Chitosan-based Nanoparticles in Mucosal Vaccine Delivery.

Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Nowadays, the use of vaccines has been widely investigated for the prevention of different infectious diseases, infertility, immune disorders, malignancies, and allergies. Broad-spectrum adjuvant substances have been studied for immune system stimulation with a greater efficiency against specific antigens. Various adjuvants have been developed such as inorganic, oil-based, and emulsion adjuvants, bacterial products and their derivatives, cytokines, cytosine-guanine dinucleotide (CpG) motifs, and particulate systems. Mucosal vaccine delivery is an alternative route to induce both humoral and cellular immune responses. Applying nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery, and consequently, more specific release of the agent of interest. Chitosan nanoparticles have immunological activity and mucoadhesive properties. They have been used as a mucosal vaccine delivery system for many antigens. This review provides an overview of the recent advances in chitosan nanoparticles as a novel mucosal vaccine delivery system.

Investigation of the Effect of Folic Acid Based Iron Oxide Nanoparticles on Human Leukemic CCRF-CEM Cell Line.

BACKGROUND: Nanoparticulate drug delivery systems have attracted significant attention in the field of cancer nanotechnology. This study determines the effect of folate-based Fe2O3 nanoparticles. This study aimed to decorate nanoparticles with folate (FA), a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. MATERIALS AND METHODS: The nanoparticles were prepared by a solvent evaporation and emulsification cross-linking method and anticancer activity of agent was evaluated on CCRF CEM cells, derived from human blood cancer samples. RESULTS: The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm were obtained. Cytotoxicity tests showed that the SPIO-FA had higher cell toxicity, and confocal microscopy analysis confirmed excellent cellular uptake efficiency. CONCLUSION: These results indicate that FA based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Immunosuppressive proteins isolated from spiral and coccoid cytoplasmic solutions of Helicobacter pylori.

The aim of this study was to investigate the antiproliferative proteins that probably have a role in Helicobacter pylori evade of immune response and cause chronic infection disease and also to see if coccoid form had a role in its chronicity. H. pylori strain VacA s2/m2 positive and CagA negative, from a gastric biopsy of a patient with peptic ulcer disease, was isolated and cultured in brucella agar. Both spiral and coccoid forms were harvested and ruptured by sonication. The cytoplasmic solutions of both forms were collected and their fractions obtained by gel chromatography and preparative polyacrylamide gel electrophoresis. The fractions were analyzed by MTT assay for their antiproliferative activity. We isolated two proteins with a significant dose dependent antiproliferative activity that analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, one of them that was urease positive showed two bands with 61 and 27 kDa, which is resumed to urease of H. pylori, another consist of 57 and 63 kDa. Helicobacterpylori secret some proteins like urease that inhibit immune cells proliferation response against its antigens.

Optimization of culture medium to increase the production of desferrioxamine B (Desferal) in Streptomyces pilosus.

The aim of this study was optimization of culture medium in direction of increasing the production rate of desferrioxamine B. Streptomycetes are the most widely studied and well known genus of the actinomycete family. Streptomycetes usually inhabit soil and are important decomposers. The genus Streptomyces are Gram-positive and GC rich bacteria that are important for production of many antibiotics and secondary metabolites. These metabolites are important in industrial and medical fields. Deferoxamines (also known as desferrioxamine B, desferoxamine B, DFO-B, DFOA, DFB or desferal) are low-molecular-weight, iron-chelating compounds (siderophores) produced and secreted by many actinomycetes, including species of Streptomyces, Nocardia and Micromonospora. Streptomyces pilosus synthesizes the siderofore desferrioxamine B. Desferrioxamine B is used clinically to treat disorders related to iron overload and pathological iron deposition in human. Our results revealed that the use of soybean as a base medium plus additives such as Na2HPO4.12H2O, NaH2PO4, MgSO4.7H2O, ZnSO4.7H2O, FeSO4.7H2O, CaCl2.2H2O, NaCl, MnSO4, NH4Cl, KH2PO4, K2HPO4, some of the amino acids and vitamins increased the production of desferrioxamine B about 8 times in comparison with the control.

The effect of iron deficiency anemia on intelligence quotient (IQ) in under 17 years old students.

The aim of this study was to evaluate the effects of iron deficiency on intelligence of 11-17 years students. This study conducted on the 540 students (11-17 years) that educated at guidance and high school of Boroujerd city. Laboratory investigations were included serum iron, TIBC (total iron binding capacity) and ferretin. Riven matrix was used in order to determine intelligence quotient. Data were analyzed using SPSS 13 and chi2 and t-tests. Results showed that 78 (14.4%) students had iron deficiency and 14 (25.9%) had iron deficiency anemia. There was no significant difference between different sexes for iron deficiency distribution (p > 0.05), while iron deficiency anemia was significantly higher in girls as compared with boys (p > 0.05). Mean quotient was 115 +/- 12.1 in iron deficiency students, while it was 113.7 +/- 13.9 in patients without iron deficiency. There was also no significant difference between normal and iron deficient students for intelligence quotient (p > 0.05).

[Immunohistochemical detection of altered low density lipoprotein (ox-LDL) in the vessel walls of patients with giant cell arteritis]. / Immunhistochemischer Nachweis veränderter Low-density-Lipoproteine (ox-LDL) in der Gefässwand bei Patienten mit Arteriitis temporalis.

