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Physiologic Concentrations (physiologic + concentration)
Selected AbstractsSex differences of chondrogenic progenitor cells in late stages of osteoarthritisARTHRITIS & RHEUMATISM, Issue 4 2010Sebastian Koelling Objective Osteoarthritis (OA), a mainly degenerative disease, is known to be multifactorial in origin. Gene expression patterns vary between populations and sexes. Sex hormone receptors have been described in the cartilage tissue of animals and humans. We undertook this study to determine whether the regenerative potential of chondrogenic progenitor cells (CPCs) present in the arthritic tissue during the late stages of human OA might also be subject to sex-specific differences and influenced by sex steroids. Methods We analyzed sex-specific differences in the regenerative potential of CPCs and the involvement of sex hormones in vitro in cartilage samples from patients with late-stage knee OA, using electrochemiluminescence immunoassay, microarray analysis, real-time reverse transcription,polymerase chain reaction, immunohistochemistry, Western blot analysis, fluorescence-activated cell sorting, and cell culture. Results We detected expression of estrogen and testosterone in the OA synovial fluid as well as CPCs positive for estrogen receptor , (ER,), ER,, and androgen receptor. Both hormones influenced the expression of all 3 receptor genes as well as the chondrogenic potential of CPCs by regulating gene expression of Sox9, Runx2, type II collagen, and type I collagen. We found regulatory effects on the collagens via Sox9 and Runx2 as well as regulatory effects independent of these transcription factors. These effects were sex-specific and relied on hormone concentrations. Conclusion Physiologic concentrations of testosterone in men and premenopausal concentrations of estrogen in women have a positive effect on the chondrogenic potential of CPCs in vitro. Therefore, strategies of hormone replacement in the synovial fluid of women and men might have beneficial effects on the regenerative potential of arthritic cartilage tissue in late stages of human OA. [source] Nitric Oxide: The "Second Messenger" of InsulinIUBMB LIFE, Issue 5 2000Nighat N. Kahn Abstract Incubation of various tissues, including heart, liver, kidney, muscle, and intestine from mice and erythrocytes or their membrane fractions from humans, with physiologic concentration of insulin resulted in the activation of a membrane-bound nitric oxide synthase (NOS). Activation of NOS and synthesis of NO were stimulated by the binding of insulin to specific receptors on the cell surface. A Lineweaver-Burk plot of the enzymatic activity demonstrated that the stimulation of NOS by insulin was related to the decrease in the Km for L-arginine, the substrate for NOS, with a simultaneous increase of Vmax. Addition of NG-nitro-L-arginine methyl ester (LNAME), a competitive inhibitor of NOS, to the reaction mixture completely inhibited the hormone-stimulated NO synthesis in all tissues. Furthermore, NO had an insulin-like effect in stimulating glucose transport and glucose oxidation in muscle, a major site for insulin action. Addition of NAME to the reaction mixture completely blocked the stimulatory effect of insulin by inhibiting both NO production and glucose metabolism, without affecting the hormone-stimulated tyrosine or phosphatidylinositol 3-kinases of the membrane preparation. Injection of NO in alloxan-induced diabetic mice mimicked the effect of insulin in the control of hyperglycemia (i.e., lowered the glucose content in plasma). However, injection of NAME before the administration of insulin to diabetic-induced and nondiabetic mice inhibited not only the insulin-stimulated increase of NO in plasma but also the glucose-lowering effect of insulin. [source] Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative responseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006Thomas S. Breza Jr Introduction:, Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. Materials and Methods:, Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. Results:, An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. Conclusion:, Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation. [source] Melatonin modulates the expression of VEGF and HIF-1, induced by CoCl2 in cultured cancer cellsJOURNAL OF PINEAL RESEARCH, Issue 2 2008Min Dai Abstract:, Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl2). Melatonin also decreases hypoxia-inducible factor (HIF)-1, protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1, under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl2 are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1, induced by CoCl2 in cultured cancer cells. [source] Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epitheliumMOLECULAR ORAL MICROBIOLOGY, Issue 4 2000D. Tanaka The bactericidal activity of synthetic LL-37, a cathelicidin, was assessed against Actinobacillus actinomycetemcomitans (three strains) and Capnocytophaga spp. (three strains). All strains were sensitive to LL-37, and exhibited 99% effective dose of 7.5-to-11.6 ,g/ml. An amidated form of LL-37, pentamide-37, killed with about the same efficacy as LL-37. Partial inhibition of killing was noted at physiologic concentrations of NaCl, and complete inhibition was observed at 400 mM NaCl. At approximately the 99% effective dose , i.e., 10 ,g/ml , LL-37 also lost activity against A. actinomycetemcomitans in the presence of native or heat-inactivated 10,15% normal human AB serum. Pentamide-37 was less sensitive to serum inhibition than LL-37. In conclusion, certain oral, gram-negative bacteria are sensitive to the bactericidal activity of LL-37 at low concentrations of serum and salt, a condition likely to be found within the membrane-delimited phagolysosome. Modified forms of LL-37, such as pentamide-37, may be more suitable for future therapeutic application in the presence of serum. [source] Phytochemical Research Using Accelerator Mass SpectrometryNUTRITION REVIEWS, Issue 10 2004Le T. Vuong PhD Vegetables and fruits provide an array of microchemicals in the form of vitamins and secondary metabolites (phytochemicals) that may lower the risk of chronic disease. Tracing these phytochemicals