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1.
Background
High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.Experimental
In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m2) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m2), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.Results
In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).Conclusions
In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity. 相似文献2.
Arregui M Fisher E Knüppel S Buijsse B di Giuseppe R Fritsche A Corella D Willich SN Boeing H Weikert C 《Gene》2012,494(2):190-195
Background
rs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study.Methods
rs2943634 was genotyped in a case-cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n = 211) and IS (n = 144) cases during a mean follow-up of 8.2 ± 2.2 years, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 27,548 middle-aged men and women.Results
rs2943634 minor allele (A) was associated in an additive fashion with lower risk of IS but not with MI [hazard ratio (HR) = 0.66; 95% confidence interval (CI): 0.50-0.87; P = 0.003; HR = 1.02; 95% CI: 0.82-1.28; P = 0.83 respectively, for the age and sex adjusted model]. Furthermore, it was related to slightly higher levels of plasma adiponectin [CC 6.94, CA 7.27, AA 7.86 μg/ml, P = 0.0002] and high density lipoprotein (HDL)-cholesterol (CC 52.08, CA 53.05 and AA 55.27 mg/dl, P = 0.002), based on additive models. Adjustment for adiponectin and HDL-cholesterol did not attenuate the association between the SNP and IS risk. In contrast, adjustment for adiponectin abolished the association between the SNP and HDL-cholesterol and adjustment for HDL-cholesterol attenuated the association between the SNP and adiponectin.Conclusions
Our findings suggest that rs2943634 is associated with IS risk and with plasma levels of HDL-cholesterol and adiponectin in this German population. Further investigations are needed to confirm these results and to clarify the mechanisms underlying the association. 相似文献3.
Fanelli F Belluomo I Di Lallo VD Cuomo G De Iasio R Baccini M Casadio E Casetta B Vicennati V Gambineri A Grossi G Pasquali R Pagotto U 《Steroids》2011,76(3):244-253
Background
The simultaneous, rapid and reliable measurement of a wide steroid panel is a powerful tool to unravel physiological and pathological hormone status. Clinical laboratories are currently dominated by high-throughput immunoassays, but these methods lack specificity due to cross-reactivity and matrix interferences. We developed and validated an isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the simultaneous measurement of cortisol, corticosterone, 11deoxycortisol, androstenedione, deoxycorticosterone (DOC), testosterone, 17OHprogesterone, dehydroepiandrosterone (DHEA) and progesterone in serum, and compared it to routine immunoassays employed in our laboratory. We also established adult reference intervals in 416 healthy subjects.Methods
0.9 ml of serum were spiked with labelled internal standards (IS) and extracted on C18 cartridges. Eluate was injected into a two-dimensional LC-system, purified in a perfusion column and separated on a C8 column during a 21 min gradient run. Analytes were revealed by atmospheric pressure chemical ionization (APCI) followed by multiple reaction monitoring (MRM) analysis.Results
Of the four immunoassays compared with the ID-LC-MS/MS method, only the results of ElecsysE170 for cortisol, testosterone in males and progesterone > 1 ng/ml were in agreement with ID-LC-MS/MS. ElecsysE170 for testosterone in females and progesterone < 1 ng/ml, Immulite2000 for androstenedione, DSL-9000 for DHEA and 17OHP Bridge for 17OHprogesterone, respectively, showed poor agreement. Reference intervals and steroid age and fertility related fluctuations were established.Conclusion
Our ID-LC-MS/MS method proved to be reliable and sensitive in revealing steroid circulating concentrations in adults and in highlighting the limits of routine immunoassays at low concentrations. 相似文献4.
