变色马兜铃中银袋内酯甲的结构测定

从变色马兜铃(Aristolochia versicolar S.M.Hwang)块根中分离得一倍半萜内酯(B₃),命名为银袋内酯甲(versicolactone A).无色菱形结晶,分子式C₁₅H₂₀O₂,mp130～132℃,[α]_D⁶+486°(c0.1267,CHCl₃)。经UV,IR,NMR(¹H,¹³C,¹H-¹H COSY,¹H-¹³C COSY,COLOC)以及MS(高分辨和亚稳跃迁)等推定B₃具十二元环状新骨架。     

雷公藤化学成分的研究 Ⅲ.两种新二萜内酯——雷酚内酯甲醚和雷酚新内酯的分离及结构

从福建产雷公藤(Tripterygium wilfordii Hook.f.)的根皮中分离到三种二萜内酯。(1)雷酚内酯(triptophenolide),C₂₀H₂₄O₃,熔点232～233℃。(2)雷酚内酯甲醚(triptophenolide methyl ether),C₂₁H₂₆O₃,熔点152～154℃。(3)雷酚新内酯(neotriptophenolide),C₂₁H₂₆O₄,熔点189～191℃。根据理化性质及UV、IR、¹HNMR、¹³CNMR、MS等光谱数据,推测化学结构分别为Ⅴ、Ⅵ及Ⅶ。Ⅵ与Ⅶ是二种新的二萜内酯化合物。     

变色马兜铃中银袋内酯乙、丙的结构测定

从变色马兜铃(Aristolochia versicolar S M Hwang)的块根中分离到两个新倍半萜内酯,分别命名为银袋内酯乙(versicolactone B)和银袋内酯丙(versicolactone C)。前者分子式C₁₅H₂₀O₃,熔点135～136℃;后者分子式C₁₅H₂₂O₄,熔点181～182℃,[α]_D³⁶—11.4°(C,2.6,EtOH)。经光谱(UV,IR,¹H NMR,¹³SCNMR,MS)分析和化学方法证明,并经x-衍射证实,两者的结构分别为(Ⅰ)和(Ⅲ)。银袋内酯丙系一新型骨架的奠类倍半萜内酯。     

用二维核磁共振技术研究赤芝孢子内酯A和B的结构

通过¹H-¹H,¹H-¹³C相关谱(COSY),¹H-¹³C远程偶合相关谱(OOLOC)及NOE二维谱(NOESY)等新的二维核磁共振技术确定了两个新化合物赤芝孢子内酯A和B的结构。     

雷公藤中的二萜内酯类成分

目的研究雷公藤(Tripterygium wilfordii Hook.F.)的化学成分。方法应用各种色谱技术进行分离纯化，用UV，IR，¹H NMR，MS，HRMS，¹H-¹H COSY，¹H-¹³C COSY和NOESY等光谱鉴定化合物的结构。结果共分离得到4个化合物：I为16-羟基雷公藤内酯醇(16-hydroxytriptolide)，II为15-羟基雷公藤内酯醇(雷醇内酯，triptolidenol)，III为雷公藤乙素(tripdiolide)，IV为雷公藤乙素的差向异构体，命名为2-表雷公藤乙素(2-epitripdiolide)。结论化合物IV为新二萜内酯化合物。     

大环骨架结构的倍半萜化合物——Ⅵ.马兜铃新内酯的化学结构测定

自绵毛马兜铃(Aristolochia mollissima Hance)根茎中分得九个化合物,其中已报道的七个化合物是尿囊素、马兜铃内酯、绵毛马兜铃内酯、β-谷甾醇、马兜铃酸A、9-乙氧基马兜铃内酯和9-乙氧基马兜铃内酰胺,本文报道结晶K₃的化学结构,经光谱分析(IR,¹H-NMR,¹³C-NMR,2D-NMR和MS),化学反应及X-衍射晶体分析,确证K₃为一个新骨架结构的倍半萜化合物,命名为马兜铃新内酯。     

雷公藤中16-羟基雷公藤内酯醇的分离与鉴定

从雷公藤(Tripterygium wilfordii Hook.f.)叶及根中分离出16-羟基雷公藤内酯醇(16-hydroxytriptolide,L₂).根据光谱(UV,IR,¹H-NMR,¹³C-NMR,2d-NMR及MS等)数据分析,推定其化学结构为L₂,并通过X-射线晶体分析确定了其结构和构型。该物是一个新化合物,具有较强的抗炎、免疫抑制和雄性抗生育作用。     

路路通内酯的化学结构

用红外,质谱,¹H,¹³CNMR和¹H-¹³CCOLOC等光谱解析,确定了新化合物路路通内酯的结构为3-羰基-11α,12α-环氧-13β-氧-齐墩果-28β-酸-13,28-γ-内酯,命名为路路通内酯。     

