米诺环素肺炎

米诺环素肺炎朱晓莉，张祖贻（南京铁道医学院附属医院，南京２１０００９）Ｍｉｎｏｃｙｃｌｉｎｅｐｎｅｕｍｏｎｉａ￥ＺｈｕＸｉａｏｌｉａｎｄＺｈａｎｇＺｕｙｅ（ＮａｎｊｉｎｇＲａｉｌｗａｙＭｅｄｉｃａｌＣｏｌｌｅｇｅ，Ｎａｎｊｉｎｇ２１０００９）米诺环素...     

米诺环素诱发急性胃出血1例

1　临床资料患者 ,男 2 7ａ,公司业务员。 1 999年 1 1月1 8日因急性胃出血就诊。患者自述无药物过敏史 ,因患尿道衣原体感染 ,在他人建议下于1 999年 1 1月 1 7日购买并在睡前口服盐酸米诺环素 0 2ｇ(商品名“美侬” ,5 0ｍｇ× 1 0片 ,昆明制药股份有限公司 ,批号 980 90 8)。次日晨起后空腹再次服用该药 0 1ｇ。约 3 0ｍｉｎ后觉上腹疼痛难忍 ,随即呕吐数次 ,呕吐物中带新鲜血液少许。患者有胃、十二指肠溃疡病史 ,长期服用雷尼替丁、氢氧化铝混悬剂等药物 ,并作不定期检查 ,上次内窥镜检查结果为 : ,内窥镜检查诊断为胃溃疡急性出…     

紫外分光光度法测定复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量

目的建立紫外分光光度法测定复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量。方法采用紫外分光光度法,测定波长为352nm。结果米诺环素的检测线性范围为4～24μg/ml,r=0.9999,平均回收率为100.2%。结论本法操作简便,准确性好,适合复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量测定。     

米诺环素治疗下呼吸道细菌感染54例

用米诺环素治疗下呼吸道细菌感染５４例（男性３６例，女性１８例。年龄４９±ｓ８ａ），剂量１００ｍｇ，ｐｏ，ｂｉｄ。结果：痊愈占４６％，显效占２４％，有效率达７０％。对急性支气管炎和哮喘伴感染治疗效果佳，而对肺癌合并感染治疗无效。本品对肺炎球菌，肺炎杆菌，大杆菌，变形杆菌和表皮葡萄球菌等细菌感染有良好的治疗效果。     

米诺环素搽剂的制备及质控

抗生素是治疗痤疮的一种有效手段,其中四环素类较常用,在四环素类抗生素中米诺环素的抗菌作用最强。因此,我们研制了米诺环素搽剂,直接应用在病损部位,使之充分发挥药物疗效     

米诺环素软膏治疗成人牙周炎临床研究

目的 探讨米诺环素软膏治疗成人牙周炎的临床效果。方法 随机选取临床确诊为成人牙周炎的患牙80颗分为盐酸米诺环素软膏治疗组和对照组（不用药），观察治疗前后的菌斑指数（PLI），龈沟出血指数（SBI），牙周袋深度（PD），牙周附着水平（AL）．牙齿松动度（MD）的变化。结果 治疗组在用药1周和1个月后，各项指标改善程度均明显优于对照组。结论 盐酸米诺环素软膏是一种有效的牙周局部缓释药物。     

米诺环素辅助治疗重度牙周炎的临床研究

目的评价派里奥软膏局部应用辅助治疗重度牙周炎的疗效。方法32例重度牙周炎患者，共192颗患牙，全口洁治和根面平整后，以患者一侧患牙局部应用派里奥软膏为实验组，对侧同名患牙局部应用牙康（甲硝唑棒）为对照组，记录基线、用药后第4周、8周菌斑指数（PLI）、龈沟出血指数（SBI）、牙周探诊深度（PD）、牙周附着水平（AL）．并进行数据分析。结果第4周、8周PLI、SBI、PD、AL较基线时均由改善（P〈0．01）；实验组第8周较第4周除PLI略有反弹外，其余指标皆进一步改善；在两个观察时段实验组较对照组在SBI、PD、AL方面，差异有统计学意义（P〈0．01），但PLI两组间差异无统计学意义（P〉0．05）。结论派里奥软膏局部应用辅助治疗重度牙周炎有较好的临床效果，优于牙康。     

米诺环素治疗下呼吸道细菌感染54例

用米诺环素治疗下呼吸道细菌感染５４例（男性３６例，女性１８例。年龄４９±ｓ８ａ），剂量１００ｍｇ，ｐｏ，ｂｉｄ。结果：痊愈占４６％，显效占２４％，有效率达７０％。对急性支气管炎和哮喘伴感染治疗效果佳，而对肺癌合并感染治疗无效。本品对肺炎球菌、肺炎杆菌、大肠杆菌、变形杆菌和表皮葡萄球菌等细菌感染有良好的治疗效果。     