Shinichiro Sano Yuichi Nakagawa Satoru Iwashima Takamichi Ishikawa Eiichiro Satake Rie Matsushita Eiko Nagata Rie Yamaguchi Toshiki Nakanishi Takehiko Ohzeki 《Steroids》2010,75(12):848-1050
Objective
Kawasaki disease (KD) is a severe inflammatory disease that occurs in childhood. Recently, the initial corticosteroid therapy for KD has been reconsidered because its efficacy is controversial. The aim of this study was to evaluate the dynamic change in endogenous glucocorticoid levels and their relation with 11beta-hydroxysteroid dehydrogenase (11β-HSD) activity in the acute phase of KD.Study design
Sixteen KD patients were investigated. Cortisol and cortisone levels, the cortisol/cortisone ratio and C-reactive protein (CRP) levels were measured on admission, before the first intravenous immunoglobulin (IVIG) therapy and convalescence.Results
The 16 patients were divided into two groups. Group A included patients who received the first IVIG on admission and blood samples were collected before the first IVIG and convalescence. Group B included patients whose blood samples were collected at three different time points (on admission, before the first IVIG, and convalescence). CRP and cortisol levels and the cortisol/cortisol ratio were markedly higher before the first IVIG than those of convalescence in all patients except in one patient. In Group B patients, both serum cortisol levels and the cortisol/cortisone ratio on admission were significantly increased compared with those before the first IVIG (cortisol: p < 0.005, cortisol/cortisone: p < 0.001).Conclusions
Decreases in cortisol levels and the cortisol/cortisone ratio before the first IVIG may be explained by a reduction in adrenal secretion and/or local glucocorticoid action through 11β-HSD activity. These findings suggest that exogenous glucocorticoid treatment in combination with the first IVIG at the acute stage may play a synergetic role in KD. 相似文献5.
Jude A. Oben Trusha Patel Angelina Mouralidarane Phillippa Matthews Maelle Morgan Junpei Soeda Lucilla Poston 《Biochemical and biophysical research communications》2010,394(1):24-1771
Background and aims
The prevalence of pancreatic adenocarcinoma (PAC) parallels rising rates of obesity and dysmetabolism, a possible link being non-alcoholic fatty pancreas disease (NAFPD). We have recently shown that maternal obesity programmes the development of a dysmetabolic and fatty liver (non-alcoholic fatty liver disease, NAFLD) phenotype in adult offspring. Since the pancreas and liver originate from the same embryonic bud, it is plausible that maternal obesity may similarly programme the development of NAFPD. Our objective was to determine the effect of maternal obesity on development of NAFPD in offspring and ascertain contributions of the intra/extra-uterine periods.Methods
Female C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a hypercalorific diet (16% fat, 33% sugar) for six weeks prior to mating and throughout pregnancy and lactation. Female offspring were cross-fostered for suckling to dams on the same or opposite diet to yield four groups: offspring of lean suckled by lean dams (n = 6), offspring of obese suckled by obese dams (n = 6), offspring of lean suckled by obese dams (n = 5) and offspring of obese suckled by lean dams (n = 6). All offspring were weaned onto a standard chow diet at 21 days and sacrificed at 3 months post-partum for tissue collection.Results
Offspring subjected to an adverse suckling environment showed significant increases in body weight, pancreatic triglyceride content, TGF-β, collagen gene expression and SBP at rest along with an enhanced restraint stress response, indicating a dysmetabolic and NAFPD phenotype.Conclusions
Developmental programming is involved in the pathogenesis of NAFPD and appears to be largely dependent on an adverse extra-uterine environment. 相似文献6.
Chien-Liang Chen Kang-Ju Chou Po-Tsang Lee Ying-Shou Chen Chih-Yang Hsu Hsiao-Min Chung Hua-Chang Fang 《Experimental cell research》2010,316(7):1109-1118
Purpose
Tumor growth factor-β1 (TGF-β1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-β1-mediated EMT and fibrosis in kidney injury.Methods
We examined apoptosis and EMT in TGF-β1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-β1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-β1 signal pathway proteins and EMT markers.Results
We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-β1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-β1-mediated apoptosis and also partially inhibited TGF-β1-mediated EMT. We showed that EPO treatment suppressed TGF-β1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-β1-treated cells.Conclusions
EPO inhibited apoptosis and EMT in TGF-β1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction. 相似文献7.
