ABSTRACT
Natural marine products show various biological properties such as antiphotoaging, antioxidant, anticancer, and anti-inflammation. This study evaluated the protective effects of the brown alga Carpomitra costata (Stackhouse) Batters (Sporochnaceae) against ultraviolet B (UVB)-provoked damage in human HaCaT keratinocytes. C. costata extract (CCE) effectively reduced superoxide anion, hydroxyl radical, and UVB-stimulated intracellular reactive oxygen species (ROS) levels. CCE also restored the expression and activity of UVB-suppressed antioxidant enzymes. Furthermore, CCE decreased UVB-triggered oxidative damage to cellular components including DNA, protein, and lipid and defended the cells against mitochondrial membrane depolarization-medicated apoptosis. The results of this study indicate that CCE can safeguard human keratinocytes against UVB-induced cellular damage via a potent antioxidant mechanism. CCE may find utility as part of a therapeutic arsenal against the damaging effects of UVB radiation on the skin.
Subject(s)
Antioxidants/metabolism , Keratinocytes/drug effects , Keratinocytes/radiation effects , Phaeophyceae/chemistry , Plant Extracts/pharmacology , Skin Aging/drug effects , Ultraviolet Rays , HumansABSTRACT
Udenafil is a selective phosphodiesterase type 5 inhibitor made available in recent years for the treatment of erectile dysfunction. Herein, we evaluated independent predictors of potency recovery in radical prostatectomy (RP) patients who underwent penile rehabilitation with udenafil 50 mg. One hundred and forty-three men who underwent RP were enrolled in a penile rehabilitation program using udenafil 50 mg every other day. The rate of regained potency in the study group was significantly higher compared with the recovery rate seen in patients who were not part of the penile rehabilitation program (41.3% vs 13.0%; P<0.001). On the multivariate Cox analyses, preoperative International Index of Erectile Function-5 scores (hazard ratio (HR), 1.049; P=0.040), alcohol consumption (HR, 2.043; P=0.020) and Gleason biopsy score (HR, 0.368; P=0.024) were independent preoperative predictors for potency recovery. Among post-RP variables, the use of robotic procedures (HR, 2.287; P=0.030) and pathologic stage (HR, 0.506; P=0.038) were significantly associated with potency recovery. This study identified predictive factors for the recovery of potency in patients undergoing penile rehabilitation with udenafil following RP. Our results could provide physicians with useful information for counseling RP patients and selecting optimal candidates for penile rehabilitation.
Subject(s)
Erectile Dysfunction , Postoperative Complications , Prostatectomy/adverse effects , Pyrimidines/administration & dosage , Sulfonamides/administration & dosage , Aged , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Erectile Dysfunction/rehabilitation , Humans , Male , Middle Aged , Phosphodiesterase 5 Inhibitors/administration & dosage , Postoperative Complications/drug therapy , Postoperative Complications/physiopathology , Postoperative Complications/rehabilitation , Prognosis , Prostatectomy/methods , Prostatic Neoplasms/surgery , Recovery of Function/drug effects , Recovery of Function/physiology , Republic of Korea , Risk Factors , Treatment OutcomeABSTRACT
AIM: We present the oncologic outcomes of laparoscopic nephroureterectomy management of pT3 upper urinary tract urothelial carcinoma. METHODS: Between October 2003 and January 2011, 50 patients with pT3 upper urinary tract urothelial carcinoma which had pathologically confirmed underwent laparoscopic nephroureterectomy at our institution. Demographic data, perioperative results, pathological findings and oncologic outcomes were reviewed and analyzed retrospectively. RESULTS: There were 36 patients (72%) of high grade lesion and 14 patients (28%) of low grade lesion. Lymphovascular invasion was observed in 16 patients (32%) and the surgical margin was positive in one patient. N stage was pN0 in 16 (32%), pN1 in 3 (6%), pN2 in 1 (2%) and pN3 in 1 (2%). The 5-year overall survival rate was 52.6% and the 5-year cancer-specific survival rate was 65.3%. Overall recurrence developed in 23 patients. There were 10 patients (20%) of urothelial recurrence which were all occurred in the bladder at the mean period of 13.6 months, and 7 patients of them were invasive bladder cancer. There were 16 patients (32%) of non-urothelial recurrence developed at the mean period of 9.69 months. On multivariate analyses lymphadenopathy and lymph node involvement of cancer (N+) were identified as independent predictive factors for the cancer-specific survival, and concomitant bladder tumor, grade and lymphovascular invasion were identified as independent predictive factors for the overall recurrence free survival. CONCLUSION: Laparoscopic nephroureterectomy in patients with high stage upper urinary tract urothelial carcinoma appear comparable to those of open surgery in the regard of oncologic outcomes.
