TMZ@ZIF-8 nanoparticles：preparation，characterization，and in vivo and in vitro anti-tumor studies / 中国药房

OBJECTIVE To prepare zeolite imidazole framework （ZIF）-8 nanoparticles （NPs） loaded with temozolomide （TMZ） （abbreviated as TMZ@ZIF-8 NPs） drug delivery system， thus increasing drug enrichment and anti-glioma effects in lesions. METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method， the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system. Characterization was carried out using transmission electron microscopy， laser particle size， and Fourier transform infrared spectroscopy， and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted. RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of （126.23±7.92） nm， drug loading amount of （28.79±1.26）%， and 72 h cumulative dissolution rate of （72.36±3.62）%. The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%； the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition， higher uptake capacity， and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ. The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats， and the enrichment effect of TMZ in the brain was not significant， while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain. CONCLUSIONS ZIF-8 NPs can effectively load TMZ， and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.

Preparation of GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect / 吉林大学学报(医学版)

objective:To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8(ZIF-8),and to evaluate its in vitro cytotoxicity,drug release capability,and antimicrobial propertie.Methods:The ZIF-8 particles were synthesized by hydrothermal method,and the microstructure characteristic was observed under scanning electron microscope(SEM).The particles were mixed with the gelatin methacryloyl(GelMA)with the mass fraction of 0.2%to obtain the composite hydrogel GelMA-Z.The atomic absorption spectroscope was used to detect the cumulative zinc ion(Zn2+)release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1,3,and 7 d;the viabilities of the cells in various groups were detected by CCK-8 assay;the GelMA-Z was co-cultured with Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for 6,12,and 24 h and divided into control group,GelMA group,and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader;the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method.Results:The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn2+ in GelMA-Z showed an initial burst phase within 1 d,followed by a slow release,and reached the equilibrium around 7 d.Compared with control group,the viabilities the cells in GelMA group and GelMA-Z group were above 90%on the 1st,3rd,and 7th days,but there was no significant difference(P>0.05).The bacterial activity detection results showed that when co-cultured with bacteria for 6,12,and 24 h,compared with control group and GelMA group,the bacterial activities of the E.coli and S.aureus in GelMA-Z group were decreased(P<0.05).The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group.The live/dead bacterial staining results showed that in GelMA-Z group,there was a large number of red fluorescence stained dead bacteria;in control group and GelMA group,there was a large number of green fluorescence stained live bacteria.Conclusion:The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn2+ release capability and antimicrobial activity,and it is a novel hydrogel dressing for treatment of the infected wounds.

Design, Synthesis and Antifungal Evaluation of N-Substituted Maleimide Derivatives with an Imidazole and 2-Methyl Imidazole Moieties

A series of N-substituted maleimide derivatives with an attached imidazole and 2-methyl imidazole heterocyclic rings were designed, synthesized and evaluated for their antifungal activity against four pathogenic fungi. The chemical structures of all synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra. Initially, all compounds 4a-4g, 5b and 5f were screened for qualitative (zone of inhibition) antifungal activity against C. albicans, A. fumigatus, A. niger, and A. oryzae. The screening results indicate that most of the synthesized compounds showed significant antifungal activity against the tested fungi. Furthermore, the compounds that showed a significant zone of inhibition were selected and tested quantitatively (MIC50 and IC50) against the same pathogenic fungi species. The MIC50 and IC50 results of selected compounds were analyzed. These results strongly suggest that compound 5f has shown promising antifungal activity. Furthermore, the structure–activity relationship of compound 5f revealed that compound substituted with the –F group possess prominent antifungal activity.

Control de la ventilación y regulación del estado ácido-base del pez al hombre / Control of ventilation and regulation of acid-base status from fish to man