Background
The aim of this work was to evaluate the hepatoprotective ability of allopurinol to prevent the liver injury induced by carbon tetrachloride (CCl4).Methods
Acute liver damage was induced with CCl4 (4 g/kg, by gavage); allopurinol (50 mg/kg, by gavage) was given 1 h before and 1 h after CCl4 intoxication and two daily doses for the previous three days. Cirrhosis was established by CCl4 administration (0.4 g/kg, i. p. three times a week, eight weeks); allopurinol was administered (100 mg/kg, by gavage, daily) during the long-term of CCl4 treatment. Alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), xanthine oxidase (XO), lipid peroxidation, reduced and oxidized glutathione (GSH, GSSG, respectively), hydroxyproline and histopathologycal analysis were performed. Nuclear factor-κB (NF-κB), pro-inflammatory and anti-inflammatory cytokines, transforming growth factor-β (TGF-β) and metalloproteinase-13 (MMP-13) were analyzed by Western blots.Results
Acute injury increased ALT and γ-GTP activities, additionally enhanced NF-κB nuclear translocation and cytokines production such as tumor necrosis factor-α, interleukine-1β, and interleukine-6. Allopurinol partially prevented these effects, while increased interleukine-10. Acute and chronic CCl4 treatments altered the levels of XO activity, lipid peroxidation, and GSH/GSSG ratio, while these remained within normal range with allopurinol administration. Necrosis, fibrosis and TGF-β production induced in chronic injury were partially prevented by allopurinol, interestingly, this drug induced MMP-13 activity.Conclusions
Allopurinol possesses antioxidant, anti-inflammatory and antifibrotic properties, probably by its capacity to reduce NF-κB nuclear translocation and TGF-β expression, as well as to induce MMP-13.General significanceAllopurinol might be effective treatment of liver diseases. 相似文献8.
Gupta V Gupta A Jafar T Gupta V Agrawal S Srivastava N Kumar S Singh AK Natu SM Agarwal CG Agarwal GG 《Cytokine》2012,57(1):32-36
Background
Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels.Methods
The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91 ± 6.05) and 272 healthy females without metabolic syndrome (age 30.96 ± 7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion.Results
Homozygous mutant genotype (AA) (p = <0.001: OR = 3.24: 95% CI = 2.15-4.89) and mutant allele (A) (p = <0.001: OR = 3.04: 95% CI = 2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors.Conclusions
Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia. 相似文献9.
Ralph Fingerhut 《Steroids》2009,74(8):662-1442
Background
While the sensitivity of newborn screening for the salt wasting form of congenital adrenal hyperplasia (CAH) is good, the positive predictive value is poor due to the high false positive rate of the immunological assays for 17-OHP. Cross-reactivity with steroid sulfates is one of the main causes for false positive results. Several approaches have been described to improve CAH screening: adjusting cut-off levels to gestational age or birth weight, and second-tier molecular genetic analysis or second-tier liquid chromatography-tandem mass spectrometry (TMS).Methods
17-OHP was extracted with diethyl ether from dried blood spots in order to separate 17-OHP from polar steroids (like steroid sulfates). The dried ether extracts of calibrators, controls, and patient samples were redissolved and measured with the 17-OHP test kit (Wallac).Results
760 normal, 1049 false positive, and 232 samples of confirmed cases with CAH were analysed. Mean 17-OHP values were significantly lower after extraction: Normal samples: 17.5 nmol/L vs. 3.2 nmol/L; false positive samples: 97.0 nmol/L vs. 25.9 nmol/L; CAH: 275 nmol/L vs. 205 nmol/L. With a cut-off value of 11.9 nmol/L (mean + 3 SD of the normal values), 404 of the false positives turned out to be normal. Ether extraction revealed two distinct subgroups of initially false positives rather than a continuum with normal distribution of 17-OHP values.Conclusion
Diethyl ether extraction provided evidence for two causes of false positive results in CAH screening. It reduced the rate of false positives by about 40% without loss of sensitivity. 相似文献10.