BACKGROUND AND PURPOSE: Recent data indicate that lipid peroxidation is implicated in the pathogenesis of giant cell arteritis with a close anatomic relationship between reactive oxygen species and oxidatively injured vascular tissue. PATIENTS AND METHODS: Immunohistochemistry utilizing anti-ox-LDL was performed on paraffin sections of isolated temporal arteries obtained from patients (n=23) suspected of having temporal arteritis. Enrichment as well as staining intensity of ox-LDL in vascular tissue was analysed by digital image planimetry. RESULTS: Temporal arteries with biopsy proven temporal arteritis (n=11) presented with significantly higher enrichment of ox-LDL in the intima (16.9+/-4.2% vs. 11.25+/-2.3%; p<0.01) and mean (9.6+/-2.4% vs. 6.75+/-1.8%; p<0.01) as compared to healthy controls. Comparable results for the staining intensity were found in the intimal (2.8+/-0.5 eU vs. 1.7+/-0.4 eU; p<0.01) and medial layer (1.55+/-0.5 eU vs. 1.04+/-0.6 eU; p<0.01) of diseased patients compared to controls. CONCLUSIONS: Accumulation of ox-LDL in the intimal layer, especially at the intima-media-border, was closely related to disruption of the elastica interna and adjacent vascular tissue, presumably contributing to the underlying process of intimal hyperplasia through unimpeded migration of smooth muscle and accumulation inflammatory cells.

Enhanced accumulation of the isoprostane, 8-epi-PGF2 alpha, in human aortic and pulmonary valves of patients with coronary heart disease.

The aim of the present study was to investigate whether the isoprostane 8-epi-PGF2 alpha differently accumulates in semilunar valves of patients suffering from coronary heart disease (CHD, n = 19) as compared to valves from healthy heart donors (controls, n = 6). Sections from isolated aortic and pulmonary valves were analyzed by semiquantitative immunohistochemistry. The 8-epi-PGF2 alpha-content was determined by using a specific radioimmunoassay. The accumulation of 8-epi-PGF2 alpha in both valves was higher in CHD-patients in comparison to controls (Aortic valves: 36.49 +/- 11.26% vs. 15.78 +/- 3.04%; pulmonary valves: 46.79 +/- 9.80% vs. 14.99 +/- 3.57%). The results from the radioimmunoassay revealed comparable findings in both groups (CHD vs. controls: 395.95 +/- 86.09 vs. 139.50 +/- 47.46 pg/mg protein in the aortic valves and 430.47 +/- 76.30 vs. 147.33 +/- 53.84 pg/mg protein in pulmonary valves). Pulmonary valves seem to be more susceptible to oxidative stress than aortic valves as evidenced by a higher accumulation of 8-epi-PGF2 alpha in CHD patients. Considering the data presented in this study, we suggest that 8-epi-PGF2 alpha is a valuable indicator of oxidative injury in human semilunar valves.

Angiogenesis stimulation in explanted hearts from patients pre-treated with intravenous prostaglandin E(1).

BACKGROUND: Prostaglandin E(1) (PGE(1)) is a potent vasodilator and induces angiogenesis in animal tissues. Previous clinical studies demonstrated that PGE(1) improves hemodynamic parameters in patients with heart failure listed for heart transplantation (HTX). Therefore, we designed a retrospective immunohistochemistry study to investigate various markers of angiogenesis using hearts explanted from PGE(1)-treated patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: We investigated neovascularization in 18 hearts explanted from patients with IDCM: 9 patients received treatment with chronic infusions of PGE(1) for end-stage heart failure before HTX, whereas the remaining patients with IDCM did not receive PGE(1) and served as controls. We used immunoreactivity against CD34, von Willebrand factor (vWf), vascular endothelial growth factor (VEGF), and MIB-1 (Ki-67) to quantify angiogenesis, and used sirius red staining to determine the degree of fibrosis. Compared with the control group, PGE(1)-treated patients had significantly more CD34-, vWf- and MIB-1-positive cells in the sub-endocardium, myocardium and sub-epicardium (p < 0.01). The degree of fibrosis in the hearts of PGE(1)-treated patients was significantly lower than in control patients (p < 0.05), but we did not see any difference in the percentage of muscle mass. Finally, throughout the ventricles, we found significantly more VEGF-positive capillaries in the PGE(1) group (p < 0.0001). CONCLUSIONS: The data suggest that PGE(1) could be a potent inducer of angiogenesis and the angiogenic factor VEGF, and could cause reduced fibrosis in the failing human heart.

Increased plasma, serum and urinary 8-epi-prostaglandin F2 alpha in heterozygous hypercholesterolemia.

Oxidation injury results in foam cell formation, which is known to be a central mechanism in atherogenesis. We investigated in this study whether 8-epi-prostaglandin (PG) F2 alpha, an in vivo indicator of oxidative stress, is elevated in hyperlipoproteinemia. The isoprostane 8-epi-PGF2 alpha levels in plasma, serum and urine were determined in 123 patients (67 m, 56 f; 17-60 years) suffering from familial heterozygous hypercholesterolemia (FH). A group of 99 normocholesterolemic adults (51 m, 48 f; 20-63 years) served as controls. Plasma, serum and urine levels of 8-epi-PGF2 alpha were significantly (p < 0.01) higher in the FH group. Smokers showed elevated 8-epi-PGF2 alpha levels; however, no correlation was observed to hypertension, age and sex. Successful dietary and drug treatment of FH patients resulted in a significant decrease in 8-epi-PGF2 alpha levels in plasma, serum and urine. These findings indicate that FH is associated with increased oxidation injury, which is beneficially influenced by successful dietary and/or drug treatment.

Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis.

Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher relative risk for advanced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low levels, with the exception that serum laminin > 2.3 U/ml was not significantly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 patients with cardiomyopathy whose explanted hearts were available for histologic evaluation, serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r = 0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p = 0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially be derived from fibrosis in the myocardium, can be measured in the serum of patients with dilated cardiomyopathy, and has an impact on risk stratification and prognosis.