RESUMEN Este artículo analiza ciertos aspectos evolutivos en el intercambio gaseoso, el desa rrollo pulmonar, la bomba respiratoria, el estado ácido-base y el control de la ventila ción en relación con un evento trascendente: el pasaje de la vida acuática a la terres tre. Su estudio puede permitir comprender ciertos aspectos con los que lidiamos en la práctica clínica: ¿Por qué las personas con debilidad muscular respiratoria extrema respiran como ranas (respiración frog)?, ¿Por qué los recién nacidos con dificultad respiratoria tienen aleteo nasal y quejido espiratorio?, ¿cómo es posible que los mús culos abdominales, típicamente espiratorios, asistan a la inspiración en casos de la parálisis diafragmática?, ¿por qué en la insuficiencia respiratoria el patrón respiratorio tiene menos variabilidad y se torna más rígido? y, por último, ¿es posible imaginar un pH neutro que no tenga el valor de 7,0, para qué sirve este conocimiento y como se deben interpretar los gases en hipotermia? La transición del agua a la tierra es una de las más importantes e inspiradoras de las grandes transiciones en la evolución de los vertebrados. Ante la sorprendente diversi dad de organismos vivos, es tentador imaginar una cantidad enorme de adaptaciones evolutivas para resolver los diferentes desafíos que cada especie tiene para la vida en la tierra. Hay desarrollos tempranos que comparten algunos factores cruciales y algunas de las redes genéticas regulatorias cercanas y lejanas están conservadas. Somos testigos de hallazgos clínicos que son el testimonio de especies que han vivido en épocas remotas y nos han legado su historia evolutiva.

ABSTRACT This article analyzes certain evolutionary aspects of gas exchange, lung development, the respiratory pump, the acid-base status and control of ventilation in relation to a significant event: the passing from aquatic to terrestrial life. By studying this, we can understand certain aspects that are present in the clinical practice: Why do people with extreme respiratory muscle weakness breathe as frogs? (frog breathing); why do newborns with breathing difficulties have nasal flaring and expiratory grunting?; how is it possible that abdominal muscles, which are typically expiratory, assist with inspira tion in cases of diaphragmatic paralysis?; why does the breathing pattern of respiratory failure has less variability and becomes more rigid? and, finally, is it possible to imagine a neutral pH that doesn't have the 7.0 value?; what's the use of this knowledge, and how should gases in hypothermia be interpreted? Water-to-land transition is one of the most important and inspiring major transitions of vertebrate evolution. Given the amazing diversity of living organisms, it is tempting to imagine an enormous amount of evolutionary adaptation processes to solve the different challenges of living on earth faced by each species. There are certain early development processes that share some crucial factors, and some of the close and distant gene regulatory networks are conserved. We are witnesses of clinical findings that serve as testimony of the species that lived in remote times and left us their evo lutionary history.

Inhibitory effect of LZJ541, a novel small molecule inhibitor of STAT3, on the proliferation of hepatocellular carcinoma cells / 药学学报

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Estudo da estabilidade e peguilação de L-asparaginase em soluções aquosas de líquidos iônicos de imidazólio / Study of the stability and pegylation of L-asparaginase in aqueous imidazole ionic liquid solutions

A enzima L-asparaginase de Escherichia coli (ASNase) é um biofármaco indicado para o tratamento de leucemia linfoblástica aguda, mas que pode causar reações de hipersensibilidade nos pacientes tratados. Na tentativa de amenizar esse efeito, foi desenvolvida a PEG-ASNase (enzima conjugada com polietilenoglicol) que apresenta a vantagem de ser menos imunogênica e ter maior meia-vida biológica. Mais recentemente, novas abordagens têm sido desenvolvidas visando aprimorar os processos de PEGuilação por meio de reações sítio dirigidas, por exemplo N-terminal, a fim de promover maior similaridade lote a lote e controle das características farmacocinéticas e farmacodinâmicas do biofármaco. Porém, existe ainda uma limitação associada à hidrólise do PEG reativo, desta forma surge a necessidade de procurar solventes alternativos para a PEGuilação que permitam manter a estabilidade das proteínas, aumentar o rendimento de PEGuilação e a estabilidade do PEG reativo. Nesse trabalho, líquidos iônicos foram investigados como solventes alternativos para a peguilação N-terminal de PEG-ASNase. Para tal, a estabilidade de ASNase em Lis foi investigada em LIs da família metil-imidazol, analisando a influência do aumento da cadeia alquílica e de diferentes ânions. A estabilidade da ASNase é favorecida quando em contato com Lis relativamente hidrofóbicos ([C2mim]Cl, [C4mim]Cl e [C6mim]Cl), mas sua a atividade é prejudicada quando o LI é muito polar, como o [C4mim][(CH3)2PO4] ou anfifílico como o [C12mim]Cl. Apesar de seu efeito desnaturante, o [C4mim][(CH3)2PO4] resultou no maior rendimento da reação de PEGuilação da ASNase (56%) quando empregado a 75% e a reação realizada em 10 min. O [C4mim]Cl resultou em rendimento semelhante ao tampão fosfato (~ 49%), mas ambos os LIs reduziram a poliPEGuilação. Portanto, os Lis [C4mim]Cl e [C4mim][(CH3)2PO4] fornecem uma alternativa viável à reação de PEGuilação pela redução na formação de espécies poliPEGuiladas, o que facilitaria os processos de purificação e permitiria maior controle lote a lote da reação, bem como pelo aumento do rendimento da reação no caso do [C4mim][(CH3)2PO4]