Agnes J. Weber Gang Li Robert Kalak Frank Buttgereit Markus J. Seibel Hong Zhou 《Steroids》2010,75(3):282-402
Objective
Glucocorticoids at pharmacological doses have been shown to interfere with fracture repair. The role of endogenous glucocorticoids in fracture healing is not well understood. We examined whether endogenous glucocorticoids affect bone healing in an in vivo model of cortical defect repair.Methods
Experiments were performed using a well characterised mouse model in which intracellular glucocorticoid signalling was disrupted in osteoblasts through transgenic overexpression of 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) under the control of a collagen type I promoter (Col2.3-11β-HSD2). Unicortical bone defects (∅0.8 mm) were created in the tibiae of 7-week-old male transgenic mice and their wild-type littermates. Repair was assessed via histomorphometry, immunohistochemistry and microcomputed tomography (micro-CT) analysis at 1-3 weeks after defect creation.Results
At week 1, micro-CT images of the defect demonstrated formation of mineralized intramembranous bone which increased in volume and density by week 2. At week 3, healing of the defect was nearly complete in all animals. Analysis by histomorphometry and micro-CT revealed that repair of the bony defect was similar in Col2.3-11β-HSD2 transgenic animals and their wild-type littermates at all time-points.Conclusion
Disrupting endogenous glucocorticoid signalling in mature osteoblasts did not affect intramembranous fracture healing in a tibia defect repair model. It remains to be shown whether glucocorticoid signalling has a role in endochondral fracture healing. 相似文献11.
Objective
Osteochondral allografting is an effective method to treat large osteochondral defects but difficulties in tissue preservation have significantly limited the application of this technique. Successful cryopreservation of articular cartilage (AC) could improve the clinical availability of osteochondral tissue and enhance clinical outcomes but cryopreservation of large tissues is hampered by a lack of knowledge of permeation kinetics within these tissues. This study describes the refinement and extension of a recently published technique to measure the permeation kinetics of cryoprotectant agents (CPAs) within porcine AC.Design
Dowels of porcine AC (10 mm diameter) were immersed in solutions containing 6.5 M concentrations of four commonly used CPAs [dimethyl sulfoxide (DMSO), propylene glycol (PG), ethylene glycol (EG) and glycerol] for different times (1 s, 1, 2, 5, 10, 15, 30, 60, 120, 180 min , 24 h) at three different temperatures (4, 22, and 37 °C). The cartilage was isolated and the amount of CPA within the matrix was determined.Results
Diffusion coefficients (DMSO = 2.4-6.2 × 10−6 cm2/s; PG = 0.8-2.7 × 10−6 cm2/s; EG = 1.7-4.2 × 10−6 cm2/s; and glycerol = 0.8-2.4 × 10−6 cm2/s) and activation energies (DMSO = 4.33 kcal/mol, PG = 6.29 kcal/mol, EG = 3.77 kcal/mol, and glycerol = 5.56 kcal/mol) were determined for each CPA.Conclusion
The results of this experiment provide accurate permeation kinetics of four commonly used CPAs in porcine articular cartilage. This information will be useful for developing effective vitrification protocols for cryopreservation of AC. 相似文献12.
Daniel Colprim Galceran Cristina Farriols DanésTeresa Prat Clusellas Montserrat Luna ArandaJosep Maria Muniesa Portolés José Planas Domingo 《Revista espa?ola de geriatría y gerontología》2011,46(5):265
Objective
To determine whether hand grip strength (HGS) is a prognostic factor for mortality in a palliative care unit (PCU), using two variables: A1: The HP on admission; A2: The progression of the HGS in the first 12 days of admission.Material and methods
A prospective, observational and comparative study of patients with advanced cancer admitted consecutively over a 4 month period into a PCU. A series of 4 determinations of HGS were made using a JAMAR® 5030J1 dynamometer. A total of 78 patients fulfilled the inclusion criteria, of which 61 (78.2%) agreed to take part.Results
Objective A1: Of the 61 enrolled patients, the survivors (n = 25) differed by -1.8 (Standard Deviation (SD) 0.8) from the reference values for age and gender, and for those that died (n = 36) it was -1.9 (1.1) (P = .6). A survival analysis was performed with this sample. The sample was subdivided into those who were > -2 SD (n = 34) and those < -2 SD (n = 27) (P = .3). Those patients who managed 4 determinations (n = 49) were included in objective A2. At discharge there were 26 deaths and 23 alive. There were no statistically significant differences between the determinations. Only the comparison between the difference between the 4th and 1st determination in the two groups showed a significant result (P = .01).Conclusions
The HGS measured at admission, as well as in the first 12 days, was not a prognostic factor for mortality in the sample studied. 相似文献13.
