Preparation and characterization of hydroxyapatite nanoparticles carrying insulin and gallic acid for insulin oral delivery

Although nanoparticles carriers for oral delivery of insulin have been researched for many years, this method still fails to solve issues with toxicity, biocompatibility, and degradability in the organism. We therefore developed an innovative conjugation system to solve this problem. Nano hydroxyapatite (HAP) particles were used as the core, then polyethylene glycol (PEG) was wrapped onto the surface of hydroxyapatite, and, finally, insulin (INS) and gallic acid (GA) were conjugated with PEG. PEG functionalized HAP was increased the hydrophilicity of the nanoparticles, also protected them from degradation in the gastrointestinal (GI) tract. Most importantly, the in vivo absorption of nanoparticles in rat small intestines revealed that HAP-PEG-GA-INS was absorbed by the small intestine epithelium. The blood glucose of the type 1 diabetes (T1D) rats that were given intragastrically HAP-PEG-GA-INS showed an obvious downward trend. Overall, we synthesized a safe, non-toxic, and effective oral insulin delivery system.     

老年人医院获得性肺炎临床的合理用药

目的探讨老年人医院获得性肺炎（HAP）的合理用药及预防。方法对我科2003年3月至2008年6月间住院老年患者发生院内获得性肺炎80例的治疗情况进行分析研究。结果通过合理用药治疗，痊愈或好转出院65例（81．3％），死亡8例（10．0％），其中死亡率远低于文献报道。结论合理用药对于降低老年HAP肺炎的病死率有显著效果，值得临床推广。     

Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy

Objective To investigate antibiotic-mediated release of tumour necrosis factor (TNF)- and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy.Design Prospective observational study with a retrospective post hoc analysis.Setting Surgical intensive care unit (ICU) at a university hospital.Patients Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society.Interventions Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins.Measurements and results Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF- was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy.Conclusions Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF- release may induce the kynurenine pathway. TNF- activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.     

哌拉西林舒巴坦治疗尘肺并发医院获得性肺炎临床观察

目的观察哌拉西林舒巴坦治疗尘肺并发医院获得性肺炎（HAP）的疗效。方法60例尘肺并发HAP患者随机分为哌拉西林舒巴坦治疗组（40例）和头孢地嗪对照组（20例）,观察二组治疗天数、临床疗效及药物安全性。结果二组患者治疗时间、临床疗效比较差异有统计学意义。结论哌拉西林舒巴坦对尘肺并发HAP患者有较好临床疗效。     

COPD急性加重期并发医院获得性肺炎51例临床分析

目的探讨慢性阻塞性肺疾病急性加重期（Acute exacerbation of chronic obstruetive pulmonary disease,AECOPD）发生医院获得性肺炎（Hospital-acquired pneumonia,HAP）的特点及高危因素,预防HAP的发生。方法对51例AECOPD并发HAP患者的临床资料进行回顾性分析。结果AECOPD患者并发HAP住院时间明显延长,死亡率增加,老年患者及有基础疾病或合并症者发生率增加,其感染病原菌以革兰阴性菌为主,混合感染常见。结论AECOPD并发HAP使患者住院时间延长,死亡率增加。在积极治疗原发病的同时,应注意基础疾病及合并症的治疗,应根据药物敏感试验合理选用抗菌药物,在获得药物敏感试验结果前应根据可能的病原菌经验性用药。     

Fabrication and characterization of poly(lactic-co-glycolic acid) microsphere/amorphous calcium phosphate scaffolds

Although hydroxyapatite (HAP) and β-tricalcium phosphate have been used extensively as osteoconductive minerals in biomaterial scaffolds for bone regeneration, they lack the capacity to stimulate osteoblastic differentiation of progenitor cells. In contrast, amorphous calcium phosphates (ACPs), which convert to HAP under aqueous conditions, have the potential to facilitate osteoblastic differentiation through the transient local release of calcium and phosphate ions. Therefore, in this study ACPs were synthesized using zinc and zirconia divalent cations as stabilizers (denoted ZnACP and ZrACP, respectively) and compared to HAP. Analysis of ion release into serum-containing cell culture medium revealed transiently elevated levels of calcium and phosphorous, consistent with the enhanced solubility of ZrACP and ZnACP relative to HAP. In addition, X-ray diffraction analysis revealed partial conversion of ZrACP to HAP but no conversion of ZnACP after 96 h. Next, scaffolds were fabricated by sintering mixtures of 300-500 μm poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres and 0.5 wt% calcium phosphate mineral (HAP, ZrACP or ZnACP) at 70 °C for 24 h. Scanning electron microscopy revealed a porous microsphere matrix with calcium phosphate particulates clinging to the microsphere surfaces both prior to and after 14 days in culture medium. Finally, the incorporation of calcium phosphate resulted in a lower compressive modulus in the range 127 to 74-89 MPa. Taken together, these results indicate that ZrACP, ZnACP and HAP minerals exhibit very different properties, and therefore may elicit different osteoblastic responses in vitro.     