Escherichia coli L-asparaginase enzyme (ASNase) is a biopharmaceutical indicated for the treatment of acute lymphoblastic leukemia, but may cause hypersensitivity in the patients used. In an attempt to alleviate this effect, PEG-ASNase (polyethylene glycol conjugated enzyme) was developed, which has the advantage of being less immunogenic and having a longer biological half-life. More recently, new approaches have been applied to improve PEGylation processes through targeted sites, for example N-terminal, in order to promote greater similarity to the batch and control of the pharmacokinetic and pharmacodynamic characteristics of the biopharmaceutical. However, there is still a limitation associated with reactive PEG hydrolysis, thus increasing the need to look for alternative PEGylation solvents to maintain protein stability, increase PEGylation yield and use reactive PEG. In this work, ions were investigated as alternative solvents for the N-terminal PEG-ASNase. For example, a stability of ASNase in ILs was investigated in imidazole ILs by analyzing the influence of increased alkyl chain and different anions. ASNase stability is enhanced when in contact with relatively hydrophobic ILs ([C2min]Cl, [C4min]Cl and [C6min]Cl), but its activity is impaired when very polar ILs such as [C4min][(CH3)2PO4] or amphiphilic as [C12mim]Cl. Despite its denaturing effect, [C4min][(CH3)2PO4] resulted in higher yield of ASNase PEGylation reaction (56%) when employed at 75% and reaction performed in 10 min. [C4min]Cl yielded similar phosphate buffer yield (~ 49%), but both ILs reduced polyPEGylation. Therefore, [C4min]Cl and [C4min][(CH3)2PO4] Ils may use a viable alternative to the PEGylation reaction and reduce the formation of polyPEGylated species, or that facilitate purification processes and allow for greater batch use of the solution, as well as increased reaction yield in the case of [C4min][(CH3)2PO4]

Mizoribine treatment in an elderly diabetic patient with antisynthetase-associated interstitial lung disease / Journal of Rural Medicine

Objective: Immunosuppressive therapy for interstitial lung disease (ILD) is often necessary, but the standard regimen for antisynthetase-associated ILD has not been established.Patient: An 80-year-old man was hospitalized for severely progressive dyspnea. Bilateral interstitial shadows occurred 1 month before the event. Serological findings showed that he had antisynthetase-associated ILD, as identified by strong positivity for anti-aminoacyl-transfer RNA synthetase (ARS) antibody, despite no evidence of myositis. He was treated transiently with noninvasive positive pressure ventilation and steroid-pulse therapy followed by 60 mg/day of oral prednisolone. However, his diabetes mellitus was aggravated by corticosteroid therapy; thus, a combination of low-dose steroid and mizoribine (MZB), which has a low risk of aggravating glucose intolerance, was used.Results: The patient’s clinical symptoms and daily life activities have been well persevered as an outpatient and well maintained with 200 mg of MZB and 10 mg of prednisolone for several months without obvious clinical recurrence and without any remarkable steroid- and MZB-related side effects.Conclusion: The use of MZB appeared to suppress the pathophysiology of anti-ARS antibody-associated ILD.

