丙种球蛋白及干扰素治疗手足口病并发病毒性脑炎疗效观察

目的观察丙种球蛋白及干扰素在治疗小儿手足口病(HFMD)并发病毒性脑炎的临床疗效、症状改善状况及安全性。方法选取我院2012-12—2013-12收治的手足口病并发病毒性脑炎患儿87例为研究对象,随机分为3组,丙种球蛋白组30例,连续5d静滴人血丙种球蛋白,剂量1g/(kg·d);干扰素组27例,采用肌内注射重组人干扰素80μg/(次·d),持续3d;联合组30例,采取丙种球蛋白和干扰素联合治疗。3组患儿在降颅压、退热、预防细菌感染、营养脑细胞等治疗和护理方式上均相同,观察3组患儿1周内临床症状改善情况,对比临床疗效及安全性。结果 3组在生理指标恢复时间上差异无统计学意义(P0.05),在热程、疱疹消失时间和神经系统病理征转阴时间上差异有统计学意义,联用组所需时间显著少于干扰素组和丙种球蛋白组(P0.01),干扰素组和丙种球蛋白组间无显著性差异(P0.05);联用组有效率(93.33%)大于干扰素组(77.78%)和丙种球蛋白组(76.67%),但两两比较差异无统计学意义(P0.05);联用组不良反应发生率高于干扰素组和丙种球蛋白组,但3组间差异无统计学意义(P0.05)。结论小儿手足口病并发病毒性脑炎采用丙种球蛋白联合干扰素治疗的效果较单独使用明显,缩短了病程,且不良反应可耐受,具有一定临床意义。     

Neuroprotective effects of SMAds in a rat model of cerebral ischemia/reperfusion

Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 m RNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the m RNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β m RNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.     

Pamidronate is superior to ibandronate in decreasing bone resorption,interleukin-6 and beta 2-microglobulin in multiple myeloma

OBJECTIVES: Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients. METHODS: Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radiotherapy were analysed. Bone resorption markers [N-terminal cross-linking telopeptide of type-I collagen (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b)], bone formation markers (bone alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, beta 2-microglobulin), and interleukin-6 (IL-6) were also studied. RESULTS: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and beta 2-microglobulin from the second month of treatment, having no effect on bone formation. TRACP-5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL-6, and beta 2-microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P = 0.014), that being continued throughout the 10-month follow-up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and beta 2-microglobulin from the second month for patients of both groups. CONCLUSIONS: These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL-6, and possibly tumour burden in MM. TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM.     

Molecular basis for amyloid fibril formation and stability

The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.     

Alpha,beta hybrid peptides: a polypeptide helix with a central segment containing two consecutive beta-amino acid residues

Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl (Boc)-Val-Ala-Phe-alpha-aminoisobutyric acid (Aib)-(R)-beta3-homovaline (betaVal)-(S)-beta3-homophenylalanine (betaPhe)-Aib-Val-Ala-Phe-Aib-methyl ester (OMe) (peptide 1; betaVal and betaPhe are beta amino acids generated by homologation of the corresponding l-residues) establish that insertion of two consecutive beta residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2-10 of peptide 1. At the site of insertion of the betabeta segment, helical hydrogen-bonded rings are expanded. A C15 hydrogen bond for the alphabetabeta segment and two C14 hydrogen bonds for the alphaalphabeta or betaalphaalpha segments have been characterized. The following conformational angles were determined from the crystal structure for the beta residues: betaVal-5 (= -126 degrees, = 76 degrees, and psi = -124) and betaPhe-6 (=-88 degrees, = 80 degrees, and psi =-118). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz 1H-NMR studies establish a continuous helix over the entire length of the peptide in CDCl3 solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.     

Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets

Inflammatory bowel disease reflects an aberrant mucosal CD4+ T cell response to commensal enteric bacteria. In addition to regulatory T cell subsets, recent studies have revealed a protective role of B cells in murine CD4+ T cell colitis, but the relationship of their action to T cell immunoregulation is unknown. Here we report that mesenteric lymph node (MLN) B cells protect mice from colitis induced by Galphai2-/- CD4+ T cells. Protection required the transfer of both B cells and CD8alpha+ T cells; neither cell type alone was sufficient to inhibit CD4+ T cell-mediated colitis. Similar results were also observed in colitis induced by CD4+CD45RBhi T cells. Immunoregulation was associated with localization of B cells and expansion of CD4-CD8- CD3+NK1.1+ T cells in the secondary lymphoid compartment, as well as expansion of CD4+CD8alpha+ T cells in the intestinal intraepithelial compartment. MLN B cells from Galphai2-/- mice were deficient in a phenotypic subset and failed to provide cotransfer colitis protection. These findings indicate that protective action of B cells is a selective trait of MLN B cells acquired through a Galphai2-dependent developmental process and link B cells with the formation of regulatory T cells associated with mucosal immune homeostasis.