毛细管气相色谱法测定化妆品中对羟基苯甲酸酯的含量

目的建立毛细管气相色谱法测定化妆品中的对羟基苯甲酸甲酯和对羟基苯甲酸乙酯。方法采用溶液直接进样法测定,DB-17毛细管柱,FID检测器,分流比10∶1。结果两种防腐剂在10～200μg·mL-1浓度范围内呈良好线性关系,相关系数分别为0.9992、0.9993,两种化合物的加标回收率为95%～98%。结论本法耗时少,分离度高,用标准曲线法测定,方法简单可靠。     

A randomized double-blind,non-inferiority Phase II trial,comparing dapaconazole tosylate 2% cream with ketoconazole 2% cream in the treatment of Pityriasis versicolor

Objectives: The objective of this research was to evaluate the efficacy of a new antifungal imidazole, dapaconazole tosylate, in the treatment of Pityriasis versicolor (PV).

Design and methods: Sixty patients with clinical and mycological diagnosis of PV were randomly assigned to receive either 1 g dapaconazole tosylate 2% cream or 1 g ketoconazole 2% cream. Treatments were applied once a day for 28 days. A dermatologist evaluated efficacy and safety daily, and weekly laboratorial tests were performed. The primary end point was a clinical and mycological cure of lesions after 28 days of treatment. The secondary end point was the time to clinical healing assessed by Kaplan–Meier analysis and Log-rank testing.

Results: Fifty-three patients adhered to protocol rules. Clinical and mycological cure was achieved in 84.6% (22/26) and 92.6% (25/27) of patients treated with ketoconazole and dapaconazole, respectively (difference [effect size] = 8.0%, Standard error of difference: 8.69%, 95% CI: –6.3 to 22.3%). Median time to healing was 23.5 and 21 days for ketoconazole and dapaconazole, respectively (p = 0.126). Adverse events occurred only in ketoconazole-treated patients (13%; 4/30).

Conclusion: Dapaconazole tosylate is non-inferior to ketoconazole when used at a dose of 20 mg/day for 28 consecutive days for the treatment of PV. Dapaconazole also demonstrated a good safety profile.     

Discoloration of Provisional Restorations after Oral Rinses

Purpose: Oral rinses are widely used to promote periodontal health with provisional restorations during the interim period. The aim of this study was to compare the discoloration of provisional restoration materials with different oral rinses.Material and Methods: A total of 140 disc-shaped specimens (shade A2) (10 mm x 2 mm) were prepared from one PMMA-based (TemDent Classic^®) and three different bis-acrylic-based (Protemp II^®, Luxatemp^® and Fill-In^®) provisional restoration materials (n=7). The color values (L*, a*, and b*) of each specimen were measured before and after exposure with a colorimeter, and the color changes (∆E) were calculated according to the CIE L*a*b* system. The specimens were immersed in each of the 4 oral rinses (alcohol-containing mouthwash, chlorhexidine, benzydamine HCl, benzydamine HCl and chlorhexidine) twice a day for 2 minutes. After 2 minutes of immersion in the oral rinses, the specimens were immersed in artificial saliva. The specimens were exposed to the oral rinses and the artificial saliva for 3 weeks. Two-way ANOVA, the Bonferroni test and the paired sample t-test were used for statistical analyses (p<0.05).Results: Comparison of the discoloration from the oral rinses after immersion for three weeks revealed no significant differences (p>0.05). The lowest color change was observed in PMMA-based Temdent in all oral rinses (p<0.05). There were no significant differences between the bis-acryl composites after immersion in saliva or the mixture of benzydamine HCl and chlorhexidine and the alcohol-containing mouthwash for 3 weeks (p>0.05). After immersion in chlorhexidine, the color change values of Protemp II and Fill-in showed significant differences (p=0.018). Protemp II also showed less discoloration than the other bis-acryl composites, and this color change was statistically significant (p <0.05). For all oral rinses, the L* value decreased while b* values increased, and this color change was found to be statistically significant (p <0.05). A* values were found to be significantly higher with oral rinses (p<0.05), except Protemp II immersed in benzydamine HCl or alcohol-containing mouthwash.Conclusions: The type of the oral rinse did not affect the discoloration process. For long-term esthetic results, choosing MMA-based materials for provisional restorations appears to be more effective.     