Application of MALDI-mass spectrometry imaging in spatial distribution of secondary metabolites in medicinal plants -- a case study of Lepdium meyenii root / 中国中药杂志

Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) is a novel technique for in-situ distribution of various substances in tissue without labeling. This technique is increasingly applied to the study of medicinal plants owing to its high spatial resolution and its potential of in-situ analysis in small molecules. In this study, the structural information and their fragmentation patterns of the midazole alkaloids(1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimi-dazolium chloride) and benzylglucosinolate in the medicinal plant Maca(Lepdium meyeni) root were analyzed by ultra-high-performance liquid phase combined with LTQ-Orbitrap mass spectrometry(UHPLC-HR-MS). The localization of these active ingredients in the cross-sections of Maca root was performed by MALDI-MSI. These results demonstrated that the two types of imidazole alkaloids had a similar distributed pattern. They were located more in the cortex and the periderm than those in the medulla of a lateral root, while the localization of benzylglucosinolate was concentrated in the center of the root rather than in the cortex and the periderm. The precise spatial distribution of various secondary metabolites in tissue provides an important scientific basis for the accumulation of medicinal plant active ingredients in tissues. In addition, this imaging method is a promising technique for the rapid evaluation and identification of the active ingredients of traditional Chinese medicine in plant tissues, as well as assisting the research on the processing of medicinal plants.

Synthesis and Anticancer Activity of Novel 2-Phenylindole Linked Imidazolothiazole, Thiazolo-s-triazine and Imidazolyl-Sugar Systems

Novel functionalized 2-phenylindole derivatives, their derived imidazolethione and 1,2,4-triazinethione weresynthesized. The bicyclic compounds thiazoloimidazole and thiazolotriazine compounds in addition to their arylidinederivatives 5-8 were synthesized. Furthermore, a thioglycoside, as well as sugar hydrazone derivatives of theimidazolylindole system, were prepared. Some of the prepared compounds were screened against four cancer celllines and compounds 2, 3a and 10 showed high cytotoxic activities. The imidazolylindol-3-one derivatives 3a showedsignificant cytotoxic effect superior to the reference drug, doxorubicin, against breast adenocarcinoma cell line.

Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human Breast Cancer Cells

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced G₁-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and G₁ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

Design and synthesis of imidazo-fused heterocycles derivatives and their anti-tumor activity against breast cancer in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To synthesize compounds based on imidazo-fused heterocycles and evaluate their anti-tumor activity against breast cancer.</p><p><b>METHODS</b>The compounds 1a-1e, 2a and 2b were synthesized by aerobic copper-catalyzed halocyclization of methyl N-heteroaromatics with aliphatic amines; 3a and 3b were generated by sonogashira reaction and Suzuki reaction, respectively; the compounds 4a-4c were obtained by Buchwald-Hartwig reaction of the corresponding amines and 1e. The effects of these compounds against breast cancer cells and their nephrotoxicity were determined using MTT assay. Annexin VFITC/PI apoptosis detection kit was used to assess the apoptosis-inducing effects of these compounds in breast cancer cells. With normal saline as the control, the safety and anti-tumor activity of the compound 2a (daily dose of 10 mg/kg for 14 days) was tested in a mouse model bearing human breast cancer xenografts.</p><p><b>RESULTS</b>The compounds 2a, 4a, 4b and 4c all showed obvious anti-tumor activities. Among these compounds, 2a showed the most potent anti-tumor effect against breast cancer cells with an IC of 9.77 ± 2.32 μmol/L, similar to that of cisplatin (IC=8.96 ± 2.35 μmol/L); 2a also showed a slightly lower nephrotoxicity than cisplatin, and their CC was 10.79±0.87 μmol/L and 8.45±0.68 μmol/L, respectively. 2a obviously promoted apoptosis of breast cancer cells and caused a moderate suppression of the breast cancer growth in the tumor-bearing mouse models without producing serious adverse effects.</p><p><b>CONCLUSIONS</b>Four compounds synthesized based on imidazo-fused heterocycles have anti-tumor activities against breast cancer. The compound 2a is capable of dose-dependently promoting apoptosis of breast cancer cells and has a good safety and a moderate efficacy for suppressing tumor growth in mouse models bearing human breast cancer xenografts.</p>

In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates / Actividad in vitro de azoles contra aislamientos clínicos de Mycobacterium tuberculosis

Background: Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. Methods: A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. Results: MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC5o and MIC90 to ECO was 4.0 µg/ml, while MIC50 to CLO was 4.0 µg/ml and MIC90 was 8.0 µg/ml respectively. Conclusion: All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates.