乌拉尔甘草三萜——甘乌内酯的化学结构

自乌拉尔甘草(Glycyrrhiza uralensis Fisch.)根茎总皂甙元中,分得一微量新三萜成分,根据IR,UV,MS,¹HNMR,¹³CNMR等光谱及NOE,COSY,NOESY,INEPT等实验方法确定结构为3β,22α-digydroxy-11-oxo-Δ¹²-olean-ene-27α-methoxy carbonyl-29-oic acid(29,22α-)lactone。命名为甘乌内酯(glyuranolide)。     

用核磁共振新技术测定日本续断皂甙E1的结构

从日本续断Dipsocus japunicus Miq.根的乙醇提到物中得到一个新三萜皂甙(5糖甙)，命名为日本续断皂甙E₁(japondipsaponin E₁)。用化学方法及¹HNMR,¹³CNMR,¹H-¹H COSY，一维多重接力COSY，选择性远程DEPT和三重共振NOE差谱等方法，鉴定其结构为3-O-α-L-吡喃鼠李糖(1-3)-β-D-吡喃葡萄糖（1→3）-α-L-吡喃鼠李糖（1→2）-α-L-吡喃阿拉伯糖常春藤皂甙元28-O-β-D-吡喃葡萄糖甙。     

Rapid and efficient synthesis of 4-substituted pyrazol-5-one under microwave irradiation in solvent-free conditions

New heterocyclic compounds containing pyrazol-5-one coupled with benzimidazole, benzothiazole, benzoxazole, quinoline, naphthyridin, and pyrazole were synthesized. Comparative investigations to synthesize these interesting classes of heterocyclic compounds through conventional heating or under microwave-irradiation conditions were presented. Synthesized compounds 1a, 2a, 4k, 3a, c, 5a, b, 6b, 7a, b, d, 8a, and 9a were evaluated for their antitumor activity. Some of these compounds exhibited promising antitumor activity.     

Symmetrical analysis of risk-benefit

To quantify the value of a medical therapy the benefits are weighed against the risks. Effectiveness is defined by objective evidence from predefined endpoints. This benefit is offset against the disadvantage of adverse events. The safety assessment is usually a subjective summary of concerns that can often be neither confirmed nor dismissed. But sometimes a clinical database is so large that a parameter common to both efficacy and safety can be quantified with reasonable certainty: myocardial infarction (MI) is used here as an example. Recently the Food and Drug Administration (FDA) proposed set limits for the incidence of MI as a safety threshold for diabetes treatment. Setting a threshold before something is considered as a safety concern opens the possibility of setting a threshold for clinically important efficacy. When a parameter is common to both safety and efficacy, then logically a unit change in either direction should be of equal weight in the risk and benefit analysis. For example, a doubling in the incidence of myocardial infarction as a safety signal should be given equal weight to the halving of the incidence of myocardial infarction as an efficacy signal. Similarly, if FDA guidance suggests that a less than a 30% increase in the incidence of MI as a safety parameter is considered acceptable, for example for diabetes treatment, when there is no other major toxicity, this opens a debate about a possible inverse threshold for clinical benefit for drugs that reduce a risk factor, such as antihypertensives.     

Effects in conscious dogs of ajmaline,propranolol, amiodarone and verapamil on right ventricular anodal strength-interval curves

We studied the effect of antiarrhythmic drugs on the right ventricular anodal strenth-interval curve in the conscious dog. The anodal strenth-interval curve differs from its cathodal homologue by a shorter refractory period, a higher late diastolic threshold and the existence of a dip corresponding to a period of rhythmic vulnerability. The dogs were equipped with permanent ventricular electrodes; the heart was driven at a constant frequency by left ventricular stimulation and the anodal extra-stimulus was delivered on the right ventricle. This technique allowed us to determine the variations in the effective refractory period, the interventricular conduction (IVC) and the specific curve thresholds (late diastolic threshold, LDT, minimal dip level, Sm, maximal post dip threshold, SM). Ajmaline, a quinidine-like drug, significantly increased IVC and all the thresholds. Only high doses lengthened the effective refractory period. Propranolol, a β-blocking agent significantly increased Sm. The intrinsic effect of amiodarone, a non-specific anti-adrenergic drug and a potent anti-anginal substance seemed to result in a significant increase in LDT, Sm, SM. Verapamil, a calcium antagonist only caused a significant increase in SM. Therefore, each of the four drugs studied, belonging to a different group of teh Vaughan Williams classification, acted in a different way on the anodal strengh-interval curve. This study clarified the mechanisms by which these drugs exert their antiarrhythmic effect.     