Subject(s)
Carcinoma, Transitional Cell/surgery , Laparoscopy/statistics & numerical data , Nephrectomy/methods , Ureter/surgery , Urologic Neoplasms/surgery , Aged , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/secondary , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Neoplasms, Multiple Primary/surgery , Nephrectomy/statistics & numerical data , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
The purpose of this study was to assess the protective effects of an ethanol extract derived from the red alga Gracilaria bursa-pastoris (Gmelin) Silva (GBE) on ultraviolet B (UVB)-irradiated human HaCaT keratinocytes. GBE exhibited scavenging activity against intracellular reactive oxygen species that were induced by either hydrogen peroxide or UVB radiation. In addition, both the superoxide anion and the hydroxyl radical were scavenged by GBE in cell-free systems. GBE absorbed light in the UVB range (280-320 nm) of the electromagnetic spectrum and lessened the extent of UVB-induced oxidative damage to cellular lipids, proteins, and DNA. Finally, GBE-treated keratinocytes showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies. These results suggest that GBE exerts cytoprotective actions against UVB-stimulated oxidative stress by scavenging ROS and absorbing UVB rays, thereby attenuating injury to cellular constituents and preventing cell death.
Subject(s)
Gracilaria , Keratinocytes/drug effects , Keratinocytes/radiation effects , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Plant Extracts/therapeutic use , Ultraviolet Rays/adverse effects , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , DNA Fragmentation/drug effects , DNA Fragmentation/radiation effects , Humans , Hydroxyl Radical/metabolism , Keratinocytes/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Plant Extracts/pharmacology , Protein Carbonylation/drug effects , Protein Carbonylation/radiation effects , Reactive Oxygen Species/metabolism , Superoxides/metabolismABSTRACT
BACKGROUND: Inflammatory chemokines, such as macrophage-derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for C-C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal. OBJECTIVES: To investigate the specific mechanisms of quercetagetin on the STAT1 signal. METHODS: We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN-γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)-ß1 induced by quercetagetin. RESULTS: Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN-γ- and TNF-α-stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN-γR1. Furthermore, quercetagetin augmented the expression of TGF-ß1, which is known to modulate the immune response and inflammation. CONCLUSIONS: These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti-inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.
Subject(s)
Chemokine CCL22/antagonists & inhibitors , Chromones/pharmacology , Keratinocytes/drug effects , STAT1 Transcription Factor/drug effects , Transforming Growth Factor beta1/drug effects , Flavones , Humans , Interferon-gamma/drug effects , Janus Kinases/drug effects , Receptors, Interferon/drug effects , Signal Transduction/drug effects , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins/drug effects , Tumor Necrosis Factor-alpha/drug effects , Interferon gamma ReceptorABSTRACT
BACKGROUND: Mesenchymal stromal cells (MSC) comprise one of the BM stromal cells that are known to support hematopoiesis. It has also been suggested recently that MSC display immunosuppressive capacities through inhibiting the differentiation of monocyte-derived DC. DC travel to the lymph nodes (LN) to present Ag to T cells, and CCL21 is the chemokine that plays an important role in DC migration into the T-cell area of LN. We addressed the effect of MSC on this chemotactic activity of DC, one of the typical characteristics upon maturation. METHODS: BM cells were isolated and then cultured for generation of myeloid DC in the presence of GM-CSF and/or lipopolysaccharide with or without MSC. MSC were identified by flow cytometry of the immunologic markers and by performing colony-forming unit fibroblast assay. Migration of DC was observed with a newly developed time-lapse video microscopic technique. RESULTS: MSC co-culture inhibited the initial differentiation of DC, as well as their maturation. The matured DC actively migrated directionally in response to CCL21, a powerful DC-attracting chemokine, whereas the MSC co-cultured DC did not. DISCUSSION: Collectively, the findings of these experiments raise the possibility that MSC suppress the migratory function of DC and so they may serve immunoregulatory activities through the modulation of the Ag-presenting function of DC.
