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Biochem Biophys Res Commun. 2002 Sep 13;297(1):83-90.
Potent CpG oligonucleotides containing phosphodiester linkages: in vitro and in vivo immunostimulatory properties.
Yu D, Zhu FG, Bhagat L, Wang H, Kandimalla ER, Zhang R, Agrawal S.
Hybridon, Inc., 345 Vassar Street, Cambridge, MA 02139, USA.
Bacterial and synthetic DNAs, containing CpG dinucleotides in specific sequence contexts, activate the vertebrate immune system. Unlike phosphorothioate (PS) CpG DNAs, phosphodiester (PO) CpG DNAs require either palindromic sequences and/or poly(dG) sequences at the 3(')-end for activity. Here, we report 'PO-immunomers' having two PO-CpG DNA molecules joined through their 3(')-ends. These PO-imunomers permitted us, for the first time, to assess immunostimulatory properties of PO-CpG DNAs in vitro and in vivo without the need for palindromic and/or poly(dG) sequences. In medium containing 10% fetal bovine serum, PO-immunomers were more resistant than PO-CpG DNAs to nucleases. Compared to PS-CpG DNA in BALB/c and C3H/HeJ mice spleen cell culture assays, PO-immunomers showed increased IL-12 secretion and minimal amounts of IL-6 secretion. PO-immunomers activated NF-kappa B and induced cytokine secretion in J774 cell cultures. In addition, PO-immunomers showed antitumor activity in nude mice bearing human breast (MCF-7) and prostate (DU145) cancer xenografts.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12220512&dopt=Abstract
FEBS Lett. 2002 Sep 11;527(1-3):95-100.
Protection against experimental malaria associated with AMA-1 peptide analogue structures.
Salazar LM, Alba MP, Torres MH, Pinto M, Cortes X, Torres L, Patarroyo ME.
Fundacion Instituto de Inmunologi;a de Colombia (FIDIC), Universidad Nacional de Colombia, Carrera 50 No. 26-00, Bogota, Colombia. mepatarail.com
One Plasmodium falciparum malaria antigen is an integral membrane protein called apical membrane antigen-1. High activity binding peptides to human red blood cells have been identified in this protein. 4337 is a conserved, non-immunogenic peptide with high activity red blood cell binding and its critical residues have already been identified. Peptide analogues (with amino acids having the same mass but different charge) were generated to change their immunogenic and protective characteristics. Three analogues having positive or negative immunological results were studied by nuclear magnetic resonance. The studied peptides all had an alpha-helix fragment, but in different peptide regions and extensions, except for randomly structured 4337. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed their three-dimensional structure, suggesting a better fit with immune system molecules and that modified peptides having better immunological properties can be included in the design of new malaria multi-component subunit-based vaccine.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12220641&dopt=Abstract
Pharmacol Res. 2002 Aug;46(2):185-90.
Anapsos (Polypodium leucotomos) modulates lymphoid cells and the expression of adhesion molecules.
Sempere-Ortells JM, Campos A, Velasco I, Marco F, Ramirez-Bosca A, Diaz J, Pardo J.
Department of Biotechnology, Division of Immunology, University of Alicante, Ctra. de Alicante a San Vicente s/n, 03690 San Vicente del Raspeig, Alicante, Spain. josemiguea.es
Anapsos is a medical prescription registered in the Health Ministry of Spain, that is obtained from the rhizomes of the fern Polypodium leucotomos. An immunomodulating effect of Anapsos on certain lymphocyte subsets and cytokines has already been described in the literature. The current study extends and supports part of the aforementioned results of the product on the immune system, showing the ability of Anapsos to stimulate proliferation and activation of T and natural killer lymphocytes, as well as an important down-regulating effect on CD11, CD18 and CD62-L adhesion molecules, both on peripheral blood mononuclear cells and on U-937 and HL-60 cell lines.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12220959&dopt=Abstract
J Biol Chem. 2002 Nov 15;277(46):44261-7. Epub 2002 Sep 06.
Homologues of human macrophage migration inhibitory factor from a parasitic nematode. Gene cloning, protein activity, and crystal structure.
Zang X, Taylor P, Wang JM, Meyer DJ, Scott AL, Walkinshaw MD, Maizels RM.
Institute of Cell, Animal & Population Biology, University of Edinburgh, United Kingdom. xxzanclink4.berkeley.edu
Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokine-like proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-alpha, and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-A resolution has been determined, revealing a trimeric assembly with an inner pore created by beta-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12221083&dopt=Abstract
J Nutr. 2002 Sep;132(9):2757-62.
Absolute counts and distribution of lymphocyte subsets in small intestine of BALB/c mice change during weaning.
Manzano M, Abadia-Molina AC, Garcia-Olivares E, Gil A, Rueda R.
R&D Department, Abbott Laboratories, Granada, Spain. manuel.manzanbbott.com
The gut immune system is an essential part of the barrier function of the gut. At weaning, major changes can be expected in the number and subset composition of lymphocytes in the small intestine since the gut is exposed to a wide variety of food and microbial antigens, especially when human milk is gradually replaced by weaning foods. The purpose of this study was to evaluate the changes in small intestine lymphocyte subsets in mice during weaning. BALB/c male mice at weaning (3 wk old) were fed a nonpurified diet for 18 d and were killed at different times (0, 4, 7, 12 and 18 d). Lymphocyte populations from lamina propria (LPL), Peyer's patches (PPL) and intestinal epithelium (IEL) were isolated. The expression of different antigens (CD3, CD4, CD8alpha, CD8beta, CD22 and CD45R) in those lymphocyte populations was analyzed by flow cytometry. The percentages of cells expressing T-cell antigens, such as CD3, were significantly higher in LPL during weaning compared to d 0. The percentages of cells expressing CD8alpha and CD8beta increased in both IEL and LPL. However, the percentage of CD4+ cells tended (P = 0.07) to decrease in IEL and to increase in LPL. The percentages of cells expressing B-cell antigens, such as CD22 or CD45R in PPL increased. Changes in the specific phenotypes of intestinal lymphocyte populations at weaning are apparently related to the maturation of the intestinal immune system during early life. Thus, B cells increase in PPL and T cell increase in IEL and LPL.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12221241&dopt=Abstract
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