Identification of the Human P-450 Enzymes Responsible for the Sulfoxidation and Thiono-Oxidation of Diethyldithiocarbamate Methyl Ester: Role of P-450 Enzymes in Disulfiram Bioactivation

Diethyldithiocarbamate methyl ester (DDTC-Me) is a precursor to the formation of S-methyl-N,N-diethyliolcarbamate sulfoxide, the active metabolite proposed to be responsible for the alcohol deterrent effects of disulfiram. The present study investigated the role of human cytochrome P-450 (CYP) enzymes in sulfoxidation and thiono-oxidation of DDTC-Me, intermediary steps in the activation of disulfiram. Several approaches were used in an attempt to delineate the particular P-450 enzyme(s) involved in the sulfoxidation and thiono-oxidation of DDTC-Me. These approaches included the use of cDNA-expressed human P-450 enzymes, correlation analysis with sample-to-sample variation in human P-450 enzymes in a bank of human liver microsomes, and chemical and antibody inhibition studies. Multiple human P-450 enzymes (CYP3A4, CYPlA2, CYP2A6, and CYP2D6) catalyzed the sulfoxidation of DDTC-Me, as determined with cDNA-expressed enzymes. Several lines of evidence suggest that the sulfoxidation of DDTC-Me by human liver microsomes is primarily catalyzed by CYP3A4/5, including (1) a high correlation between DDTC-Me sulfoxidation and testosterone 6β-hydroxylation; (2) increased DDTC-Me sulfoxidation in the presence of α-naphthoflavone, an activator of CYP3A enzymes; (3) inhibition of this reaction by inhibitors of CYP3A4/5 enzymes, such as troleandomycin and ketoconazole; and (4) inhibition of DDTC-Mesulfoxidation by antibodies against CYP3A enzymes. On the other hand, several lines of evidence suggested that the thiono-oxidation of DDTC-Me by human liver microsomes is catalyzed in part by CYPlA2, CYP266, CYPPEl, and CYP3A4/5, including (1) these human P450 enzymes among others have the capacity to catalyze this reaction, as determined with cDNA-expressed enzymes; (2) a high correlation between DDTC-Me thiono-oxidation and testosterone 6β-hydroxylation, weak inhibition by ketoconazole, troleandomycin, and anti-CYP3A antibodies suggested a minor role for CYP3A4; (3) a high correlation with immunoreactive CYP2B6 suggested involvement of this enzyme; (4) weak inhibition of DDTC-Me thiono-oxidation by furafylline and anti-CYPlA antibody suggested involvement of CYPlA2, and (5) inhibition of DDTC-Me thiono-oxidation by DDTC and anti-CYP2E antibodies suggested a role for CYP2E1. Collectively, these data suggested CYP3A4/5 enzymes are the major contributors to the sulfoxidation of DDTC-Me by human liver microsomes, and CYPlA2, CYP2B6, CYP2E1, and CYP3A4/5 contribute toward DDTC-Me thiono-oxidation by human liver microsomes. This study, in conjunction with others (Madan et al., Drug Metab. Dispos. 23:1153–1162, 1995), may help explain the variability in disulfiram's effectiveness as an alcohol deterrent.     

In vitro study of fracture strength of provisional crown materials

PURPOSE

The purpose of this report was to evaluate the effect of the fabrication method and material type on the fracture strength of provisional crowns.

MATERIALS AND METHODS

A master model with one crown (maxillary left second premolar) was manufactured from Cr-Co alloy. The master model was scanned, and the data set was transferred to a CAD/CAM unit (Yenamak D50, Yenadent Ltd, Istanbul, Turkey) for the Cercon Base group. For the other groups, temporary crowns were produced by direct fabrication methods (Imident, Temdent, Structur Premium, Takilon, Systemp c&b II, and Acrytemp). The specimens were subjected to water storage at 37℃ for 24 hours, and then they were thermocycled (TC, 5000×, 5-55℃) (n=10). The maximum force at fracture (Fmax) was measured in a universal test machine at 1 mm/min. Data was analyzed by non-parametric statistics (α=.05).