Subject(s)
Cell Communication/immunology , Cell Differentiation/immunology , Cell Movement/immunology , Dendritic Cells/immunology , Mesenchymal Stem Cells/immunology , Stromal Cells/immunology , Animals , Cells, Cultured , Chemokine CCL21 , Chemokines, CC/immunology , Coculture Techniques , Dendritic Cells/cytology , Immune Tolerance/immunology , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Receptors, CCR1 , Receptors, Chemokine/genetics , Receptors, Chemokine/immunology , Stromal Cells/cytologyABSTRACT
The efficacy of mobilizing peripheral blood progenitor cells (PBPC) with continuous intravenous (c.i.v.) administration of rhG-CSF was randomly compared to subcutaneous (s.c.) administration, in 15 normal donors in each arm of the study for 6 days. The percentage and absolute numbers of CD34+ cells in the c.i.v. and s.c. groups increased maximally at day 3 and 5, respectively, when compared with the steady-state (day 0) level. Peak CD34+ cell levels were achieved on day 3 in the c.i.v. group, with more rapid results than in the s.c. group (49.3/microl vs 35.9/microl, P=0.043). Plasma rhG-CSF levels declined progressively during mobilization in each group as the WBC increased. The serum level of rhG-CSF did not correlate with CD34+ cell counts in the peripheral blood. Toxicity profiles in the c.i.v. and s.c. groups were similar. Each regimen was effective in successfully mobilizing the target CD34 cell number.
Subject(s)
Antigens, CD34/biosynthesis , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Infusions, Intravenous/methods , Injections, Subcutaneous/methods , Adolescent , Adult , Cell Separation , Female , Flow Cytometry , Humans , Immunophenotyping , Kinetics , Male , Middle Aged , Models, Statistical , Phenotype , Prospective Studies , Recombinant Proteins , Time FactorsABSTRACT
We conducted a series of steady-state and short-term experiments on a three-phase circulating-bed biofilm reactor (CBBR) for removing toluene from gas streams. The goal was to investigate the effect of macroporous-carrier size (1-mm cubes versus 4-mm cubes) on CBBR performance over a wide range of oxygen loading. We hypothesized that the smaller biomass accumulation with 1-mm carriers would minimize dissolved-oxygen (DO) limitation and improve toluene removal, particularly when the DO loading is constrained. The CBBR with 1-mm carriers overcame the performance limitation observed with the CBBR with 4-mm carriers: i.e., oxygen depletion inside the biofilm. The 1-mm carriers consistently gave superior removal of toluene and chemical oxygen-demand, and the advantage was greatest for the lowest oxygen loading and the greatest toluene loading. The 1-mm carriers achieved superior performance because they minimized the negative effects of oxygen depletion, while continuing to provide protection from excess biomass detachment and inhibition from toluene.
Subject(s)
Biofilms , Bioreactors , Gases/metabolism , Oxygen/metabolism , Toluene/metabolism , Air Pollutants/metabolism , BiomassABSTRACT
The mechanism of decolorization of azo dyes based on the extracellular chemical reduction with sulfide (H2S, HS-, S2-) was postulated for sulfate reducing environments. To design technical decolorization processes of textile wastewater treatment with sulfide produced by sulfate reducing bacteria (SRB), kinetics is of great significance. Batch experiments were made in order to investigate the kinetics of abiotic decolorization of the reactive mono-azo dye C.I. Reactive Orange 96 (RO 96) with sulfide, with varying pH. The decolorization of RO 96 by sulfide under the exclusion of O2 corresponded to first-order kinetics with respect to both dye and sulfide concentration. The decolorization of RO 96 with sulfide at neutral pH (7.1) was advantageous compared with that at pH for 4.1, 6.3, and 6.5. This is attributed to an increase in the fraction of HS- of total sulfide species at neutral pH. The rate constants k for the decolorization at 37 degrees C were obtained as 0.01 for pH = 4.1, 0.06 for pH = 6.3, 0.08 for pH = 6.5, and 0.09 for pH = 7.1 in mM(-1) min(-1). The high rate constants for sulfide at pH 6.5-7.1 support that the decolorization through SRB (i.e. by bio-sulfide) can be effective in anaerobic bacterial systems with sulfate.
