Immunogenicity of Intranasally Administered Meningococcal Native Outer Membrane Vesicles in Mice

Colonization of the human nasopharyngeal region by Neisseria meningitidis is believed to lead to natural immunity. Although the presence of bactericidal antibody in serum has been correlated with immunity to meningococcal disease, mucosal immunity at the portal of entry may also play an important role. This study was undertaken to examine in mice the possibility of safely using native outer membrane vesicles (NOMV) not exposed to detergent as an intranasal (i.n.) vaccine. The mucosal and systemic responses of mice to intranasal and intraperitoneal (i.p.) vaccination with NOMV were compared over a range of doses from 0.1 to 20 μg. Intranasal vaccination of mice with NOMV induced a strong systemic bactericidal antibody response, as well as a strong local immunoglobulin A immune response in the lung as determined by assay of lung lavage fluid by enzyme-linked immunosorbent assay and lung antibody secreting cells by enzyme-linked immunospot assay. However, 8- to 10-fold-higher doses of NOMV were required i.n. compared to i.p. to elicit an equivalent bactericidal antibody response in serum. Some NOMV vaccine was aspirated into the lungs of mice during i.n. immunization and resulted in an acute inflammatory response that peaked at 1 to 2 days postimmunization and was cleared by day 7. These results indicate that i.n. delivery of meningococcal NOMV in mice is highly effective in eliciting the production of both a mucosal immune response and a systemic bactericidal antibody response.     

Toxic and Genotoxic Effects of Silver Nanoparticles in Drosophila

The in vivo model Drosophila melanogaster was used here to determine the detrimental effects induced by silver nanoparticles (AgNPs) exposure. The main aim was to explore its interaction with the intestinal barrier and the genotoxic effects induced in hemocytes. The observed effects were compared with those obtained by silver nitrate, as an agent acting via the release of silver ions. Larvae were fed in food media containing both forms of silver. Results indicated that silver nitrate was more toxic than AgNPs when the viability “egg-to-adult” was determined. Depigmentation was observed in adults including those exposed to nontoxic concentrations, as indicative of exposure action. Interestingly, AgNPs were able to cross the intestinal barrier affecting hemocytes that show significant increases in the levels of intracellular reactive oxygen species. Additionally, significant levels of genotoxic damage, as determined by the comet assay, were also induced. When the expression of different stress-response genes was determined, for both AgNPs and silver nitrate, significant upregulation of Sod2 and p53 genes was observed. Our results confirm for the first time that in an in vivo model as Drosophila, AgNPs are able to cross the intestinal barriers and produce primary DNA damage (comet assay) via oxidative stress induction. In general, the effects induced by silver nitrate were more pronounced than those induced by AgNPs what would emphasize the role of silver ions in the observed effects. Environ. Mol. Mutagen. 60:277–285, 2019. © 2018 Wiley Periodicals, Inc.     

Host-Etiological Agent Interactions in Intranasally and Intraperitoneally Induced Cryptococcosis in Mice

Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 10³ viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.     

Bacterial Lysate Complex Administered Intranasally Suppresses Inflammation in an In Vivo Model of Aseptic Lymphadenitis

Bulletin of Experimental Biology and Medicine - The effect of a bacterial lysate complex IRS 19 on local and systemic manifestations of inflammation was studied in a rat model of aseptic...     

阿霉素纳米微粒经动脉给药对兔肝肿瘤的疗效观察

目的 观察阿霉素纳米微粒经动脉给药对免肝肿瘤的疗效.方法 将阿霉素纳米微粒(小粒径脂质体与毫微粒)与碘油制成乳剂,建立兔肝VX-2移植癌改良模型并随机分为六组,经肝动脉分别注入生理盐水(NS)、碘油(Lipi)、游离丝裂霉素(ADM,2mg/kg)、游离阿霉素加空白纳米微粒(ADM+NP,2mg/kg)、阿霉素纳米微粒组(NADM,2mg/kg)与阿霉素纳米微粒-碘油乳剂(Lip-NADM,2mg/kg).结果 经Lip-NADM治疗的兔生存期显著延长(P<0.01),与其它各组相比对肿瘤生长的抑制更为明显(P<0.01),肿瘤坏死更广泛,更彻底.结论 与其它各组相比,Lip-NADM经动脉给药具有更好的疗效.     