Introducción: La tuberculosis (TB) latente ha sido asociada a la persistencia de Mycobacterium tuberculosis durmientes en el organismo de las personas infectadas, las cuales constituyen un reservorio del bacilo y una fuente de diseminación de la enfermedad en la comunidad. Urge la necesidad de contar con nuevos fármacos antituberculosos con acción sobre el bacilo en estado latente/durmiente, a fin de evitar reactivaciones endógenas y para ser incluidas en el tratamiento de la TB multirresistente y extensivamente resistente (M/XDR-TB). Se ha reportado que los azoles son activos contra M. tuberculosis. Por esta razón, los objetivos del presente estudio fueron determinar la actividad in vitro sobre aislamientos clínicos de M/XDR-TB de distintos azoles, incluyendo los imidazoles econazol (ECO) y clotrimazol (CLO) y los 5-nitro-imidazoles ipronidazol (IPZ) y metronidazol (MZ), así como analizar su potencial uso contra las formas latente y activa de esta enfermedad. Métodos: Fueron incluidos 55 aislamientos clínicos de M. tuberculosis MDR y la cepa de referencia H37Rv. Se evaluó la actividad del MZ y el IPZ sobre los aislamientos en condiciones de cultivo anaeróbico, mientras que la actividad del ECO y el CLO fue estimada determinando la concentración inhibitoria mínima (CIM) mediante el método colorimétrico de microdilución en placa. Resultados: El MZ y el IPZ presentaron actividad bacteriostática frente a las cepas de M. tuberculosis. La CIM50 y CIM90 del ECO fue de 4 µg/ml, mientras que el CLO presentó una CIM50 de 4 µg/ml y una CIM90 de 8 µg/ml. Conclusión: Todos los compuestos azólicos evaluados presentaron actividad inhibitoria frente a aislamientos clínicos de M. tuberculosis.

Promotion on in vitro percutaneous absorption of trace ginsenoside Rh1 using imidazole type-ionic liquids / 中草药

Objective: To evaluate the in vitro percutaneous absorption profiles of ginsenoside Rh1 using ionic liquids [BMIM][Cl] as a novel permeation enhancer and to investigate the mechanism. Methods: Mice skin and porcine skin were used as skin model. Oil acid, isopropyl myristate, and menthol were used as comparing skin enhancers. The solubility of Rh1 (with or without enhancer) in water was measured by shake-flask method. Skin permeation experiment was performed using Franz diffusion cells. Skin structure change after treatment of [BMIM][Cl] was measured by FTIR. Results: By comparing with commonly used enhancers, 5% [BMIM][Cl] significantly increased the solubility of Rh1 and gave an excellent improvement on the skin penetrability of Rh1. The FTIR results suggested that [BMIM][Cl] accelerated the drug skin permeation by disrupting the lipid bilayer of skin stratum corneum. Conclusion: [BMIM][Cl] can serve as a novel skin permeation enhancer, and show a broad application prospect in transdermal drug delivery system.

The effect study of fentanyl combined with imidazole valium anesthesia used in gynecological surgery / 中国现代医生

Objective To study the clinical efficacy and safety of gynecological operation in the fentanyl combined with Imidazole anesthesia. Methods In our hospital from June 2011 to June 2012 gynecological operation treatment of 78 cases of patients as the research objects,they were randomly divided into observation and control group,39 patients in each group, treated fentanyl combined with imidazole and propofol respectively combined with fentanyl anesthesia re-spectively,and compared the clinical efficacy and safety of two groups. Results In the observation group,the object of study in the anesthetic effect and safety were superior to the control group, and had statistical significance (P<0.05). Conclusion Fentanyl combined with Imidazole anesthesia in gynecologic operation has good effect of anesthesia, and high security advantages.

Synthesis and biological evaluation of 2,4,5-triphenyl-1H-imidazole-1-yl Derivatives.

In the present investigation, our aim of synthesis is to find a molecule having multi drug treatment means the drug which resists the inflammation produce due to microbial infection. So, 2,4,5-triphenyl-1H-imidazole-1-yl derivatives were synthesized and tested for their antiinflammatory activity in-vitro using Phenylbutazone as a reference drug and antimicrobial activity using clotrimazole and ciprofloxacin as a standard drug. Compound 6b was found to be the most potent derivative of the series.

Structure activity relationship studies of synthesised pyrazolone derivatives of imidazole, benzimidazole and benztriazole moiety for anti-inflammatory activity.

