Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi’s diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm²) than LNCs (12.7 ± 1.52 µg/cm²). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.     

Association between Dietary Nitrate,Nitrite Intake,and Site-Specific Cancer Risk: A Systematic Review and Meta-Analysis

Background: People consume nitrates, nitrites, nitrosamines, and NOCs compounds primarily through processed food. Many studies have yielded inconclusive results regarding the association between cancer and dietary intakes of nitrates and nitrites. This study aimed to quantify these associations across the reported literature thus far. Methods: We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using Web of Science, Embase, PubMed, the Cochrane library, and google scholar up to January 2020. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis. Results: A total of 41 articles with 13 different cancer sites were used for analysis. Of these 13 cancer types/sites, meta-regression analysis showed that bladder and stomach cancer risk was greater, and that pancreatic cancer risk was lower with increasing nitrite intakes. Kidney and bladder cancer risk were both lower with increasing nitrate intakes. When comparing highest to lowest (reference) categories of intake, meta-analysis of studies showed that high nitrate intake was associated with an increased risk of thyroid cancer (OR = 1.40, 95% CI: 1.02, 1.77). When pooling all intake categories and comparing against the lowest (reference) category, higher nitrite intake was associated with an increased risk of glioma (OR = 1.12, 95% CI: 1.03, 1.22). No other associations between cancer risk and dietary intakes of nitrates or nitrites were observed. Conclusion: This study showed varied associations between site-specific cancer risks and dietary intakes of nitrate and nitrite. Glioma, bladder, and stomach cancer risks were higher and pancreatic cancer risk was lower with higher nitrite intakes, and thyroid cancer risk was higher and kidney cancer risk lower with higher nitrate intakes. These data suggest type- and site-specific effects of cancer risk, including protective effects, from dietary intakes of nitrate and nitrite.     

Intactness of membranous structure in canine stunned myocardium shown with colloidal lanthanum nitrate

ＩｎｔａｃｔｎｅｓｓｏｆｍｅｍｂｒａｎｏｕｓｓｔｒｕｃｔｕｒｅｉｎｃａｎｉｎｅｓｔｕｎｎｅｄｍｙｏｃａｒｄｉｕｍｓｈｏｗｎｗｉｔｈｃｏｌｌｏｉｄａｌｌａｎｔｈａｎｕｍｎｉｔｒａｔｅＺｈｕＹｏｎｇｈｏｎｇ（朱永宏），ＬｉＬａｎｓｕｎ（李兰荪），Ｃｈｅｎ...     

特殊染色技术在艾滋病合并真菌病理诊断中的应用

目的 探讨特殊染色技术在艾滋病合并真菌病理诊断中的应用价值.方法 选取2010年2月至2013年11月上海市（复旦大学附属）公共卫生临床中心确诊为艾滋病合并真菌感染的患者20例,回顾性分析经苏木素-伊红（HE）染色、过碘酸希夫染色（PAS）和六胺银染色的病理资料,观察常见真菌在光镜下的形态.结果 20例艾滋病合并真菌感染的患者中,肺部隐球菌2例,皮肤、肺、腹腔肠系膜淋巴结马尔尼菲青霉菌3例,会厌、颈部淋巴结、口腔、腹腔及皮肤组织胞浆菌5例,上颌窦、肺及声带曲霉4例（合并结核3例）,肝、咽、食道及胃部白色假丝酵母菌6例.HE染色组织中炎性细胞浸润,可见肉芽肿形成,凝固性坏死,真菌形态尚能辨认,但需仔细观察,否则易漏诊或误诊;PAS染色,真菌孢子和假菌丝呈亮丽的紫红色,细胞核紫蓝色;六胺银染色,真菌孢子和假菌丝呈清晰可辨的黑褐色.结论 除常规进行HE染色外,联合应用PAS染色和六胺银染色,有助于提高真菌的病理诊断率.     