E.G. VelliouE. Van Derlinden A.M. CappuynsA.H. Geeraerd F. DevlieghereJ.F. Van Impe 《Journal of thermal biology》2012,37(1):72-78
Aim
The effect of spent medium, obtained after different time-temperature pre-histories, on the heat inactivation of Escherichia coli K12 MG1655 is studied.Methods and results
Stationary E. coli cells were heated in BHI broth (initial pH 7.5) at different time-temperature scenarios, i.e., (1) 30 °C to 55 °C at 0.14 °C/min, (2) 30 °C to 42 °C at 0.14 °C/min and (3) 30 °C to 42 °C at 0.8 °C/min. After the heat treatment, spent medium was filter-sterilized, non-stressed cells were added and inactivation experiments took place at 54 °C and 58 °C. In all scenarios, increased resistance was observed. The main characteristics of the spent medium - compared to the unmodified BHI broth - are (1) the presence of proteins (proven via SDS-PAGE) and (2) a lower pH of approximately 6. Possibly, the increased resistance is due to these proteins and/or the lower pH. Further experiments revealed that each factor separately may lead to an increased heat resistance.Conclusions
It can be concluded that this increased heat resistance resulted from both the presence of the heat shock proteins in the spent medium and the lowered pH. Experiments, which separate both effects, showed that mainly the lower pH resulted in the increased thermotolerance.Significance and impact of study
This study may lead to a better understanding and control of the heat stress adaptation phenomenon as displayed by E. coli at lethal temperatures. Therefore, it contributes to an improved assessment of the effect of temperature during thermal processes in the food industry. 相似文献14.
The Amazonian herbal Marapuama attenuates cognitive impairment and neuroglial degeneration in a mouse Alzheimer model 总被引:1,自引:0,他引:1
M. Figueiró J. Ilha V.M. Linck A.P. Herrmann P. NardinC.B. Menezes M. Achaval C.A. GonçalvesL.O. Porciúncula D.S. NunesE. Elisabetsky 《Phytomedicine》2011,18(4):327-333
Alzheimer's disease (AD) is expected to affect more than 22 million people worldwide by 2025, causing devastating suffering and enormous costs to families and society. AD is a multifactorial disease, with a complex pathological mosaic. In rodents, AD-like dementia can be induced by cerebral microinjection of Aβ peptide, leading to amyloid deposits, amnesia and various features of neurodegeneration. Marapuama (Ptychopetalum olacoides) is regarded as a “brain tonic” in the Amazon region and shows a nootropic profile in rodents.
Aim of the study
Because a specific extract (POEE) of Marapuama was shown to possess promnesic and anti-amnesic properties, the aim of this study was to verify if POEE is also effective against Aβ1-42-induced cognitive deficit in mice. Additionally, Aβ deposits (Congo red), GFAP immunoreactivity (immunohistochemistry), and neurodegenerative changes in the hippocampal pyramidal layer (Nissl) were examined as measures of Aβ1-42-induced neurodegeneration.Materials and methods
CF1 mice were subjected to the experimental Alzheimer model with the Aβ1-42 i.c.v. administration. The effects of POEE 800 mg/kg were evaluated over 14 consecutive days of treatment.Results
The data show that 14 days of oral treatment with POEE (800 mg/kg) was effective in preventing Aβ-induced cognitive impairment, without altering the levels of BDNF and with parallel reductions in Aβ deposits and astrogliosis. CA1 hippocampus loss induced by Aβ1-42 was also diminished in POEE-treated mice.Conclusion
This study offers evidence of functional and neuroprotective effects of two weeks treatment with a Ptychopetalum olacoides extract against Aβ peptide-induced neurotoxicity in mice. Given the multifactorial nature of neurodegeneration, the considerable potential for an AChE inhibitor displaying associated neuroprotective properties such as here reported warrants further clinic evaluation. 相似文献15.
Luo DX Xia CL Li JM Xiong Y Yuan HY Tang ZW Zeng Y Liao DF 《Biochemical and biophysical research communications》2010,403(1):52-58
Objective
To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism.Methods
Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure.Results
Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0 mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated.Conclusion
Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1. 相似文献16.
17.