不同表型的双价痢疾菌苗的滴鼻免疫研究

为了探讨滴鼻免疫不同表型的双价痢疾菌苗的免疫效果 ,应用FSM 2 117(Ipa )及FS 5 40 2 (Ipa+)、FS 5 411(Ipa+)、FS 5 414(Ipa+)、FS 5 416 (Ipa+) 5株菌苗株分别滴鼻免疫小鼠 ,4× 10 7CFU/只 ,间隔 14d ,3次免疫后第 7天收集血清和小肠、鼻咽、肺、阴道冲洗液 ,ELISA法检测其中特异性福氏、宋内LPSIgA和IgG抗体水平 ,发现滴鼻免疫能够诱生血清中的双价IgA、IgG抗体显著升高 ,Ipa+株较Ipa 株升高显著 (P <0 0 1)。同时诱生鼻咽、肺、小肠内特异性抗体升高 ,尤其是生殖道冲冼液内抗体升高极为明显。表明鼻粘膜免疫不仅诱导多个粘膜部位 (特别是生殖道 )的抗体反应 ,且能诱导系统免疫反应 ,是一个安全有效的免疫途径。研究中发现侵袭蛋白表达在鼻粘膜部位能够显著加强系统特异性抗体生成。     

Distribution of Transglutaminase 6 in the Central Nervous System of Adult Mice

Our previous study identified a new form of spinocerebellar ataxia (SCA), in which mutations in the gene coding for transglutaminase 6 (TG6) were suggested to be causative. However, the data concerning cellular distribution of TG6 in the brain is still fragmentary. Therefore, we now report a comprehensive immunohistochemical examination of the expression profile of TG6 in adult mouse brain. TG6 was abundantly expressed in the septal region, basal ganglia, hypothalamus and brainstem. Notably, numerous TG6‐positive neurons were found in the key brain regions involved in regulating locomotion activity, including the globus pallidus, subthalamic nucleus, substantia nigra, cerebellum, some precerebellar nuclei, and spinal motor neurons. Double immunostaining showed that the vast majority of TG6‐positive neurons in the reticular nigra were GABAergic and those in the compact nigra were not dopaminergic. In addition, double staining for TG6 with either anti‐NeuN or glial fibrillary acidic protein (GFAP) antibodies demonstrated exclusive NeuN‐TG6 co‐localization. This study presents a comprehensive overview of TG6 expression in the mouse brain, and provides insight for investigating the role of TG6 in the development of SCA. Anat Rec, 296:1576–1587, 2013. © 2013 Wiley Periodicals, Inc.     

Immunogenicity of an Intranasally Administered Modified Live Canine Parvovirus Type 2b Vaccine in Pups with Maternally Derived Antibodies

The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of ≤80 and in 51.6% of pups with titers between 160 and 320.     

Long‐Term Effects of Neonatal Hyperoxia in Adult Mice

The outcomes of premature infants have improved greatly; however, the health risks in adulthood are still relatively unclear. Bronchopulmonary dysplasia (BPD) in premature infants is a major risk factor for alteration in lung function and predisposition to respiratory morbidity, and is associated with hyperoxia. The study explores the effect of neonatal hyperoxia on organ systems in adult mice. Newborn mouse litters were randomized to 85%O₂ or room air (RA) on P3 for 12 days; mice were sacrificed at P3, P7, P15, 3 months and 9 months. Lungs were assessed by histopathology, radial alveolar count, mean linear intercept, and α‐Smooth muscle actin immunohistochemistry. Aortic assessment included histology, wall thickness, elastin, and collagen content. Glomerular histology and nephron number were assessed in the kidneys. Hyperoxia‐exposed mice had progressive alveolar simplification and poor weight gain over time. Greater thickness of pulmonary arterioles by 3 months and a higher Fulton index by 9 months suggest worsening pulmonary hypertension. Aortic wall thickness to lumen ratio was greater with a lower aortic elastin‐to‐collagen ratio suggesting long‐term effects of neonatal hyperoxia. Hyperoxia‐exposed mice at 9 months had smaller glomeruli as indicated by glomerular diameter and volume. Prolonged neonatal hyperoxia during the critical period of development induces irreversible lung damage, pulmonary hypertension and structural changes in the kidneys and aorta in adult mice. This could have implications for chronic adult diseases following exposure to high levels of oxygen in the newborn period. Anat Rec, 301:717–726, 2018. © 2017 Wiley Periodicals, Inc.     

Combined Effects of Alcohol and Stress during the Prenatal Period on Behavior in Adult Mice

The aim of the present work was to study the effects of prenatal alcohol and stress on behavior in adult mice. Pregnant females received drinking solution containing 11% ethanol from days 1–21 of pregnancy and were subjected to stress (restriction for 2 h) on days 15–21. Their offspring (the Alcohol + Stress group) were tested at age three months using standard behavioral tests. Animals of the Alcohol + Stress group buried more marbles in the marble test, which models obsessive-compulsive disorder (OCD). In the “social behavior” test, males of the Alcohol + Stress group licked and sniffed a juvenile male longer than did controls. Prenatal alcohol and stress had no significant influence on motor activity, anxiety, or investigative behavior in adult male mice. These results led to the conclusion that the combined actions of ethanol and stress during the prenatal period induced a predisposition to the development of OCD.     

纳米银的抗菌特性及其在医学中的应用

纳米银是利用现代纳米技术制造的新一代抗菌材料,因其具有优异的抗菌杀菌活性及在伤口修复方面的积极作用,在医学生物学领域获得了广泛应用.目前已有一些纳米银产品应用于临床,如纳米银抗菌凝胶、纳米银敷料、纳米银心血管支架、纳米银导管、纳米银骨水泥等.近年来的研究表明,纳米银的长效、广谱、强效的抗菌活性源于其对微生物复杂而特异的抗菌机制.尽管纳米银不会使病菌产生耐药性,是人们期望中的理想抗菌材料,但研究人员对其毒性机制依然不甚了解.本文就纳米银的合成、抗菌机制、毒性及在医学中的应用做了简要总结和展望.     