RESULTS

Fmax values varied between 711.09-1392.1 N. In the PMMA groups, Takilon showed the lowest values (711.09 N), and Cercon Base showed the highest values (959.59 N). In the composite groups, Structur Premium showed the highest values (1392.1 N), and Acrytemp showed the lowest values (910.05 N). The composite groups showed significantly higher values than the PMMA groups (P=.01).

CONCLUSION

Composite-based materials showed significantly higher fracture strengths than PMMA-based materials. The CAD-CAM technique offers more advantages than the direct technique.     

Medicinal applications of (benz)imidazole‐ and indole‐based macrocycles

Macrocyclic chemistry is one of the emerging research areas in the chemical science. Macrocyclic compounds continue to attract significant attention due to their numerous possible applications particularly in the areas like biology, catalysis and industry. This review article summarizes the developments and advances in synthesis and medicinal applications of macrocyclic compounds derived from (benz)imidazole‐ and indole‐based heterocycles. Important medicinal applications of (benz)imidazole‐ and indole‐based macrocycles include antimicrobial and anticancer activities. The representative lead compounds in each series of macromolecules have been discussed. All these initial lead breakthroughs help validate the great potential of (benz)imidazole‐ and indole‐based macrocyclic compounds as a class of effective medicinal agents.     

Design,synthesis, and antitumor evaluation of quinoline‐imidazole derivatives

A series of compounds bearing quinoline‐imidazole ( 8a–e , 9a–e , 10a–e , 11a–e , and 12a–e ) not reported previously were designed and synthesized. The target compounds were evaluated for antitumor activity against A549, PC‐3, HepG2, and MCF‐7 cells by the MTT method, with NVP‐BEZ235 being the positive control. Most compounds showed moderate activity and compound 12a showed the best activity against HepG2, A549, and PC‐3 cells, with half‐maximal inhibitory concentration (IC₅₀) values of 2.42 ± 1.02 µM, 6.29 ± 0.99 µM, and 5.11 ± 1.00 µM, respectively, which was equal to NVP‐BEZ235 (0.54 ± 0.13 µM, 0.36 ± 0.06 µM, 0.20 ± 0.01 µM). Besides, the IC₅₀ value of 12a against the cell line WI‐38 (human fetal lung fibroblasts) was 32.8 ± 1.23 µM, indicating that the target compounds were selective for cancer cells. So, 11a and 12a were evaluated against PI3Kα and mTOR to find out if the compounds acted through the PI3K‐Akt‐mTOR signal transduction pathway. The inhibition ratios to PI3Kα and mTOR were slightly lower than that of NVP‐BEZ235, suggesting there may be some other mechanisms of action. The structure–activity relationships and docking study of 11a and 12a revealed that the latter was superior. Moreover, the target compounds showed better in vitro anticancer activity when the C‐6 of the quinoline ring was replaced by a bromine atom.

     

建立HPLC法测定盐酸洛美沙星滴眼液中5种抑菌剂

目的 建立同时测定盐酸洛美沙星滴眼液中5种抑菌剂(羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵和苯扎氯铵)的HPLC方法。方法 采用Extend C18(4.6mm×250mm, 5μm)色谱柱,流动相为1%三乙胺溶液(磷酸调pH值至3.0)-甲醇,梯度洗脱,流速为1.0mL/min,柱温35℃,检测波长为262nm。结果 羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵/苯扎氯铵各峰均分离良好;羟苯甲酯在0.0410~0.8204mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.2%(RSD=0.8%, n=9);羟苯乙酯在0.0400~0.7996mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.3%(RSD=0.7%, n=9);硫柳汞在0.0806~1.6112mg/mL范围内线性关系良好(r=0.9995),平均回收率为100.8%(RSD=0.9%, n=9);苯扎溴铵在0.0204~0.4076mg/mL范围内线性关系良好(r=0.9998),平均回收率为100.0%(RSD=0.9%, n=9);苯扎氯铵0.0197~0.3932mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.4%(RSD=1.0%, n=9)。结论 该方法准确、灵敏、简便,可用于盐酸洛美沙星滴眼液中羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵及苯扎氯铵5种抑菌剂的检查。