Background
Inflammation appears to be involved in processes leading to organ damage in preterm newborns, yet little is known about the relationships among elevated concentrations of inflammation-associated proteins in the blood of preterm newborns.Methods
In this exploratory study, we used an electrochemiluminescence method to measure 25 proteins in blood obtained on postnatal day 1 (range 1-3), day 7 (range 5-8), and day 14 (range 12-15) from 939 children born before the 28th week of gestation and evaluated to what extent those whose concentration of each protein was elevated (defined as in the highest quartile for gestational age and day the specimen was obtained) also had an elevated concentration of every other protein the same day or on a day 1 or 2 weeks later (p < .0001).Results
On each of the 3 days assessed, elevated concentrations of 17 proteins were associated with elevated concentrations of 15 or more of the other 24 proteins. VEGF, VEGF-R1, VEGF-R2 were among these proteins, while IGFBP-1 was associated with 13 other proteins on day 7. An elevated concentration of eight proteins on day 1 predicted an elevated concentration of 10 or more proteins on day 7, while an elevated concentration of only two proteins on day 7 were associated with elevated concentrations of 10 or more proteins on day-14. Few associations were seen between days 1 and 14.Conclusions/inferences
Inflammation is a diffuse process in ELGANs, with elevated concentrations of cytokines, chemokines, adhesion molecules, matrix metalloproteinases, a growth factor and its receptors, as well as a growth factor binding protein associated with each other the same day, as well as on subsequent days. 相似文献18.
Guzmán Rodrigo Antonio Silvestre RonyRodríguez Francisco Aniceto Arriagada David AndrésOrtega Pablo Andrés 《Revista espa?ola de geriatría y gerontología》2011,46(5):256
Introduction
Frequent falls are one of the most important health problems in the elderly population. The unipedal stance test (UPST), asses postural stability and is used in fall risk measures. Despite this, there is little information about its relationship with posturographic parameters (PP) that characterizes postural stability. Center of pressure velocity (CoPV) is one of the best PP that describes postural stability. The aim of this study was to analyze the relation between UST score and CoPV in elderly population.Materials and methods
A sample of 38 healthy elderly subjects where divided in two groups according to their UPST score, low performance (LP, n = 11) and high performance (HP, n = 27). The correlation between UPST score and COP mean velocity (CoPmV), recorded from a posturographic test, was analyzed between both groups.Results
An inverse correlation between UPST score and CoPmV was found in both groups. However, this was higher in the LP group (r = −0.69, P = .02) compared to the HP (r = −0.39, P = .04).Conclusions
Based on the results of this investigation, it may be concluded that the achievement on UPST has an inverse relationship with CoPmV, especially in subjects with low performance in the UPST. 相似文献19.
Susan Kidd Paula Midgley Nazir Lone Mary Nicol John Smith Neil McIntosh 《Steroids》2009,74(8):666-1890
Background
The use of saliva for measurement of cortisol permits non-invasive study of adrenal function, but collection can be technically difficult, particularly in small infants. Saliva collection can be assisted by citric acid to increase saliva flow, or by the use of cotton or polyester swabs in the mouth.Aim
To determine whether different methods of saliva collection affect cortisol radioimmunoassay (RIA) performance.Experimental
Cortisol was measured in saliva collected from 16 adults using intra-oral cotton swabs or polyester swabs, compared with saliva dribbled directly into a pot either alone (plain saliva) or after citric acid had been placed on the tongue. An in-house RIA, without prior extraction, was used to measure cortisol with an encapsulated sheep antibody.Results
Mean (median) salivary cortisol was 10.9 (10.5) nmol L−1 in plain saliva, 10.4 (8.4) nmol L−1 in citric acid stimulated saliva; 25.3 (25.1) nmol L−1 in saliva collected on cotton swabs, and 27.9 (27.3) nmol L−1 collected on polyester swabs. Cortisol in saliva collected using citric acid was not significantly different from plain saliva (p = 0.997), but cortisol in saliva collected using cotton and polyester swabs was significantly higher than that of plain saliva (p < 0.01).Conclusion
The use of cotton or polyester swabs for collection of saliva can result in spuriously high levels of cortisol when measured by RIA. 相似文献20.
The current study was conducted to assess 3435C>T multidrug resistance 1 gene polymorphism and the efficacy of high dose methylprednisolone (HDMP) in childhood acute idiopathic thrombocytopenic purpura patients.