健脾清化汤结合西药治疗耐药幽门螺杆菌相关性溃疡的临床观察

目的观察健脾清化汤结合西药治疗耐药幽门螺杆菌(HP)相关性溃疡的临床疗效.方法将68例耐药HP相关性消化性溃疡患者,随机分为治疗组和对照组,在分别给予抗HP标准三联7d后,治疗组改用中药健脾清化汤3周,对照组改用奥美拉唑3周.疗程结束后,观察主要症状改善、胃镜变化、耐药HP根除情况及不良反应.结果在主要症状改善、耐药HP根除方面,中药加西药组明显优于西药组(P《0.05).结论中药健脾清化汤结合西药对耐药HP相关性溃疡有较好的临床疗效.     

金匮肾气丸加味治疗阳虚喘证90例

喘证在临床上可出现于许多急、慢性疾病过程中,如西医的急、慢性支气管炎,肺部感染,肺气肿,慢性肺源性心脏病,心力衰竭以及肾功能衰竭等.中医辨证有虚实之分.笔者自2004年以来,用金匮肾气丸加味治疗阳虚喘证90例,获得了良好效果.现报道如下.     

Dehydroascorbic Acid and pGPMA Dual Modified pH-Sensitive Polymeric Micelles for Target Treatment of Liver Cancer

In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised biodegradable poly(ethylene glycol)-poly(aspartate) polymers, in which paclitaxel can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures. In vitro drug release studies showed that these structures were stable in physiological condition, whereas collapsed once internalized into cells due to the mildly acidic environment in endo/lysosomes, resulting in facilitated intracellular paclitaxel release. In addition, dehydroascorbic acid and guanidinopropyl methacrylamide polymers were decorated on the surface of micelles to achieve specific tumor accumulation and tumor penetration. Cellular uptake and in vivo imaging studies proved that these micelles had remarkable targeting property toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the micelles was also confirmed both in vitro and in vivo. Therefore, this micellar system may be a potential platform of chemotherapeutics delivery for HCC therapy.     

Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15～0.3 and 1:3:0.2～0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.     

Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca²⁺, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl₂, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca²⁺, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.     

PM<Subscript>10</Subscript> concentration in relation to clinic visits for anxiety disorders: a population-based study of a high river-dust episode region in Taiwan

PM₁₀ exposure has been found to have significant effects on a variety of physical conditions. However, whether it acts on psychopathology remains unclear. This study used 8-year data to examine the relationship between PM₁₀ concentration and daily clinic visits of anxiety disorders. All residents of Yunlin County, Taiwan, which is a high river-dust exposure area, were selected as subjects. Data from the Taiwan National Health Insurance Research Database (NHIRD), 2002–2009, were analyzed. Individuals with any ICD code of 300.0 and 300.2 were categorized as with anxiety disorders. PM₁₀ data were based on the Lunbei station (located at Yunlin County) of EPA, Taiwan. Time-series analysis showed that, during the observed 8 years, the number of daily clinic visits for anxiety disorders increased with PM₁₀ levels, and the relationship remained significant after unemployment rate, and the Weighted Price Index of Taiwan Stock Exchange in the same period were controlled for. In particular, we found that there is a linear dose-response effect between daily clinic visits and PM₁₀ levels when PM₁₀ <?300 μg/m³; whereas a dramatically elevated daily clinic visits of anxiety disorders was found when PM₁₀ >?300 μg/m³. Findings from this study highlight that high level of PM₁₀ exposure derived from severe weather or environment condition may affect the occurrence of anxiety disorders. In addition, there seems to have a threshold of PM₁₀ in elevating the risk of anxiety disorders.     

Enzymatic glycosylation of oleanane-type triterpenoids

Abstract

Glycosylation is an effective approach to improve the druggability of natural products by increasing their water solubility. In this work, we report the glycosylation of oleanane-type triterpenoids by a recombinant microbial glycosyltransferase YjiC1. A preliminary screening test indicated YjiC1 exhibited robust capabilities for O-glycosylation of triterpenoids, based on LC/MS analysis. Among the products, two new compounds (2a and 3a), together with a known one (1a), were isolated and characterized. These products exhibited improved water solubility, and 3a showed moderate anti-HIV activities at 100 μM. This reaction provides a facile and efficient approach to synthesize the glucosides of triterpenoids.     

Enzymatic synthesis of glucuronidated metabolites of two neurological active agents using plant glucuronosyltransferases

Abstract

Glucuronidation is an important and popular metabolic reaction in vivo of drugs. The further evaluation of biological activity and toxicity of glucuronides is necessary in the course of the drug research and development. However, the synthesis of glucuronides is limited by the lack of efficient approach. Herein, we have developed a new glucuronide synthesis method using plant uridine diphosphate-dependent glucuronosyltransferases (UGTs), UGT88D4, UGT88D7, and EpGT8, enabling the convenient preparation for corresponding O-glucuronide metabolites (1a, 2a, 3a, and 3b) in milligram scale of two neurological active agents, IMM-H004 (1) and FLZ (2). Their structures were characterized by spectroscopic data analyses.