Macrophage Colony-stimulating Factor Levels Research Articles

Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (P<0.05). The comparison of the two groups in terms of daily dose and time of oral pioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (P<0.05), but were not associated with daily dose and time of oral pioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

Role of macrophage colony-stimulating factor in the development of neointimal thickening following arterial injury.

Evidence suggests that macrophage colony-stimulating factor (M-CSF) participates critically in atherosclerosis; little is known about the role of M-CSF in the development of neointimal hyperplasia following mechanical vascular injury. We examined the expression of M-CSF and its receptor, c-fms, in rodent and rabbit models of arterial injury. Injured rat carotid arteries expressed 3- to 10-fold higher levels of M-CSF and c-fms mRNA and protein following balloon injury as compared to uninjured arteries. In the rabbit, M-CSF protein expression was greatest in neointimal smooth muscle cells (SMCs) postinjury, with some expression in medial SMCs. M-CSF-positive SMCs exhibited markers of proliferation. At 30days postinjury, neointimal SMCs in the adjacent healed area near the border between injured and uninjured zone lost both proliferative activity and overexpression of M-CSF. The presence of induced M-CSF and c-fms expression correlated with the initiation of SMCs proliferation. M-CSF stimulated incorporation of [(3)H] thymidine in human aortic smooth muscle cells in a concentration-dependent manner. Serum-free conditioned medium from aortic SMCs also promoted DNA synthesis, and this effect was blocked by M-CSF specific antibody. To test further the role of M-CSF in vivo, we induced arterial injury by placing a periadventitial collar around the carotid arteries in compound mutant mice lacking apolipoprotein apoE (apoE(-/-)) and M-CSF. Loss of M-CSF abolished the neointimal hyperplastic response to arterial injury in apoE(-/-) mice. Local delivery of M-CSF to the injured artery restored neointimal proliferation, suggesting a critical role of M-CSF for the development of neointimal thickening following arterial injury.

Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures

The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing.

Effect of a Mushroom (&lt;i&gt;Coriolus versicolor&lt;/i&gt;) Based Probiotic on Goat Health

Maintenance of an adequate immune response is essential to goat health. CorPet biomass is a mushroom (Coriolus versicolor) based probiotic used as an immune-stimulant in man, horses and small animals. Fifteen BoerXSpanish goats were used in a crossover design to evaluate the effect of a commercial mushroom based probiotic across two periods on resilience of goats to gastrointestinal parasites in pasture based systems. Following initial screening for infection, goats were assigned to three groups of five (n = 15) individuals. Powdered CorPet was soaked in hot or cold water and sterile filtered. Goats were drenched daily with 10 mL of the hot (treatment I) or cold (treatment II) extract daily for an 8 week period. A control group of five age-matched goats received sterile water (treatment III). Body Weight (BW), Fecal Egg Count (FEC), FAMACHA scores, Packed Cell Volume (PCV) and White Blood Cell Differential counts (WBC) were determined weekly. The concentration of total serum protein, 8 Pro-inflammatory cytokines and Prostaglandin (PGE2) secretion was evaluated using commercial ELISAs for each. Treatment had no effect on BW, FEC, FAMACHA scores, PCV and WBC. Total serum protein concentration (p<0.001) increased. Increased levels of interferon production regulator (IFNr), Rantes and Granulocyte-Colony Stimulating Factor (GCSF) and decreased levels of Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) were observed in treated goats. The concentration of PGE2 decreased in all groups over the study period of 8 weeks. Greater changes were observed in treated goats (65-80%) compared to control (50%). Thus in goats CorPet may modulate innate immunity through differential regulation of the secretion of serum proteins including cytokines and PGE2 to impact goat health.

Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer.

BackgroundMacrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups.MethodsThe cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA).ResultsThe results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653).ConclusionsThese findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling

Toll-like receptor (TLR) 4 mediates inflammation and is also known to trigger apoptosis in microglia. Our time-lapse observations showed that lipopolysaccharide (LPS) stimulation induced rapid death in primary cultures of rat microglia, while a portion of the microglia escaped from death and survived for much longer than 2 days, in which time, all of the control cells had died. However, it remains unclear how the LPS-stimulated microglia subpopulation could continue to survive in the absence of any supplied growth factors. In the present study, to clarify the mechanism underlying the LPS-stimulated survival, we investigated whether microglia could produce their own survival factors in response to LPS, focusing on macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-34, which are mainly supplied by astrocytes or neurons. The LPS-stimulated microglia drastically induced the expression of the GM-CSF mRNA and protein, while M-CSF and IL-34 levels were unchanged. The surviving microglia also significantly upregulated the expression of GM-CSF receptor (GM-CSFR) mRNA without affecting M-CSFR. As for the GM-CSFR downstream signal, LPS resulted in the phosphorylation of STAT5 and its translocation to the nucleus in the surviving microglia. Moreover, a specific JAK2 inhibitor, NVP-BSK805, suppressed STAT5 phosphorylation and microglia survival in response to LPS, indicating a critical role of the JAK2/STAT5 pathway in this survival mechanism. Together, these results suggest that a subpopulation of TLR4-activated microglia may survive by producing GM-CSF and up-regulating GM-CSFR. This autocrine GM-CSF pathway may activate the JAK2/STAT5 signaling pathway, which controls the transcription of survival-related genes. Finally, these surviving microglia may have neuroprotective functions because the neurons remained viable in co-cultures with these microglia.

Impaired differentiation of macrophage lineage cells attenuates bone remodeling and inflammatory angiogenesis in Ndrg1 deficient mice.

N-myc downstream regulated gene 1 (NDRG1) is a responsible gene for a hereditary motor and sensory neuropathy-Lom (Charcot–Marie–Tooth disease type 4D). This is the first study aiming to assess the contribution of NDRG1 to differentiation of macrophage lineage cells, which has important implications for bone remodeling and inflammatory angiogenesis. Ndrg1 knockout (KO) mice exhibited abnormal curvature of the spine, high trabecular bone mass, and reduced number of osteoclasts. We observed that serum levels of macrophage colony-stimulating factor (M-CSF) and macrophage-related cytokines were markedly decreased in KO mice. Differentiation of bone marrow (BM) cells into osteoclasts, M1/M2-type macrophages and dendritic cells was all impaired. Furthermore, KO mice also showed reduced tumor growth and angiogenesis by cancer cells, accompanied by decreased infiltration of tumor-associated macrophages. The transfer of BM-derived macrophages from KO mice into BM-eradicated wild type (WT) mice induced much less tumor angiogenesis than observed in WT mice. Angiogenesis in corneas in response to inflammatory stimuli was also suppressed with decreased infiltration of macrophages. Taken together, these results indicate that NDRG1 deficiency attenuates the differentiation of macrophage lineage cells, suppressing bone remodeling and inflammatory angiogenesis. This study strongly suggests the crucial role of NDRG1 in differentiation process for macrophages.

Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research.

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

Background/Aims: Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections. Methods: A total of 183 and 236 hospitalized children with acute encephalitis-like syndrome and respiratory tract infection, respectively, were screened for anti-CoV IgM antibodies. The expression profiles of multiple cytokines were determined in CoV-positive patients. Results: Anti-CoV IgM antibodies were detected in 22/183 (12.02%) and 26/236 (11.02%) patients with acute encephalitis-like syndrome and respiratory tract infection, respectively. Cytokine analysis revealed that the level of serum granulocyte colony-stimulating factor (G-CSF) was significantly higher in both CoV-CNS and CoV-respiratory tract infection compared with healthy controls. Additionally, the serum level of granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly higher in CoV-CNS infection than in CoV-respiratory tract infection. In patients with CoV-CNS infection, the levels of IL-6, IL-8, MCP-1, and GM-CSF were significantly higher in their cerebrospinal fluid samples than in matched serum samples. Conclusion: To the best of our knowledge, this is the first report showing a high incidence of CoV infection in hospitalized children, especially with CNS illness. The characteristic cytokine expression profiles in CoV infection indicate the importance of host immune response in disease progression.

Macrophage colony-stimulating factor (M-CSF) in first trimester maternal serum: correlation with pathologic pregnancy outcome.

To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies. This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free β-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling. 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270±91 pg/ml (p=0.032), whereas cases of trisomy 13 (183±68 pg/ml) and trisomy 18 (143±40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free β-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M-CSF. M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research.

Avemar and Echinacea extracts enhance mobilization and homing of CD34(+) stem cells in rats with acute myocardial infarction.