盐酸米诺环素原位凝胶的药效学研究

目的探讨盐酸米诺环素原位凝胶治疗牙周炎的药效学作用。方法以大鼠为模型动物,建立了与临床病理特征相一致的稳定的大鼠实验牙周炎模型,并以此模型进行了药效学研究。结果对比给药组与正常对照组、牙周炎组、空白对照组对牙周病各项临床指标(探诊出血、牙龈指数、牙周袋深度)的改善和病理照片表明,盐酸米诺环素原位凝胶在给药第1周内探诊出血、牙龈指数、牙周袋深度逐渐减小,4周时与正常对照组各项指标差异无统计学意义。结论盐酸米诺环素原位凝胶能有效地改善牙周炎炎症反应,是一种理想的治疗牙周炎的药物传递系统。     

米诺环素治疗尿路感染临床及实验室研究

应用米诺环素治疗尿路感染３０例，结果表明：本药对尿路感染治愈率达８６．７％以上。对金葡菌、大肠埃希氏菌的药物敏感率达９３．３％以上。对Ｇ＾＋和Ｇ＾－菌的最低抑菌浓度为０．５－４．０μｇ／ｍｌ，明显优于庆大霉素和氨苄青霉素。本药口服后血药浓度高，维持有效药物浓度时间较长。显示本药具有高效、长效、广谱抗菌活性，是目前治疗尿路感染较理想的抗生素。     

Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells

As the applications of industrial nanoparticles are being developed, the concerns on the environmental health are increasing. Cytotoxicities of titanium dioxide nanoparticles of different concentrations (5, 10, 20 and 40mug/ml) were evaluated in this study using a cultured human bronchial epithelial cell line, BEAS-2B. Exposure of the cultured cells to nanoparticles led to cell death, reactive oxygen species (ROS) increase, reduced glutathione (GSH) decrease, and the induction of oxidative stress-related genes such as heme oxygenase-1, thioredoxin reductase, glutathione-S-transferase, catalase, and a hypoxia inducible gene. The ROS increase by titanium dioxide nanoparticles triggered the activation of cytosolic caspase-3 and chromatin condensation, which means that titanium dioxide nanoparticles exert cytotoxicity by an apoptotic process. Furthermore, the expressions of inflammation-related genes such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), TNF-a, and C-X-C motif ligand 2 (CXCL2) were also elevated. The induction of IL-8 by titanium dioxide nanoparticles was inhibited by the pre-treatment with SB203580 and PD98059, which means that the IL-8 was induced through p38 mitogen-acitvated protein kinase (MAPK) pathway and/or extracellular signal (ERK) pathway. Uptake of the nanoparticles into the cultured cells was observed and titanium dioxide nanoparticles seemed to penetrate into the cytoplasm and locate in the peri-region of the nucleus as aggregated particles, which may induce direct interactions between the particles and cellular molecules, to cause adverse biological responses.     

Effects of titanium dioxide nanoparticles on human keratinocytes

Titanium dioxide (TiO₂) is a ubiquitous whitening compound widely used in topical products such as sunscreens, lotions and facial creams. The damaging health effects of TiO₂ inhalation has been widely studied in rats, mice and humans showing oxidative stress increase, DNA damage, cell death and inflammatory gene upregulation in lung and throat cells; however, the effects on skin cells from long-term topical use of various products remain largely unknown. In this study, we assessed the effect of specific TiO₂ nanoparticles (H₂TiO₇) on a human keratinocyte cell line (HaCaT). We performed a comparative analysis using three TiO₂ particles varying in size (Fine, Ultrafine and H₂TiO₇) and analyzed their effects on HaCaTs. There is a clear dose-dependent increase in superoxide production, caspase 8 and 9 activity, and apoptosis in HaCaTs after treatment with all three forms of TiO₂; however, there is no consistent effect on cell viability and proliferation with either of these TiO₂ particles. While there is data suggesting UV exposure can enhance the carcinogenic effects of TiO₂, we did not observe any significant effect of UV-C exposure combined with TiO₂ treatment on HaCaTs. Furthermore, TiO₂-treated cells showed minimal effects on VEGF upregulation and Wnt signaling pathway thereby showing no potential effect on angiogenesis and malignant transformation. Overall, we report here an increase in apoptosis, which may be caspase 8/Fas-dependent, and that the H₂TiO₇ nanoparticles, despite their smaller particle size, had no significant enhanced effect on HaCaT cells as compared to Fine and Ultrafine forms of TiO₂.     