硝酸镓对胃癌细胞增殖与凋亡的作用

目的通过硝酸镓、顺铂单药及二者联合用药对胃癌BGC823细胞作用,观察其对胃癌BGC823细胞诱导凋亡、抑制增殖的影响。方法通过对胃腺癌BGC823细胞培养及干预,采用流式细胞仪技术对凋亡细胞进行测定;MTT技术对肿瘤细胞增殖进行测定。结果MTT及流式细胞仪检测结果显示：硝酸镓对BGC823细胞作用呈剂量一时间依赖效应;小剂量硝酸镓与顺铂配伍应用能大大提高顺铂作用效应,配伍高浓度组在24h、48h、72h的抑制率为70．0％、71．4％、72．3％。结论硝酸镓对胃癌细胞的作用与顺铂无明显差异,为肿瘤治疗及制备抗肿瘤药物提供新的途径。     

Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases

ObjectiveMost of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO₃⁻–NO₂⁻–NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD).MethodsThe NO₃⁻, NO₂⁻ and NO levels were examined in the NO₃⁻–NO₂⁻–NO pathway. High-performance ion chromatography was used to quantify NO₃⁻ and NO₂⁻ levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system.ResultsHigh content of NO₃⁻ and low content of NO₂⁻ was found in CR, and which could potently convert NO₃⁻ to NO₂⁻ in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO₃⁻ content and increased the levels of NO₂⁻ and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l-arginine –NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL.ConclusionCR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO₃⁻–NO₂⁻–NO pathway, thereby making up for the deficiency caused by the lack of NO after the l-arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.     

Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum

Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero‐salivary re‐circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal‐type homeobox 2, and the shifting of carcinogenic N‐nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender‐related difference in NO‐related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO‐related esophageal damage could explain the well‐recognized male predominance in the GERD spectrum in humans.     

Arabidopsis V-ATPase activity at the tonoplast is required for efficient nutrient storage but not for sodium accumulation

The productivity of higher plants as a major source of food and energy is linked to their ability to buffer changes in the concentrations of essential and toxic ions. Transport across the tonoplast is energized by two proton pumps, the vacuolar H⁺-ATPase (V-ATPase) and the vacuolar H⁺-pyrophosphatase (V-PPase); however, their functional relation and relative contributions to ion storage and detoxification are unclear. We have identified an Arabidopsis mutant in which energization of vacuolar transport solely relies on the activity of the V-PPase. The vha-a2 vha-a3 double mutant, which lacks the two tonoplast-localized isoforms of the membrane-integral V-ATPase subunit VHA-a, is viable but shows day-length-dependent growth retardation. Nitrate content is reduced whereas nitrate assimilation is increased in the vha-a2 vha-a3 mutant, indicating that vacuolar nitrate storage represents a major growth-limiting factor. Zinc is an essential micronutrient that is toxic at excess concentrations and is detoxified via a vacuolar Zn²⁺/H⁺-antiport system. Accordingly, the double mutant shows reduced zinc tolerance. In the same way the vacuolar Na⁺/H⁺-antiport system is assumed to be an important component of the system that removes sodium from the cytosol. Unexpectedly, salt tolerance and accumulation are not affected in the vha-a2 vha-a3 double mutant. In contrast, reduction of V-ATPase activity in the trans-Golgi network/early endosome (TGN/EE) leads to increased salt sensitivity. Taken together, our results show that during gametophyte and embryo development V-PPase activity at the tonoplast is sufficient whereas tonoplast V-ATPase activity is limiting for nutrient storage but not for sodium tolerance during vegetative and reproductive growth.     

硝酸酯类药物耐药的研究进展

硝酸酯类药物在临床上广泛用于冠心病和充血性心力衰竭的治疗；但硝酸酯耐药的出现，使其临床应用受到一定限制。目前有关硝酸酯耐药的机制、预防等方面的研究已取得了一定的进展，本文对此进行综述。     

银染法观察铜绿假单胞菌生物被膜变化初探

目的探讨银染法观察细菌生物被膜在药物作用前后变化的可靠性。方法建立细菌生物被膜,分别用银染法和扫描电镜进行观察生物被膜的变化。结果银染后普通光学显微镜观察和扫描电镜观察对生物被膜变化的观察结果完全相符。结论用银染法观察细菌生物膜的变化便捷、可靠。