IntroductionActivation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34+ stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI).MethodsAMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either post-treated or pre- and post-treated daily with oral doses of Avemar (121 mg/kg) or Echinacea (130 mg/kg). In whole blood, the number of CD34+ cells was measured by flow cytometry and their homing to the myocardium was immunohistochemically assessed. Serum creatine kinase, vascular endothelial growth factor, interleukin-8 and granulocyte macrophage colony stimulating factor were determined on days 1, 7 and 14 after AMI. Sections of the myocardium were histopathologically assessed.ResultsRats pre- and post-treated with Avemar or Echinacea exhibited substantial increases in the number of circulating CD34+ cells, peaking on the first day after AMI to approximately 13-fold and 15-fold, respectively, with a decline in their level on day 7 followed by a significant increase on day 14 compared to their corresponding AMI levels. Only post-treatment with Echinacea caused a time-dependent increase in circulating CD34+ cells on days 7 and 14. Such increases in circulating CD34+ cells were accompanied by increased homing to myocardial tissue 14 days after AMI. Interestingly, pre- and post-treatment with Avemar or Echinacea substantially increased serum creatine kinase on day 1, normalized its activity on day 7 and, on continued treatment, only Echinacea markedly increased its activity on day 14 compared to the corresponding AMI values. Moreover, both treatments modified differently the elevated serum vascular endothelial growth factor and the lowered granulocyte macrophage colony stimulating factor levels of the AMI group but did not affect the level of interleukin-8. These results were supported histopathologically by reduced inflammatory reactions and enhanced neovascularization.ConclusionAvemar and Echinacea extracts can effectively induce mobilization and homing of CD34+ stem cells to the myocardial tissue and thus may help in stem cell-based regeneration of the infarcted myocardium.

Long-term efficacy of subtotal splenectomy due to portal hypertension in cirrhotic patients.

BackgroundPortal hypertension (PHT) requires invasive measures to prevent rupture and bleeding of esophagogastric varices; however, the long-term results of subtotal splenectomy plus fixation of the retrosternal omentum majus (SSFROM) have not been reported. Specifically, the advantages and disadvantages of surgery that preserves the spleen and the long-term hematologic effects have not been described.Study designOur studies relating to SSFROM commenced in February 1999. As of April 2014 we have performed 256 subtotal splenectomies The records of 65 patients with PHT who underwent SSFROM were reviewed retrospectively.ResultsFour patients died within 4 years of surgery, with a 4-year survival rate of 94 %; the 11-year survival rate was 60 %. Eleven patients (17 %) had re-bleeding from esophagogastric varices. The white blood cell and platelet counts were higher 6 and 11 years post-operatively compared with pre-operative values (P < 0.01). Portal venous diameter, portal venous flow volume, splenic artery flow volume, as well as splenic length, thickness, and average cross-sectional areas were shown to be significantly constricted or decreased (P < 0.01). The proportion of serum CD3+ T cells, CD4+ T cells, and CD8+ T cells was increased (P < 0.01), while the serum levels of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor were significantly decreased (P < 0.01). There was no significant change in the serum levels of IgA, IgM, IgG, and Tuftsin (P > 0.05). DSA demonstrated that 15 cases formed collateral circulations between the portal vein and superior vena cava.ConclusionSSFROM provide long-term hemostasis for esophagogastric variceal bleeding in PHT and corrected hypersplenism. SSFROM is an effective treatment for patients with PHT in whom long-term survival is expected.

Evaluation of biomarkers for in vitro prediction of drug-induced nephrotoxicity: comparison of HK-2, immortalized human proximal tubule epithelial, and primary cultures of human proximal tubular cells.

There has been intensive effort to identify in vivo biomarkers that can be used to monitor drug-induced kidney damage and identify injury before significant impairment occurs. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and human macrophage colony stimulating factor (M-CSF) have been validated as urinary and plasma clinical biomarkers predictive of acute and chronic kidney injury and disease. Similar validation of a high throughput in vitro assay predictive of nephrotoxicity could potentially be implemented early in drug discovery lead optimization to reduce attrition at later stages of drug development. To assess these known in vivo biomarkers for their potential for in vitro screening of drug-induced nephrotoxicity, we selected a panel of nephrotoxic agents and examined their effects on the overexpression of nephrotoxicity biomarkers in immortalized (HK-2) and primary (commercially available and freshly in-house produced) human renal proximal tubule epithelial cells. Traditional cytotoxicity was contrasted with expression levels of KIM-1, NGAL, and M-CSF assessed using ELISA and real-time quantitative reverse transcription PCR. Traditional cytotoxicity assays and biomarker assays using HK-2 cells were both unsuitable for prediction of nephrotoxicity. However, increases in protein levels of KIM-1 and NGAL in primary cells were well correlated with dose levels of known nephrotoxic compounds, with limited correlation seen in M-CSF protein and mRNA levels. These results suggest that profiling compounds against primary cells with monitoring of biomarker protein levels may have potential as in vitro predictive assays of drug-induced nephrotoxicity.