In the present investigation, a series of some synthesis and biological evaluation of some pyrazolone derivatives with imidazole, benzimidazole and benztriazole moiety were synthesized and tested for their anti-inflammatory activity in-vitro using celecoxib as a reference drug. Compound 8d was found to be the most potent derivative of the series with 75 %inhibition of inflammation.

Synthesis and characterization of novel series of the imidazoles under solvent free conditions by using sodium dihydrogen phosphate.

2,4,5-triphenylimidazoles/1-(2-Methyl)-3-(2-hydroxyphenyl)imidazo[1,5- a]pyridine could be obtained in excellent yields by the one-pot three-component condensation of benzil/2-acetyl pyridine, aldehyde and ammonium acetate in the presence of catalytic amount of the inexpensive, readily available NaH2PO4 under solvent-free condition. The mixture was ground together in a mortar with a pestle at room temperature for short reaction time and easy operation under solvent free condition.

Dual-Sensitive Probe of 2-( Benzoacridin) ethyl-imidazole-1-carboxylate for Determination of Aliphatic Amine with Fluorescence and Online Atmospheric Pressure Chemical Ionization Mass Spectrometry Identification / 分析化学

With comparison of three different methods for the marking of amines compound, an optimal deri vatization method was selected.5-(2-Hydroxyethyl) benzoacridine (HBA) reacts with coupling agent N,N'-carbonyldiimidazole(CDI) to form an activated amide intermediate 2-(benzoacridin) ethyl-imidazole-1-carbox-ylate(BAEIC).BAEIC, which is dual-sensitive probe, reacts preferably with amino compounds at 80 ℃ in the presence of 4-dimethylaminopyridine(DMAP) catalyst in N,N-dimethylformamide(DMF) solvent to give the corresponding sensitively fluorescent derivatives with an excitation maximum at λ_(ex) of 280 nm and an emis sion maximum at λ_(em) of 510 nm.BAEIC-amine derivatives simultaneously exhibited high ionization potential with percent ionization (changing from 5.62% to 58.08% in aqueous acetonitrile and from 2.14% to 56.58% in aqueous methanol.Derivatives were not only sensitive to fluorescence but also to MS ionizable potential.The fluorescence detection limits(5/iV = 3) were 0.12-0.59 μg/L.The online APCI-MS detection limits were 1.9-14 μg/L(S/N=5).

Novel Anti-Fatigue Compound: Imidazole Dipeptide / 日本補完代替医療学会誌

According to a 1999 epidemiological survey by the Fatigue Study Group of the Ministry of Health, Labor and Welfare in Japan, 60% (47 million) of workers complained of fatigue. However, there have been no established recommendations for fatigue, and few anti-fatigue medicines or foods have been developed. Physical or mental load induces oxidative stress, resulting in fatigue. Accordingly, antioxidants are candidate anti-fatigue substances. Imidazole dipeptides (carnosine and anserine) have strong anti-oxidative effects, and chicken breast is rich in such dipeptides. The results of two human studies suggested imidazole dipeptides were effective and useful in attenuating fatigue induced by physical loads and daily activity. In short, imidazole dipeptides are novel anti-fatigue ingredients.<br>

Synthesis and Properties Study of Ternary Complex of Rare Earth with L-Leucine and Imidazoles / 中国药房

OBJECTIVE:To synthesize ternary complex of rare earth with L-Leucine and imidazoles and to determine its properties.METHODS:The ternary solid complex was synthesized from the reaction of rare earth chlorate with L-Leucine and imidazoles in the medium of alcohol,and the compositional analysis,properties,mechanism of thermolysis,thermostability and the bacteriostatic action of the ternary complex were studied by chemistry analysis,chemical elements analysis,infrared spectral(IR)analysis,molar conductivity measurement and derivative thermogravimetry(TG-DTG)analysis,bioactivity experiments etc.RESULTS:The constitute structure of the ternary complexes was detected to be electrolyte1∶3type RE(Leu) 3 Im(H 2 O)Cl 3 ?2H 2 O,meanwhile,the thermolysis dynamics,thermostability and the bacteriostatic action against E coli of the ternary complex were established preliminarily.CONCLUSION:The composition and the property of the ternary complexes are stable and which were found to be of good bacteriostatic action in the preliminary examination.