A mechanistic review of particle overload by titanium dioxide

Chronic exposure to titanium dioxide (TiO₂) induces slight but significant pulmonary inflammation in experimental animals, and among potential mechanisms, particle overload is likely. Although mechanisms of particle overload are poorly understood, excess accumulation of dust particles in dust containing macrophages (dust cells) can impair their mobility, resulting in reduced clearance ability. Accordingly, retention half-times of inhaled TiO₂ increase linearly with lung burden in rodents, and mathematical (Michaelis–Menten-like) models for pulmonary clearance rates of TiO₂ as a function of lung burden have suggested an alternative mechanism for particle overload, involving excess accumulation of macrophages in the translocation pathway due to the narrow exit to the ciliated airway region, and leading to reduced pulmonary TiO₂ clearance rates. This mechanism is consistent with observations showing that TiO₂ retention half-times in the lungs of rats and mice show no change from the initial value until the lung burden exceeds around mass burden of 3?mg or surface area burden of 1000?cm². In addition, excess accumulation of macrophages is consistent with several particle overload-associated pathological changes, including accelerated neutrophilic inflammation, elevation of lymph node burden, and epithelial cell hyperplasia. Because excessive alveolar accumulation of macrophages may accelerate interstitialization of macrophages (including dust cells) and subsequent migration into lymph nodes, alveolar macrophages and dust cells likely migrate into interstitial spaces and escape to the luminal side of the ciliated airway region.     

Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation

Titanium dioxide nanoparticles (TNP) are nanomaterials which have various applications including photocatalysts, cosmetics, and pharmaceuticals because of their high stability, anticorrosiveness, and photocatalytic properties. Induction of cytokines and potential chronic inflammation were investigated in mice treated with TNP (5 mg/kg, 20 mg/kg, and 50 mg/kg) by a single intratracheal instillation. Pro-inflammatory cytokines such as IL-1, TNF-a, and IL-6 were significantly induced in a dose-dependent manner at day 1 after instillation. The levels of Th1-type cytokines (IL-12 and IFN-γ) and Th2-type cytokines (IL4, IL-5 and IL-10) were also elevated dose-dependently at day 1 and the inflammatory responses were sustained until the remainder of experimental period for 14 days. By the induction of Th2-type cytokines, the increased B cell distributions both in spleen and in blood, and increased IgE production in BAL fluid and serum were observed. In lung tissue, increase of inflammatory proteins (MIP and MCP) and granuloma formation were observed. Furthermore, the expressions of genes related with antigen presentation (H2-T23, H2-T17, H2-K1, and H2-Eb1) and genes related with the induction of chemotaxis of immune cells (Ccl7, Ccl3, Cxcl1, Ccl4, Ccl2) were markedly increased using microarray analysis. From these data, it could be suggested that TNP possibly cause chronic inflammatory diseases through Th2-mediated pathway in mice.     

Titanium dioxide nanoparticles induced intracellular calcium homeostasis modification in primary human keratinocytes. Towards an in vitro explanation of titanium dioxide nanoparticles toxicity

Abstract

Deciphering the molecular basis of toxicology mechanism induced by nanoparticles (NPs) remains an essential challenge. Ion Beam Analysis (IBA) was applied in combination with Transmission Electron Microscopy and Confocal Microscopy to analyze human keratinocytes exposed to TiO₂-NPs. Investigating chemical elemental distributions using IBA gives rise to a fine quantification of the TiO₂-NPs uptake within a cell and to the determination of the intracellular chemical modifications after TiO₂-NPs internalization. In addition, fluorescent dye-modified TiO₂-NPs have been synthesized to allow their detection, precise quantification and tracking in vitro. The internalization of these TiO₂-NPs altered the calcium homeostasis and induced a decrease in cell proliferation associated with an early keratinocyte differentiation, without any indication of cell death. Additionally, the relation between the surface chemistry of the TiO₂-NPs and their in vitro toxicity is clearly established and emphasizes the importance of the calcium homeostasis alteration in response to the presence of TiO₂-NPs.     