at physiologic concentrations has been hindered by a lack of quantitative sensitivity for chemically equivalent tracers that could be used safely in healthy people. Accelerator mass spectrometry is a relatively new technique that provides the necessary sensitivity (in attomoles) and measurement precision (<3%) towards 14Clabeled phytochemicals for detailed kinetic studies in humans at dietary levels. [source] Folate synthesis in plants: the last step of the p -aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyaseTHE PLANT JOURNAL, Issue 4 2004Gilles J.C. Basset Summary In plants, the last step in the synthesis of p -aminobenzoate (PABA) moiety of folate remains to be elucidated. In Escherichia coli, this step is catalyzed by the PabC protein, a , -lyase that converts 4-amino-4-deoxychorismate (ADC) , the reaction product of the PabA and PabB enzymes , to PABA and pyruvate. So far, the only known plant enzyme involved in PABA synthesis is ADC synthase, which has fused domains homologous to E. coli PabA and PabB and is located in plastids. ADC synthase has no lyase activity, implying that plants have a separate ADC lyase. No such lyase is known in any eukaryote. Genomic and phylogenetic approaches identified Arabidopsis and tomato cDNAs encoding PabC homologs with putative chloroplast-targeting peptides. These cDNAs were shown to encode functional enzymes by complementation of an E. coli pabC mutant, and by demonstrating that the partially purified recombinant proteins convert ADC to PABA. Plant ADC lyase is active as dimer and is not feedback inhibited by physiologic concentrations of PABA, its glucose ester, or folates. The full-length Arabidopsis ADC lyase polypeptide was translocated into isolated pea chloroplasts and, when fused to green fluorescent protein, directed the passenger protein to Arabidopsis chloroplasts in transient expression experiments. These data indicate that ADC lyase, like ADC synthase, is present in plastids. As shown previously for the ADC synthase transcript, the level of ADC lyase mRNA in the pericarp of tomato fruit falls sharply as ripening advances, suggesting that the expression of these two enzymes is coregulated. [source] C1q inhibits immune complex,induced interferon-, production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesisARTHRITIS & RHEUMATISM, Issue 10 2009Christian Lood Objective C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor,induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-, (IFN,). Methods Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFN, production was determined by an immunoassay. Results C1q significantly inhibited PBMC IFN, production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFN, production induced by ICs and CpG DNA but increased PDC IFN, production induced by HSV. The regulatory role of C1q was not specific for IFN, but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor ,. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. Conclusion Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients. [source] Colonic short-chain fatty acids inhibit encystation of Entamoeba invadensCELLULAR MICROBIOLOGY, Issue 2 2005Jennifer Byers Summary Entamoeba parasites multiply as trophozoites in the layer of mucus that overlies the colonic epithelium. In response to stimuli that are not understood, trophozoites stop multiplying and differentiate into cysts that are released to infect another host. In the colon, Entamoeba trophozoites are exposed to the large variety of biochemicals that are carried into or are produced within this organ. The normal bacterial population of the colon releases large amounts of short-chain fatty acids (SCFAs). These compounds have effects on the growth, differentiation and repair of the colonic epithelium that correlate with de-creased activity of a Class I/II histone deacetylase (HDAC). We found that the formation of cysts, but not the growth of trophozoite-stage Entamoeba invadens parasites, was inhibited by physiologic concentrations of SCFAs. Variable levels of cyst formation did occur if SCFA concentrations were lowered. Specific inhibitors of Class I/II-type HDACs also prevented encystation, and trophozoites exposed to these compounds had increased levels of acetylation of histone H4 and other nuclear proteins. These results suggest that production of the infectious cyst stage of Entamoeba parasites is regulated in part by the levels of SCFAs made by the bacterial population of the colon. [source] Effect of some fractions of alveolar surfactant (phospholipids and SP-A) on the bactericidal activity of different antimicrobials against some respiratory pathogensCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2001A. Ferrara Objectives To investigate the effects of physiologic concentrations, at alveolar level, of some fractions of pulmonary surfactant (phospholipids and SP-A) on the bactericidal activity of different antimicrobials against some respiratory pathogens. Methods The antimicrobial agents cefdinir, sparfloxacin, clarithromycin, teicoplanin, cefepime, ciprofloxacin, netilmicin and tobramycin, depending on their specific activity, were investigated against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Pseudomonas aeruginosa. Killing curves were carried out with antimicrobials at 0.5 and 2 MIC, SP-A at 1 and 5 mg/L and phospholipids at 50 mg/L. Results Time-kill experiments showed that while SP-A never modified the activity of antimicrobials, phospholipids exerted, in some cases, a weak antagonistic effect. Among antibacterials and pathogens investigated, phospholipids were able to decrease the rate of killing of cefepime and ciprofloxacin only on P. aeruginosa, both at 0.5 and at 2 MIC, with an increase of about 1 log in CFU. The combination of SP-A and phospholipids never modified the effect observed in the presence of lipids alone. Conclusions The paucity of data only allow us to observe that the examined antibiotics do not have substantially reduced activity against respiratory pathogens studied in the presence of physiologic concentrations of some fractions of surfactant. Cefepime alone already exerted a small effect, and ciprofloxacin at 2 MIC, even in the presence of phospholipids, retained its bactericidal activity. [source] | |||||||||||||