124 research outputs found
DEVELOPMENT OF A MULTI-DOSE FORMULATION FOR PREVNAR 13â„¢
Streptococcus pneumoniae causes up to a million cases per year of invasive disease in young children and infants, most occurring in developing countries. Pfizer is partnering with WHO and the GAVI alliance to support the developing world on immunization against pneumococcal disease. Prevnar 13â„¢ is currently approved for the prevention of invasive pneumococcal disease in twenty seven countries. If used widely, this pneumococcal conjugate vaccine could prevent hundreds of thousands of additional cases of child mortality each year.
Use of single-dose preservative-free vaccine formulations will raise the overall cost of vaccination programs and may jeopardize the effectiveness of immunization programs in developing countries. Multi-dose vials lower the cost for each vaccination but typically need to include a preservative to prevent contamination that might be introduced during the withdrawal of vaccine doses from such vials. To develop a multi-dose formulation of Prevnar 13â„¢ for the developing world, a preservative effective in meeting antimicrobial efficacy test requirements, that would maintain vaccine stability, and have an established safety record in infants was required.
Multiple preservatives which include phenol, 2-phenoxyethanol (2-PE), meta-cresol, methylparaben and propyl paraben and thimerosal (as a control) were evaluated as potential candidates for a multi-dose formulation of Prevenar 13 based on preservative effectiveness and product stability. 2-PE showed superior antimicrobial effectiveness in Prevnar 13 formulations as per European Pharmacopoeia (EP) requirements and in multiple challenge studies with various organisms, as per WHO Open Vial Policy, to mimic worst case inadvertent microbial contamination that might occur during immunization of subjects when the formulation is presented in multi-dose vials. Prevnar 13 in the presence of 5mg dose of 2-PE is stable for over two years and meets the preservative effectiveness standards based on the EP 5.1.3 as well as WHO multi-organism challenge test. The data support the use of 2-PE as a more effective preservative with the potential to replace thimerosal, the most commonly used preservative in multi-dose vaccine formulations
Epidermal growth factor and transforming growth factor-alpha decrease gamma interferon receptors and induction of intercellular adhesion molecule (ICAM-1) on cultured keratinocytes
The link between the epidermal keratinocytes of the skin and the activated T lymphocytes of the immune system is mediated by a variety of cytokines, including gamma interferon (IFN-Γ). We studied the influence of keratinocyte mitogens such as transforming growth factor-alpha (TGF-Α), epidermal growth factor (EGF), and somatomedin-C (SM-C) on the ligand binding of 32 P-labelled IFN-Γ to cultured keratinocytes derived from normal appearing adult human skin. Keratinocytes placed in a medium devoid of mitogens become growth arrested, and these quiescent cells expressed 2.4 times (28,900 versus 12,200 sites/cell) as many high affinity IFN-Γ receptors (Kd = 0.22 nM) compared to keratinocytes which were actively growing in medium containing TGF-Α (25 ng/ml) or EGF (10 ng/ml). The reduction in IFN-Γ receptor sites by TGF-Α/EGF was mitogen specific, as adding SM-C (500 ng/ml) did not have any effect on ligand binding, although it similarily stimulated keratinocyte growth. The reduction in IFN-Γ receptors was time dependent, occurring primarily after 24–48 hours of change in tissue culture conditions. The reduction in the number of high affinity IFN-Γ receptors by TGF-Α/EGF had immunobiological consequences, because quiescent keratinocytes in basal medium had an increased expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) induced by IFN-Γ, compared to actively growing TGF-Α/EGF treated keratinocytes. These results suggest that rapidly proliferating keratinocytes exposed to TGF-Α/EGF but not SM-C are capable of altering their response to IFN-Γ by decreasing their number of cell surface high affinity receptors for IFN-Γ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49881/1/1041500207_ftp.pd
A Signet Cell Carcinoma of the Ileum: A Rare Differential Diagnosis of Intestinal Pathology with Fistula Mimicking Crohn’s Disease
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death in the USA. Primary signet ring cell carcinoma (SRCC) of the colon and rectum is extremely rare with a reported incidence of less than 1%. Here we present the case of a 41-year-old man who presented with abdominal pain, severe microcytic anaemia and a negative faecal occult blood test (FOBT). A CT scan of the abdomen revealed thickening of the terminal ileum and proximal right colon with extensive lymphadenopathy and a fistula tract extending from the terminal ileum to the right buttock. Endoscopic features like cobblestoning of the ileocolic junction along with elevated blood and stool inflammatory markers raised suspicion of Crohn’s disease (CD). However, histopathological study surprisingly revealed primary colorectal signet cell carcinoma (PCRSCC) with no evidence of CD. Cases of simultaneous PCRSCC and CD have been reported, but no clear association has been established. Our case is unique in that it presented with classic clinical features of CD, but PCRSCC without any histological evidence of underlying CD was found on histology
Photoaffinity labelling of mammalian beta-adrenergic receptors: Metal-dependent proteolysis explains apparent heterogeneity
Photoaffinity labeling of the β-adrenergic receptor in synaptic membranes of rat cerebral cortex and cerebellum
N-(3-(p-azido-m-[125I]iodophenyl)propionyl)-succinimide—A heterobifunctional reagent for the synthesis of radioactive photoaffinity ligands: Synthesis of a carrier-free 125I-labeled cardiac glycoside photoaffinity label
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