In vitro phototoxicity and hazard identification of nano-scale titanium dioxide

Titanium dioxide nanoparticles (nano-TiO₂) catalyze reactions under UV radiation and are hypothesized to cause phototoxicity. A human-derived line of retinal pigment epithelial cells (ARPE-19) was treated with six samples of nano-TiO₂ and exposed to UVA radiation. The TiO₂ nanoparticles were independently characterized to have mean primary particle sizes and crystal structures of 22 nm anatase/rutile, 25 nm anatase, 31 nm anatase/rutile, 59 nm anatase/rutile, 142 nm anatase, and 214 nm rutile. Particles were suspended in cell culture media, sonicated, and assessed for stability and aggregation by dynamic light scattering. Cells were treated with 0, 0.3, 1, 3, 10, 30, or 100 μg/ml nano-TiO₂ in media for 24 hrs and then exposed to UVA (2 hrs, 7.53 J/cm²) or kept in the dark. Viability was assessed 24 hrs after the end of UVA exposure by microscopy with a live/dead assay (calcein-AM/propidium iodide). Exposure to higher concentrations of nano-TiO₂ with UVA lowered cell viability. The 25 nm anatase and 31 nm anatase/rutile were the most phototoxic (LC₅₀ with UVA < 5 μg/ml), while the 142 nm anatase and 214 nm rutile were the least phototoxic. An acellular assay ranked TiO₂ nanoparticles for their UVA photocatalytic reactivities. The particles were found to be capable of generating thiobarbituric acid reactive substances (TBARS) under UVA. Flow cytometry showed that nano-TiO₂ combined with UVA decreased cell viability and increased the generation of reactive oxygen species (ROS, measured by Mitosox). LC₅₀ values under UVA were correlated with TBARS reactivity, particle size, and surface area.     

The immunomodulatory effects of titanium dioxide and silver nanoparticles

Due to their characteristic physical, chemical and optical properties, titanium dioxide and silver nanoparticles are attractive tools for use in a wide range of applications. The use of nanoparticles for biological applications is, however, dependent upon their biocompatibility with living cells. Because of the importance of inflammation as a modulator of human health, the safe and efficacious in vivo use of titanium dioxide and silver nanoparticles is inherently linked to a favorable interaction with immune system cells. However, both titanium dioxide and silver nanoparticles have demonstrated potential to exert immunomodulatory and immunotoxic effects. Titanium dioxide and silver nanoparticles are readily internalized by immune system cells, may accumulate in peripheral lymphoid organs, and can influence multiple manifestations of immune cell activity. Although the factors influencing the biocompatibility of titanium dioxide and silver nanoparticles with immune system cells have not been fully elucidated, nanoparticle core composition, size, concentration and the duration of cell exposure seem to be important. Because titanium dioxide and silver nanoparticles are widely utilized in pharmaceutical, commercial and industrial products, it is vital that their effects on human health and immune system function be more thoroughly evaluated.     

Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability

An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8 nm) and TiO₂ nanoparticles (TiO₂NPs; 6 nm and 35 nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO₂NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO₂NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO₂NPs in BBB.     

Cell uptake and oral absorption of titanium dioxide nanoparticles

Large efforts are invested on the development of in vitro tests to evaluate nanomaterial (NM) toxicity. In order to assess the relevance of the adverse effects identified in in vitro toxicity tests a thorough understanding of the biokinetics of NMs is critical. We used different in vitro and in vivo test methods to evaluate cell uptake and oral absorption of titanium dioxide nanoparticles (TiO₂ NPs). These NPs were readily uptaken by A549 cells (carcinomic human alveolar basal epithelial cells) in vitro. Such rapid uptake contrasted with a very low oral absorption in a differentiated Caco-2 monolayer system (human epithelial colorectal adenocarcinoma cells) and after oral gavage administration to rats. In this oral study, no significant increase in the levels of titanium was recorded by ICP-MS in any of the tissues evaluated (including among other: small intestine, Peyer's patches, mesenteric lymph nodes, liver, and spleen). No NPs were observed by TEM in sections of the small intestine, except for several particles in the cytoplasm of a cell from a Peyer's Patch area. The observation of NPs in Peyer's Patch suggests that the Caco-2 monolayer system is likely to underestimate the potential for oral absorption of NPs and that the model could be improved by including M-cells in co-culture.     

二氧化钛马来酸氯苯那敏乳膏剂的制备和抗过敏作用初探

目的优选二氧化钛马来酸氯苯那敏乳膏剂的最优处方,并初步考察其抗过敏作用。方法以乳膏剂色泽光泽度考察、稳定性考察及显微镜法观察作为考察指标,采用单因素考察和正交试验优选最优处方。并将该制剂涂抹于被紫外线照射的小鼠皮肤上。结果制备40 g乳膏中二氧化钛的投药量为3 g、扑尔敏的投药量为0.2 g、乳化时间为30 min、乳化温度为70℃时,乳膏效果较好。小鼠背部皮肤HE染色观察显示其有明显的抗过敏作用。结论二氧化钛马来酸氯苯那敏乳膏可有效抗紫外线过敏。