An Organic/Inorganic Nanocomposite Consisting of Polymuconate and Silver Nanoparticles

Summary: We have fabricated a nanocomposite consisting of a crystalline polymer and fine metal particles. The intercalation of alkali metal ions into the layered polymer crystals, which were prepared by the solid state polymerization of dodecylammonium muconate, was achieved by heterogeneously stirring the reacting solid polymers in a solution of sodium hydroxide in methanol at room temperature. An ion exchange reaction was similarly carried out in a silver nitrate solution, which was followed by photoreduction, leading to the formation of fine silver particles in the crystalline polymer (the organic matrix). By controlling the amount of silver ions introduced, we have fabricated an organic/inorganic nanocomposite containing silver nanoparticles with well controlled size and distribution, the characteristics of which were measured by transmission electron microphotography, UV‐visible diffuse reflectance spectroscopy and a small‐angle X‐ray scattering method.

     

Anti-Idiotypic Antibody Used for the Localization of Parenterally Administered Monoclonal Anti-Progesterone Antibody in Mice

Affinity-purified rabbit and sheep anti-idiotypic antisera raised against mouse monoclonal anti-progesterone IgG1 antibody (DB3) or mouse myeloma IgG1 protein P3 (MOPC 21) showed high binding specificities to the respective idiotypes used for immunization as determined by RIA or ELISA. They have been used in an indirect immunofluorescent method to demonstrate the localization of parenterally administered idiotypes in pregnant or pseudopregnant BALB/c mouse frozen tissue preparations, at known stages post coitum after a single intraperitoneal or intravenous injection of DB3 or P3. DB3 was visualized on the surface of uterine luminal and glandular epithelia of pregnant mice 36 h after treatment; the localization was DB3-specific as it was not seen in mice treated with P3 (using sheep anti-P3 anti-idiotype as a probe) or saline. The fluorescent staining reaction in oviduct was weak and only appeared on the surface of the oviducal serosa (peritoneal side). Both DB3 and P3 were also localized in liver (granules of Kupffer cells), kidney (glomerular basement membrane), spleen (on the membrane surface of mononuclear cells in the white pulp), and peritoneal exudate cells (on the membrane surface). Staining could be completely blocked by the addition of the free idiotypes against which the anti-idiotypes were made but not by the unrelated idiotype. Anti-idiotypic labelling in vivo is more specific and selective than anti-whole immunoglobulin labelling.     

The Systemic Metabolic Profile Early after Allogeneic Stem Cell Transplantation: Effects of Adequate Energy Support Administered through Enteral Feeding Tube

Patients undergoing allogeneic stem cell transplantation usually require nutritional support. There is no consensus on whether enteral support through tube feeding should be preferred. A recent randomized study could not detect any difference between enteral and parenteral feeding with regard to post-transplant outcomes, whereas 2 retrospective studies described an association between enteral feeding and a favorable post-transplant outcome. We compared pre- and post-transplant plasma metabolomic profiles for 10 patients receiving mainly enteral nutritional support and 10 patients receiving mainly parenteral support. Samples were collected before conditioning and 3 weeks post-transplant; 824 metabolites were analyzed using mass spectrometry. The pretransplant metabolite profiles showed a significant overlap between the 2 groups. Post-transplant samples for both patient groups showed an increase of secondary bile acids and endocannabinoids, whereas reduced levels were seen for food preservatives, plasmalogens, and retinol metabolites. The main post-transplant differences between the groups were decreased levels of fatty acids and markers of mitochondrial activation in the control group, indicating that these patients had insufficient energy intake. A significant effect was also seen for heme/bilirubin metabolism for the parenteral support. To conclude, allotransplant recipients showed altered metabolic profiles early after transplantation; this was mainly due to the conditioning/transplantation/reconstitution, whereas the type of nutritional support had minor effects.     

Influence of low Environmental Temperature on Systemic Anaphylaxis in Mice

The effect of cold-exposure on the response of sensitized mice to BSA-pertussis was studied. Animals were given two sensitizing injections of a mixture of alum-precipitated BSA and pertussis cells. They were challenged one week later with a saline solution of BSA plus pertussis cells. The proportion of deaths was greater among controls than among cold-exposed animals, 82% vs 38%, and the mean survival time was shorter in controls than in cold-exposed animals, 15 ± 2 vs 75 hours. Serum samples, obtained after the sensitizing injections and just prior to the administration of the challenge injection were tested in agglutination tests with tanned erythrocytes coated with BSA. There was no difference in circulating antibody levels between cold-exposed animals (mean titre 26 ± 6) and controls (mean titre 20 ± 4). Injections at 22d` ± 2d`C of unsensitized mice with pertussis alone did not produce any deaths among animals previously exposed to cold for 6 weeks nor among control animals.