Abstract 96: Changes In HDL Cholesterol During The Acute Phase of Kawasaki Disease

To determine the correlations between changes in high-density lipoprotein cholesterol (HDL-C) and other blood variables during the acute phase of Kawasaki disease (KD), we investigated changes in the plasma level of HDL-C, serum apolipoproteins and number of peripheral blood monocytes. 26 Japanese patients with KD were subjects of this study. Plasma HDL-C decreased during the 1st week of illness, and increased during the 2nd week. The mean levels of minimum HDL-C in KD patients treated with total intravenous immunoglobulin (IVIG) dose ≧ 4g/kg, was significantly lower than those treated with total IVIG dose &lt; 4g/kg (p=0.0005). There was a strong direct correlation between minimum HDL-C in KD patients and HDL-C on 5th day of KD onset (r=0.71, p &lt; 0.0001). Assessing the performance of plasma HDL-C on 5th day of KD onset in predicting the necessity for high-dose IVIG treatment to KD, ROCs were plotted and the AUC was 0.82. A cutoff value of 16mg/dl had a specificity of 0.82 and sensitivity of 0.80 for predicting those. The apo A-I and A-II levels were correlated with plasma HDL-C, respectively. And the peripheral blood monocytes counts which correlated with serum levels of macrophage-colony stimulating factor, were not correlated with plasma HDL-C. Plasma HDL-C levels during the 1st week of illness might serve as a predictor for non-responder to low-dose IVIG treatment in patients with acute KD.

Increased endothelial progenitor cells and nitric oxide in young prehypertensive women.

This study investigated the effect of sex differences on circulating endothelial progenitor cells (EPCs) in prehypertension and its underlying mechanism. The authors found that premenopausal women show increased number and activity of circulating EPCs when compared with men, which was similar to enhanced nitric oxide (NO) level in plasma or culture medium. There was no difference in the number and activity of circulating EPCs and NO level between normotensive and prehypertensive premenopausal women. There was also no difference seen in levels of vascular endothelial growth factor and granulocyte macrophage colony-stimulating factor. Both number and activity of circulating EPCs were correlated with the level of NO. The present study firstly demonstrated that the number and activity of circulating EPCs were preserved in prehypertensive premenopausal women, which was related to the restoration of NO production. The sex differences in EPCs in prehypertension may be involved in the mechanism underlying vascular protection in premenopausal women.

Plasma levels of M-CSF are increased in ANCA-associated vasculitides with active nephritis

Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-associated vasculitides (AAV) are characterized by small vessel injury and in some cases granulomatous lesions and glomerular inflammation. The pathogenic bases of these clinical phenotypes are incompletely understood, but evidence from patients with AAV and other inflammatory diseases suggest a role for monocyte/macrophages in the perpetuation of tissue injury. Macrophage colony stimulating factor (M-CSF) is a promoter of monocyte recruitment and macrophage proliferation, involved in mesangial cell proliferation and experimental nephritis development. Serum concentrations of M-CSF mark and herald the onset of lupus nephritis. Plasma samples from 29 patients with AAV (18 granulomatosis with polyangiitis, GPA, 6 eosinophilic granulomatosis with polyangiitis, EGPA, and 5 microscopic polyangiitis, MPA) and from 10 healthy controls were collected together with clinical data. Patients with AAV had higher levels of M-CSF when compared to controls. M-CSF levels correlated positively with the BVAS, serum C-reactive protein and erythrocyte sedimentation rate, while haemoglobin correlated inversely with M-CSF. Patients with active renal disease had significantly higher levels of M-CSF when compared to the other subgroups. M-CSF levels did not differ between ANCA subserotypes and were not associated with the involvement of other organs. In conclusion, M-CSF is higher in patients with AAV and active nephritis and could contribute to the pathogenesis of these diseases. In addition, M-CSF could behave as a useful marker of renal involvement in AAV.

Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease

To study the relationship between serum inflammatory cytokine levels in chronic kidney disease patients with type 2 diabetes. Sixty-four patients aged 43 to 70 years with a glomerular filtration rate (GFR) of > 30 ml/min/1.73 m2 were examined. A control group consisted of 15 healthy individuals. The serum concentration of macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein 1α (MIP-1α), macrophage migration inhibitory factor (MIF), interleukin 6 (IL-6), as well as the urinary excretion of albumin and type IV collagen was determined by enzyme immunoassay. In patients with a GFR of > 60 ml/min/1.73 m2, M-CSF and MIF concentrations proved to be significantly higher than those in the control group (p = 0.0003 and p = 0.001, respectively). In those with a GFR of 30-59 ml/min/1.73 m2, there was an increase in the levels of M-CSF (p < 0.0001), MIP-1α (p = 0.002), MIF (p = 0.02), and IL-6 (p = 0.02). The decline in GFR was associated with the higher levels of M-CSF (p = 0.02) and MIP-1α (p = 0.02) and with the higher urinary excretion of type IV collagen (p = 0.01). M-CSF, MIP-1α, and IL-6 correlated positively with the urinary excretion of albumin (r = 0.34, r = 0.28, and r = 0.28, respectively; all p < 0.05) and type IV collagen (r = 0.31, r = 0.4, and r = 0.43, respectively; all p < 0.05). The findings confirm the concept that chronic inflammation is involved in the development of diabetic kidney disease.

Serum Biopterin and Neopterin Levels as Predictors of Empty Follicles.

OBJECTIVEThis study measured serum and follicular fluid (FF) levels of biopterin, neopterin, vascular endothelial growth factor (VEGF), and macrophage colony-stimulating factor (M-CSF) in patients receiving mild ovarian stimulation for oocyte retrieval.PATIENTS AND METHODSInfertile patients who underwent ovarian stimulation were divided into the following: Group 1, no oocyte retrieval (n = 12), and Group 2, retrieval of more than four oocytes (n = 13). Median total gonadotropin dose in both groups was 150 IU. Biopterin and neopterin levels were measured using high-performance liquid chromatography. VEGF and M-CSF levels were measured by enzyme-linked immunosorbent assay.RESULTSCompared to Group 2, serum and FF levels of neopterin and VEGF and serum levels of M-CSF were significantly increased, and serum and FF levels of biopterin were significantly decreased in Group 1 (P < 0.05 each).CONCLUSIONBiopterin and neopterin levels showed similar differences in FF and serum of patients with empty follicles. Decreased biopterin and increased neopterin in serum could predict poor oocyte retrieval.

The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing.

Objectives. Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-β1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone. Methods. 92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-β1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks. Results. MCSF serum concentrations were higher in the group with multiple fractures as also TGF-β1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point. Conclusion. We did observe a correlation between the quantity of the M-CSF and TGF-β1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones.

Immunomodulatory and clinical effects of the "tiaomian III decoction" in patients with blood blocking antibody deficiency and recurrent spontaneous abortion.

We studied the immunomodulatory and clinical effects of the empirical formula "tiaomian III decoction" on maternal blood blocking antibody deficiency and recurrent spontaneous abortion. Sixty-one patients with blocking antibody deficiency were divided in the experimental group (N = 31), who took tiaomian III decoction, and the control group (N = 30), who received active immunotherapy with paternal lymphocytes; both treatments lasted 3 months. Blocking antibodies, anti-idiotypic antibodies, interleukin, T-lymphocyte subsets, and macrophage colony-stimulating factor (M-CSF) were tested. After treatment, the positive conversion rate reached 87.1 and 86.7% in the experimental and control groups, respectively. After treatment, CD4 levels decreased while CD8 levels increased in both groups. The CD4/CD8 ratio was higher than normal and increased significantly from pre-treatment (P < 0.05). IL-10 and M-CSF levels increased significantly in both groups (P < 0.05). The 1-year conception rates of the experimental and control groups were 58.1 and 46.7%, respectively (P < 0.05). The results show the tiaomian III decoction can increase the positive conversion rate of maternal blocking antibodies and promote the production of IL-10 and M-CSF. Thus, it strengthens the maternal body's protection of the fetus and maintenance of conception. The higher conception rate of the experimental group demonstrates the positive clinic efficacy of the tiaomian III decoction on maternal blood blocking antibody deficiency and recurrent spontaneous abortion.