) group introduced as a versatile new 0⁴-blocking group.     

7-Deaza-2′-Deoxyxanthosine: Nucleobase Protection and Base Pairing of Oligonucleotides

Oligonucleotides containing 7-deaza-2′-deoxyxanthosine (1) and 2′-deoxyxanthosine (2) were prepared. The 2-(4-nitrophenyl)ethyl group is applicable for 7-deazaxanthine protection that is removed with DBU by β-elimination, while the deprotection of the allyl residue with Pd (0) catalyst failed. Contrarily, the allyl group was found to be an excellent protecting group for 2′-deoxyxanthosine (2). The base pairing of nucleosides 1 and 2 with the four canonical DNA constituents as well as with 3 within the 12-mer duplexes is studied.     

6-N-(N-Methylanthranylamido)-4-Oxo-Hexanoic Acid: A New Fluorescent Protecting Group Applicable To A New Dna Sequencing Method

Abstract

6-Amino-4-oxo-hexanoic acid with a fluorescent probe attached to the amino function, derivative of the levulinic acid has been developed for protection of hydroxyl groups. It is introduced by reaction of its symetrical anhydride and rapidly removed under mild conditions using a hydrazine-pyridinium acetate buffer at near neutral pH and room temperature. It can be used within the scope of a new DNA sequencing method and as a sensitive detectable protecting group.     

A New Protecting Group Strategy for Amino Groups in Oligonucleotide Chemistry: CEOC Group

Abstract

A new protecting group, 2-cyanoethyloxycarbonyl, or CEOC, has been developed for amino groups and utilized in synthesizing modified oligonucleotides. (CEOC)-oxy-succinimide reagent has been synthesized to introduce this protecting group. The protecting group is removed by standard oligonucleotide deprotection protocols. Using this approach, oligonucleotides have been synthesized with various types of alkylamine substituents.     

4-Cyano-2-butenyl Group: A New Type of Protecting Group in Oligonucleotide Synthesis via Phosphoramidite Approach

Abstract

4-Cyano-2-butenyl (CB) is a new type of protecting group for the intemucleotidic bonds in the synthesis of oligodeoxyribonucleotides by the phosphoramidite approach. This group is stable to acidic conditions and can be removed under mild conditions by a δ-elimination pathway using aqueous ammonium hydroxide.     

团体心理咨询对甲减患者焦虑抑郁情绪的影响

目的:探讨团体心理咨询对甲减患者焦虑、抑郁情绪的影响,为改善甲减患者心理健康状况提供参考依据。方法:选择2014年1月至2016年1月在我院确诊为甲减后焦虑、抑郁的60例患者,按照随机数字表法分为对照组(n=30)和研究组(n=30)。对照组给予常规药物治疗,研究组在对照组基础上给予6周的团体心理咨询治疗。治疗后6周、3个月测量两组患者的甲状腺功能情况,并对比治疗前、治疗后6周及治疗后3个月两组的汉密尔顿焦虑量表(HAMA)评分和汉密尔顿抑郁量表(HAMD)评分,另外治疗后3个月比较两组患者的满意度。结果:治疗后6周对照组甲状腺功能正常24例,异常6例,研究组正常25例,异常5例;治疗3个月两组甲状腺功能正常均为30例,两组患者治疗后6周、3个月的甲状腺功能情况比较无统计学差异(P0.05)。治疗后6周、3个月两组HAMA、HAMD评分较治疗前降低,且研究组较对照组的评分更低(P0.05)。治疗后3个月研究组患者满意度为96.67%(29/30),明显高于对照组的66.67%(20/30)(P0.05)。结论:团体心理咨询在甲减后焦虑、抑郁患者的治疗中的作用明显,可显著改善患者的心理健康状况,提高患者的满意度。     

Efficient Synthesis of 8-Thiosubstituted Guanine Derivatives as Potential Tools for Biochemical and Biological Studies

Abstract

A method for the selective introduction of the N²-(dimethylamino)methylene group into 8-thio-9-(2-hydroxyethoxymethyl)guanine (1) has been developed. The effect of the N²-amidine protection on the S-alkylation of 1 was studied.     

New Results in Oligoribonucleotide Synthesis

Abstract

A new blocking group for 2′-OH protection of ribonucleosides was found in the p-cyanophenylethylsulfonyl (CPES) and the carbomethoxyethylsulfonyl (CMES) group. The former functionality is more stable than the p-nitrophenylethylsulfonyl (NPES) group, but can be cleaved by fluoride ion and DBU respectively.     

Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group

ObjectiveTo evaluate the efficacy and safety of galantamine in the treatment of Alzheimer''s disease.DesignRandomised, double blind, parallel group, placebo controlled trial.Setting86 outpatient clinics in Europe and Canada.Participants653 patients with mild to moderate Alzheimer''s disease.InterventionPatients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg.ResultsAt six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer''s disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P<0.001 for both doses). Galantamine was more effective than placebo on the clinician''s interview based impression of change plus caregiver input (P<0.05 for both doses v placebo). At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points, P<0.05). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study.ConclusionGalantamine is effective and well tolerated in Alzheimer''s disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.     

Red propolis ameliorates ischemic-reperfusion acute kidney injury

IntroductionAcute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated.MethodsMale Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis.ResultsI/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue.ConclusionRed propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation.     

The Use of Triisopropylsilyl-oxymethyl (TOM) in the Synthesis of Anti-telomerase 2-5A Antisense Compound RBI 011

Abstract

The 2-5A antisense compound RBI 011 targeting telomerase RNA was synthesized using the triisopropylsilyl-oxymethyl (TOM) group for the 3′-hydroxyl protection of 2′,5′-linked RNA.     

腹腔镜下头侧中间入路治疗直肠癌患者的近期疗效及对第253组淋巴结的清扫效果分析

摘要 目的：分析头侧中间入路对腹腔镜直肠癌患者的近期疗效及第253组淋巴结的清扫效果。方法：2017年6月到2020年6月选择在江苏省中医院诊治的80例直肠癌作为研究对象,根据手术入路方式的不同分为中间组42例与外侧组38例。所有患者都给予腹腔镜直肠癌根治术治疗,中间组采用头侧中间入路,外侧组给予外侧入路,记录与随访近期疗效及第253组淋巴结的清扫效果。结果：所有患者手术过程顺利,吻合后系膜、肠管均无张力;中间组的第253组淋巴结清扫时间少于外侧组(P<0.05),两组的第253组淋巴结清扫数量对比差异无统计学意义(P>0.05)。两组的手术时间、术中出血量对比差异无统计学意义(P>0.05),中间组的术后肛门首次排气时间、术后拔除引流管时间、术后住院时间显著少于外侧组(P<0.05)。中间组术后9个月的肠梗阻、吻合口漏、吻合口出血、切口感染等并发症发生率为4.8 %,显著低于外侧组23.7 %(P<0.05)。所有患者术后随访9个月,中间组的复发率为2.4 %,显著低于外侧组的15.8 %(P<0.05)。结论：头侧中间入路在腹腔镜直肠癌患者中的应用能提高第253组淋巴结的清扫效率,促进患者康复,减少术后并发症的发生,降低近期复发率。     

Different Types of Interactions Involving Cysteine Sulfhydryl Group in Proteins

Abstract

Various types of interactions involving the sulfhydryl group of free cysteine residues have been analyzed using known protein structures. In a hydrogen bond the -SH group is more amenable to donating its proton to a carbonyl group, rather than acting as a proton acceptor. It rarely interacts with a carboxylate group, and is a poor ligand to bind an anionic substrate. It is quite prone to make contacts that are definitely non-hydrogen bond type. In the S…C=0 interaction the S atom is placed on the face of an amide group (mostly from the main-chain, but there are cases from the side-chain also) close to the C atom. Cases of S…N interaction, where the S atom is on top of the N atom of another residue (both main-, as well as side-chains, including the guanidinium group) are also observed. A considerable number of Cys residues have aromatic residues as neighbors, and here too, the preferred mode of interaction is along the face. The intra-residue S…C=0 interaction constrains the main-chain and side-chain torsion angles (ψ and x₁), whereas the inter-residue interactions are non-local and stabilize the tertiary structure. The S…C=0 interaction may have a role in lowering the pK _avalues of the Cys residues in enzyme active sites.     

The 1,1-Dianisyl-2,2,2-trichloroethyl Moiety as a New Protective Group for the Synthesis of Dinucleostde Trifluoromethylphosphonates

Abstract

The new 1,1-Dianisyl-2,2,2-trichloroethyl moiety (DATE) is used as an acid and base stable protective group for nucleosides. 5′-O-DATE-thymidine and 3′-O-acetyl-thymidine are phosphorylated with CF₃P(NR₂)₂ to the corresponding thymidine trifluoromethylphosphonous amidites. These building blocks are coupled with appropriate protected thymidines to a dinucleotide trifluoromethylphosphonate.

     

Synthesis,Stability, and Biological Evaluation of 1,3-Dihydrobenzo[c]furan Analogue of d4T and Its SATE Pronucleotide

Abstract

The anti-HIV activity and stability studies of 1,3-dihydrobenzo[c]furan analogue of d4T are reported. The corresponding mononucleoside phosphotriester derivative bearing a S-pivaloyl-2-thioethyl (tBuSATE) group, as biolabile phosphate protection, is also studied.     

