Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

增溶分光光度法测定人发中铝

目的：建立一种测定人发中铝的新方法。方法：以铬天青S－溴化十六烷基三甲铵为表面活性剂增溶分光光度法测定人发中铝。结果：方法检出限为0.006μg/ml，相对标准偏差小于1．3％，加标回收率在91％－104％之间。结论：方法简便，不需要特殊仪器，易于推广使用。     

Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum‐treated rabbits

We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum‐treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum‐treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum‐treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non‐phosphorylated high molecular weight neurofilament (neurofilament‐H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament‐H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum‐treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum‐treated rabbits.     

Nasal septum lesions caused by chromium exposure among chromium electroplating workers

A chromium electroplating worker, suffering from epistaxis during work, was found to have nasal septum perforation. To determine the etiology and prevalence of nasal septum lesions, we conducted a survey of seven chromium electroplating factories and examined 79 workers. Forty workers from three aluminum electroplating factories were also enrolled as the reference group. Subjects were thoroughly examined by an otolaryngologist and each of them provided a blood and urine sample. A questionnaire interview regarding symptoms of the upper respiratory tract, past medical history, life style, and work history was also conducted. Air chromium concentrations were measured by taking area samples for 4–6 hours. Based on field observation and chromium measurements, we divided chromium electroplating into three different exposure zones: workers directly dealing with electroplating tanks (n = 31), other process workers (n = 29), and office workers and drivers (n = 19). Among the 79 chromium electroplating workers, there were 16 cases of nasal septum perforation, and 42 with either scar formation or ulceration; 10 chromium electroplating workers developed skin ulcers after performing chrome plating. No workers from aluminum electroplating factories had any nasal septum or skin abnormalities. There was a consistent trend between the degree of chromium exposure and the signs and symptoms related to the nose, throat, and skin. Immediate improvement of occupational hygiene is warranted.     

磷酸铝凝胶剂的研制

以微粒沉降速度、粒度分布、粘度大小等为指标，利用正交试验法筛选出磷酸铝凝胶剂的最佳处方。结果表明，磷酸铝凝胶剂的沉降容积比可达９３．１％，其粒度均小于１０μｍ，而且沉降速度较小。     

Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats

The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.     

聚乙烯醇在α-Al_2O_3颗粒上的吸附平衡

考察了温度、悬浮液浓度、相对分子质量对聚乙烯醇 ( PVA)在 α- Al2 O3颗粒上吸附的影响 ,实验测定了相对分子质量为 80 0 0 0和 56 0 0的 PVA在 2 88.1 5K、2 98.1 5K和 30 8.1 5K、α- Al2 O3悬浮液质量浓度为 0 .0 5、0 .1 0和 0 .1 5时的吸附等温线 ,用 Langmuir吸附模型对实验数据进行了关联。结果表明 ,吸附量随悬浮液浓度的增加或温度的升高而降低 ,随 PVA相对分子质量的增加而增加。PVA相对分子质量越大 ,其吸附等温线受温度、悬浮液浓度的影响也越大。     

Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine

OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05). CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers.     

天麻对铝染毒大鼠大脑皮质氨基酸递质的影响

[目的]探讨天麻对铝染毒大鼠大脑皮质氨基酸类神经递质的影响。[方法]将SD大鼠36只在动物室适应性喂养1周后 ,分成6组 ,腹腔注射生理盐水或AlCl3 溶液0.2ml/d ,60d。每连续注射3d间歇1d ,60d内共计注射45次。在间歇天肌肉注射青链霉素以抗感染。整个染毒期间 ,动物室以自然节律采光 ,温度18～23℃ ,湿度40%～60 % ,清洁 ,安静。所有动物饲以普通饲料 ,自由饮水和进食 ,加天麻组 ,以0.4g/kg体重的剂量在饮水中加入天麻。每周定时称体重一次 ,调整Al的浓度和饮水中天麻的浓度。染毒期结束后 ,将大鼠断头取脑 ,在冰冷的生理盐水中漂洗、去脑膜、用滤纸拭干。取大脑皮质0.2g(湿重 ) ,加浓硝酸1.6ml,高氯酸0.4ml,消化后 ,用去离子水定容至1.5ml,用石墨炉原子吸收光谱法测定脑铝含量。取左侧大脑半球额叶皮质0.1g,用脑组织处理液以1:50( g:ml)作成匀浆 ,用HLPC法测定氨基酸含量。[结果]与生理盐水组相比 ,Al3 +5mg/kg组和Al3+10mg/kg组脑铝含量均显著升高 (P<0.01) ;生理盐水 +天麻组与生理盐水组相比、Al3+5mg/kg+天麻组与Al3+5mg/kg组相比及Al3 +10mg/kg+天麻组与Al3 +10mg/kg组相比 ,大鼠大脑皮质铝含量差异未见统计学意义(P>0.05)。大脑皮质氨基酸含量结果显示 ,与生理盐水组相比 ,Al3+ 5mg/kg组谷氨酸 (G     

铝神经毒性的线粒体机制

探讨铝致神经毒性的机制.铝具有神经毒性,其毒性作用的确切机制目前尚不清楚.本文综述了国内外关于铝致神经毒性的作用机制研究,提出了新的研究设想并阐述其研究意义.