肿瘤坏死因子α-308位点基因多态性与医院获得性肺炎易感性关系的研究

目的探讨肿瘤坏死因子α基因启动子308位点(TNF--α308)G/A多态性与医院获得性肺炎(HAP)易感性以及肺炎严重程度的关系。方法以167例医院获得性肺炎患者(HAP组)和110例健康人群(对照组)为研究对象,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对TNF-α基因启动子区308位点进行基因分型,用SPSS统计软件分析此多态性位点与肺炎严重程度的相关性。结果轻度肺炎患者TNF--α308位点GG、GA、AA基因型频率和A、G等位基因频率分别为77.5%、20.0%、2.5%、87.5%和12.5%,与对照组比较,各基因型和等位基因频率差异无统计学意义;重度肺炎患者TNF--α308位点GA、AA基因型和A等位基因频率分别为34.1%、8.5%、25.5%,其与轻度肺炎患者相比差异有统计学意义(P0.05),死亡病例GA、AA基因型和A等位基因频率分别为57.1%、21.4%和50.0%,与存活病例比较,差异有统计学意义(P0.05)。结论TNF-α基因启动子区308位点基因多态性可能不是医院获得性肺炎易感性因素,但可能通过影响TNF-α水平而影响重度HAP的发病和预后。     

HAP涂层镍钛记忆合金的组织相容性

目的 评价HAP涂层镍钛记忆合金的组织相容性,为其在骨缺损修复的临床应用提供理论依据. 方法 取24只青紫兰兔,体重2.0～2.5 kg,随机分为实验组和对照组,每组12只.行左侧股外侧切口,分离显露股骨后,选取股骨下1/3处手术钻孔作为种植区,实验组植入HAP涂层镍钛记忆合金,对照组不植入材料.大腿后外侧肌肉覆盖缺损区.分别于术后7、14、28、56 d每组各处死3只动物,取材行大体观察、组织学观察、BMP.2免疫组织化学染色观察及图像灰度值分析,组织学观察结果 按照中华人民共和国国家标准GB/T16886.6-1997从炎症、纤维组织囊壁形成、材料降解及周边组织反应4个方面进行组织学评价. 结果 所有兔均存活至取材,两组植入物完全包埋于骨组织内部,无松动,无明显骨吸收现象.材料植入后7 d,两组炎性细胞浸润和纤维增生最明显,纤维组织囊壁形成,植入材料呈大片状被囊壁包裹;术后56 d,实验组部分标本囊壁结缔组织增生反应仍较明显,劣于对照组,但分级符合GB/T16886.6-1997体内植入标准.免疫组织化学染色示内源性BMP-2定位于多能MSCs、成骨细胞的胞质内;两组图像分析结果 显示,BMP-2随骨缺损的修复过程呈阶段性分泌,两组BMP-2在术后14 d时表达最高,以后逐渐降低.BMP.2在各时间点染色灰度值比较差异均无统计学意义(P>0.05). 结论 HAP涂层镍钛记忆合金作为生物医学材料具有良好的骨组织相容性.     

羟基磷灰石法和葡聚糖活性炭法测定雌激素受体的比较

目的：建立一种比葡聚糖活性炭（ＤＣＣ）法更灵敏、准确、简便的羟基磷灰石（ＨＡＰ）法测定雌激素受体（ＥＲ）的含量。方法：以ＳＤ雌性大鼠子宫胞浆抽提液为材料，用ＨＡＰ法多点饱和分析和单点饱和分析ＥＲ含量；比较在测定反应中总蛋白量对ＨＡＰ法和ＤＣＣ法测定值的影响，并比较两者在３０例乳腺癌和３０例子宫肌瘤中ＥＲ测定值的差异。结果：大鼠子宫胞浆ＥＲ含量为１３５ｆｍｏｌ／ｍｇ蛋白，Ｋｄ＝０．５８ｎＭ。当测定反应中总蛋白量低于２００μｇ时，ＤＣＣ法测定值严重失真，而ＨＡＰ法在总蛋白量为５０μｇ时仍能准确测出真实值。在３０例乳腺癌和３０例子宫肌瘤ＥＲ测定值中，当ＥＲ含量较低时，ＤＣＣ法测定值偏低甚至有假阴性．而ＥＲ含量高时两者接近。在ＥＲ含量较高时，两者测定值相近。结论：ＨＡＰ法比ＤＣＣ法灵敏、可靠。用以测定甾体激素高非特异性结合的靶组织与非靶组织中的ＥＲ低含量时，ＨＡＰ法更有价值。     

Incorporation of labelled galactose into glycoconjugates by bulk isolated rat brain astroglial and neuronal cells in vitro

Neuronal and astroglial cells isolated from 5-day-old rat brains were found to incorporate [³H]galactose into glycosphingolipids and glycoproteins. Glycosphingolipid labelling was higher in astroglial cells but glycoprotein labelling was similar in both cell types. Galactose incorporation into glucocerebrosides was higher compared to galactocerebrosides. Labelled galactose can also be incorporated into gangliosides and other minor glycosphingolipids by both neuronal and astroglial cells.