Base Labile Protecting Groups for Hydroxyl Functions in Ribonucleosides and Deoxyribonucleosides

Abstract

The use of the base labile 2-(p-nitrophenyl)-ethoxycarbonyl (NPEOC), 2-(2,4-dinitrophenyl)-ethoxycarbonyl (DNPEOC) and 2-cyanoethoxy-carbonyl (CEOC) group for hydroxyl protection of the sugar moiety in ribo-nucleosides and deoxyribonucleosides are described and discussed.     

免疫磁珠技术分离唾液A/B血型抗原并用于吸附血清A/B抗体

目的:应用免疫磁珠分离技术获得具有良好抗原性的A/B血型抗原,并探究其作为ABO血型抗体吸附剂去除A/B抗体的可行性。方法:将含有血型物质的唾液进行预处理,再与包被了抗体的磁珠混合,分离出纯度较高的A/B抗原,运用酶联免疫及凝集抑制试验验证所得抗原的抗原性及是否存在交叉反应。用未纯化A/B抗原和纯化A/B抗原包被磁珠,对含有抗A/B IgM、IgG的血清进行抗体吸附,用纯化A/B抗原对100份来自O型血孕妇的临床血清样本进行抗体吸附,分别评价其吸附效果。结果:纯化抗原与对应抗体反应后,其吸光度显著高于对照组(A抗原与A抗体0.85±0.12 vs.0.27±0.03,P0.01;B抗原与B抗体0.86±0.09 vs.0.24±0.06,P0.01),与其它类型抗体反应后的吸光度值与对照组比较差异无统计学意义(P0.05)。进行红细胞凝集抑制试验时,纯化抗原可显著抑制相应抗体与红细胞的凝集反应,对其它类型抗体与红细胞的凝集没有抑制作用。血清抗体吸附实验表明纯化抗原的吸附效率比未纯化抗原的高(97.00%vs.88.00%,P0.001)。临床样本抗体吸附实验显示,纯化A抗原对抗A IgM/IgG的吸附效率分别为96.88%、98.44%;纯化B抗原对抗B IgM/IgG的吸附效率分别为96.88%、98.44%。结论:磁珠纯化抗原能特异性地与对应抗体结合,有效吸附血清中的血型抗体,有望作为合成A/B抗原的替代品。     

Fluorescence Properties and Base Pair Stability of Oligonucleotides Containing 8-Aza-7-deaza-2′-deoxyisoinosine or 2′-Deoxyisoinosine

Abstract

The fluorescence and the base pairing properties of 8-aza-7-deaza-2′-deoxyisoinosine (1) are described and compared with those of 2′-deoxyisoinosine (2). The corresponding phosphoramidites (11,12) are synthesized using the diphenyl-carbamoyl (DPC) residue for the 2-oxo group protection. The nucleosides 1 and 2 base pair with 2′-deoxy-5-methylisocytidine in DNA duplexes with antiparallel chain orientation and with 2′-deoxycytidine in a parallel DNA. These base pairs are less stable than the canonical dA-dT pair and that of 2′-deoxyinosine (4) with 2′-deoxycytidine. The fluorescence of the nucleosides 1 and 2 is quenched (～95%) in duplex DNA. The residual fluorescence is used to determine the T_m-values, which are found to be the same as determined UV-spectrophotometrically.     

Diagnosis and Management of Pheochromocytoma in an Academic Hospital 3 Years After Formation of A Pheochromocytoma Interest Group

ObjectiveTo examine whether establishment of a pheochromocytoma interest group improves diagnosis and management of pheochromocytoma in an academic hospital.MethodsThe medical records of patients who had preoperative or pathologic diagnosis of pheochromocytoma at a large academic hospital from July 2007 to July 2010 were retrieved and pertinent information was gathered. Quality measures for diagnosis and management of pheochromocytoma before and after establishment of a pheochromocytoma interest group, and by group and nongroup physicians, were compared.ResultsBetween 2007 and 2010, 16 patients were confirmed to harbor pheochromocytoma. The rates of overdiagnosis and underdiagnosis were similar before and after establishment of the pheochromocytoma interest group (23%-25% vs 17%, respectively); however, after interest group formation, pheochromocytoma was excluded in 9 patients for whom other physicians recommended adrenalectomy. Compared with nonmembers, members of the pheochromocytoma interest group more frequently performed pheochromocytoma testing before adrenal biopsy or adrenalectomy in patients with adrenal masses (71% vs 13%), including those with suspected malignancy (50% vs 7%). After interest group formation, many more patients were optimally prepared preoperatively and advised on follow-up plan and genetic testing.ConclusionsFormation of a pheochromocytoma interest group significantly enhances the quality of diagnosis and management of pheochromocytoma. The key to the group’s success is its incorporation of members’ formal or informal opinions into the care of patients with suspected pheochromocytoma. This model may be applied to other rare endocrine diseases. (Endocr Pract. 2011;17:356-362)