Subject(s)
Azo Compounds/chemistry , Triazines/chemistry , Hydrogen-Ion Concentration , Kinetics , Sulfides/chemistry , Textile Industry , Waste Disposal, FluidABSTRACT
This study describes the synthesis and in vitro evaluation of noble 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone derivatives for the inhibition of TNF-alpha production. Among these compounds, 2-[3-(cyclopentyloxy)-4-methoxyphenyll-3-methyl-1-isoindolinone (5) was the most potent in inhibitory activity of TNF-alpha production in LPS-stimulated RAW264.7 cells.
Subject(s)
Indoles/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Cell Line , Indicators and Reagents , Indoles/chemical synthesis , Mice , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Syringin was found to possess immunomodulatory activity by which it inhibited the in-vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea-pig serum through suppression of C3-convertase of the classical complement. In this study, we examined its in-vitro and in-vivo activity on tumour necrosis factor (TNF)-alpha and nitric oxide (NO) production, CD4+ T cell and CD8+ cytotoxic T cell (CTLL-2) proliferation, and croton oil-, arachidonic acid- and fluorescein-isothiocynate (FITC)-induced mouse ear oedema model. Syringin significantly inhibited both TNF-alpha production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and CD8+ T cell (CTLL-2) proliferation in a dose-dependent manner, whereas neither NO production nor CD4+ T cell proliferation were blocked even by high concentrations of syringin. In the invivo experiments, syringin also significantly suppressed FITC-induced ear oedema in mice but not the ear oedema induced by croton or arachidonic acid. These results suggest that syringin may be implicated as an immunomodulator having an anti-allergic effect rather than an anti-inflammatory effect. The anti-allergic effect of syringin seems to be due, in part, to inhibition of TNF-alpha production and cytotoxic T cell proliferation.
Subject(s)
Adjuvants, Immunologic/pharmacology , Glucosides/immunology , Glucosides/pharmacology , Phenylpropionates/immunology , Phenylpropionates/pharmacology , T-Lymphocytes, Cytotoxic/drug effects , Tumor Necrosis Factor-alpha/drug effects , Animals , Cell Culture Techniques , Cell Division/drug effects , Guinea Pigs , Immune System/drug effects , Male , Mice , Mice, Inbred BALB C , Mice, Inbred ICR , Sheep , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Ginsenosides are the major principles of Panax ginseng C. A. Meyer (Araliaceae) used as a mild oriental folk medicine. In this report, we have examined the inhibitory potency of protopanaxadiol ginsenosides (PPDGs) such as Rb1, Rb2 and Rc, and their co-treatment effect with known tumor necrosis factor (TNF)-alpha antagonists on TNF-alpha production in either murine (RAW264.7) or human (U937) macrophages stimulated with lipopolysaccharide (LPS). Rb1, and Rb2 strongly suppressed TNF-alpha production in RAW264.7 cells with an IC50 of 56.5 and 27.5 microM, respectively, and in differentiated U937 cells with an IC50 of 51.3, and 26.8 microM, respectively. The inhibitory activity of Rb1 and Rb2 was significantly increased by pharmacological agents against protein kinase C, protein tyrosine kinase, and protein kinase A, and anti-rheumatoid arthritis drugs, such as chloroquine and steroid drugs. In contrast, only cyclic AMP phosphodiesterase (cAMP PDE) inhibitors among cAMP-elevating agents did not change the inhibitory potency of PPDGs. These data suggest that PPDGs may possess potential therapeutic efficacy against TNF-alpha mediated disease and the therapeutic potency of PPDGs may be enhanced when co-treated with various kinds of known TNF-alpha antagonists but not with cAMP PDE inhibitors.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Intracellular Signaling Peptides and Proteins , Saponins/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Animals , Carrier Proteins/pharmacology , Cells, Cultured , Chloroquine/pharmacology , Dibutyryl Cyclic GMP/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Enzyme Inhibitors/pharmacology , Ginsenosides , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Panax , Plants, Medicinal , Saponins/antagonists & inhibitors , Steroids/pharmacology , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Division/drug effects , Lignans/isolation & purification , Rosales/chemistry , T-Lymphocytes/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Line , Lignans/pharmacology , Male , Mice , Mice, Inbred BALB C , T-Lymphocytes/cytology , Tumor Necrosis Factor-alpha/biosynthesisSubject(s)
Kidney Transplantation/physiology , Postoperative Complications/classification , Acute Disease , Adult , Cadaver , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/drug therapy , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Living Donors , Male , Postoperative Period , Retrospective Studies , Time Factors , Tissue Donors , Transplantation, Homologous , Treatment FailureABSTRACT
The hepatoprotecive effects of recombinant human epidermal growth factor (hEGF) on chemically and immunologically induced experimental liver injury models were examined. The hEGF clearly decreased serum transaminase levels in D-galactosamine (D-GalN) and D-GalN/lipopolysaccharide (LPS)-induced liver injury models under sub-lethal conditions. However, it has not significantly changed either serum or in vitro tumor necrosis factor (TNF)-alpha production or in vitro nitric oxide (NO) production, suggesting that the hepatoprotection by EGF is not mediated by inhibiting these pathological mediators produced in D-GalN and D-GalN/LPS-induced liver injury.
Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Epidermal Growth Factor/therapeutic use , Galactosamine/antagonists & inhibitors , Lipopolysaccharides/antagonists & inhibitors , Animals , Galactosamine/toxicity , Humans , Lipopolysaccharides/toxicity , Liver Function Tests , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/toxicity , Rats , Rats, Sprague-Dawley , Recombinant Proteins/therapeutic use , Transaminases/blood , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/toxicityABSTRACT
Five dihydrobenzofuran neolignans, woorenosides I (1), II (2), III (3), IV (4), and V (5), isolated from Coptis japonica (Ranunculaceae), suppressed tumor necrosis factor (TNF)-alpha and nitric oxide (NuOmicron) production, as well as lymphocyte proliferation triggered by inflammatory signals such as various mitogens, in a dose-dependent manner. The results indicate that the woorenosides strongly inhibit the mitogenic response by activated macrophage and lymphocytes and suggest that these compounds may participate in regulating inflammatory processes.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Lignans/pharmacology , Plants, Medicinal/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Line , Interleukin-2/pharmacology , Lignans/isolation & purification , Lymphocytes/drug effects , Lymphocytes/metabolism , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Spleen/cytology , Spleen/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
This study describes the synthesis, in vitro evaluation and molecular modeling study of novel compounds for the inhibition of TNF-alpha production. Among these compounds, 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (9) was selected as a lead compound and its pyridine derivative 10 was more potent in activity and safer than rolipram.
Subject(s)
Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Mice , Models, Biological , Phosphodiesterase Inhibitors/pharmacology , Rolipram/pharmacology , Structure-Activity Relationship , Thalidomide/pharmacology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The aim of the present study is to evaluate the kinetics of CD34(+) cells and investigate the potential modulation of CD44 and CD31 expression on CD34(+) cells during continuous i.v. administration of G-CSF, thus to elucidate the possible mechanism of peripheral blood progenitor cell (PBPC) mobilization. Fifteen healthy donors were enrolled in this study. G-CSF (10 microg/kg/day) was administered for four consecutive days through continuous 24-h i.v. infusion. For measurement of complete blood counts, CD34(+) cell levels and their expression of CD44 and CD31, PB sampling was performed immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, and 120 h of G-CSF administration. The percentage and absolute number of CD34(+) cells significantly increased at day 3 (0. 55 +/- 0.09%, 51.12 +/- 24.83 x 10(3)/ml) and day 4 (0.47 +/- 0.09%, 46.66 +/- 24.93 x 10(3)/ml), compared to the steady-state level (0. 06 +/- 0.09%, 2.03 +/- 5.69 x 10(3)/ml). At day 3 to day 5 following the onset of G-CSF administration, a strong decrease of CD44 and CD31 expression was observed on mobilized CD34(+) cells compared to controls: the relative fluorescence intensity of CD44 and CD31 was, respectively, 50%-70% and 40%-90% lower than that of controls. We conclude that continuous i.v. administration of G-CSF apparently results in more rapid mobilization of CD34(+) cells, and downregulation of CD44 and CD31 on CD34(+) cells is likely to be involved in the mobilization of PBPC after treatment with G-CSF.