Protective effect of resveratrol against 6-hydroxydopamine-induced impairment of renal<Emphasis Type="Italic"> p</Emphasis>-aminohippurate transport

In the present study, the effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced p-aminohippurate (PAH) transport impairment were investigated in vitro using rat renal cortical slices. Cisplatin and cephaloridine (CPH), known nephrotoxins, were used as positive controls. In one series of experiments, renal cortical slices were incubated in a cisplatin-containing medium or a cisplatin-free medium. In another series of experiments, renal cortical slices were incubated in a CPH-containing medium, in a CPH- and probenecid-containing medium, or in a CPH-free medium. Subsequently, for each series of experiments kidney slices were incubated in a media containing PAH or tetraethylammonium. In a further series of experiments, renal cortical slices were incubated in a 6-OHDA-containing medium and in a 6-OHDA-free medium. In another series of experiments, renal cortical slices were incubated in a medium containing 50 µM 6-OHDA, in a 6-OHDA- and resveratrol-containing medium or in a 6-OHDA- and resveratrol-free medium. Subsequently, for each series of experiments kidney slices were incubated in media containing PAH. The results of this study in which slices were incubated in 6-OHDA-containing media indicate that 6-OHDA induced a time- and concentration-dependent decrease in PAH accumulation by renal cortical slices. Resveratrol inhibited the 6-OHDA-induced time-dependent decrease of PAH accumulation in a concentration-dependent manner. Therefore, 6-OHDA causes functional injuries of renal proximal tubule cell membrane, thus leading to impairment of transport processes across the cell membrane and to nephrotoxicity. Resveratrol has a nephroprotective effect.     

Bilateral acute iris transillumination following a fumigation therapy: a village-based traditional method for the treatment of ophthalmomyiasis

Bilateral acute iris transillumination (BAIT) is a relatively new clinical entity characterized by bilateral acute loss of iris pigment epithelium, iris transillumination, pigment dispersion in the anterior chamber and atonic pupilla. We report herein a 50-year-old female who presented with bilateral ocular pain, severe photophobia and red eyes. One month ago, a fly hit her eye, and she instantly complained of a discomfort and sensation of a foreign body in both eyes. She used a fumigation therapy, a traditional method for the treatment of ophthalmomyiasis. During follow-up examinations, intraocular pressures increased over 40?mmHg bilaterally despite maximal medical therapy, which necessitated trabeculectomy surgery with mitomycin. This is a typical BAIT case with no antecedent fluoroquinolone use or viral disease, but a fumigation therapy. There might be a possible relationship between BAIT and traditional fumigation therapy or this association might be coincidental, both of which need further evaluation.     

Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist

Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly expressed by peripheral sensory neurones, which is known to play a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. To date, a number of antagonists have been used to study the physiological role of TRPV1; however, antagonists such as capsazepine are somewhat compromised by non-selective actions at other receptors and apparent modality-specific properties. SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated via high-throughput screening of a large chemical library. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.     

Creening of combinatorial peptide libraries: Identification of ligands for affinity purification of proteins using a radiological approach

Peptides deduced from peptide libraries may serve as affinity ligands for protein purification. Identification of a ligand that binds the protein of interest depends highly on the screening method used. One approach which offers simple and direct detection involves screening a solid-phase peptide library against a radiolabeled target protein. We have developed a radiological screening method, using ¹⁴C as a radioactive label, that offers high resolution and sensitivity. Less than 100 DPM/bead are detectable after a one-day exposure using autoradiography. The validity of the technique was illustrated by screening a solid-phase hexameric-peptide library spiked with YNFEVL-beads against ¹⁴C-labeled ribonuclease S-protein. For this particular system, the amount of protein bound to a single bead was estimated to be in the femtomolar range with a peptide:protein ratio of 500:1. Finally, a portion of the library was screened against ¹⁴C-labeled fibrinogen. Three peptides deduced from the library, WQEHYN, WQEHYN, and YENYGY, purified fibrinogen from a mixture with albumin.     

糖尿病足感染的病原菌分布与耐药性分析

目的了解糖尿病足感染细菌的分布及耐药状况。方法收集2010年至2017年门诊和住院患者的糖尿病足感染标本,常规方法进行细菌培养和鉴定,按纸片法、微量稀释法或E-test法测定细菌药物敏感性。结果共分离出非重复细菌304株,排在前4位的依次是金黄色葡萄球菌、铜绿假单胞菌、无乳链球菌和奇异变形杆菌,分别占29.3%,8.6%,5.9%,5.6%。未检出万古霉素耐药的革兰氏阳性细菌,未检出碳青霉烯类耐药的革兰氏阴性细菌。结论糖尿病足感染的主要致病菌仍以金黄色葡萄球菌为主。     

Synthesis of 3- or 4-phenyl-1,8-naphthyridine derivatives and evaluation of antimycobacterial and antimicrobial activity

A series of 3- or 4-phenyl-1,8-naphthyridine derivatives variously substituted in the positions 2, 6 and 7 were synthesized and evaluated for in vitro evaluation for their antimycobacterial activity as part of a TAACF TB screening program under the direction of the US National Institute of Health, NIAID division. Several compounds showed an interesting activity when tested at a concentration of 6.25 microg/ml against Mycobacterium tuberculosis H(37)Rv and in particular compounds 2a, 4a,d, 8a,d and 8i, exhibit a % inhibition from 91 to 99. Among these, compounds 2a, 8a and 8d appeared to have a good activity with minimum inhibitory concentrations (MICs) of 6.25 microg/ml. On the basis of the biological results, the most effective substituent in position 2 or 7 seems to be the piperidinyl group. The introduction of a morpholinyl group either in position 2 or 7 of the heterocycle ring caused a decrease in activity. The 1,8-naphthyridine derivatives were also tested in vitro for their antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria.