Circulating endothelial cells are increased in chronic myeloid leukemia blast crisis.

PubMed

Godoy, C R T; Levy, D; Giampaoli, V; Chamone, D A F; Bydlowski, S P; Pereira, J

2015-06-01

We measured circulating endothelial precursor cells (EPCs), activated circulating endothelial cells (aCECs), and mature circulating endothelial cells (mCECs) using four-color multiparametric flow cytometry in the peripheral blood of 84 chronic myeloid leukemia (CML) patients and 65 healthy controls; and vascular endothelial growth factor (VEGF) by quantitative real-time PCR in 50 CML patients and 32 healthy controls. Because of an increase in mCECs, the median percentage of CECs in CML blast crisis (0.0146%) was significantly higher than in healthy subjects (0.0059%, P<0.01) and in the accelerated phase (0.0059%, P=0.01). There were no significant differences in the percentages of CECs in chronic- or active-phase patients and healthy subjects (P>0.05). In addition, VEGF gene expression was significantly higher in all phases of CML: 0.245 in blast crisis, 0.320 in the active phase, and 0.330 in chronic phase patients than it was in healthy subjects (0.145). In conclusion, CML in blast crisis had increased levels of CECs and VEGF gene expression, which may serve as markers of disease progression and may become targets for the management of CML.

Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.

PubMed

Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

2016-06-17

Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels.

Complement Factor H Is Expressed in Adipose Tissue in Association With Insulin Resistance

PubMed Central

Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

2010-01-01

OBJECTIVE Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances. PMID:19833879

Effect of aerobic training and resistance training on circulating irisin level and their association with change of body composition in overweight/obese adults: a pilot study.

PubMed

Kim, H-J; Lee, H-J; So, B; Son, J S; Yoon, D; Song, W

2016-06-20

The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m(2)) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=-0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels.

Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study.

PubMed

Huang, Junhao; Wang, Shen; Xu, Fengpeng; Wang, Dan; Yin, Honggang; Lai, Qinhao; Liao, Jingwen; Hou, Xiaohui; Hu, Min

2017-01-01

Circulating endothelial progenitor cells (EPCs) correlate negatively with obesity. Previous studies have shown that exercise significantly restores circulating EPC levels in obese people; however, the underlying mechanisms have not been elucidated. Recently, irisin has been reported to have a critical role in the regulation of EPCs. This exercise-induced myokine has been demonstrated to play a therapeutic role in obesity. In this study, we hypothesized that the increase in circulating irisin may form a link with increasing EPC levels in obese people after exercise. Seventeen obese adults completed an 8-week program of combined exercise and dietary intervention. Clinical characteristics, blood biochemistry, and circulating irisin levels of subjects were measured before and after eight weeks of training. EPC levels were evaluated via flow cytometry, and EPC migratory and adhesive functions were also determined. Circulating irisin levels significantly increased following the 8-week training program ( P  < 0.05). We furthermore observed an improvement in EPC numbers ( P  < 0.05), and EPC migratory and adhesive functions ( P  < 0.001 and P  < 0.05, respectively) after the intervention. Additionally, we detected a positive correlation between changes in irisin and changes in EPC number ( r  = 0.52, P  < 0.05). For the first time, a positive correlation between increasing irisin levels and increasing EPC levels has been reported after an 8-week program, consisting of exercise and dietary intervention. This result suggests a novel effect of irisin on the regulation of EPC mobilization, which might contribute to improvement of endothelial function in obese people.

The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity.

PubMed

Can, U; Buyukinan, M; Yerlikaya, F H

2016-06-01

Childhood obesity is an increasing health challenge related to increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA molecules regulating multiple biological processes linked to obesity. We aimed at evaluating the association between circulating miRNA levels and lipid metabolism in obese and non-obese children and adolescents. By constituting study group, 45 obese children and adolescents were recruited. To perform comparisons with study group, 41 lean controls were matched for age and sex. Using real-time quantitative PCR analysis, circulating miRNAs were evaluated in both groups. Circulating miR-335 (P < 0.001), miR-143 (P = 0.001) and miR-758 (P = 0.006) in obese children were significantly lower than those of controls. However, circulating miR-27 (P = 0.032), miR-378 (P < 0.001) and miR-370 (P = 0.045) in obese children were significantly higher, compared with those of controls. In addition, circulating miR-33 in obese children was higher than those of controls, but no significant difference was present (P = 0.687). Our findings showed that a significant association is present between circulating miR-370, miR-33, miR-378, miR-27, miR-335, miR-143 and miR-758 values, and childhood obesity. Low levels of miR-335, miR-143 and miR-758, and high levels of miR-27, miR-378, miR-33 and miR-370 may have been responsible for elevated triglycerides and low-density lipoprotein (LDL-C) levels, and low level of high-density lipoprotein (HDL-C) in obese subjects. Therefore, miRNAs may be a good novel biomarker for childhood obesity. © 2015 World Obesity.

Possible Role of Hadley Circulation Strengthening in Interdecadal Intensification of Snowfalls Over Northeastern China Under Climate Change

NASA Astrophysics Data System (ADS)

Zhou, Botao; Wang, Zunya; Shi, Ying

2017-11-01

This article revealed that strengthening of winter Hadley circulation in the context of climate change may partially contribute to interdecadal increasing of snowfall intensity over northeastern China in recent decades. This hypothesis is well supported by the process-based linkage between Hadley circulation and atmospheric circulations over the Asian-Pacific region on the interdecadal time scale. The strengthening of winter Hadley circulation corresponds to a weakening of the Siberian high, an eastward shifting of the Aleutian low, a reduction of the East Asian trough, and anomalous southwesterly prevailing over northeastern China. These atmospheric situations weaken the East Asian winter monsoon and lead to an increase of air temperature over northeastern China. Increased local evaporation due to the increase of air temperature, concurrent with more water vapor transported from the Pacific Ocean, can significantly enhance atmospheric water vapor content in the target region. Meanwhile, the ascending of airflows is also strengthened over northeastern China. All of these provide favorable interdecadal backgrounds for the occurrence of intense snowfalls, and thus, snowfall intensity is intensified over northeastern China after the 1980s. Further analysis suggests that the circum-Pacific-like teleconnection pattern may play an important role in connecting Hadley circulation strengthening signal and atmospheric circulation anomalies favoring interdecadal intensification of snowfalls over northeastern China.

Prostate Cancer Detection by Molecular Urinalysis

DTIC Science & Technology

2008-04-01

proteins.13 We did not specifically assess whether the urinary endoglin we detected was a result of circulating and filtered endoglin or a result of...a marker of pan-endothelial damage and angiogenesis, it is unlikely that circulating endoglin levels would be significantly affected by localized... circulating endoglin is 33 15 increased in metastatic disease states.8,10, 11 Presumably, the angiogenic cascade necessary for metastasis is

Relationship between High Red Cell Distribution Width and Systemic Inflammatory Response Syndrome after Extracorporeal Circulation.

PubMed

Seth, Harsh Sateesh; Mishra, Prashant; Khandekar, Jayant V; Raut, Chaitanya; Mohapatra, Chandan Kumar Ray; Ammannaya, Ganesh Kumar K; Saini, Jaskaran Singh; Shah, Vaibhav

2017-01-01

Cardiac surgical operations involving extracorporeal circulation may develop severe inflammatory response. This severe inflammatory response syndrome (SIRS) is usually associated with poor outcome with no predictive marker. Red cell distribution width (RDW) is a routine hematological marker with a role in inflammation. We aim to determine the relationship between RDW and SIRS through our study. A total of 1250 patients who underwent cardiac surgery with extracorporeal circulation were retrospectively analyzed out of which 26 fell into the SIRS criteria and 26 consecutive control patients were taken. RDW, preoperative clinical data, operative time and postoperative data were compared between SIRS and control groups. The demographic profile of the patients was similar. RDW was significantly higher in the SIRS versus control group (15.5±2.0 vs. 13.03±1.90), respectively with P value <0.0001. There was significant mortality in the SIRS group, 20 (76.92%) as compared to 2 (7.6%) in control group with a P value of <0.005. Multiple logistic regression analysis revealed that there was significant association with high RDW and development of SIRS after extracorporeal circulation (OR for RDW levels exceeding 13.5%; 95% CI 1.0-1.2; P<0.05). Increased RDW was significantly associated with increased risk of SIRS after extracorporeal circulation. Thus, RDW can act as a useful tool to predict SIRS in patients undergoing cardiac surgery with extracorporeal circulation. Hence, more aggressive measures can be taken in patients with high RDW to prevent postoperative morbidity and mortality.

Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals.

PubMed

Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effect of low-sodium diet on uteroplacental circulation.

PubMed

Delemarre, F M; van Leest, L A; Jongsma, H W; Steegers, E A

2000-01-01

To study the influence of chronic dietary sodium restriction on uteroplacental circulation. In a randomized trial, Doppler flow velocity waveforms of the uterine and umbilical artery were studied at monthly intervals during pregnancy in 59 women on a low-sodium diet and in 68 controls. Pulsatility index (PI), resistance index (RI), and A/B ratio of the uterine artery were significantly lower during sodium restriction, whereas PI, RI, and A/B ratio of the umbilical artery were significantly higher. The lower resistance indices of the uterine artery during sodium restriction might reflect an increase in pulse pressure/impedance ratio as a result of activation of the renin-angiotensin system. The increase in umbilical artery resistance indices supports the hypothesis that fetal circulation might be altered by chronic dietary sodium restriction.

Multidecadal Weakening of Indian Summer Monsoon Circulation Induces an Increasing Northern Indian Ocean Sea Level

NASA Astrophysics Data System (ADS)

Swapna, P.; Jyoti, J.; Krishnan, R.; Sandeep, N.; Griffies, S. M.

2017-10-01

North Indian Ocean sea level has shown significant increase during last three to four decades. Analyses of long-term climate data sets and ocean model sensitivity experiments identify a mechanism for multidecadal sea level variability relative to global mean. Our results indicate that North Indian Ocean sea level rise is accompanied by a weakening summer monsoon circulation. Given that Indian Ocean meridional heat transport is primarily regulated by the annual cycle of monsoon winds, weakening of summer monsoon circulation has resulted in reduced upwelling off Arabia and Somalia and decreased southward heat transport, and corresponding increase of heat storage in the North Indian Ocean. These changes in turn lead to increased retention of heat and increased thermosteric sea level rise in the North Indian Ocean, especially in the Arabian Sea. These findings imply that rising North Indian Ocean sea level due to weakening of monsoon circulation demands adaptive strategies to enable a resilient South Asian population.

Angular circulation speed of tablets in a vibratory tablet coating pan.

PubMed

Kumar, Rahul; Wassgren, Carl

2013-03-01

In this work, a single tablet model and a discrete element method (DEM) computer simulation are developed to obtain the angular circulation speed of tablets in a vibratory tablet coating pan for range of vibration frequencies and amplitudes. The models identify three important dimensionless parameters that influence the speed of the tablets: the dimensionless amplitude ratio (a/R), the Froude number (aω2/g), and the tablet-wall friction coefficient, where a is the peak vibration amplitude at the drum center, ω is the vibration angular frequency, R is the drum radius, and g is the acceleration due to gravity. The models predict that the angular circulation speed of tablets increases with an increase in each of these parameters. The rate of increase in the angular circulation speed is observed to decrease for larger values of a/R. The angular circulation speed reaches an asymptote beyond a tablet-wall friction coefficient value of about 0.4. Furthermore, it is found that the Froude number should be greater than one for the tablets to start circulating. The angular circulation speed increases as Froude number increases but then does not change significantly at larger values of the Froude number. Period doubling, where the motion of the bed is repeated every two cycles, occurs at a Froude number larger than five. The single tablet model, although much simpler than the DEM model, is able to predict the maximum circulation speed (the limiting case for a large value of tablet-wall friction coefficient) as well as the transition to period doubling.

Can increased poleward oceanic heat flux explain the warm Cretaceous climate?

NASA Astrophysics Data System (ADS)

Schmidt, Gavin A.; Mysak, Lawrence A.

1996-10-01

The poleward transport of heat in the mid-Cretaceous (100 Ma) is examined using an idealized coupled ocean-atmosphere model. The oceanic component consists of two zonally averaged basins representing the proto-Pacific and proto-Indian oceans and models the dynamics of the meridional thermohaline circulation. The atmospheric component is a simple energy and moisture balance model which includes the diffusive meridional transport of sensible heat and moisture. The ocean model is spun up with a variety of plausible Cretaceous surface temperature and salinity profiles, and a consistent atmosphere is objectively derived based on the resultant sea surface temperature and the surface heat and freshwater fluxes. The coupled model does not exhibit climate drift. Multiple equilibria of the coupled model are found that break the initial symmetry of the ocean circulation; several of these equilibria have one-cell (northern or southern sinking) thermohaline circulation patterns. Two main classes of circulation are found: circulations where the densest water is relatively cool and is formed at the polar latitudes and circulations where the densest water is warm, but quite saline, and the strongest sinking occurs at the tropics. In all cases, significant amounts of warm, saline bottom water are formed in the proto-Indian basin which modify the deepwater characteristics in the larger (proto-Pacific) basin. Temperatures in the deep ocean are warm, 10°-17°C, in agreement with benthic foraminiferal oxygen isotope data. The poleward transport of heat in the modeled Cretaceous oceans is larger than in some comparable models of the present day thermohaline circulation and significantly larger than estimates of similar processes in the present-day ocean. It is consistently larger in the polar sinking cases when compared with that seen in the tropical sinking cases, but this represents an increase of only 10%. The largest increase over present-day model transports is in the atmospheric latent heat transport, where an increased hydrological cycle (especially in the tropical sinking cases) contributes up to an extra 1 PW of poleward heat transport. Better constraints on the oceanic deepwater circulation during this period are necessary before the meridional circulation can be unambiguously described.

Recent intensification of the Walker Circulation and the role of natural sea surface temperature variability

NASA Astrophysics Data System (ADS)

Zhao, X.; Allen, R.

2017-12-01

In a warming world, the tropical atmospheric overturning circulation-including the Walker Circulation-is expected to weaken due to thermodynamic constraints. Tropical precipitation increases at a slower rate than water vapor-which increases according to Clausius Clapeyron scaling, assuming constant relative humidity-so the tropical overturning circulation slows down. This is supported by both observations and model simulations, which show a slowdown of the Walker Circulation over the 20th century. Model projections suggest a further weakening of the Walker Circulation in the 21st century. However, over the last several decades (1979-2014), multiple observations reveal a robust strengthening of the Walker Circulation. Although coupled CMIP5 simulations are unable to reproduce this strengthening, AMIP simulations-which feature the observed evolution of SSTs-are generally able to reproduce it. Assuming the ensemble mean sea surface temperatures (SSTs) from historical CMIP5 simulations accurately represent the externally forced SST response, the observed SSTs can be decomposed into a forced and an unforced component. CAM5 AMIP-type simulations driven by the unforced component of observed SSTs reproduce the observed strengthening of the Walker Circulation. Corresponding simulations driven by the forced component of observed SSTs yield a weaker Walker Circulation. These results are consistent with the zonal tropical SST gradient and the Bjerknes feedback. The unforced component of SSTs yield an increased SST gradient over tropical Pacific (a La Nina like pattern) and strengthening of the tropical trade winds, which constitute the lower branch of the Walker Circulation. The forced component of SSTs yields a zonally uniform tropical Pacific SST warming and a marginal weakening of the Walker Circulation. Our results suggest significant modulation of the tropical Walker Circulation by natural SST variability over the last several decades.

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

PubMed

Lu, Wei-Qun; Qiu, Ji-Liang; Huang, Zhi-Liang; Liu, Hai-Ying

2016-12-20

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

PubMed Central

de Moura, R; Lopes, M A

1995-01-01

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

Does 8 weeks of strenuous bicycle exercise improve diabetes-related inflammatory cytokines and free fatty acids in type 2 diabetes patients and individuals at high-risk of metabolic syndrome?

PubMed

Madsen, Søren Møller; Thorup, Anne Cathrine; Bjerre, Mette; Jeppesen, Per Bendix

2015-01-01

In the present study, the effects of 8 weeks of low volume high intensity interval training (HIIT) was investigated on circulating diabetes-related cytokines and free fatty acids (FFA) in adults with type 2 diabetes (T2D) and matched controls (CON). Participants exercised for 8 weeks (3 weekly sessions: 10 × 60 sec HIIT) on a cycle ergometer supervised by medical staff. Prior to the intervention and after the last HIIT session, venous blood samples were collected. Circulating omentin-1 concentrations increased significantly in both the CON-group (p = 0.003) and in the T2D-group (p = 0.002). Pentraxin-3 (p = 0.010) and IL-1ra (p = 0.031) levels increased significantly in the CON-group. Plasma FFA in the T2D-group was significantly reduced after 60 min (p = 0.011). Post HIIT area under curve of circulating FFAs was reduced by -17.73 ± 6.99% (p = 0.041) in the T2D-group. We observed only modest exercise-induced improvements of multiple diabetes-related cytokines. Circulating levels of FFAs were significantly lowered in the T2D-group.

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study.

PubMed

Morinaga, Jun; Zhao, Jiabin; Endo, Motoyoshi; Kadomatsu, Tsuyoshi; Miyata, Keishi; Sugizaki, Taichi; Okadome, Yusuke; Tian, Zhe; Horiguchi, Haruki; Miyashita, Kazuya; Maruyama, Nobuhiro; Mukoyama, Masashi; Oike, Yuichi

2018-01-01

Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

PubMed

Shi, Xiulin; Lin, Mingzhu; Liu, Changqin; Xiao, Fangsen; Liu, Yongwen; Huang, Peiying; Zeng, Xin; Yan, Bing; Liu, Suhuan; Li, Xiaoying; Yang, Shuyu; Li, Xuejun; Li, Zhibin

2016-07-29

Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.

PubMed

Huang, Po-Hsun; Chen, Yung-Hsiang; Tsai, Hsiao-Ya; Chen, Jia-Shiong; Wu, Tao-Cheng; Lin, Feng-Yen; Sata, Masataka; Chen, Jaw-Wen; Lin, Shing-Jong

2010-04-01

Red wine (RW) consumption has been associated with a reduction of cardiovascular events, but limited data are available on potential mediating mechanisms. This study tested the hypothesis that intake of RW may promote the circulating endothelial progenitor cell (EPC) level and function through enhancement of nitric oxide bioavailability. Eighty healthy, young subjects were randomized and assigned to consume water (100 mL), RW (100 mL), beer (250 mL), or vodka (30 mL) daily for 3 weeks. Flow cytometry was used to quantify circulating EPC numbers, and in vitro assays were used to evaluate EPC functions. After RW ingestion, endothelial function determined by flow-mediated vasodilation was significantly enhanced; however, it remained unchanged after water, beer, or vodka intake. There were significantly increased numbers of circulating EPC (defined as KDR(+)CD133(+), CD34(+)CD133(+), CD34(+)KDR(+)) and EPC colony-forming units only in the RW group (all P<0.05). Only RW ingestion significantly enhanced plasma levels of nitric oxide and decreased asymmetrical dimethylarginine (both P<0.01). Incubation of EPC with RW (but not beer or ethanol) and resveratrol in vitro attenuated tumor necrosis factor-alpha-induced EPC senescence and improved tumor necrosis factor-alpha-suppressed EPC functions and tube formation. Incubation with nitric oxide donor sodium nitroprusside significantly ameliorated the inhibition of tumor necrosis factor-alpha on EPC proliferation, but incubation with endothelial nitric oxide synthase inhibitor l-NAME and PI3K inhibitor markedly attenuated the effect of RW on EPC proliferation. The intake of RW significantly enhanced circulating EPC levels and improved EPC functions by modifying nitric oxide bioavailability. These findings may help explain the beneficial effects of RW on the cardiovascular system. This study demonstrated that a moderate intake of RW can enhance circulating levels of EPC in healthy subjects by increasing nitric oxide availability. Direct incubation of EPC with RW and resveratrol can modify the functions of EPC, including attenuation of senescence and promotion of EPC adhesion, migration, and tube formation. These data suggest that RW ingestion may alter the biology of EPC, and these alterations may contribute to its unique cardiovascular-protective effect.

Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans

PubMed Central

Micallef, Michelle; Lexis, Louise; Lewandowski, Paul

2007-01-01

Background Red wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation. Methods 20 young (18–30 yrs) and 20 older (≥ 50 yrs) volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH), plasma malondialdehyde (MDA) and serum total antioxidant status. Results Results from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P < 0.03), and significant decreases in plasma MDA (P < 0.001) and GSH (P < 0.004) in young and old subjects. The results show that the consumption of 400 mL/day of red wine for two weeks, significantly increases antioxidant status and decreases oxidative stress in the circulation Conclusion It may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status. PMID:17888186

Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

PubMed

Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

2015-07-01

Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p <0.001). A colony of circulating endothelial progenitor cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p <0.001). The culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p <0.001). The circulating endothelial progenitor cell level correlated positively with the number of patient colonies (r = 0.762, p <0.001). Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p <0.001). Earlier emergence of circulating endothelial progenitor cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

2016-01-01

Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200

Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer.

PubMed

Catarino, Raquel; Ferreira, Maria M; Rodrigues, Helena; Coelho, Ana; Nogal, Ana; Sousa, Abreu; Medeiros, Rui

2008-08-01

To determine whether the amounts of circulating DNA could discriminate between breast cancer patients and healthy individuals by using real-time PCR quantification methodology. Our standard protocol for quantification of cell-free plasma DNA involved 175 consecutive patients with breast cancer and 80 healthy controls. We found increased levels of circulating DNA in breast cancer patients compared to control individuals (105.2 vs. 77.06 ng/mL, p < 0.001). We also found statistically significant differences in circulating DNA amounts in patients before and after breast surgery (105.2 vs. 59.0 ng/mL, p = 0.001). Increased plasma cell-free DNA concentration was a strong risk factor for breast cancer, conferring an increased risk for the presence of this disease (OR, 12.32; 95% CI, 2.09-52.28; p < 0.001). Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of breast cancer with a potential to clinical applicability together with other current methods used for monitoring the disease.

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

PubMed Central

Chen, Tianbao; Wu, Bing; Lin, Rong

2017-01-01

It is well established that apelin-APLNR (apelin receptor) pathway plays a central role in cardiovascular system. In this meta-analysis, we summarized published results on circulating apelin concentration in association with coronary artery disease (CAD), apelin and APLNR genetic polymorphism(s) in predisposition to CAD risk and circulating apelin changes after surgical treatment for CAD. The results from 15 articles were pooled. Two authors independently took charge of literature search, article selection and information collection. Overall, circulating apelin concentration was significantly lower in CAD patients (N=1021) than in controls (N=654) (weighted mean difference [WMD]: -1.285 ng/mL, 95% confidence interval [CI]: -1.790 to -0.780, P<0001), with significant heterogeneity (I2=99.3%) but without publication bias. For the association of APLNR gene rs9943582 polymorphism with CAD (patients/controls: 5975/4717), the mutant T allele was associated with a 5.2% increased risk relative to the wild C allele (odds ratio: 1.052, 95% CI: 0.990 to 1.117, P=0.100), without heterogeneity (I2=0.0%) or publication bias. Circulating apelin was increased significantly after surgical treatment for CAD (N=202) (WMD: 2.011 ng/mL, 95% CI: 0.541 to 3.481, P=0.007), with significant heterogeneity (I2=98.0%). Stratified analyses showed that circulating apelin was significantly reduced in studies with age- and sex-matched patients and controls (WMD: -1.881 ng/mL, 95% CI: -2.457 to -1.304, P<0.001) and with total sample size ≥125 (WMD: -1.657 ng/mL, 95% CI: -2.378 to -0.936, P<0.001), relative to studies without matching reports and with total sample size <125. In brief, our results suggested that circulating apelin was a prominent athero-protective marker against the development of CAD. PMID:28915675

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

PubMed

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

Exposure to a Social Stressor Alters the Structure of the Intestinal Microbiota: Implications for Stressor-Induced Immunomodulation

PubMed Central

Bailey, Michael T.; Dowd, Scot E.; Galley, Jeffrey D.; Hufnagle, Amy R.; Allen, Rebecca G.; Lyte, Mark

2010-01-01

The bodies of most animals are populated by highly complex and genetically diverse communities of microorganisms. The majority of these microbes reside within the intestines in largely stable but dynamically interactive climax communities that positively interact with their host. Studies from this laboratory have shown that stressor exposure impacts the stability of the microbiota and leads to bacterial translocation. The biological importance of these alterations, however, is not well understood. To determine whether the microbiome contributes to stressor-induced immunoenhancement, mice were exposed to a social stressor called social disruption (SDR), that increases circulating cytokines and primes the innate immune system for enhanced reactivity. Bacterial populations in the cecum were characterized using bacterial tag-encoded FLX amplicon pyrosequencing. Stressor exposure significantly changed the community structure of the microbiota, particularly when the microbiota were assessed immediately after stressor exposure. Most notably, stressor exposure decreased the relative abundance of bacteria in the genus Bacteroides, while increasing the relative abundance of bacteria in the genus Clostridium. The stressor also increased circulating levels of IL-6 and MCP-1, which were significantly correlated with stressor-induced changes to three bacterial genera (i.e., Coprococcus, Pseudobutyrivibrio, and Dorea). In follow up experiments, mice were treated with an antibiotic cocktail to determine whether reducing the microbiota would abrogate the stressor-induced increases in circulating cytokines. Exposure to SDR failed to increase IL-6 and MCP-1 in the antibiotic treated mice. These data show that exposure to SDR significantly affects bacterial populations in the intestines, and remarkably also suggest that the microbiota are necessary for stressor-induced increases in circulating cytokines. PMID:21040780

Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles.

PubMed

List, Edward O; Berryman, Darlene E; Funk, Kevin; Jara, Adam; Kelder, Bruce; Wang, Feiya; Stout, Michael B; Zhi, Xu; Sun, Liou; White, Thomas A; LeBrasseur, Nathan K; Pirtskhalava, Tamara; Tchkonia, Tamara; Jensen, Elizabeth A; Zhang, Wenjuan; Masternak, Michal M; Kirkland, James L; Miller, Richard A; Bartke, Andrzej; Kopchick, John J

2014-05-01

GH is an important regulator of body growth and composition as well as numerous other metabolic processes. In particular, liver plays a key role in the GH/IGF-I axis, because the majority of circulating "endocrine" IGF-I results from GH-stimulated liver IGF-I production. To develop a better understanding of the role of liver in the overall function of GH, we generated a strain of mice with liver-specific GH receptor (GHR) gene knockout (LiGHRKO mice). LiGHRKO mice had a 90% decrease in circulating IGF-I levels, a 300% increase in circulating GH, and significant changes in IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, IGFBP-5, and IGFBP-7. LiGHRKO mice were smaller than controls, with body length and body weight being significantly decreased in both sexes. Analysis of body composition over time revealed a pattern similar to those found in GH transgenic mice; that is, LiGHRKO mice had a higher percentage of body fat at early ages followed by lower percentage of body fat in adulthood. Local IGF-I mRNA levels were significantly increased in skeletal muscle and select adipose tissue depots. Grip strength was increased in LiGHRKO mice. Finally, circulating levels of leptin, resistin, and adiponectin were increased in LiGHRKO mice. In conclusion, LiGHRKO mice are smaller despite increased local mRNA expression of IGF-I in several tissues, suggesting that liver-derived IGF-I is indeed important for normal body growth. Furthermore, our data suggest that novel GH-dependent cross talk between liver and adipose is important for regulation of adipokines in vivo.

ALTERATION OF CIRCULATING ANTIBODY RESPONSE OF MICE EXPOSED TO 9-GHZ PULSED MICROWAVES

EPA Science Inventory

A significant increase was observed in the circulating antibody titers of mice exposed to 9-GHz pulsed microwaves at an average power density of 10 mW/sq. cm., two hours per day for five days compared with sham-irradiated animals. The mice were previously immunized with type III ...

Observing a fictitious stressful event: haematological changes, including circulating leukocyte activation.

PubMed

Mian, Rubina; Shelton-Rayner, Graham; Harkin, Brendan; Williams, Paul

2003-03-01

The aim of this study was to assess the effect of watching a psychological stressful event on the activation of leukocytes in healthy human volunteers. Blood samples were obtained from 32 healthy male and female subjects aged between 20 and 26 years before, during and after either watching an 83-minute horror film that none of the subjects had previously seen (The Texas Chainsaw Massacre, 1974) or by sitting quietly in a room (control group). Total differential cell counts, leukocyte activation as measured by the nitroblue tetrazolium (NBT) test, heart rate and blood pressure (BP) measurements were taken at defined time points. There were significant increases in peripheral circulating leukocytes, the number of activated circulating leukocytes, haemoglobin (Hb) concentration and haematocrit (Hct) in response to the stressor. These were accompanied by significant increases in heart rate, systolic and diastolic BP (P<0.05 from baseline). This is the first reported study on the effects of observing a psychologically stressful, albeit fictitious event on circulating leukocyte numbers and the state of leukocyte activation as determined by the nitrotetrazolium test.

Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and prognostic value for uterine cervical cancer.

PubMed

Zhang, Xin; Wang, Chuanxin; Wang, Lili; Du, Lutao; Wang, Shun; Zheng, Guixi; Li, Wei; Zhuang, Xuewei; Zhang, Xuhua; Dong, Zhaogang

2012-07-01

Bmi-1 is overexpressed in uterine cervical cancer (UCC) and is found to be associated with adverse clinical characteristics and poor prognosis. However, little information is available on the status of circulating Bmi-1 mRNA in UCC. Because circulating cell-free nucleic acids have emerged as a novel class of markers for cancer detection, our research aims to address this question by detecting the circulating Bmi-1 mRNA and to assess its diagnostic and prognostic potential in UCC. Reverse transcription quantitative real-time PCR method was established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy volunteers, and found that it was significantly increased in UCC compared with CINs and healthy controls (all at p < 0.001). Moreover, its high level was significantly correlated with advanced clinical stage (p < 0.001) and positive lymph nodes metastasis (p = 0.002). The area under the receiver operating characteristic curve (AUC) was 0.881, and the optimal cut-off value was 0.057, providing a sensitivity of 69.7% and a specificity of 95.9%. The AUC for circulating Bmi-1 mRNA showed higher diagnosis capability than that for SCC-Ag (p = 0.035) or CA125 (p < 0.001) currently utilized. Kaplan-Meier analysis demonstrated a correlation between increased circulating Bmi-1 mRNA level and reduced disease-free survival (DFS) (p = 0.001) and overall survival (OS) (p = 0.015). And, Cox analysis indicated that it was an independent prognostic factor for DFS and OS. We conclude that circulating Bmi-1 mRNA may be a potential noninvasive molecular marker for diagnosis and prognosis of UCC. Copyright © 2011 UICC.

Circulating interleukin-6 is not altered while γ-tocopherol is increased in subjects scheduled for knee surgery with low vitamin D.

PubMed

Barker, Tyler; Henriksen, Vanessa T; Rogers, Victoria E; Momberger, Nathan G; Rasmussen, G Lynn; Trawick, Roy H

2016-12-01

The purpose of this study was to identify if circulating interleukin (IL)-6 and γ-tocopherol (γT) fluctuate with vitamin D status in subjects with an underlying knee joint injury or disease. We hypothesized that low vitamin D associates with an increase in plasma γT while serum IL-6 remains unchanged in subjects with an underlying knee joint trauma or disease. Fifty-four subjects scheduled to undergo primary, unilateral anterior cruciate ligament reconstructive surgery (ACL; n=27) or total knee arthroplasty (TKA; n=27) were studied. Circulating γT, α-tocopherol (αT), lipids (cholesterol and triglycerides), IL-6, and 25-hydroxyvitamin D (25(OH)D) were measured in fasting blood samples obtained prior to surgery. Subjects were classified as vitamin D deficient, insufficient, or sufficient if they had a serum 25(OH)D concentration <50, 50-75, or >75nM, respectively. The majority (57%) of the subjects possessed a serum 25(OH)D less than 50nM. Circulating cholesterol, triglycerides, and IL-6 were not significantly (all p>0.05) different between vitamin D status groups. However, lipid corrected αT was significantly (p<0.05) decreased and both lipid- and non-lipid-corrected plasma γT concentrations were significantly (both p<0.05) increased with low serum 25(OH)D (i.e., <50nM). A significant (p<0.05) multi-variate analysis revealed that an increase in plasma γT per lipids was significantly (p<0.05) predicted by a decrease in serum 25(OH)D but not by a decrease in plasma αT per lipids. We conclude that low vitamin D associates with an increase in plasma γT but not IL-6 in subjects with an underlying joint injury or disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

PubMed Central

Sarrion, Irene; Milian, Lara; Juan, G.; Ramon, Mercedes; Furest, Idelfonso; Carda, Carmen; Cortijo Gimeno, Julio; Mata Roig, Manuel

2015-01-01

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients' pulmonary function. We also studied the expression profile of circulating messenger RNA (mRNAs) and found that miR23a controlled 17% of the significantly changed mRNA, including PGC1α, which was recently associated with the progression of IPAH. Finally we found that silencing of miR23a resulted in an increase of the expression of PGC1α, as well as in its well-known regulated genes CYC, SOD, NRF2, and HO1. The results point to the utility of circulating miRNA expression as a biomarker of disease progression. PMID:25815108

Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

NASA Astrophysics Data System (ADS)

McNeeley, Kathleen M.; Annapragada, Ananth; Bellamkonda, Ravi V.

2007-09-01

Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice

PubMed Central

Chung, Rosanna W. S.; Wang, Zeneng; Bursill, Christina A.; Wu, Ben J.; Barter, Philip J.

2017-01-01

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice. PMID:29240800

Changes in endometrial natural killer cell expression of CD94, CD158a and CD158b are associated with infertility.

PubMed

McGrath, Emma; Ryan, Elizabeth J; Lynch, Lydia; Golden-Mason, Lucy; Mooney, Eoghan; Eogan, Maeve; O'Herlihy, Colm; O'Farrelly, Cliona

2009-04-01

Cycle-dependent fluctuations in natural killer (NK) cell populations in endometrium and circulation may differ, contributing to unexplained infertility. NK cell phenotypes were determined by flow cytometry in endometrial biopsies and matched blood samples. While circulating and endometrial T cell populations remained constant throughout the menstrual cycle in fertile and infertile women, circulating NK cells in infertile women increased during the secretory phase. However, increased expression of CD94, CD158b (secretory phase), and CD158a (proliferative phase) by endometrial NK cells from infertile women was observed. These changes were not reflected in the circulation. In infertile women, changes in circulating NK cell percentages are found exclusively during the secretory phase and not in endometrium; cycle-related changes in NK receptor expression are observed only in infertile endometrium. While having exciting implications for understanding NK cell function in fertility, our data emphasize the difficulty in attaching diagnostic or prognostic significance to NK cell analyses in individual patients.

A Study of Permeability Changes Due to Cold Fluid Circulation in Fractured Geothermal Reservoirs.

PubMed

Gholizadeh Doonechaly, Nima; Abdel Azim, Reda R; Rahman, Sheik S

2016-05-01

Reservoir behavior due to injection and circulation of cold fluid is studied with a shear displacement model based on the distributed dislocation technique, in a poro-thermoelastic environment. The approach is applied to a selected volume of Soultz geothermal reservoir at a depth range of 3600 to 3700 m. Permeability enhancement and geothermal potential of Soultz geothermal reservoir are assessed over a stimulation period of 3 months and a fluid circulation period of 14 years. This study-by shedding light onto another source of uncertainty-points toward a special role for the fracture surface asperities in predicting the shear dilation of fractures. It was also observed that thermal stress has a significant impact on changing the reservoir stress field. The effect of thermal stresses on reservoir behavior is more evident over longer circulation term as the rock matrix temperature is significantly lowered. Change in the fracture permeability due to the thermal stresses can also lead to the short circuiting between the injection and production wells which in turn decreases the produced fluid temperature significantly. The effect of thermal stress persists during the whole circulation period as it has significant impact on the continuous increase in the flow rate due to improved permeability over the circulation period. In the current study, taking into account the thermal stress resulted in a decrease of about 7 °C in predicted produced fluid temperature after 14 years of cold fluid circulation; a difference which notably influences the potential prediction of an enhanced geothermal system. © 2015, National Ground Water Association.

Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity

PubMed Central

Lindqvist, D; Fernström, J; Grudet, C; Ljunggren, L; Träskman-Bendz, L; Ohlsson, L; Westrin, Å

2016-01-01

Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic–pituitary–adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values<2.98E−12, Cohen's d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49, P<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression. PMID:27922635

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women.

PubMed

Dumesic, Daniel A; Akopians, Alin L; Madrigal, Vanessa K; Ramirez, Emmanuel; Margolis, Daniel J; Sarma, Manoj K; Thomas, Albert M; Grogan, Tristan R; Haykal, Rasha; Schooler, Tery A; Okeya, Bette L; Abbott, David H; Chazenbalk, Gregorio D

2016-11-01

Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. This is a prospective cohort study. The setting was an academic medical center. Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction.

Global warming hiatus contributed to the increased occurrence of intense tropical cyclones in the coastal regions along East Asia.

PubMed

Zhao, Jiuwei; Zhan, Ruifen; Wang, Yuqing

2018-04-16

The recent global warming hiatus (GWH) was characterized by a La Niña-like cooling in the tropical Eastern Pacific accompanied with the Indian Ocean and the tropical Atlantic Ocean warming. Here we show that the recent GWH contributed significantly to the increased occurrence of intense tropical cyclones in the coastal regions along East Asia since 1998. The GWH associated sea surface temperature anomalies triggered a pair of anomalous cyclonic and anticyclonic circulations and equatorial easterly anomalies over the Northwest Pacific, which favored TC genesis and intensification over the western Northwest Pacific but suppressed TC genesis and intensification over the southeastern Northwest Pacific due to increased vertical wind shear and anticyclonic circulation anomalies. Results from atmospheric general circulation model experiments demonstrate that the Pacific La Niña-like cooling dominated the Indian Ocean and the tropical Atlantic Ocean warming in contributing to the observed GWH-related anomalous atmospheric circulation over the Northwest Pacific.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors.

PubMed

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2(-/-) Cxcr6(Gfp/+) reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow.

HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection

PubMed Central

Abbate, Valeria; Marcantoni, Margherita; Giuliante, Felice; Vecchio, Fabio M.; Gatto, Ilaria; Mele, Caterina; Saviano, Antonio; Arciuolo, Damiano; Gaetani, Eleonora; Ferrari, Maria C.; Giarretta, Igor; Ardito, Francesco; Riccardi, Laura; Nicoletti, Alberto; Ponziani, Francesca R.; Gasbarrini, Antonio; Pompili, Maurizio; Pola, Roberto

2017-01-01

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients. PMID:28498353

Effect of a low dose of sea buckthorn berries on circulating concentrations of cholesterol, triacylglycerols, and flavonols in healthy adults.

PubMed

Larmo, Petra S; Yang, Baoru; Hurme, Saija A M; Alin, Jouni A; Kallio, Heikki P; Salminen, Eeva K; Tahvonen, Raija L

2009-08-01

Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease (CVD) risk. To study the effect of flavonoid-rich sea buckthorn berry (SBB) on circulating lipid markers associated with CVD risk and plasma flavonol concentration. Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein (CRP) concentration observed previously. In all 229 healthy participants completed the randomized double-blind study and consumed daily 28 g of SBB or placebo for 3 months. Fasting blood samples for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study. Compared to the placebo, the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [treatment differences 3.0 ng/ml (P = 0.03) and 3.9 ng/ml (P < 0.01), respectively]. The increase of kaempferol concentration was not significant [treatment difference 0.7 ng/ml (P = 0.08)]. SBB did not affect the serum total, HDL, LDL cholesterol, or the serum triacylglycerol concentrations. There was no correlation between the changes in flavonol and CRP concentrations of participants. The consumption of SBB significantly increased the fasting plasma concentration of quercetin and isorhamnetin indicating that it is a good dietary source of flavonols. However, this did not convert to affecting the circulating concentrations of lipid markers in healthy, normolipidemic adults having healthy diets.

Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes.

PubMed

Giudice, Valentina; Wu, Zhijie; Kajigaya, Sachiko; Fernandez Ibanez, Maria Del Pilar; Rios, Olga; Cheung, Foo; Ito, Sawa; Young, Neal S

2018-06-26

The alarmin family members S100A8 and S100A9 are acute phase inflammation proteins, but they also have been proposed as biomarkers in many malignant and non-malignant diseases. In this study, circulating S100A8 and S100A9 homodimers and S100A8/A9 heterodimers in plasma were systematically investigated by ELISA in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Plasma was obtained from 58 severe AA (SAA) and 30 MDS patients, and from 47 age- and sex-matched healthy donors. In 40 out of the 58 AA subjects, S100A protein levels were measured before and 6 months after immunosuppressive therapy (IST). No differences were observed in AA patients at diagnosis compared to healthy controls for circulating S100A homodimers and heterodimers. After therapy, SAA-responders showed significantly increased circulating S100A8. Non-responding patients had significantly higher levels of circulating S100A8/A9 compared to responders and healthy controls, but without variations of S100A8 and S100A9 homodimers. In MDS patients, circulating S100A8 was significantly elevated compared to those of AA and/or healthy controls. By Pearson correlation analysis of protein levels and blood counts, multiple correlations were found. However, as S100A8 and S100A9 are abundantly present in white blood cells and platelets, correlations with blood counts likely mirror the higher number of cells in the blood of some patients. In conclusion, our findings indicate that circulating S100A8 is increased in MDS but not in AA, and that may be useful to distinguish these diseases in the differential diagnosis of bone marrow failure syndromes. Clinicaltrials.gov identifiers: NCT00260689, NCT00604201, NCT01328587, NCT01623167, NCT00001620, NCT00001397. Published by Elsevier Ltd.

Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery: on-pump versus off-pump.

PubMed

Pizon, M T; Gburek, T; Pizon, M; Sztefko, K

2006-12-01

Heat shock protein HSP-70 is known as protective chaperone molecule synthetized in response following ischemia and stress agents. It is detected in the myocardium and endothelium as well as in the circulation. Damaged as well as viable but exposed to stress cells contribute to the release of HSP-70 into the circulation. The aim of the study was to investigate if cardiopulmonary bypss (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump surgery (OPCAB group). Blood samples were taken preoperatively, twice intraoperatively, immediately after surgical procedure (1 h) and 24-hours thereafter. The concentration of plasma HSP-70 was measured by means of immunoassay. The derived results were compared statistically with the frequency of incidence postoperative atrial fibrillation (AF). In CABG group was observed continuous gradual increase of plasma HSP-70 concentration during the operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB group, in which was detected small, but non statistically significant increase of HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB, respectively P<0.015 and P<0.028). In both groups among patients witch AF it was found higher postoperative values of circulating HSP-70 compared with the non-AF group (P=0.0415). The use of CPB leads to significant more release of HSP-70 into the circulation. According to our findings high plasma concentration of HSP-70 may be the measure of operative cellular stress, ischemia or injury and may be related with greater onset of postoperative AF. High circulating HSP-70 levels is connected with higher incidence of postoperative AF after open heart surgery.

Effect of temperature stress on circulating biogenic amines in bovine.

PubMed

Davis, T P; Johnson, H D; Gehrke, C W

1984-01-01

A sensitive, simple and selective chromatographic method using high performance liquid chromatography was developed to measure circulating levels of histamine (HI), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) as indicators of response to thermal stress in two breeds of cattle. Duplicate exposures for 8 hr to 13 degrees C resulted in significantly elevated plasma NE and DA in longhorns but not in Herefords and suggest a relatively greater sensitivity to the cold (13 degrees C) in the longhorn. Environmental temperatures of 32 and 42 degrees C significantly increased rectal temperatures of both breeds with much higher rectal temperatures in Herefords. The 32 and 42 degrees C effects on circulating NE and DA of Herefords were highly significant but not in the longhorn. However, heat stress significantly elevated HI and 5-HT in the longhorn which may account for their relatively greater heat tolerance based on their lower rectal temperatures.

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

PubMed

Papazyan, Romeo; Liu, Xueqing; Liu, Jingwen; Dong, Bin; Plummer, Emily M; Lewis, Ronald D; Roth, Jonathan D; Young, Mark A

2018-06-01

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

[Establishment and evaluation of extracorporeal circulation model in rats].

PubMed

Xie, Xiao-Jun; Tao, Kai-Yu; Tang, Meng-Lin; Du, Lei; An, Qi; Lin, Ke; Gan, Chang-Ping; Chen, You-Wen; Luo, Shu-Hua

2012-09-01

To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.

Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Background Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by increased inflammation with elevated circulating levels of inflammatory cytokines and other factors. Circulating angiogenic factors are intricately involved in the angiogenesis-inflammation nexus. Methods To study the association of angiogenic factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n=44) or TB alone (n=44). Results Circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly higher in TB-DM compared to TB individuals. Moreover, the levels of VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or cavitary disease or with hemoptysis, suggesing an association with both disease severity and adverse clinical presentation. The levels of these factors also exhibited a significant positive relationship with bacterial burdens and HbA1c levels. In addition, VEGF-A, C and R2 levels were signifantly higher (at 2 months of treatment) in culture positive compared to culture negative TB-DM individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly reduced following successful chemotherapy at 6 months. Conclusion Our data demonstrate that TB-DM is associated with heightened levels of circulating angiogenic factors, possibly reflecting both dysregulated angiogenesis and exaggerated inflammation. PMID:27717783

Wind, Circulation, and Topographic Effects on Alongshore Phytoplankton Variability in the California Current

NASA Astrophysics Data System (ADS)

Fiechter, Jerome; Edwards, Christopher A.; Moore, Andrew M.

2018-04-01

A physical-biogeochemical model is used to produce a retrospective analysis at 3-km resolution of alongshore phytoplankton variability in the California Current during 1988-2010. The simulation benefits from downscaling a regional circulation reanalysis, which provides improved physical ocean state estimates in the high-resolution domain. The emerging pattern is one of local upwelling intensification in response to increased alongshore wind stress in the lee of capes, modulated by alongshore meanders in the geostrophic circulation. While stronger upwelling occurs near most major topographic features, substantial increases in phytoplankton biomass only ensue where local circulation patterns are conducive to on-shelf retention of upwelled nutrients. Locations of peak nutrient delivery and chlorophyll accumulation also exhibit interannual variability and trends noticeably larger than the surrounding shelf regions, thereby suggesting that long-term planktonic ecosystem response in the California Current exhibits a significant local scale (O(100 km)) alongshore component.

Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.

PubMed

Villanova, Federica; Flutter, Barry; Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

2014-04-01

Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

Characterization of innate lymphoid cells (ILC) in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis

PubMed Central

Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

2013-01-01

Innate lymphoid cells (ILC) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterise the ILC in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in skin and blood of normal individuals and psoriasis patients are CD3 negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in blood of psoriasis patients compared to healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILC in skin compared to blood. Moreover the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared to normal skin. A detailed time course of a psoriasis patient treated with anti-TNF showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis. PMID:24352038

Phagocytosis, bacterial killing, and cytokine activation of circulating blood neutrophils in horses with severe equine asthma and control horses.

PubMed

Vanderstock, Johanne M; Lecours, Marie-Pier; Lavoie-Lamoureux, Annouck; Gottschalk, Marcelo; Segura, Mariela; Lavoie, Jean-Pierre; Jean, Daniel

2018-04-01

OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from horses with severe equine asthma and control horses. Phagocytosis was evaluated by use of flow cytometry. Bactericidal activity of circulating blood neutrophils was assessed by use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS Circulating blood neutrophils from horses with severe equine asthma had significantly lower bactericidal activity toward S zooepidemicus but not toward S equi, compared with results for control horses. Phagocytosis and mRNA expression of TNF-α, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood neutrophils in horses with severe equine asthma could contribute to an increased susceptibility to infections.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

Body composition changes in men and women after 2-3 weeks of bed rest

NASA Technical Reports Server (NTRS)

Pace, N.; Kodama, A. M.; Grunbaum, B. W.; Rahlmann, D. F.; Price, D. C.; Newsom, B. D.

1976-01-01

Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.

Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol.

PubMed

Matsui, Sumika; Yasui, Toshiyuki; Kasai, Kana; Keyama, Kaoru; Yoshida, Kanako; Kato, Takeshi; Uemura, Hirokazu; Kuwahara, Akira; Matsuzaki, Toshiya; Irahara, Minoru

2017-07-01

Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group. In addition, the women received dydrogesterone continuously (5 mg) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.

Summertime land-sea thermal contrast and atmospheric circulation over East Asia in a warming climate—Part I: Past changes and future projections

NASA Astrophysics Data System (ADS)

Kamae, Youichi; Watanabe, Masahiro; Kimoto, Masahide; Shiogama, Hideo

2014-11-01

Land-sea surface air temperature (SAT) contrast, an index of tropospheric thermodynamic structure and dynamical circulation, has shown a significant increase in recent decades over East Asia during the boreal summer. In Part I of this two-part paper, observational data and the results of transient warming experiments conducted using coupled atmosphere-ocean general circulation models (GCMs) are analyzed to examine changes in land-sea thermal contrast and the associated atmospheric circulation over East Asia from the past to the future. The interannual variability of the land-sea SAT contrast over the Far East for 1950-2012 was found to be tightly coupled with a characteristic tripolar pattern of tropospheric circulation over East Asia, which manifests as anticyclonic anomalies over the Okhotsk Sea and around the Philippines, and a cyclonic anomaly over Japan during a positive phase, and vice versa. In response to CO2 increase, the cold northeasterly winds off the east coast of northern Japan and the East Asian rainband were strengthened with the circulation pattern well projected on the observed interannual variability. These results are commonly found in GCMs regardless of future forcing scenarios, indicating the robustness of the East Asian climate response to global warming. The physical mechanisms responsible for the increase of the land-sea contrast are examined in Part II.

Circulating T-Regulatory Cells, Exercise and the Elite Adolescent Swimmer

PubMed Central

Wilson, Lori D.; Zaldivar, Frank P.; Schwindt, Christina D.; Wang-Rodriguez, Jessica; Cooper, Dan M.

2014-01-01

Brief high intensity exercise induces peripheral leukocytosis possibly leading to a higher incidence of allergic symptoms in athletes undergoing excessive training. We studied the exercise-induced alternation of circulating Tregs and FoxP3+ Tregs due to acute intense swim exercise in elite swimmers (n = 22, 12 males, age = 15.4 yrs). Twelve had prior or current rhinitis or asthma and 10 had no current or prior allergy or asthma. Circulating Tregs increased significantly (p < .001) following exercise (pre = 133 ± 11.2, post = 196 ± 17.6) as did FoxP3+ cells (pre = 44, post = 64 cells/µl). Increases in Tregs and FoxP3+ Tregs occurred to the same extent in both groups of adolescent swimmers. PMID:19827454

Changes in Large-Scale Atmospheric Circulation Associated with Increased Extreme Precipitation Events in the Northeast United States

NASA Astrophysics Data System (ADS)

Collow, A.; Bosilovich, M. G.; Koster, R. D.

2016-12-01

Over the past two decades a statistically significant increase in the frequency of summertime extreme precipitation events has been observed over the northeastern United States - the largest such increase in the US in terms of area and magnitude. In an effort to characterize synoptic scale patterns and changes to the atmospheric circulation associated with extreme precipitation events in this region, atmospheric fields from the Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) are composited on days that exceed the 90th percentile of precipitation from the CPC-Unified daily gauge-based precipitation observations. Changes over time in composites of sea level pressure, 500 hPa height, and the vertical profile of equivalent potential temperature indicate that the observed increase in extreme precipitation events is associated with extratropical cyclones, including cut off low pressure and frontal systems. Analysis of the Eady maximum growth rate, an indicator for storm tracks, shows that storms tracks in recent years have shifted southward. In addition, mean summertime transient meridional winds have decreased over time, slowing baroclinic systems and causing stationary systems to become more frequent, in agreement with previous studies examining blocking due to high pressure systems. The Atlantic Ocean provides a significant supply of moisture that converges over the region when a cyclonic circulation is situated to the south, and the statistically significant increase in Eady maximum growth rate over time there provides an increasingly improved thermodynamic environment for extreme precipitation events.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women

PubMed Central

Akopians, Alin L.; Madrigal, Vanessa K.; Ramirez, Emmanuel; Margolis, Daniel J.; Sarma, Manoj K.; Thomas, Albert M.; Grogan, Tristan R.; Haykal, Rasha; Schooler, Tery A.; Okeya, Bette L.; Abbott, David H.; Chazenbalk, Gregorio D.

2016-01-01

Context: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. Objective: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. Design: This is a prospective cohort study. Setting: The setting was an academic medical center. Patients: Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. Intervention(s): All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. Main Outcome Measure(s): Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. Results: Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. Conclusion: Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction. PMID:27571186

Circulating testosterone and inhibin levels at different ages in the male beluga (Delphinapterus leucas).

PubMed

Katsumata, Etsuko; Ueda, Yoko; Arai, Kazutoshi; Katsumata, Hiroshi; Kishimoto, Miori; Watanabe, Gen; Taya, Kazuyoshi

2012-03-01

This study is the first report on circulating testosterone and inhibin levels in a species of whales, the beluga. Circulating testosterone and immunoreactive (ir-) inhibin levels in two captive male belugas ("Nack", originally from Canada and "Duke", from the Okhotsk Sea) were measured every month for 9 years between 1995 and 2003. Assuming that clearly increased testosterone levels in the circulation indicates that the belugas had reached sexual maturity, at the ages of 10 ("Nack") and 11 years old ("Duke"). Their testosterone levels before the significant increase (pre-pubertal) were 0.42 ± 0.07 ng/ml (n=18) and 0.35 ± 0.10 ng/ml (n=18) and, those of after the increase (maturity) were 1.65 ± 0.14 ng/m l (n=74) and 2.06 ± 0.14 ng/ml (n=74). Circulating ir-inhibin levels before sexual maturity were 0.78 ± 0.04 ng/ml (n=18) and 0.64 ± 0.04 ng/ml (n=15) and, after sexual maturity were 0.52 ± 0.02 ng/ml (n=56) and 0.43 ± 0.02 ng/ml (n=67). Seasonal changes were observed in the testosterone levels after sexual maturity and the levels increased during March and April in Canadian origin "Nack", and peaked in February in Okhotsk origin "Duke". Circulating ir-inhibin level gradually decreased as they aged. A negative correlation between the circulating testosterone and ir-inhibin was observed. No seasonal changes were observed in the ir-inhibin levels after sexual maturity. These data will surely correspond to clarification of endocrinology and the successful reproduction of the beluga.

Sustained apnea induces endothelial activation.

PubMed

Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

2017-09-01

Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

Aerosol- and greenhouse gas-induced changes in summer rainfall and circulation in the Australasian region: a study using single-forcing climate simulations

NASA Astrophysics Data System (ADS)

Rotstayn, L. D.; Jeffrey, S. J.; Collier, M. A.; Dravitzki, S. M.; Hirst, A. C.; Syktus, J. I.; Wong, K. K.

2012-07-01

We use a coupled atmosphere-ocean global climate model (CSIRO-Mk3.6) to investigate the drivers of trends in summer rainfall and circulation in the vicinity of northern Australia. As part of the Coupled Model Intercomparison Project Phase 5 (CMIP5), we perform a 10-member 21st century ensemble driven by Representative Concentration Pathway 4.5 (RCP4.5). To investigate the roles of different forcing agents, we also perform multiple 10-member ensembles of historical climate change, which are analysed for the period 1951-2010. The historical runs include ensembles driven by "all forcings" (HIST), all forcings except anthropogenic aerosols (NO_AA) and forcing only from long-lived greenhouse gases (GHGAS). Anthropogenic aerosol-induced effects in a warming climate are calculated from the difference of HIST minus NO_AA. CSIRO-Mk3.6 simulates a strong summer rainfall decrease over north-western Australia (NWA) in RCP4.5, whereas simulated trends in HIST are weakly positive (but insignificant) during 1951-2010. The weak rainfall trends in HIST are due to compensating effects of different forcing agents: there is a significant decrease in GHGAS, offset by an aerosol-induced increase. Observations show a significant increase of summer rainfall over NWA during the last few decades. The large magnitude of the observed NWA rainfall trend is not captured by 440 unforced 60-yr trends calculated from a 500-yr pre-industrial control run, even though the model's decadal variability appears to be realistic. This suggests that the observed trend includes a forced component, despite the fact that the model does not simulate the magnitude of the observed rainfall increase in response to "all forcings" (HIST). We investigate the mechanism of simulated and observed NWA rainfall changes by exploring changes in circulation over the Indo-Pacific region. The key circulation feature associated with the rainfall increase in reanalyses is a lower-tropospheric cyclonic circulation trend off the coast of NWA, which enhances the monsoonal flow. The model shows an aerosol-induced cyclonic circulation trend off the coast of NWA in HIST minus NO_AA, whereas GHGAS shows an anticyclonic circulation trend. This explains why the aerosol-induced effect is an increase of rainfall over NWA, and the greenhouse gas-induced effect is of opposite sign. Possible explanations for the cyclonic (anticyclonic) circulation trend in HIST minus NO_AA (GHGAS) involve changes in the Walker circulation or the local Hadley circulation. In either case, a plausible atmospheric mechanism is that the circulation anomaly is a Rossby wave response to convective heating anomalies south of the Equator. We also discuss the possible role of air-sea interactions, e.g. an increase (decrease) of sea-surface temperatures off the coast of NWA in HIST minus NO_AA (GHGAS). Further research is needed to better understand the mechanisms and the extent to which these are model-dependent. In summary, our results suggest that anthropogenic aerosols may have "masked" greenhouse gas-induced changes in rainfall over NWA and in circulation over the wider Indo-Pacific region. Due to the opposing effects of greenhouse gases and anthropogenic aerosols, future trends may be very different from trends observed over the last few decades.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors

PubMed Central

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2 −/− Cxcr6 Gfp/+ reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow. PMID:26494947

Relationship between Circulating and Tissue microRNAs in a Murine Model of Breast Cancer

PubMed Central

Waters, Peadar S.; McDermott, Ailbhe M.; Wall, Deirdre; Heneghan, Helen M.; Miller, Nicola; Newell, John; Kerin, Michael J.; Dwyer, Roisin M.

2012-01-01

MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development. PMID:23226290

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study.

PubMed

Gao, Jinming; Xu, Xiaohua; Ying, Zhekang; Jiang, Lei; Zhong, Mianhua; Wang, Aixia; Chen, Lung-Chi; Lu, Bo; Sun, Qinghua

2017-08-01

This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation.

PubMed

Melek, Flora Eli; Baroncini, Liz Andréa Villela; Repka, João Carlos Domingus; Nascimento, Celso Soares; Précoma, Dalton Bertolim

2012-01-01

Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of C-reactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

IGF-1 REGULATES VERTEBRAL BONE AGING THROUGH SEX-SPECIFIC AND TIME-DEPENDENT MECHANISMS

PubMed Central

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L.; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-01-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, while others report that loss of IGF-1 is beneficial as it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan- early in postnatal development (crossing albumin-Cre mice with Igff/f mice), or early adulthood, and late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using microCT and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NFkB-ligand levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2 fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. PMID:26260312

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research.

Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

PubMed

Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

2018-02-15

Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

Arctic Ocean Freshwater Content and Its Decadal Memory of Sea-Level Pressure

NASA Astrophysics Data System (ADS)

Johnson, Helen L.; Cornish, Sam B.; Kostov, Yavor; Beer, Emma; Lique, Camille

2018-05-01

Arctic freshwater content (FWC) has increased significantly over the last two decades, with potential future implications for the Atlantic meridional overturning circulation downstream. We investigate the relationship between Arctic FWC and atmospheric circulation in the control run of a coupled climate model. Multiple linear lagged regression is used to extract the response of total Arctic FWC to a hypothetical step increase in the principal components of sea-level pressure. The results demonstrate that the FWC adjusts on a decadal timescale, consistent with the idea that wind-driven ocean dynamics and eddies determine the response of Arctic Ocean circulation and properties to a change in surface forcing, as suggested by idealized models and theory. Convolving the response of FWC to a change in sea-level pressure with historical sea-level pressure variations reveals that the recent observed increase in Arctic FWC is related to natural variations in sea-level pressure.

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs.

PubMed

Abu-Farha, Mohamed; Behbehani, Kazem; Elkum, Naser

2014-04-09

Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47-6.19) and (OR = 2.52, 95% CI = 1.45-4.35), (OR = 4.26, 95% CI = 2.39-7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12-0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs.

PROTEIN METABOLISM AND EXCHANGE AS INFLUENCED BY CONSTRICTION OF THE VENA CAVA

PubMed Central

McKee, Frank W.; Hyatt, Robert E.; Wilt, William G.; Tishkoff, Garson H.; Whipple, George H.

1949-01-01

Further studies of ascitic fluid production and related factors in dogs with constriction of the vena cava above the diaphragm are reported. Whole dog plasma given intravenously to such animals produces a rise in circulating plasma protein to normal levels, but increases the output of ascitic fluid with a loss of protein via the ascites equivalent to 72, 76, and 65 per cent respectively, of the injected protein. Forced ingestion of water in excess of the test animal's normal needs and desires produces no significant changes in the circulating plasma protein level or in ascitic fluid production. Amino acid growth mixtures given intravenously in distilled water cause weight loss, elevation of circulating plasma proteins, a slightly negative nitrogen balance, but no ascitic fluid production. Amino acid growth mixtures given intravenously in normal saline cause depression of the circulating plasma proteins, negative nitrogen balance, and significant ascitic fluid production. Ascitic fluid given intravenously to the test animals causes a marked depression of circulating plasma proteins, a marked increase in ascitic fluid production containing the equivalent of 116 and 98 per cent of the injected protein, and a negative nitrogen balance. Ascitic fluid given orally produces a marked depression of circulating plasma proteins, and a marked increase in ascitic fluid secretion, containing the equivalent of 66, 66, and 54 per cent respectively, of the ingested protein. Sodium chloride is a dominant factor in some of these experiments where abundant ascites production is recorded. Protein levels and intake are important, but take second place to sodium. Ascitic fluids show electrophoretic patterns which are almost identical to the plasma patterns. The A/G ratios are often equal in ascitic fluid and plasma, sometimes even lower in the ascitic fluid. This emphasizes the ease with which globulins pass cell or other membrane barriers in these experiments. PMID:18143588

Kinetics of Neutrophils in Mice Exposed to Radiation and/or Granulocyte Colony-Stimulating Factor Treatment

PubMed Central

Romero-Weaver, A. L.; Wan, X. S.; Diffenderfer, E. S.; Lin, L.; Kennedy, A. R.

2014-01-01

Astronauts have the potential to develop the hematopoietic syndrome as a result of exposure to radiation from a solar particle event (SPE) during exploration class missions. This syndrome is characterized by a reduction in the number of circulating blood cells (cytopenias). In the present study the effects of SPE-like proton and γ radiation on the kinetics of circulating neutrophils were evaluated during a one-month time period using mice as a model system. The results revealed that exposure to a 2 Gy dose of either SPE-like proton or γ radiation significantly decreased the number of circulating neutrophils, with two nadirs observed on day 4 and day 16 postirradiation. Low circulating neutrophil count (neutropenia) is particularly important because it can increase the risk of astronauts developing infections, which can compromise the success of the mission. Thus, two granulocyte colony-stimulating factors (G-CSFs), filgrastim and pegfilgrastim were evaluated as countermeasures for this endpoint. Both forms of G-CSF significantly increased neutrophil counts in irradiated mice, however, the effect of pegfilgrastim was more potent and lasted longer than filgrastim. Using the expression of CD11b, CD18 and the production of reactive oxygen species (ROS) as markers of neutrophil activation, it was determined that the neutrophils in the irradiated mice treated with pegfilgrastim were physiologically active. Thus, these results suggest that pegfilgrastim could be a potential countermeasure for the reduced number of circulating neutrophils in irradiated animals. PMID:23829559

Time courses and value of circulating microparticles in patients with operable stage non-small cell lung cancer undergoing surgical intervention.

PubMed

Tseng, Chia-Cheng; Wang, Chin-Chou; Hsiao, Chang-Chun; Lu, Hung-I; Leu, Steve; Chang, Huang-Chih; Huang, Kuo-Tung; Fang, Wen-Feng; Chen, Yu-Mu; Liu, Shih-Feng; Yang, Cheng-Ta; Lin, Meng-Chih; Yip, Hon-Kan

2016-09-01

Microparticles (MPs) are substantially increased in patients with operable stage non-small cell lung cancer (NSCLC) prior to lung resection surgery. This study tested the hypothesis that there is a decrease in MPs after surgical intervention. Between March 2012 and January 2015, 33 patients who had operable stage NSCLC were consecutively and prospectively enrolled into the study. Additionally, 31 healthy subjects who were consecutively enrolled in the study period served as age- and gender-matched controls. Circulating MPs (EDAc-MPs, EDAp-MPs, PDAc-MPs, PDAp-MPs) were measured by flow cytometry once in control subjects and twice (i.e., prior to and three months later after surgical intervention) in NSCLC patients. Compared with control subjects, these four types of circulating MPs were significantly higher in NSCLC patients prior to operation (all P < 0.005), but did not differ among the controls and NSCLC patients at 3 months after surgery (all P > 0.2). Additionally, a receiver operating characteristic curve (ROC) showed that these four types of MPs were significantly valuable predictors for detecting early stage NSCLC (all P < 0.004). Circulating MPs which were remarkably increased in the operable stage of NSCLC prior to surgery were substantially decreased 3 months later after surgery. These findings show that circulating MPs might be an accessory biomarker for monitoring those of NSCLC after receiving lung resection surgery.

Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

PubMed

Jalkanen, Juho; Hautero, Olli; Maksimow, Mikael; Jalkanen, Sirpa; Hakovirta, Harri

2018-04-21

The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Circulating Endothelial Progenitor Cells Present an Inflammatory Phenotype and Function in Patients With Alcoholic Liver Cirrhosis

PubMed Central

Kaur, Savneet; Sehgal, Rashi; Shastry, Saggere M.; McCaughan, Geoffrey; McGuire, Helen M.; Fazekas St de Groth, Barbara; Sarin, Shiv; Trehanpati, Nirupma; Seth, Devanshi

2018-01-01

Background and Aim: Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Methods: Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients (n = 7) and healthy controls (HC, n = 7). A comprehensive characterization of circulating EPCs using more than 30 phenotype markers was performed by mass cytometer time of flight (CyTOF) in an independent cohort of age and gender matched ALC patients (n = 4) and controls (n = 5). Ex vivo cultures of circulating EPCs from ALC patients (n = 20) and controls (n = 18) were also tested for their functions, including colony formation, LDL uptake, lectin binding and cytokine secretion (ELISA). Results: Three distinct populations of circulating EPCs (CD34+CD133+CD31+) were identified, classified on their CD45 expression (negative: CD45−; intermediate: CD45int; high: CD45hi). CD45int and CD45hi EPCs significantly increased in ALC patients compared to controls (p-val = 0.006). CyTOF data showed that CD45hi EPCs were distinct from CD45− and CD45int EPCs, with higher expression of T cell and myeloid markers, including CD3, CD4, HLA-DR, and chemokine receptors, CCR2, CCR5, CCR7, and CX3CR1. Similar to circulating EPCs, percentage of CD45hiCD34+CD31+ EPCs in ex-vivo cultures from patients, were significantly higher compared to controls (p < 0.05). Cultured EPCs from patients also showed increased LDL uptake, lectin binding and release of TNF-alpha, RANTES, FGF-2, and VEGF. Conclusions: We report the first extensive characterization of circulating human EPCs with distinct EPC subtypes. Increase in CD45hi EPC subtype in ALC patients with enhanced functions, inflammatory cytokines and angiogenic mediators in patients suggests an inflammatory role for these cells in ALC. PMID:29872403

Treatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations

PubMed Central

Imel, Erik A.; DiMeglio, Linda A.; Hui, Siu L.; Carpenter, Thomas O.; Econs, Michael J.

2010-01-01

Context: X-Linked hypophosphatemia (XLH) is characterized by renal phosphate wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D concentrations causing rickets and osteomalacia. Mutations in PHEX result in increased fibroblast growth factor 23 (FGF23) expression, elevating circulating FGF23 concentrations. Treating XLH with phosphate and calcitriol may further increase FGF23 concentrations, based on in vitro and in vivo models. Objective: The aim of the study was to investigate whether current standard XLH therapies increase circulating FGF23 concentrations. Design and Setting: We conducted a prospective observational study of XLH subjects during routine clinical management at two tertiary referral centers. Patients: The study included 10 XLH patients (seven children, three adults; age, 2–30 yr) initiating therapy and five XLH patients (age, 18–41 yr) electing not to undergo therapy. Intervention(s): Oral calcitriol and phosphate were administered. Main Outcome Measures: We measured circulating intact FGF23 concentrations. Results: Baseline circulating FGF23 concentrations were elevated in 14 of 15 subjects, increasing after treatment in most subjects. Follow-up was 14.4 ± 11.7 months (treatment cohort) and 25 ± 32 months (nontreatment cohort). FGF23 concentrations increased 132.7 ± 202.4% from pretreatment to peak during therapy but did not change significantly over time in the nontreatment cohort. FGF23 concentrations were related to phosphate doses (P = 0.04) and nonsignificantly to calcitriol doses (P = 0.06). Conclusions: Treating XLH with phosphate and calcitriol was associated with concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. Because it is unknown whether the degree of FGF23 elevation correlates with disease severity in XLH, further study is needed to determine whether adjusting therapy to minimize effects on FGF23 concentration is warranted. PMID:20157195

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance.

PubMed

Moreno-Navarrete, J M; Manco, M; Ibáñez, J; García-Fuentes, E; Ortega, F; Gorostiaga, E; Vendrell, J; Izquierdo, M; Martínez, C; Nolfe, G; Ricart, W; Mingrone, G; Tinahones, F; Fernández-Real, J M

2010-02-01

Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

PubMed

Adrian, T E; Sagor, G R; Savage, A P; Bacarese-Hamilton, A J; Hall, G M; Bloom, S R

1986-10-01

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.

Lamin A/C deficiency reduces circulating tumor cell resistance to fluid shear stress

PubMed Central

Denais, Celine; Chan, Maxine F.; Wang, Zhexiao; Lammerding, Jan

2015-01-01

Metastasis contributes to over 90% of cancer-related deaths and is initiated when cancer cells detach from the primary tumor, invade the basement membrane, and enter the circulation as circulating tumor cells (CTCs). While metastasis is viewed as an inefficient process with most CTCs dying within the bloodstream, it is evident that some CTCs are capable of resisting hemodynamic shear forces to form secondary tumors in distant tissues. We hypothesized that nuclear lamins A and C (A/C) act as key structural components within CTCs necessary to resist destruction from elevated shear forces of the bloodstream. Herein, we show that, compared with nonmalignant epithelial cells, tumor cells are resistant to elevated fluid shear forces in vitro that mimic those within the bloodstream, as evidenced by significant decreases in cellular apoptosis and necrosis. Knockdown of lamin A/C significantly reduced tumor cell resistance to fluid shear stress, with significantly increased cell death compared with parental tumor cell and nontargeting controls. Interestingly, lamin A/C knockdown increased shear stress-induced tumor cell apoptosis, but did not significantly affect cellular necrosis. These data demonstrate that lamin A/C is an important structural component that enables tumor cell resistance to fluid shear stress-mediated death in the bloodstream, and may thus facilitate survival and hematogenous metastasis of CTCs. PMID:26447202

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

PubMed Central

Maharaj, Chrisen H; O'Toole, Daniel; Lynch, Tadhg; Carney, John; Jarman, James; Higgins, Brendan D; Morrison, John J; Laffey, John G

2009-01-01

Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO. PMID:19389232

Effect of hCG administration during corpus luteum establishment on subsequent corpus luteum development and circulating progesterone concentrations in beef heifers.

PubMed

Maillo, V; Duffy, P; O'Hara, L; de Frutos, C; Kelly, A K; Lonergan, P; Rizos, D

2014-03-01

This study examined the effect of a single administration of human chorionic gonadotrophin (hCG) on Day 1 to 4 after oestrus on corpus luteum (CL) development and circulating progesterone (P4). Oestrus-synchronized heifers (n=43) were administered a single intramuscular injection of saline on Day 1 (control) or 3000IU hCG on Day 1, 2, 3 or 4 after oestrus. Administration of hCG on Day 1 had no effect on CL area, on Day 2 increased CL area from Day 6 to 12 (P<0.05), on Day 3 increased CL area from Day 9 to 11, while on Day 4 increased CL size on Days 9 and 10 (P<0.05). Administration of hCG on Day 4 induced the formation of an accessory CL in 89% of heifers, resulting in a significant increase in total luteal tissue area on the ovaries compared with all other groups. Consistent with the effects on the CL, hCG on Day 1 did not affect P4 concentrations, on Day 2 significantly increased P4 compared with the control from Day 6 to 11 (P<0.05), on Day 3 resulted in a non-significant increase in P4 while hCG on Day 4 increased P4 from Day 8 to 13 compared with the control (P<0.05). In conclusion, administration of hCG as early as Day 2 after oestrus results in increased P4 in circulation from Day 6, which should have beneficial downstream effects in terms of uterine receptivity and conceptus elongation.

Increased Levels of Circulating Anti-ANXA1 IgG Antibody in Patients with Non-Small Cell Lung Cancer.

PubMed

Liang, Tingting; Han, Zhifeng; Zhao, Huan; Zhang, Xuan; Wang, Yao

2018-06-01

Our previous studies revealed that concentrations of circulating antibodies to annexin A1 (ANXA1) were increased in non-small lung cancer (NSCLC). This study was thus designed to replicate this initial finding with an independent sample set. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma antiANXA1 IgG levels in 220 patients with NSCLC and 200 control subjects. Mann-Whitney U test showed that patients with NSCLC had significantly higher anti-ANXA1 IgG levels than control subjects (Z = -4.02, p < 0.001); male patients appeared to mainly contribute to the increased antibody level (Z = -3.09, p = 0.002). Receiver operating characteristic (ROC) curve analysis showed an overall area under the ROC curve (AUC) of 0.61 (95% CI: 0.56 - 0.67), with sensitivity of 8% against a specificity of 95.0%. Spearman's correlation analysis failed to show a significant correlation between the anti-ANXA1 IgG levels and the expression of three tumor-associated antigens including p53 (r = 0.156, p = 0.027), Ki67 (r = -0.048, p = 0.489), and EGFR (r = 0.02, p = 0.782). Increased levels of circulating anti-ANXA1 IgG antibody may have a prognostic value for NSCLC.

Circulating CD34-positive cells, glomerular filtration rate and triglycerides in relation to hypertension.

PubMed

Shimizu, Yuji; Sato, Shimpei; Koyamatsu, Jun; Yamanashi, Hirotomo; Nagayoshi, Mako; Kadota, Koichiro; Maeda, Takahiro

2015-11-01

Serum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status. We conducted a cross-sectional study of 274 elderly Japanese men aged ≥ 60 years (range 60-79 years) undergoing general health checkups. Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (β = -2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34-positive cells (β = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (β = -2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (β = -0.004, p = 0.974). Since endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non-hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[In vivo measurement of ocular circulation with the laser speckle method--development of apparatus and application in ophthalmological research].

PubMed

Araie, M

1999-12-01

We have developed an apparatus utilizing laser speckle phenomenon which can measure the peripheral circulation in the iris, choroid, retina and optic nerve head (ONH) and blood velocity through retinal vessels in the living eye non-invasively and quantitatively. A blue-component argon laser (wavelength 488 nm) was used for measurement of peripheral circulation in the retina and a diode laser (wavelength 808 nm) for measurements of peripheral circulation in the iris, posterior choroid and ONH, and measurement of centerline blood velocity through retinal vessels. A fundus camera (TRC-WT 3, Topcon) was equipped with a laser source and an image sensor where the speckle pattern from the fundus appears, and the data were analyzed with a personal computer to give a normalized blur (NB) value or a square blur rate (SBR) value, both quantitative indices of blood velocity. The NB value, whose computation requires much less time, was adopted to evaluate peripheral circulation because of non-linear correlation between the NB and actual blood velocity in the range above 20 mm/sec. The SBR value, whose computation requires a longer time, was adopted for measurement of blood velocity through retinal vessels. Measurement field in the living eye was 1.06 x 1.06 mm at its maximum and reproducibility index of the in vivo measurement in the rabbit iris, choroid, retina, and ONH was approximately 10%. When blood flow was changed by intraocular pressure (IOP) change in rabbit eyes, NB values obtained from the iris, choroid, and retina showed a significant correlation with the blood flow simultaneously determined with the colored microsphere technique in the same eye, and the NB obtained from the ONH also correlated with the blood flow determined with the H2 gas clearance method. Stepwise reduction in the ocular perfusion pressure (OPP) by stepwise increment of IOP resulted in proportional reduction in the iris- and choroid-NB. On the other hand, the retina- or ONH-NB remained almost unaltered at OPP levels above 50 mmHg, and decreased along with OPP at levels less than 50 mmHg. By monitoring NB values for 2 hours, presence or absence of autoregulatory mechanism against OPP change in the choroidal and ONH circulation was studied in rabbits. Throughout the experimental period of 2 hours, the choroidal NB was changed along with the OPP change, suggesting absence of blood flow autoregulation in this tissue. In the ONH, however, the NB returned to the baseline after its transient increase or decrease when the OPP was continuously increased or decreased, showing the presence of an autoregulatory mechanism in the ONH circulation. However, the time course of the NB resumption depended on the extent of OPP change. These results indicated that the laser speckle method can be useful in investigating the autoregulatory mechanism and processes of peripheral circulation in ocular tissues. Unilateral instillation of drugs with vasodilative activity (ifenprodil, betaxolol or nipradilol) in rabbit eyes significantly increased ONH and/or choroidal circulation. The extent in change in the ONH and/or choroidal circulation correlated with the number of doses, but not with the extent of IOP reduction, which suggested that the observed effects were attributable to the drug which penetrated locally. Intravenous administration of a Ca(2+)-antagonist (nicardipine, nilvadipine or pranidipine) significantly increased choroidal or retinal circulation in rabbits. The ONH circulation, however, was not affected by nicardipine, but affected by nilvadipine or pranidipine. Given the same effect on the ONH circulation, systemic hypotensive effect was stronger in pranidipine than in nilvadipine, which suggested that nilvadipine can be used in patients with ocular circulatory insufficiency. A modification of the laser speckle apparatus used for animal experiments was devised so that the NB or SBR values could be measured in human eyes every 0.12 sec on a real-time basis. (ABSTRACT TRUN

Preferential Elimination of Older Erythrocytes in Circulation and Depressed Bone Marrow Erythropoietic Activity Contribute to Cadmium Induced Anemia in Mice

PubMed Central

Chatterjee, Sreoshi; Saxena, Rajiv K.

2015-01-01

Feeding cadmium chloride (50 or 1000 ppm CdCl2 in drinking water, ad libitum) to C57BL/6 mice resulted in a significant and sustained fall in blood erythrocyte count and hemoglobin levels that started 4 and 3 weeks after the start of 50 and 1000 ppm cadmium doses respectively. A transient yet significant reticulocytosis occurred during the first 4 weeks of cadmium treatment. Using the recently developed double in vivo biotinylation (DIB) technique, turnover of erythrocyte cohorts of different age groups was simultaneously monitored in control and cadmium treated mice. A significant accumulation of younger erythrocytes and a concomitant decline in the relative proportions of older erythrocytes in circulation was observed in both 50 and 1000 ppm cadmium groups indicating that older erythrocytes were preferentially eliminated in cadmium induced anemia. A significant increase in the erythropoietin levels in plasma was seen in mice exposed to 1000 ppm cadmium. Levels of inflammatory cytokines (IL1A, IL6, TNFα, IFNγ) were however not significantly altered in cadmium treated mice. A significant increase in cellular levels of reactive oxygen species (ROS) was observed in older erythrocytes in circulation but not in younger erythrocytes. Erythropoietic activity in the bone marrows and spleens of cadmium treated mice was examined by monitoring the relative proportion of cells belonging to the erythroid line of differentiation in these organs. Erythroid cells in bone marrow declined markedly (about 30%) in mice in the 1000 ppm cadmium group but the decline was not significant in the 50 ppm cadmium group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Decline of erythroid cells was essentially confined to pro-erythroblast and erythroblast-A, along with a concurrent increase in the splenic erythroid population indicating a stress response. In short cadmium exposure causes preferential clearance of older erythrocytes from circulation along with a depressed erythropoietic activity at higher doses. PMID:26161863

Increase of endothelial progenitor cells in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

PubMed

Medinger, Michael; Heim, Dominik; Gerull, Sabine; Halter, Jörg; Krenger, Werner; Buser, Andreas; Lengerke, Claudia; Bucher, Christoph; Passweg, Jakob

2016-08-01

Circulating endothelial progenitor cells (EPCs; CD31+ CD34(bright)CD133+ CD45(dim) cells) are novel markers of endothelial dysfunction and related to inflammatory processes such as acute graft-versus-host disease (aGvHD). 47 patients with acute myeloid leukaemia (AML) who were in complete remission as they underwent allogeneic hematopoietic stem cell transplantation with myeloablative conditioning with PBSC as stem cell source were enrolled in the study. Blood samples for the quantitative analysis of circulating EPC levels were drawn at different time points in patients with and without aGvHD. CD34+ VEGFR2/KDR+ CD133+ triple-positive cells identified among CD34+ cells by FACS. EPC were quantified and data are presented as cells/ml whole blood. Circulating EPC levels were not significantly different in patients with and without aGvHD prior to conditioning (baseline) and at the time of engraftment. However, at diagnosis of aGvHD≥grade 2, EPC levels increased whereas in patients without aGvHD the EPC levels remained significantly lower (3021±278 versus 2322±195 cells/ml; p<0.001). Patients with steroid-refractory aGvHD had high levels of EPC throughout. EPC levels fell in responding patients. Our results demonstrate that the number of circulating EPCs is increased in patients with aGvHD compared to patients without aGvHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury.

PubMed

Wetmore, Barbara A; Brees, Dominique J; Singh, Reetu; Watkins, Paul B; Andersen, Melvin E; Loy, James; Thomas, Russell S

2010-06-01

Serum aminotransferases have been the clinical standard for evaluating liver injury for the past 50-60 years. These tissue enzymes lack specificity, also tracking injury to other tissues. New technologies assessing tissue-specific messenger RNA (mRNA) release into blood should provide greater specificity and permit indirect assessment of gene expression status of injured tissue. To evaluate the potential of circulating mRNAs as biomarkers of liver injury, rats were treated either with hepatotoxic doses of D-(+)-galactosamine (DGAL) or acetaminophen (APAP) or a myotoxic dose of bupivacaine HCl (BPVC). Plasma, serum, and liver samples were obtained from each rat. Serum alanine aminotransferase and aspartate aminotransferase were increased by all three compounds, whereas circulating liver-specific mRNAs were only increased by the hepatotoxicants. With APAP, liver-specific mRNAs were significantly increased in plasma at doses that had no effect on serum aminotransferases or liver histopathology. Characterization of the circulating mRNAs by sucrose density gradient centrifugation revealed that the liver-specific mRNAs were associated with both necrotic debris and microvesicles. DGAL treatment also induced a shift in the size of plasma microvesicles, consistent with active release of microvesicles following liver injury. Finally, gene expression microarray analysis of the plasma following DGAL and APAP treatment revealed chemical-specific profiles. The comparative analysis of circulating liver mRNAs with traditional serum transaminases and histopathology indicated that the circulating liver mRNAs were more specific and more sensitive biomarkers of liver injury. Further, the possibility of identifying chemical-specific transcriptional profiles from circulating mRNAs could open a range of possibilities for identifying the etiology of drug/chemical-induced liver injury.

Rotor Wake Development During the First Revolution

NASA Technical Reports Server (NTRS)

McAlister, Kenneth W.

2003-01-01

The wake behind a two-bladed model rotor in light climb was measured using particle image velocimetry, with particular emphasis on the development of the trailing vortex during the first revolution of the rotor. The distribution of vorticity was distinguished from the slightly elliptical swirl pattern. Peculiar dynamics within the void region may explain why the peak vorticity appeared to shift away from the center as the vortex aged, suggesting the onset of instability. The swirl and axial velocities (which reached 44 and 12 percent of the rotor-tip speed, respectively) were found to be asymmetric relative to the vortex center. In particular, the axial flow was composed of two concentrated zones moving in opposite directions. The radial distribution of the circulation rapidly increased in magnitude until reaching a point just beyond the core radius, after which the rate of growth decreased significantly. The core-radius circulation increased slightly with wake age, but the large-radius circulation appeared to remain relatively constant. The radial distributions of swirl velocity and vorticity exhibit self-similar behaviors, especially within the core. The diameter of the vortex core was initially about 10 percent of the rotor-blade chord, but more than doubled its size after one revolution of the rotor. According to vortex models that approximate the measured data, the core-radius circulation was about 79 percent of the large-radius circulation, and the large-radius circulation was about 67 percent of the maximum bound circulation on the rotor blade. On average, about 53 percent of the maximum bound circulation resides within the vortex core during the first revolution of the rotor.

Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation.

PubMed

Dedeoglu, B; de Weerd, A E; Huang, L; Langerak, A W; Dor, F J; Klepper, M; Verschoor, W; Reijerkerk, D; Baan, C C; Litjens, N H R; Betjes, M G H

2017-05-01

Ageing is associated with changes in the peripheral T cell immune system, which can be influenced significantly by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T cell populations correlate with T cell composition of the lymph node (LN) is unclear, but is crucial for a comprehensive understanding of the T cell system. T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analysed for frequency of recent thymic emigrants using CD31 expression and T cell receptor excision circle content, relative telomere length and expression of differentiation markers. Compared with PB, LN contained relatively more CD4 + than CD8 + T cells (P < 0·001). The percentage of naive and central memory CD4 + and CD8 + T cells and thymic output parameters showed a strong linear correlation between PB and LN. Highly differentiated CD28 null T cells, being CD27 - , CD57 + or programmed death 1 (PD-1 + ), were found almost exclusively in the circulation but not in LN. An age-related decline in naive CD4 + and CD8 + T cell frequency was observed (P = 0·035 and P = 0·002, respectively) within LN, concomitant with an increase in central memory CD8 + T cells (P = 0·033). Latent CMV infection increased dramatically the frequency of circulating terminally differentiated T cells, but did not alter T cell composition and ageing parameters of LN significantly. Overall T cell composition and measures of thymic function in PB and LN are correlated strongly. However, highly differentiated CD28 null T cells, which may comprise a large part of circulating T cells in CMV-seropositive individuals, are found almost exclusively within the circulation. © 2017 British Society for Immunology.

High proportions of regulatory B and T cells are associated with decreased cellular responses to pH1N1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088)

PubMed Central

Weinberg, Adriana; Muresan, Petronella; Fenton, Terence; Richardson, Kelly; Dominguez, Teresa; Bloom, Anthony; Petzold, Elizabeth; Anthony, Patricia; Cunningham, Coleen K.; Spector, Stephen A.; Nachman, Sharon; Siberry, George K.; Handelsman, Edward; Flynn, Patricia M.

2013-01-01

HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism. PMID:23370281

Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

PubMed Central

TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

2013-01-01

Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0–27.7% vs. median, 17.6%; range, 2.8–49.6%), suggesting an increased CD34+ cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution. PMID:23756559

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Low-dose endotoxemia and human neuropsychological functions.

PubMed

Krabbe, Karen Suárez; Reichenberg, Abraham; Yirmiya, Raz; Smed, Annelise; Pedersen, Bente Klarlund; Bruunsgaard, Helle

2005-09-01

Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure.

PubMed

Kocić, Gordana; Radenkovic, Sonja; Cvetkovic, Tatjana; Cencic, Avrelija; Carluccio, Francesco; Musovic, Dijana; Nikolić, Goran; Jevtović-Stoimenov, Tatjana; Sokolović, Dusan; Milojkovic, Boban; Basic, Jelena; Veljkovic, Andrej; Stojanović, Svetlana

2010-05-01

Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV-V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-kappaB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.

Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

PubMed

Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

2016-01-01

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

Increased circulating procoagulant and anticoagulant factors as TF and TFPI according to severity or infecting serotypes in human dengue infection.

PubMed

Leal de Azeredo, Elzinandes; Solórzano, Victor Edgar Fiestas; de Oliveira, Débora Batista; Marinho, Cintia Ferreira; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de-Oliveira-Pinto, Luzia Maria

2017-01-01

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

PubMed

Moreau, Joséphine; Pelletier, Fabien; Biichle, Sabeha; Mourey, Guillaume; Puyraveau, Marc; Badet, Nicolas; Caubet, Matthieu; Laresche, Claire; Garnache-Ottou, Francine; Saas, Philippe; Seilles, Estelle; Aubin, François

2017-10-01

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL -1 ) than in patients with stage III (2041 μL -1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL -1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Idealised modelling of ocean circulation driven by conductive and hydrothermal fluxes at the seabed

NASA Astrophysics Data System (ADS)

Barnes, Jowan M.; Morales Maqueda, Miguel A.; Polton, Jeff A.; Megann, Alex P.

2018-02-01

Geothermal heating is increasingly recognised as an important factor affecting ocean circulation, with modelling studies suggesting that this heat source could lead to first-order changes in the formation rate of Antarctic Bottom Water, as well as a significant warming effect in the abyssal ocean. Where it has been represented in numerical models, however, the geothermal heat flux into the ocean is generally treated as an entirely conductive flux, despite an estimated one third of the global geothermal flux being introduced to the ocean via hydrothermal sources. A modelling study is presented which investigates the sensitivity of the geothermally forced circulation to the way heat is supplied to the abyssal ocean. An analytical two-dimensional model of the circulation is described, which demonstrates the effects of a volume flux through the ocean bed. A simulation using the NEMO numerical general circulation model in an idealised domain is then used to partition a heat flux between conductive and hydrothermal sources and explicitly test the sensitivity of the circulation to the formulation of the abyssal heat flux. Our simulations suggest that representing the hydrothermal flux as a mass exchange indeed changes the heat distribution in the abyssal ocean, increasing the advective heat transport from the abyss by up to 35% compared to conductive heat sources. Consequently, we suggest that the inclusion of hydrothermal fluxes can be an important addition to course-resolution ocean models.

Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

PubMed

Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

2012-01-01

Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a combination of other metals present in welding fume.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery.

PubMed

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M J; de Geus, Hilde H R; Scholten, Evert W; de Mol, Bas A J M; Ince, Can

2012-09-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm(2) (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm(2) before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system.

β-Hydroxy-β-methylbutyrate (HMB)-free acid attenuates circulating TNF-α and TNFR1 expression postresistance exercise.

PubMed

Townsend, Jeremy R; Fragala, Maren S; Jajtner, Adam R; Gonzalez, Adam M; Wells, Adam J; Mangine, Gerald T; Robinson, Edward H; McCormack, William P; Beyer, Kyle S; Pruna, Gabriel J; Boone, Carleigh H; Scanlon, Tyler M; Bohner, Jonathan D; Stout, Jeffrey R; Hoffman, Jay R

2013-10-15

The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyrate-free acid (HMB-FA) and cold-water immersion (CWI) on circulating concentrations of TNF-α and monocyte TNF-α receptor 1 (TNFR1) expression. Forty resistance-trained men (22.3 ± 2.4 yr) were randomized into four groups [placebo (PL), HMB-FA, CWI, and HMB-FA-CWI] and performed an acute, intense exercise protocol (four sets of up to 10 repetitions of the squat, dead lift, and split squat). Participants also performed four sets of up to 10 repetitions of the squat at 24 and 48 h following the initial exercise bout. Blood was sampled before exercise (PRE), immediately postexercise (IP), and 30 min, 24 h, and 48 h postexercise (30P, 24P, and 48P, respectively). Circulating TNF-α was assayed, and TNFR1 expression on CD14+ monocytes was measured by flow cytometry. The exercise protocol significantly elevated TNF-α in only PL (P = 0.006) and CWI (P = 0.045) IP. Mean percent changes show that TNF-α significantly increased from PRE to IP for only PL and CWI groups (P < 0.05), whereas the percent change of TNF-α for HMB-FA and HMB-FA-CWI was not significant. TNFR1 expression was elevated in PL (P = 0.023) and CWI (P = 0.02) at 30P compared with PRE, whereas both HMB-FA-treated groups did not increase significantly. In conclusion, HMB-FA attenuated circulating TNF-α IP and TNFR1 expression during recovery compared with PL and CWI. HMB-FA supplementation may attenuate the initial immune response to intense exercise, which may reduce recovery time following intense exercise.

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs

PubMed Central

2014-01-01

Background Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. Methods We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Results Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47 – 6.19) and (OR = 2.52, 95% CI = 1.45 – 4.35), (OR = 4.26, 95% CI = 2.39 – 7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12 – 0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Conclusion Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs. PMID:24716628

Influence of voluntary control of masticatory side and rhythm on cerebral hemodynamics.

PubMed

Hasegawa, Yoko; Ono, Takahiro; Sakagami, Joe; Hori, Kazuhiro; Maeda, Yoshinobu; Hamasaki, Toshimitsu; Nokubi, Takashi

2011-02-01

The aim of this study was to investigate the influence on cerebral hemodynamics of voluntary control of masticatory side and rhythm during gum chewing. Blood flow velocity in the middle cerebral artery was measured using transcranial Doppler ultrasonography to evaluate cerebral circulation in healthy volunteers. Heart rate and masseter muscle activity were recorded simultaneously. Volunteers performed three tasks: (1) free gum chewing, (2) gum chewing in which mastication was limited to the right side, and (3) gum chewing in which mastication was limited to the right side and rhythm was set at 1.0 Hz. Changes in cerebral circulation during pre-task, on-task, and post-task periods were analyzed using random effects model, and differences in cerebral circulation and muscle activity between tasks were analyzed using the Friedman test. In all tasks, on-task cerebral circulation was greater than pre-task. Muscle activity and masticatory rhythm varied between tasks, whereas the rate of increase in cerebral circulation did not differ significantly among tasks. These results suggest that cerebral circulation is activated during gum chewing, irrespective of voluntary control of masticatory side and rhythm.

Robust impact of coupled stratospheric ozone chemistry on the response of the Austral circulation to increased greenhouse gases

NASA Astrophysics Data System (ADS)

Chiodo, G.; Polvani, L. M.

2016-12-01

Due to computational constraints, interactive stratospheric chemistry is commonly neglected in most GCMs participating in inter-comparison projects. The impact of this simplification on the modeled response to external forcings remains largely unexplored. In this work, we examine the impact of the stratospheric chemistry coupling on the SH circulation response to an abrupt quadrupling of CO2. We accomplish this with a version of the Whole Atmosphere Community Climate (WACCM) model, which allows coupling and de-coupling stratospheric chemistry, without altering any other physical parameterization. We find that the chemistry coupling in WACCM significantly reduces (by about 20%) the response of both eddy-driven mid-latitude jet and the Hadley Cell strength, without altering the surface temperature response. This behavior is linked to the representation of stratospheric ozone, and its effects on the meridional temperature gradient at the extratropical tropopause. Our results imply that neglecting stratospheric ozone chemistry results in a potential overestimation of the circulation response to GHGs. Hence, stratospheric ozone chemistry produces a substantial negative feedback on the response of the atmospheric circulation to increased greenhouse gases.

Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification.

PubMed

Fang, Shimeng; Tian, Hongzhu; Li, Xiancheng; Jin, Dong; Li, Xiaojie; Kong, Jing; Yang, Chun; Yang, Xuesong; Lu, Yao; Luo, Yong; Lin, Bingcheng; Niu, Weidong; Liu, Tingjiao

2017-01-01

Increasing attention has been attracted by exosomes in blood-based diagnosis because cancer cells release more exosomes in serum than normal cells and these exosomes overexpress a certain number of cancer-related biomarkers. However, capture and biomarker analysis of exosomes for clinical application are technically challenging. In this study, we developed a microfluidic chip for immunocapture and quantification of circulating exosomes from small sample volume and applied this device in clinical study. Circulating EpCAM-positive exosomes were measured in 6 cases breast cancer patients and 3 healthy controls to assist diagnosis. A significant increase in the EpCAM-positive exosome level in these patients was detected, compared to healthy controls. Furthermore, we quantified circulating HER2-positive exosomes in 19 cases of breast cancer patients for molecular classification. We demonstrated that the exosomal HER2 expression levels were almost consistent with that in tumor tissues assessed by immunohistochemical staining. The microfluidic chip might provide a new platform to assist breast cancer diagnosis and molecular classification.

Experimental and analytical study of stability characteristics of natural circulation boiling water reactors during startup transient

NASA Astrophysics Data System (ADS)

Woo, Kyoungsuk

Two-phase natural circulation loops are unstable at low pressure operating conditions. New reactor design relying on natural circulation for both normal and abnormal core cooling is susceptible to different types of flow instabilities. In contrast to forced circulation boiling water reactor (BWR), natural circulation BWR is started up without recirculation pumps. The tall chimney placed on the top of the core makes the system susceptible to flashing during low pressure start-up. In addition, the considerable saturation temperature variation may induce complicated dynamic behavior driven by thermal non-equilibrium between the liquid and steam. The thermal-hydraulic problems in two-phase natural circulation systems at low pressure and low power conditions are investigated through experimental methods. Fuel heat conduction, neutron kinetics, flow kinematics, energetics and dynamics that govern the flow behavior at low pressure, are formulated. A dimensionless analysis is introduced to obtain governing dimensionless groups which are groundwork of the system scaling. Based on the robust scaling method and start-up procedures of a typical natural circulation BWR, the simulation strategies for the transient with and without void reactivity feedback is developed. Three different heat-up rates are applied to the transient simulations to study characteristics of the stability during the start-up. Reducing heat-up rate leads to increase in the period of flashing-induced density wave oscillation and decrease in the system pressurization rate. However, reducing the heat-up rate is unable to completely prevent flashing-induced oscillations. Five characteristic regions of stability are discovered at low pressure conditions. They are stable single-phase, flashing near the separator, intermittent oscillation, sinusoidal oscillation and low subcooling stable regions. Stability maps were acquired for system pressures ranging 100 kPa to 400 kPa. According to experimental investigation, the flow becomes stable below a certain heat flux regardless of the inlet subcooling at the core and system pressure. At higher heat flux, unstable phenomena were indentified within a certain range of inlet subcooling. The unstable region diminishes as the system pressure increases. In natural circulation BWRs, the significant gravitational pressure drop over the tall chimney section induces a Type-I instability. The Type-I instability becomes especially important during low power and pressure conditions during reactor start-up. Under these circumstances the effect of pressure variations on the saturation enthalpy becomes significant. An experimental study shows that the flashing phenomenon in the adiabatic chimney section is dominant during the start-up of a natural circulation BWR. Since flashing occurs outside the core, nuclear feedback effects on the stability are small. Furthermore, the thermal-hydraulic oscillation period is much longer than power fluctuation period caused by void reactivity feedback. In the natural circulation system increasing the inlet restriction reduces the natural circulation flow rate, shifting the unstable region to higher inlet subcooling.

Microplasmin-Induced Posterior Vitreous Detachment Affects Vitreous Oxygen Levels

PubMed Central

Quiram, Polly A.; Leverenz, Victor R.; Baker, Robert M.; Dang, Loan; Giblin, Frauk J.; Trese, Michael T.

2009-01-01

Purpose To determine if enzymatic induction of a posterior vitreous detachment (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous cavity in animals with vascularized and avascular retinal circulations. Methods Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs (avascular retinal circulation), brown Norway rats (vascularized retinal circulation without fovea), or cats (vascularized retinal circulation with fovea) with the contralateral eye used as a control. One to 2 weeks post injection, vitreal oxygen concentration was measured using a highly sensitive, platinum-based fluorophore O2 sensor. In addition, control and microplasmin-injected rats, guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were measured over time. Scanning electron microscopy (SEM) was used to evaluate the vitreoretinal interface for the presence of a PVD. Results In animals with a vascularized retinal circulation (brown Norway rats and cats), intravitreal injection of microplasmin with induction of a PVD significantly increased baseline O2 concentration in the vitreous cavity compared to hyaluronidase injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P < 0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001, respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous liquefaction without induction of a PVD) did not significantly increase vitreal O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen levels compared to hyaluronidase injected animals and controls, indicating that the presence of a PVD allows rapid O2 exchange within the vitreous cavity. Similarly, once O2 was discontinued, the O2 concentration decreased in a similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected cat eyes, indicating the presence of a PVD which was not present in hyaluronidase injected or control eyes. Conclusion The results suggest that enzymatic-assisted PVD with microplasmin increases vitreal O2 levels and increases the rate of O2 exchange within the vitreous cavity. PMID:18040251

Increased levels of circulating CD34+ cells in neovascular age-related macular degeneration: relation with clinical and OCT features.

PubMed

Kara, Caner; Özdal, Pınar Ç; Beyazyıldız, Emrullah; Özcan, Nurgül E; Teke, Mehmet Y; Vural, Gülden; Öztürk, Faruk

2018-01-01

To investigate the levels of circulating CD34+ stem cells in patients with neovascular type age-related macular degeneration (AMD) and its relation with clinical and optical coherence tomography (OCT) findings. The study consisted of 55 patients: 28 patients (18 male and 10 female) with neovascular type AMD as a study group and 27 patients (12 male and 15 female) scheduled for cataract surgery as a control group. The level of CD34+ stem cells was measured by flow cytometry. Demographic and clinical data were recorded. The mean ages of patients in the study and control groups were 71 ± 8 and 68 ± 6 years, respectively. There was no statistically significant difference in terms of age, sex, or systemic disease association between study and control groups. However, smoking status was significantly higher in the study group (67.9% vs 37.0%; p = 0.02). Stem cell levels were significantly higher in the study group (1.5 ± 0.9 vs 0.5 ± 0.3; p<0.001), but there was no relation between stem cell levels and clinical and OCT findings. Increased circulating CD34+ stem cell levels were observed in patients with choroidal neovascular membrane associated with AMD, but no significant relation was found between cell levels and clinical and OCT findings.

Decreased steady-state cerebral blood flow velocity and altered dynamic cerebral autoregulation during 5-h sustained 15% O2 hypoxia.

PubMed

Nishimura, Naoko; Iwasaki, Ken-ichi; Ogawa, Yojiro; Aoki, Ken

2010-05-01

Effects of hypoxia on cerebral circulation are important for occupational, high-altitude, and aviation medicine. Increased risk of fainting might be attributable to altered cerebral circulation by hypoxia. Dynamic cerebral autoregulation is reportedly impaired immediately by mild hypoxia. However, continuous exposure to hypoxia causes hyperventilation, resulting in hypocapnia. This hypocapnia is hypothesized to restore impaired dynamic cerebral autoregulation with reduced steady-state cerebral blood flow (CBF). However, no studies have examined hourly changes in alterations of dynamic cerebral autoregulation and steady-state CBF during sustained hypoxia. We therefore examined cerebral circulation during 5-h exposure to 15% O2 hypoxia and 21% O2 in 13 healthy volunteers in a sitting position. Waveforms of blood pressure and CBF velocity in the middle cerebral artery were measured using finger plethysmography and transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis. As expected, steady-state CBF velocity decreased significantly from 2 to 5 h of hypoxia, accompanying 2- to 3-Torr decreases in end-tidal CO2 (ETCO2). Furthermore, transfer function gain and coherence in the very-low-frequency range increased significantly at the beginning of hypoxia, indicating impaired dynamic cerebral autoregulation. However, contrary to the proposed hypothesis, indexes of dynamic cerebral autoregulation showed no significant restoration despite ETCO2 reductions, resulting in persistent higher values of very-low-frequency power of CBF velocity variability during hypoxia (214+/-40% at 5 h of hypoxia vs. control) without significant increases in blood pressure variability. These results suggest that sustained mild hypoxia reduces steady-state CBF and continuously impairs dynamic cerebral autoregulation, implying an increased risk of shortage of oxygen supply to the brain.

Immune and endocrine responses of adult spring Chinook salmon during freshwater migration and sexual maturation

USGS Publications Warehouse

Maule, A.G.; Schrock, R.M.; Slater, C.; Fitzpatrick, M.S.; Schreck, C. B.

1996-01-01

The immune –endocrine responses in spring chinook salmon (Oncorhynchus tshawytscha) were examined during their freshwater migration and final maturation. In 1990, migrating fish had high plasma cortisol titres (means 200 ng ml−1) and generated relatively few antibody-producing cells (APC) from peripheral blood leukocytes (PBL) (100 –200 per culture). After three weeks acclimation in constant environmental conditions, plasma cortisol was reduced and APC increased. There were no changes in number or affinity of glucocorticoid receptors. Concentrations of several sex steroids correlated with APC in females, but there were no such correlations in males. In 1993, fish in a hatchery had significantly greater cortisol concentrations in primary circulation than in secondary circulation, but sex steroid concentrations did not differ between circulations. Mean lysozyme activity in the primary and secondary circulation did not differ in June. In August, activity in the primary circulation was significantly less than that of the secondary, perhaps the result of acute stress associated with sampling. While some sex steroids correlated with lysozyme activity, the fact that in both years all endocrine and immune variables that correlated with each other also correlated with the date of sample, raises the question as to whether or not these are cause-and-effect relations.

Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes.

PubMed

Yamada, Hodaka; Saito, Tomoyuki; Aoki, Atsushi; Asano, Tomoko; Yoshida, Masashi; Ikoma, Aki; Kusaka, Ikuyo; Toyoshima, Hideo; Kakei, Masafumi; Ishikawa, San-E

2015-01-01

There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.

Effects of Packed Structure and Operation Conditions on Liquid Flow Behavior in Blast Furnace Hearth

NASA Astrophysics Data System (ADS)

Zuo, Haibin; Hong, Jun; Zhang, Jianliang; Zheng, Jin

The circulating flow of molten iron is an important reason that results in the erosion of blast furnace hearth. In order to prolong the campaign life of blast furnace, it is necessary to analysis the flow state of molten iron. The three-dimensional mathematical model at steady state which takes the standard k-e and porous zone model into consideration is applied to simulate the flow field under different conditions. The results showed that floating of the deadman did strengthen molten iron circulating flow. Increasing the deadman diameter will increase the erosion of hearth and bottom. Deepen the depth of the taphole and reduce the taphole diameter can reduce the circulating flow. Effect of the taphole angle from 10° to 15° is not significant. The results can be used to provide guidance for protecting the blast furnace hearth.

Progranulin is increased in human and murine lipodystrophy.

PubMed

Miehle, Konstanze; Ebert, Thomas; Kralisch, Susan; Hoffmann, Annett; Kratzsch, Jürgen; Schlögl, Haiko; Stumvoll, Michael; Fasshauer, Mathias

2016-10-01

Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD. Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation. Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Endocan is a predictor of increased cardiovascular risk in women with polycystic ovary syndrome.

PubMed

Bicer, Merve; Guler, Aslı; Unal Kocabas, Gokcen; Imamoglu, Cetin; Baloglu, Ali; Bilgir, Oktay; Yuksel, Arif; Bozkaya, Giray; Calan, Mehmet

2017-05-01

Endocan is a proteoglycan secreted mainly from endothelial cells. It has been implicated that there is a link between endocan and endothelial dysfunction. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with increased risk of cardiovascular events. The aims of this study were to ascertain whether circulating endocan levels are altered in women with PCOS, and whether there is an association between endocan and carotid intima media thickness (cIMT). This cross-sectional study included 80 women with PCOS and 80 age- and BMI-matched controls without PCOS. Circulating endocan levels were measured using ELISA. Metabolic, hormonal parameters and cIMT were determined. 2-h oral glucose tolerance test (2-h OGTT) was performed on all women. Circulating endocan levels were significantly elevated in women with PCOS compared with controls (5.99 ± 2.37 vs. 3.66 ± 1.79 ng/ml, P < 0.001). Endocan levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), high-sensitivity C-reactive protein (hs-CRP), and cIMT in both PCOS and control groups. Endocan levels did not correlate with fasting blood glucose, 2-h OGTT, A1 C and lipid parameters. Multiple linear regression analysis revealed that endocan is an independent predictor for cIMT (β = 0.128, 95% CI = 0.118-0.138, P = 0.011). Circulating endocan levels are significantly higher in women with PCOS and endocan is independently associated with cIMT. Elevated endocan levels can be a predictor of increased cardiovascular risk in PCOS subjects.

Online tables of contents for books: effect on usage*

PubMed Central

Morris, Ruth C.

2001-01-01

Objectives: To explore whether the presence of online tables of contents (TOC) in an online catalog affects circulation (checkouts and inhouse usage). Two major questions were posed: (1) did the presence of online tables of contents for books increase use, and, (2) if it did, what factors might cause the increase? Method: A randomized and stratified design was used in tracking usage of 3,957 book titles that were previously divided into two groups: one with TOC and one without TOC. Stratification was done for year of imprint, location, subject, previous use, circulating or non-circulating status, and presence of TOC. The use was tracked by the online catalog statistics in the InnoPac online catalog for fourteen months. Results: The study found that tables of contents do increase usage. It also showed a correlation in the size of the effect based on the currency of the titles. In general, even after adjusting for all of the variables (publication date, location, circulation status, subject, and previous use), the odds of a title being used increased by 45% if the titles had online tables of contents, a statistically significant impact at the 0.05 level. Conclusions: This case-control study presents new information about the impact on circulation and inhouse use when tables of contents for books are added to the online catalog record. The study helps to establish the positive role of tables of contents in online catalogs. The research establishes TOC as a major parameter that can be successfully studied using quantitative methods. The study also provides information professionals with some guidance on when enhancement of TOC is likely to be most effective in increasing the use of existing collections. PMID:11209798

Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

PubMed

Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

2012-09-01

We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

Online tables of contents for books: effect on usage.

PubMed

Morris, R C

2001-01-01

To explore whether the presence of online tables of contents (TOC) in an online catalog affects circulation (checkouts and inhouse usage). Two major questions were posed: (1) did the presence of online tables of contents for books increase use, and, (2) if it did, what factors might cause the increase? A randomized and stratified design was used in tracking usage of 3,957 book titles that were previously divided into two groups: one with TOC and one without TOC. Stratification was done for year of imprint, location, subject, previous use, circulating or non-circulating status, and presence of TOC. The use was tracked by the online catalog statistics in the InnoPac online catalog for fourteen months. The study found that tables of contents do increase usage. It also showed a correlation in the size of the effect based on the currency of the titles. In general, even after adjusting for all of the variables (publication date, location, circulation status, subject, and previous use), the odds of a title being used increased by 45% if the titles had online tables of contents, a statistically significant impact at the 0.05 level. This case-control study presents new information about the impact on circulation and inhouse use when tables of contents for books are added to the online catalog record. The study helps to establish the positive role of tables of contents in online catalogs. The research establishes TOC as a major parameter that can be successfully studied using quantitative methods. The study also provides information professionals with some guidance on when enhancement of TOC is likely to be most effective in increasing the use of existing collections.

Effects of parasagittal meningiomas on intracranial venous circulation assessed by the virtual reality technology.

PubMed

Wang, Shousen; Ying, Jianbin; Wei, Liangfeng; Li, Shiqing; Jing, Junjie

2015-01-01

This study is to investigate the compensatory intracranial venous pathways in parasagittal meningiomas (PSM) patients by virtual reality technology. A total of 48 PSM patients (tumor group) and 20 patients with trigeminal neuralgia and hemifacial spasm but without intracranial venous diseases (control group) were enrolled. All patients underwent 3D CE-MRV examination. The 3D reconstructed images by virtual reality technology were used for assessment of diameter and number of intracranial veins, tumor location, venous sinus invasion degree and collateral circulation formation. Diameter of bridging veins in posterior 1/3 superior sagittal sinus (SSS) in tumor group was significantly smaller than that of the control group (P < 0.05). For tumors located in mid 1/3 SSS, diameter of bridging veins and vein of Labbé (VL) in posterior 1/3 SSS decreased significantly (P < 0.05). For tumors located in posterior 1/3 SSS, bridging vein number and transverse sinus (TS) diameter significantly decreased while superficial Sylvian vein (SSV) diameter increased significantly (P < 0.05). Compared with tumor in posterior 1/3 SSS subgroup, number of bridging veins in the tumor in mid 1/3 SSS subgroup increased significantly (P < 0.05). Compared with control group, only the bridging vein number in anterior 1/3 SSS segment in invasion Type 3-4 tumor subgroup decreased significantly (P < 0.05). Diameter of TS and bridging veins in posterior 1/3 SSS segment in sinus invasion Type 5-6 tumor subgroup decreased significantly (P < 0.05). Compared with control group, only the diameter of VL and TS of collateral circulation Grade 1 tumor subgroup decreased significantly (P < 0.05) while in Grade 3 tumor subgroup, TS diameter decreased and SSV diameter increased significantly (P < 0.05). The intracranial blood flow is mainly drained through SSV drainage after SSS occlusion by PSM.

Effects of parasagittal meningiomas on intracranial venous circulation assessed by the virtual reality technology

PubMed Central

Wang, Shousen; Ying, Jianbin; Wei, Liangfeng; Li, Shiqing; Jing, Junjie

2015-01-01

Objective: This study is to investigate the compensatory intracranial venous pathways in parasagittal meningiomas (PSM) patients by virtual reality technology. Methods: A total of 48 PSM patients (tumor group) and 20 patients with trigeminal neuralgia and hemifacial spasm but without intracranial venous diseases (control group) were enrolled. All patients underwent 3D CE-MRV examination. The 3D reconstructed images by virtual reality technology were used for assessment of diameter and number of intracranial veins, tumor location, venous sinus invasion degree and collateral circulation formation. Results: Diameter of bridging veins in posterior 1/3 superior sagittal sinus (SSS) in tumor group was significantly smaller than that of the control group (P < 0.05). For tumors located in mid 1/3 SSS, diameter of bridging veins and vein of Labbé (VL) in posterior 1/3 SSS decreased significantly (P < 0.05). For tumors located in posterior 1/3 SSS, bridging vein number and transverse sinus (TS) diameter significantly decreased while superficial Sylvian vein (SSV) diameter increased significantly (P < 0.05). Compared with tumor in posterior 1/3 SSS subgroup, number of bridging veins in the tumor in mid 1/3 SSS subgroup increased significantly (P < 0.05). Compared with control group, only the bridging vein number in anterior 1/3 SSS segment in invasion Type 3-4 tumor subgroup decreased significantly (P < 0.05). Diameter of TS and bridging veins in posterior 1/3 SSS segment in sinus invasion Type 5-6 tumor subgroup decreased significantly (P < 0.05). Compared with control group, only the diameter of VL and TS of collateral circulation Grade 1 tumor subgroup decreased significantly (P < 0.05) while in Grade 3 tumor subgroup, TS diameter decreased and SSV diameter increased significantly (P < 0.05). Conclusions: The intracranial blood flow is mainly drained through SSV drainage after SSS occlusion by PSM. PMID:26550184

Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy

PubMed Central

Grisar, Johannes; Aletaha, Daniel; Steiner, Carl W; Kapral, Theresa; Steiner, Sabine; Säemann, Marcus; Schwarzinger, Ilse; Buranyi, Barbara; Steiner, Günter; Smolen, Josef S

2007-01-01

Objectives To study the effects of short‐term intermediate dose glucocorticoid (GC) therapy in patients with active rheumatoid arthritis (RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA. Methods EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF. Results After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 (SD 0.010)% (p<0.01), and from 12 (SD 4) to 27 (SD 7) CFU/well (p<0.02); CAC also increased from 7 (SD 2) to 29 (SD 8) cells/high power field (p<0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 (SD 10) to 14 (SD 6) pg/ml (p<0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU. Conclusions Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC. PMID:17293363

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

PubMed

Wu, Q; Li, J V; Seyfried, F; le Roux, C W; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, J K; Holmes, E; Gooderham, N J

2015-07-01

Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery

PubMed Central

Wu, Q; Li, J V; Seyfried, F; le Roux, C W; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, J K; Holmes, E; Gooderham, N J

2015-01-01

Background/Objectives: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. Subjects/Methods: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. Conclusions: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting. PMID:25783038

Functional and structural vascular adaptations following 8 weeks of low volume high intensity interval training in lower leg of type 2 diabetes patients and individuals at high risk of metabolic syndrome.

PubMed

Madsen, Søren Møller; Thorup, Anne Cathrine; Overgaard, Kristian; Bjerre, Mette; Jeppesen, Per Bendix

2015-01-01

We wished to investigate the effects of 8 weeks of low volume high intensity interval training (HIIT) on endothelial function of popliteal artery and circulating cell adhesion molecules in type 2 diabetes (T2D) patients and matched controls (CON). Over 8 weeks, non-active T2D patients and CONs cycled three times per week (10 × 60 sec HIIT). Pre- and post-HIIT measurements of endothelial function were conducted by applying flow-mediated dilation (FMD) along with taking venous blood samples. Baseline diameter of popliteal artery increased significantly from an average of 5.53 mm to 5.97 mm (∼8%) in the CON-group (p = 0.006) and 5.32 mm to 5.61 mm (∼6%) in the T2D-group (p = 0.009). Peak diameter increased significantly from 5.82 mm to 6.36 mm (∼9%) in the CON-group (p = 0.001) and 5.57 mm to 5.93 mm (∼7%) in the T2D-group (p = 0.004). FMD% increased significantly from 5.12% to 6.58% in the CON-group (p = 0.004) and 4.84% to 5.66% in the T2D-group: (p = 0.045). The shear rate reduced significantly in both groups (CON-group: p = 0.04; T2D-group: p = 0.002). Circulating cell adhesion molecules remained unchanged (p > 0.05). HIIT induced an improvement of endothelium-dependent FMD and significant outwards artery modelling. No changes in circulating cell adhesion molecules were observed.

[Neuroprotective properties of pyroglutamic acid in combination with pyrrolidone].

PubMed

Lun'shina, E V; Gan'shina, T S; Makarova, L M; Pogorelyĭ, V E; Mirzoian, R S

2003-01-01

A new drug composition containing pyroglutamic acid and pyrrolidone produces a significant effect on the cerebral circulation in rats with global recurrent brain ischemia and in a model ischemic state under high radial gravitational overload. In the former case, the new drug increases the blood circulation in rats with the global ischemic damage to a greater extent than in the intact control group. Pretreatment with the pyroglutamic acid--pyrrolidone composition produced a 2-2.5-fold increase in the survival of rats in the ischemic state caused by the radial gravitational overload. The data obtained show evidence of a substantial neuroprotector action of the new drug composition.

Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration

NASA Technical Reports Server (NTRS)

Mills, P. J.; Meck, J. V.; Waters, W. W.; D'Aunno, D.; Ziegler, M. G.

2001-01-01

OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p <.01), including neutrophils (p <.01), monocytes (p <.05), CD3+CD4+ T-helper cells (p <.05), and CD19+ B cells (p <.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p <.01). Plasma norepinephrine levels were increased at landing (p <.01) and were significantly correlated with the number of white blood cells (p <.01), neutrophils (p <.01), monocytes (p <.01), and B cells (p <.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p <.05) and CD3+CD8+ T-cytotoxic cells (p <.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study.

PubMed

Garamvölgyi, Zoltán; Prohászka, Zoltán; Rigó, János; Kecskeméti, András; Molvarec, Attila

2015-07-01

Recent data indicate that serum Hsp70 (HSPA1A) levels are increased in type 1 and 2 diabetes mellitus. However, there is no report in the literature on circulating Hsp70 levels in gestational diabetes mellitus. In this pilot study, we measured serum Hsp70 levels in 11 pregnant women with pregestational diabetes, 38 women with gestational diabetes, and 40 healthy pregnant women with ELISA. Plasma glucose levels, serum insulin concentrations, HbA1c values, and the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were also determined. According to our results, serum Hsp70 concentrations were significantly higher in women with pregestational and gestational diabetes mellitus than in healthy pregnant women. In addition, pregestational diabetic women had significantly higher Hsp70 levels than those with gestational diabetes. Furthermore, in the group of women with gestational diabetes mellitus, serum Hsp70 levels showed a significant positive correlation with HbA1c values. However, there was no other relationship between clinical features and metabolic parameters of the study subjects and their serum Hsp70 levels in either study group. In conclusion, we demonstrated for the first time in the literature that serum Hsp70 levels are increased and correlate with HbA1c values in women with gestational diabetes mellitus. Nevertheless, further studies are needed to determine whether circulating Hsp70 plays a causative role in the pathogenesis of gestational diabetes or elevated serum Hsp70 levels are only consequences of the disease.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

PubMed

Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

2017-11-27

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

PubMed

Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

2012-06-01

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

PubMed

Roy-O'Reilly, Meaghan; Ritzel, Rodney M; Conway, Sarah E; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D

2017-12-01

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

Effects of Southern Hemisphere Wind Changes on the Meridional Overturning Circulation in Ocean Models.

PubMed

Gent, Peter R

2016-01-01

Observations show that the Southern Hemisphere zonal wind stress maximum has increased significantly over the past 30 years. Eddy-resolving ocean models show that the resulting increase in the Southern Ocean mean flow meridional overturning circulation (MOC) is partially compensated by an increase in the eddy MOC. This effect can be reproduced in the non-eddy-resolving ocean component of a climate model, providing the eddy parameterization coefficient is variable and not a constant. If the coefficient is a constant, then the Southern Ocean mean MOC change is balanced by an unrealistically large change in the Atlantic Ocean MOC. Southern Ocean eddy compensation means that Southern Hemisphere winds cannot be the dominant mechanism driving midlatitude North Atlantic MOC variability.

Elite Circulation and the Convertibility of Knowledge: Comparing Different Types and Forms of Knowledge and Degrees of Elite Circulation in Europe

ERIC Educational Resources Information Center

Mangset, Marte

2017-01-01

According to classical elite theory, increased circulation is related to increased integration which is thought to increase elites' power. Based on a comparative analysis of some European countries' elite education systems, recruitment to elite positions and degrees of circulation--with a specific focus on administrative elites--this article…

Plasma enteroglucagon and CCK levels and cell proliferation in defunctioned small bowel in the rat.

PubMed

Gornacz, G E; Ghatei, M A; Al-Mukhtar, M Y; Yeats, J C; Adrian, T E; Wright, N A; Bloom, S R

1984-11-01

Luminal nutrients exert a powerful trophic effect on small bowel mucosa. Recent evidence suggests that a circulating factor, possibly enteroglucagon, is also growth-promoting. In order to study the isolated effect of nonluminal influences on bowel mucosa, Thiry-Vella fistulae (TVF) were constructed in rats. Circulating enteric hormone concentrations were manipulated by resecting different lengths of remaining gut. Thirty-two male Wistar rats had either 25%, 50%, 75%, or 90% proximal small bowel resection. In each animal the first 25% of resected bowel was exteriorized as a Thiry-Vella fistula. Seven control rats underwent jejunal transection. Twelve days postoperatively the fasted animals were killed, and circulating and tissue concentrations of enteroglucagon and CCK were estimated by radioimmunoassay. Crypt-cell production rate was used as an index of cellular proliferation in the Thiry-Vella fistulae. Proximal small bowel defunctioned in the Thirty-Vella fistulae had a significantly lower crypt-cell production rate and enteroglucagon and CCK content than the equivalent segment in transected rats. Further small bowel resection produced a subsequent increase in circulating enteroglucagon and CCK concentrations, an increase in the Thiry-Vella fistula content of these hormones, and a doubling of the crypt-cell production rate in the Thiry-Vella fistulae. These results show that circulating enteroglucagon and CCK concentrations match closely with enterocyte production even when luminal influences are excluded. It is suggested that circulating factors may play a major role in postresectional ileal hyperplasia. This hyperplasia apparently affects endocrine cells as well as enterocytes.

Detection of HER2 polymorphism and expression using circulating DNA and RNA as a tool in lung adenocarcinoma patients: a case control study.

PubMed

Mirza, Masroor; Javid, Jamsheed; Yadav, Prasant; Mohan, Anant; Ray, Prakash Chandra; Saxena, Alpana

2016-06-01

Circulating DNA and RNA is an important prognostic tool for noninvasive malignant disease detection and in disease prognosis. Study aimed to evaluate the possible prognostic role of HER2 (-3444C/T) promoter polymorphism and its mRNA expression in Lung adenocarcinoma patients using circulating DNA and RNA. One hundred newly diagnosed lung adenocarcinoma patients and 100 age and sex matched healthy controls were included and allele specific (AS) polymerase chain reaction (PCR) was used for genotyping and expression was analyzed by quantitative real time PCR. Overall survival of patients was analyzed by Kaplan-Meier method. We observed a statistically significant difference in the frequency of HER2 CC, CT, and CT genotype among lung adenocarcinoma cases vs. healthy controls (P=0.001). Compared to the CC genotype, OR 2.51 (1.4-4.51), 5.97 (1.17-30.41) and RR 1.56 (1.17-2.07), 2.83 (0.82-9.73) for heterozygous CT and homozygous TT genotypes suggesting possible dominant effect on risk of lung adenocarcinoma. Cases with CC genotype showed 9.29 fold increased mRNA expression while cases with heterozygous CT and homozygous TT genotype showed 16.26, 16.72 fold increased mRNA expression (P<0.0001). We observed 13.92 fold increased HER2mRNA expression Lung adenocarcinoma patients. Patients in different TNM stages showed significant difference in HER2 mRNA expression which was found to be significantly associated (P<0.0001). Patients with distant metastases and without distant metastases had 17.44 and 11.16 fold increased HER2 mRNA expression was also found to be significantly associated (P<0.0001). It was also observed that patients with pleural effusion and without pleural effusion showed significant difference in HER2 mRNA expression (P=0.03). We also analysed patients with CC, TT, CT (P=0.02) and CT + TT (P=0.008) genotype showed 15.8, 7.9, 9.5 and 7.9 months of overall median survival time and found to be significantly associated, respectively. Patients with >13 and ≤13 fold increased HER mRNA expression also showed 7.9 and 11.5 months of overall median survival time was also found to be significantly associated (P=0.01). Our work provides evidence that circulating DNA and RNA may be a potential prognostic tool in Lung adenocarcinoma patients. Promoter polymorphism of HER2 (-3444C/T) gene had significant impact on higher HER2 mRNA expression could be a predictive factor for patients' worse overall survival and metastatic behaviour.

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression.

PubMed

Roth, Carina; Pantel, Klaus; Müller, Volkmar; Rack, Brigitte; Kasimir-Bauer, Sabine; Janni, Wolfgang; Schwarzenbach, Heidi

2011-01-06

As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.

Relationship between atmospheric circulation weather types and seasonal precipitation in Serbia

NASA Astrophysics Data System (ADS)

Putniković, Suzana; Tošić, Ivana

2017-04-01

An automated version of the Lamb weather type classification scheme was used to classify daily circulation types over Serbia. The synoptic characteristics of 26 weather types and their relative frequencies are discussed for spring and autumn, complementing research previously published by Putniković et al. (Meteorol Atmos Phys 128:649-662, 2016) for winter and summer. Trends of the circulation types are presented, as well as precipitation trends during the period 1961-2010. Precipitation was modeled by the stepwise regression at six stations, defining weather types as independent variables. The anticyclonic (A) type is the most frequent class occurring in autumn (23.87%), displaying a positive trend for spring and significant negative trend for autumn. The frequencies of anticyclonic and cyclonic (C) types are almost the same for spring: 14.33 and 14.02%, respectively. The C type shows a significant negative trend only in spring. The increasing trend of the frequency of the C types and decreasing trend of the A types are in agreement with the increasing trend of precipitation in Serbia during autumn. Results suggest that the C type affects precipitation occurrence over most of the country, while the remaining 25 types provide more negligible or regional contributions to precipitation.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery

PubMed Central

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M.J.; de Geus, Hilde H.R.; Scholten, Evert W.; de Mol, Bas A.J.M.; Ince, Can

2012-01-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm2 (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm2 before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system. PMID:22700685

Possible influence of atmospheric circulations on winter haze pollution in Beijing-Tianjin-Hebei region, northern China

NASA Astrophysics Data System (ADS)

Zhang, Z. Y.

2016-12-01

Using the daily records derived from the synoptic weather stations and the NCEP/NCAR and ERA-Interim reanalysis data, the variability of the winter haze pollutions (indicated by the mean visibility and number of hazy days) in Beijing-Tianjin-Hebei (BTH) region during the period 1981 to 2015 and its relationship to the atmospheric circulations in middle-high latitude were analyzed in this study. The winter haze pollution in BTH had distinct inter-annual and inter-decadal variabilities without a significant long-term trend. According to the spatial distribution of correlation coefficients, six atmospheric circulation indices (I1 to I6) were defined from the key areas in sea level pressure (SLP), zonal and meridional winds at 850 hPa (U850, V850), geopotential height field at 500 hPa (H500), zonal wind at 200 hPa (U200), and air temperature at 200 hPa (T200), respectively. All of the six indices have significant and stable correlations with the winter visibility and number of hazy days in BTH. The six circulation indices together can explain 77.7% (78.7%) and 61.7% (69.1%) variances of the winter visibility and number of hazy days in the year-to-year (inter-annual) variability, srespectively. The increase of Ic(a comprehensive index derived from the six individual circulation indices) can cause a shallowing of the East Asian trough at the middle troposphere and a weakening of the Siberian high pressure field at sea level, and then accompanied by a reduction (increase) of horizontal advection and vertical convection (relative humidity) in the lowest troposphere and a reduced boundary layer height in BTH and its neighboring areas, which are favorable for the formation of haze pollutions in BTH winter, and vice versa. The high level of the prediction statistics and the reasonable mechanism suggested that the winter haze pollutions in BTH can be forecasted or estimated credibly based on the optimized atmospheric circulation indices. Thus it is helpful for government decision-making departments to take actions in advance in dealing with probably severe haze pollutions in BTH indicated by the atmospheric circulation conditions.

Recent and possible future variations in the North American Monsoon

USGS Publications Warehouse

Hoell, Andrew; Funk, Chris; Barlow, Mathew; Shukla, Shraddhanand

2016-01-01

The dynamics and recent and possible future changes of the June–September rainfall associated with the North American Monsoon (NAM) are reviewed in this chapter. Our analysis as well as previous analyses of the trend in June–September precipitation from 1948 until 2010 indicate significant precipitation increases over New Mexico and the core NAM region, and significant precipitation decreases over southwest Mexico. The trends in June–September precipitation have been forced by anomalous cyclonic circulation centered at 15°N latitude over the eastern Pacific Ocean. The anomalous cyclonic circulation is responsible for changes in the flux of moisture and the divergence of moisture flux within the core NAM region. Future climate projections using the Coupled Model Intercomparison Project Phase 5 (CMIP5) models, as part of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5), support the observed analyses of a later shift in the monsoon season in the presence of increased greenhouse gas concentrations in the atmosphere under the RCP8.5 scenario. The CMIP5 models under the RCP8.5 scenario predict significant NAM-related rainfall decreases during June and July and predict significant NAM-related rainfall increases during September and October.

Transcapillary protein flux following blood volume modification in dog.

PubMed

Miki, K; Nose, H; Tanaka, Y; Morimoto, T

1984-01-01

The net fluid and protein movements between intravascular and interstitial space following blood withdrawal and retransfusion of 15% of circulating blood volume were measured in dogs using a continuous monitoring method of circulating blood volume. A significant (p less than 0.01) increase in transvascular fluid shift was observed after the start of blood withdrawal and a new equilibrium state was reached within 15 to 20 min. Associated with the fluid shift, a significant increase in plasma protein of about 1 g was observed. On the other hand, blood retransfusion caused significant (p less than 0.01) increases in the shift of fluid and protein from intravascular space to interstitial space. The magnitudes of the shift of fluid and protein were almost identical in both blood withdrawal and retransfusion. The Kedem-Katchalsky transport equation was applied to the results obtained in the present study in order to analyze the relative role of diffusion and convection and to estimate the reflection coefficient for protein. A significant (p less than 0.01) linear relationship was observed between fluid and protein movement. These results suggest that the convective process is involved in the shift of protein between intravascular and interstitial space observed after blood volume modification.

Red Sea circulation during marine isotope stage 5e

NASA Astrophysics Data System (ADS)

Siccha, Michael; Biton, Eli; Gildor, Hezi

2015-04-01

We have employed a regional Massachusetts Institute of Technology oceanic general circulation model of the Red Sea to investigate its circulation during marine isotope stage (MIS) 5e, the peak of the last interglacial, approximately 125 ka before present. Compared to present-day conditions, MIS 5e was characterized by higher Northern Hemisphere summer insolation, accompanied by increases in air temperature of more than 2°C and global sea level approximately 8 m higher than today. As a consequence of the increased seasonality, intensified monsoonal conditions with increased winds, rainfall, and humidity in the Red Sea region are evident in speleothem records and supported by model simulations. To assess the dominant factors responsible for the observed changes, we conducted several sensitivity experiments in which the MIS 5 boundary conditions or forcing parameters were used individually. Overall, our model simulation for the last interglacial maximum reconstructs a Red Sea that is colder, less ventilated and probably more oligotrophic than at present day. The largest alteration in Red Sea circulation and properties was found for the simulation of the northward displacement and intensification of the African tropical rain belt during MIS 5e, leading to a notable increase in the fresh water flux into the Red Sea. Such an increase significantly reduced the Red Sea salinity and exchange volume of the Red Sea with the Gulf of Aden. The Red Sea reacted to the MIS 5e insolation forcing by the expected increase in seasonal sea surface temperature amplitude and overall cooling caused by lower temperatures during deep water formation in winter.

Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers.

PubMed

Heiss, Christian; Kleinbongard, Petra; Dejam, Andrè; Perré, Sandra; Schroeter, Hagen; Sies, Helmut; Kelm, Malte

2005-10-04

This study was designed to assess the effect of flavanol-rich food on the circulating pool of bioactive nitric oxide (NO) and endothelial dysfunction in smokers. Studies suggest that smoking-related vascular disease is caused by impaired NO synthesis and that diets rich in flavanols can increase bioactive NO in plasma. In smokers (n = 11), the effects of flavanol-rich cocoa on circulating NO species in plasma (RXNO) measured by reductive gas-phase chemiluminescence and endothelial function as assessed by flow-mediated dilation (FMD) were characterized in a dose-finding study orally administering cocoa containing 88 to 370 mg flavanols and in a randomized double-blind crossover study using 100 ml cocoa drink with high (176 to 185 mg) or low (<11 mg) flavanol content on two separate days. In addition to cocoa drink, ascorbic acid and NO-synthase inhibitor L-NMMA (n = 4) were applied. There were significant increases in RXNO (21 +/- 3 nmol/l to 29 +/- 5 nmol/l) and FMD (4.5 +/- 0.8% to 6.9 +/- 0.9%, each p < 0.05) at 2 h after ingestion of 176 to 185 mg flavanols, a dose potentially exerting maximal effects. These changes correlated with increases in flavanol metabolites. Cocoa-associated increases in RXNO and FMD were reversed by L-NMMA. Ascorbic acid had no effect. The circulating pool of bioactive NO and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink. The increase in circulating NO pool may contribute to beneficial vascular health effects of flavanol-rich food.

Spatio-temporal changes in atmospheric precipitation over south-western Poland between the periods 1891-1930 and 1981-2010

NASA Astrophysics Data System (ADS)

Szymanowski, Mariusz; Wieczorek, Małgorzata; Namyślak, Marika; Kryza, Maciej; Migała, Krzysztof

2018-02-01

In this paper, we quantify the changes in precipitation distribution in south-western Poland between the periods 1891-1930 and 1981-2010. The average monthly precipitation totals available for 368 and 245 stations, respectively, are spatially interpolated and processed to calculate maps of differences and pluvial continentality indices for both periods. The maps are analysed against changes in atmospheric circulation and take into account the potential role of the mountain barrier of the Sudetes. The main findings are (1) winter totals generally increased in conjunction with a higher frequency of zonal circulation; it is more pronounced in the upper parts of the Sudetes due to orographic effects; (2) a decreased frequency of zonal circulation together with an increased frequency of southern flows has likely led to the reduction of precipitation in spring and autumn. These changes have led to a significant modification of the region's pluvial regime, mostly by decreasing continentality features (especially in the Sudetes and the western lowlands). In addition, the strong sheltering influence of the mountain barrier is observed, driving the preservation or even the enhancement of the continental pluvial characteristics in the north-eastern to eastern foregrounds of the Sudetes. This leads to the conclusion that in areas where long-term observed trends or future projections of precipitation are ambiguous, there may occur significant modifications in regional characteristics, especially as a result of changes in atmospheric circulation modified by local orography.

Hepatitis C virus prevalence and genetic diversity among pregnant women in Gabon, central Africa

PubMed Central

Ndong-Atome, Guy-Roger; Makuwa, Maria; Njouom, Richard; Branger, Michel; Brun-Vézinet, Francoise; Mahé, Antoine; Rousset, Dominique; Kazanji, Mirdad

2008-01-01

Background Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women. Methods Blood samples (947) were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis. Results Twenty pregnant women (2.1%) were infected with HCV. The seroprevalence differed significantly by region (p = 0.004) and increased significantly with age (p = 0.05), being 1.3% at 14–20 years, 1.1% at 21–25 years, 1.9% at 26–30 years, 4.1% at 31–35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c). Conclusion We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c) was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed. PMID:18559087

Free androgen index and Irisin in polycystic ovary syndrome.

PubMed

Li, H; Xu, X; Wang, X; Liao, X; Li, L; Yang, G; Gao, L

2016-05-01

PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects. 166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays. PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI. The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

PubMed Central

2012-01-01

Background The pleiotropic pro-inflammatory cytokine Interleukin (IL)-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ) and 77 healthy control subjects (HC) for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP). Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease. PMID:22913567

Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

PubMed Central

Vilas-Boas, Walkíria Wingester; Jr, Antônio Ribeiro-Oliveira; da Cunha Ribeiro, Renata; Vieira, Renata Lúcia Pereira; Almeida, Jerusa; Nadu, Ana Paula; Silva, Ana Cristina Simões e; Santos, Robson Augusto Souza

2008-01-01

AIM: To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS: Patients were allocated into two groups: outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA), Angiotensin(Ang) I, Ang II, and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation, hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components. RESULTS: PRA, Ang I, Ang II and Ang-(1-7) were significantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang I levels and between Ang II and Ang I were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang II remained unchanged in splanchnic and peripheral circulation in patients under β-blockade, whereas the relationship between Ang II and Ang I was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation, cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION: In LD group, propranolol treatment reduced RAS mediators, but did not change the ratio between Ang-(1-7) and Ang II in splanchnic and peripheral circulation. Furthermore, the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio. PMID:19058308

Wavelet-based variability of Yellow River discharge at 500-, 100-, and 50-year timescales

NASA Astrophysics Data System (ADS)

Su, Lu; Miao, Chiyuan; Duan, Qingyun

2017-04-01

Water scarcity in the Yellow River, China, has become increasingly severe over the past half century. In this paper, wavelet transform analysis was used to detect the variability of observed and reconstructed streamflow in the Yellow River at 500-, 100-, and 50-year timescales. The periodicity of the streamflow series and the co-varying relationships between streamflow and atmospheric circulation indices / sunspot number were assessed via the continuous wavelet transform (CWT) and the wavelet coherence transform (WTC). The CWT results showed intermittent oscillations in streamflow with increasing periodicities of 1-6 years at all timescales. Significant multidecadal and century-scale periodicities were identified in the 500-year streamflow series. The WTC results showed intermittent interannual covariance of streamflow with atmospheric circulation indices and sunspots. At the 50-year timescale, there were significant decadal oscillations between streamflow and the Arctic Oscillation (AO) and the Pacific Decadal Oscillation (PDO), and bidecadal oscillations with the PDO. At the 100-year timescale, there were significant decadal oscillations between streamflow and Niño 3.4, the AO, and sunspots. At the 500-year timescale, streamflow in the middle reaches of the Yellow River showed prominent covariance with the AO with an approximately 32-year periodicity, and with sunspots with an approximately 80-year periodicity. Atmospheric circulation indices modulate streamflow by affecting temperature and precipitation. Sunspots impact streamflow variability by influencing atmospheric circulation, resulting in abundant precipitation. In general, for both the CWT and the WTC results, the periodicities were spatially continuous, with a few gradual changes from upstream to downstream resulting from the varied topography and runoff. At the temporal scale, the periodicities were generally continuous over short timescales and discontinuous over longer timescales.

Wavelet-based Variability of Yellow River Discharge at 500-, 100-, and 50-Year Timescales

NASA Astrophysics Data System (ADS)

Su, L.

2017-12-01

Water scarcity in the Yellow River, China, has become increasingly severe over the past half century. In this paper, wavelet transform analysis was used to detect the variability of natural, observed, and reconstructed streamflow in the Yellow River at 500-, 100-, and 50-year timescales. The periodicity of the streamflow series and the co-varying relationships between streamflow and atmospheric circulation indices/sunspot number were assessed by means of continuous wavelet transform (CWT) and wavelet transform coherence (WTC) analyses. The CWT results showed intermittent oscillations in streamflow with increasing periodicities of 1-6 years at all timescales. Significant multidecadal and century-scale periodicities were identified in the 500-year streamflow series. The WTC results showed intermittent interannual covariance of streamflow with atmospheric circulation indices and sunspots. At the 50-year timescale, there were significant decadal oscillations between streamflow and the Arctic Oscillation (AO) and the Pacific Decadal Oscillation (PDO), and bidecadal oscillations with the PDO. At the 100-year timescale, there were significant decadal oscillations between streamflow and Niño 3.4, the AO, and sunspots. At the 500-year timescale, streamflow in the middle reaches of the Yellow River showed prominent covariance with the AO with an approximately 32-year periodicity, and with sunspots with an approximately 80-year periodicity. Atmospheric circulation indices modulate streamflow by affecting temperature and precipitation. Sunspots impact streamflow variability by influencing atmospheric circulation, resulting in abundant precipitation. In general, for both the CWT and the WTC results, the periodicities were spatially continuous, with a few gradual changes from upstream to downstream resulting from the varied topography and runoff. At the temporal scale, the periodicities were generally continuous over short timescales and discontinuous over longer timescales.

Modulation of ovarian steroidogenesis by adiponectin during delayed embryonic development of Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-09-01

The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3β-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Extreme cyclone events in the Arctic: Wintertime variability and trends

NASA Astrophysics Data System (ADS)

Rinke, A.; Maturilli, M.; Graham, R. M.; Matthes, H.; Handorf, D.; Cohen, L.; Hudson, S. R.; Moore, J. C.

2017-09-01

Typically 20-40 extreme cyclone events (sometimes called ‘weather bombs’) occur in the Arctic North Atlantic per winter season, with an increasing trend of 6 events/decade over 1979-2015, according to 6 hourly station data from Ny-Ålesund. This increased frequency of extreme cyclones is consistent with observed significant winter warming, indicating that the meridional heat and moisture transport they bring is a factor in rising temperatures in the region. The winter trend in extreme cyclones is dominated by a positive monthly trend of about 3-4 events/decade in November-December, due mainly to an increasing persistence of extreme cyclone events. A negative trend in January opposes this, while there is no significant trend in February. We relate the regional patterns of the trend in extreme cyclones to anomalously low sea-ice conditions in recent years, together with associated large-scale atmospheric circulation changes such as ‘blockinglike’ circulation patterns (e.g. Scandinavian blocking in December and Ural blocking during January-February).

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

PubMed

Huber, Vincent J; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L; Nakada, Tsutomu

2018-06-13

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

Fontan Circulation in Adult Patients: Acoustic Radiation Force Impulse Elastography as a Useful Tool for Liver Assessment.

PubMed

Melero-Ferrer, Josep Lluís; Osa-Sáez, Ana; Buendía-Fuentes, Francisco; Ballesta-Cuñat, Antonio; Flors, Lucía; Rodríguez-Serrano, María; Calvillo-Batllés, Pilar; Arnau-Vives, Miguel-Ángel; Palencia-Pérez, Miguel A; Rueda-Soriano, Joaquín

2014-07-01

The development of liver fibrosis and cirrhosis due to long-standing liver congestion is known to occur in adult patients with Fontan circulation. Hepatic elastography has shown to be a useful tool for the noninvasive assessment and staging of liver fibrosis in chronic liver diseases, although the utility of this technique in Fontan patients remains to be adequately studied. Twenty-one patients with Fontan circulation underwent an abdominal ultrasound and an acoustic radiation force impulse (ARFI) elastography. In order to compare the results from this group, a cohort of 14 healthy controls and another group containing 17 patients with cirrhosis were included. The association between the velocity values measured with elastography and clinical and analytical parameters were also studied. Mean shear waves propagation velocity in liver tissue in the Fontan group was 1.86 ± 0.5 m/s, with 76% of patients over the cirrhosis threshold (1.55 m/s). The control group had a mean velocity of 1.09 ± 0.06 m/s, while the cirrhotic group obtained 2.71 ± 0.51 m/s. Seven patients with Fontan circulation had increased liver enzymes. Liver ultrasound showed evidence of chronic liver disease in six patients. Velocity values obtained in the presence or absence of analytical or liver ultrasound abnormalities showed significant differences in the univariate analysis (P = .04 and P = .03 respectively). In conclusion, ARFI elastography showed increased wave propagation velocity values in the Fontan population suggesting increased liver stiffness which could be related to advanced fibrosis. A statistically significant association between ARFI values and the presence of analytical and ultrasound abnormalities has been demonstrated. © The Author(s) 2014.

The assessment of circulating volume using inferior vena cava collapse index and carotid Doppler velocity time integral in healthy volunteers: a pilot study.

PubMed

Peachey, Tom; Tang, Andrew; Baker, Elinor C; Pott, Jason; Freund, Yonathan; Harris, Tim

2016-09-02

Assessment of circulating volume and the requirement for fluid replacement are fundamental to resuscitation but remain largely empirical. Passive leg raise (PLR) may determine fluid responders while avoiding potential fluid overload. We hypothesised that inferior vena cava collapse index (IVCCI) and carotid artery blood flow would change predictably in response to PLR, potentially providing a non-invasive tool to assess circulating volume and identifying fluid responsive patients. We conducted a prospective proof of concept pilot study on fasted healthy volunteers. One operator measured IVC diameter during quiet respiration and sniff, and carotid artery flow. Stroke volume (SV) was also measured using suprasternal Doppler. Our primary endpoint was change in IVCCI after PLR. We also studied changes in IVCCI after "sniff", and correlation between carotid artery flow and SV. Passive leg raise was associated with significant reduction in the mean inferior vena cava collapsibility index from 0.24 to 0.17 (p < 0.01). Mean stroke volume increased from 56.0 to 69.2 mL (p < 0.01). There was no significant change in common carotid artery blood flow. Changes in physiology consequent upon passive leg raise normalised rapidly. Passive leg raise is associated with a decrease of IVCCI and increase in stroke volume. However, the wide range of values observed suggests that factors other than circulating volume predominate in determining the proportion of collapse with respiration. In contrast to other studies, we did not find that carotid blood flow increased with passive leg raise. Rapid normalisation of post-PLR physiology may account for this.

The level of circulating octanoate does not predict ghrelin O-acyl transferase (GOAT)-mediated acylation of ghrelin during fasting.

PubMed

Nass, Ralf; Nikolayev, Alexander; Liu, Jianhua; Pezzoli, Suzan S; Farhy, Leon S; Patrie, James; Gaylinn, Bruce D; Heiman, Mark; Thorner, Michael O

2015-01-01

Acyl-ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin O-acyl transferase (GOAT) attaches an 8-carbon medium-chain fatty acid (MCFA) (octanoate) to serine 3 of ghrelin. This acylation is necessary for the activity of ghrelin. Animal data suggest that MCFAs provide substrate for GOAT and an increase in nutritional octanoate increases acyl-ghrelin. To address the question of the source of substrate for acylation, we studied whether the decline in ghrelin acylation during fasting is associated with a decline in circulating MCFAs. Eight healthy young men (aged 18-28 years, body mass index range, 20.6-26.2 kg/m(2)) had blood drawn every 10 minutes for acyl- and desacyl-ghrelin and every hour for free fatty acids (FFAs) during the last 24 hours of a 61.5-hour fast and during a fed day. FFAs were measured by a highly sensitive liquid chromatography-mass spectroscopy method. Acyl- and desacyl-ghrelin were measured in an in-house assay; the results were published previously. Ghrelin acylation was assessed by the ratio of acyl-ghrelin to total ghrelin. With the exception of MCFAs C8 and C10, all other FFAs, the MCFAs (C6 and C12), and the long-chain fatty acids (C14-C18) significantly increased with fasting (P < .05). There was no significant association between the fold change in ghrelin acylation and circulating FFAs. These results suggest that changes in circulating MCFAs are not linked to the decline in ghrelin acylation during fasting and support the hypothesis that acylation of ghrelin depends at least partially on the availability of gastroluminal MCFAs or the regulation of GOAT activity.

Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay.

PubMed

Ayers, Lisa; Kohler, Malcolm; Harrison, Paul; Sargent, Ian; Dragovic, Rebecca; Schaap, Marianne; Nieuwland, Rienk; Brooks, Susan A; Ferry, Berne

2011-04-01

Circulating cell-derived microparticles (MPs) have been implicated in several disease processes and elevated levels are found in many pathological conditions. The detection and accurate measurement of MPs, although attracting widespread interest, is hampered by a lack of standardisation. The aim of this study was to establish a reliable flow cytometric assay to measure distinct subtypes of MPs in disease and to identify any significant causes of variability in MP quantification. Circulating MPs within plasma were identified by their phenotype (platelet, endothelial, leukocyte and annexin-V positivity (AnnV+). The influence of key variables (i.e. time between venepuncture and centrifugation, washing steps, the number of centrifugation steps, freezing/long-term storage and temperature of thawing) on MP measurement were investigated. Increasing time between venepuncture and centrifugation leads to increased MP levels. Washing samples results in decreased AnnV+MPs (P=0.002) and platelet-derived MPs (PMPs) (P=0.002). Double centrifugation of MPs prior to freezing decreases numbers of AnnV+MPs (P=0.0004) and PMPs (P=0.0004). A single freeze thaw cycle of samples led to an increase in AnnV+MPs (P=0.0020) and PMPs (P=0.0039). Long-term storage of MP samples at -80° resulted in decreased MP levels. This study found that minor protocol changes significantly affected MP levels. This is one of the first studies attempting to standardise a method for obtaining and measuring circulating MPs. Standardisation will be essential for successful development of MP technologies, allowing direct comparison of results between studies and leading to a greater understanding of MPs in disease. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Outcomes of early carotid stenting and angioplasty in large-vessel anterior circulation strokes treated with mechanical thrombectomy and intravenous thrombolytics.

PubMed

Mehta, T; Desai, N; Mehta, K; Parikh, R; Male, S; Hussain, M; Ollenschleger, M; Spiegel, G; Grande, A; Ezzeddine, M; Jagadeesan, B; Tummala, R; McCullough, L

2018-01-01

Introduction Proximal cervical internal carotid artery stenosis greater than 50% merits revascularization to mitigate the risk of stroke recurrence among large-vessel anterior circulation strokes undergoing mechanical thrombectomy. Carotid artery stenting necessitates the use of antiplatelets, and there is a theoretical increased risk of hemorrhagic transformation given that such patients may already have received intravenous thrombolytics and have a significant infarct burden. We investigate the outcomes of large-vessel anterior circulation stroke patients treated with intravenous thrombolytics receiving same-day carotid stenting or selective angioplasty compared to no carotid intervention. Materials and methods The study cohort was obtained from the National (Nationwide) Inpatient Sample database between 2006 and 2014, using International Statistical Classification of Diseases, ninth revision discharge diagnosis and procedure codes. A total of 11,825 patients with large-vessel anterior circulation stroke treated with intravenous thrombolytic and mechanical thrombectomy on the same day were identified. The study population was subdivided into three subgroups: no carotid intervention, same-day carotid angioplasty without carotid stenting, and same-day carotid stenting. Outcomes were assessed with respect to mortality, significant disability at discharge, hemorrhagic transformation, and requirement of percutaneous endoscopic gastronomy tube placement, prolonged mechanical ventilation, or craniotomy. Results This study found no statistically significant difference in patient outcomes in those treated with concurrent carotid stenting compared to no carotid intervention in terms of morbidity or mortality. Conclusions If indicated, it is reasonable to consider concurrent carotid stenting and/or angioplasty for large-vessel anterior circulation stroke patients treated with mechanical thrombectomy who also receive intravenous thrombolytics.

Improvement in intra-aortic balloon pumping and evaluation of its efficacy by electrode methods of control.

PubMed

Ioseliani, G D; Chilaia, S M

1983-02-01

A basically new design for the reversing balloon pump has been proposed for increasing the efficacy of intra-aortic balloon pumping (IABP). The device not only causes a significant increase in discharge, but also permits control of the central and peripheral circulation within the desired limits owing to back-and-forth movements (like a piston) of the balloon pump. Standard one- and two-chamber balloon pumps were compared. In addition to traditional hemodynamic and biochemical indexes, the efficacy of IABP was assessed based on electrode monitor control of PO2 and pH in the myocardium, peripheral tissues, and circulating blood. Based on 54 experiments on dogs, it was found that IABP with reversing balloon pumps in synchronous pulsation resulted in survival of 69% of the cases; PO2 and pH levels in the myocardium, tissues, and blood in the coronary sinus were close to normal, and coronary blood flow and peripheral circulation were increased. With standard one-chamber balloon pumps, the survival rate did not exceed 33.4%; PO2 and pH in the peripheral tissues reached critical levels.

Biochemical changes in response to intensive resistance exercise training in the elderly.

PubMed

Bautmans, Ivan; Njemini, Rose; Vasseur, Sabine; Chabert, Hans; Moens, Lisa; Demanet, Christian; Mets, Tony

2005-01-01

It is assumed that low-grade inflammation, characterized by increased circulating IL-6 and TNF-alpha, is related to the development of sarcopenia. Physical exercise, especially high intensity resistance training, has been shown to be effective in restoring the strength deficit in the elderly. Intensive exercise is accompanied by significant release of IL-6 and TNF-alpha into the blood circulation, but does not result in muscle wasting. Exercise-induced changes in heat-shock protein (Hsp), responsible for cellular protection during stressful situations, might interfere with the acute phase reaction and muscle adaptation. To investigate if intensive strength training in elderly persons induces changes in Hsp70 expression, and if these changes are related to changes in the acute phase reaction or muscle adaptation. 31 elderly persons (aged 68.4+/-5.4 years) performed 6 weeks' intensive strength training. At baseline and after 6 weeks, muscle strength, functional performance (physical activity profile, 6-min walk, 30- second chair stand, grip strength, chair sit & reach and back scratch), linear isokinetic leg extension, circulating IL-6, TNF-alpha, IL-10 and TGF-beta, and Hsp70 in monocytes (M) and lymphocytes (L) immediately after sampling (IAS), after incubation at 37 and 42 degrees C were determined. In 12 participants, cytokines were determined in untrained and trained conditions before and after a single training session. After 6 weeks' training, muscle strength and functional performance improved significantly, together with decreased Hsp70 IAS and Hsp70 37 degrees C and increased Hsp70 42 degrees C (all p<0.05). Strength gains correlated positively with baseline Hsp70 37 degrees C and training-induced changes of Hsp70 42 degrees C in M and L. In an untrained condition, training induced an increase of IL-6 (p<0.05) and a tendency of IL-10 to decrease (p=0.06). In a trained condition the decrease of IL-10 disappeared. Baseline physical activity and 6-min walk distance correlated negatively with circulating IL-6 (p<0.05); except for a negative correlation between TGF-beta and Hsp70 37 degrees C L (p<0.05), no significant relationships were found between cytokines and Hsp70. After the training program, Hsp70 37 degrees C was negatively related to circulating TNF-alpha, IL-10 and TGF-beta. Strength training in the elderly induces changes in Hsp70 expression, associated to strength gains and circulating cytokines. Copyright (c) 2005 S. Karger AG, Basel.

Clinical significance of circulating immune cells in left- and right-sided colon cancer.

PubMed

Di, Jiabo; Zhuang, Meng; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Su, Xiangqian

2017-01-01

Left-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis. This study aimed to determine the clinical significance of circulating immune cells with respect to colon tumor locations. Different types of circulating immune cells were separated and analysed based on their surface markers by flow cytometry. We compared the numbers of dendritic cells (DCs) and T cell subsets in the peripheral blood of 94 patients with RCC or LCC and analysed the proportions of these immune cells in relation to tumor stage, tumor differentiation and lymphatic metastasis. We show that at later tumor stages, patients with LCC had higher levels of circulating myeloid DCs ( P  = 0.049) and plasmacytoid DCs ( P  = 0.018) than patients with RCC. In poorly differentiated tumors, LCC patients had significantly higher amount of plasmacytoid DCs ( P  = 0.036), CD4 + memory T (Tm) cells ( P  = 0.012), CD4 + T cells ( P  = 0.028), Tm cells ( P  = 0.014), and regulatory T cells ( P  = 0.001) than RCC patients. The levels of circulating CD4 + T cells, Tm cells and CD4 + Tm cells were significantly elevated at later stages in patients with LCC or RCC, while these cells decreased in poorly differentiated tumors in patients with RCC. Moreover, CD4 + Tm cell and CD4 + T cell levels are significantly associated with lymph node metastasis in patients with LCC and RCC. Circulating immune cells were associated with tumor location, tumor stage and tumor differentiation, and can be used to predict lymphatic metastasis in patients with colon cancer. This variation in systemic immunity could contribute to the differential prognosis of patients with colon cancer.

Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

PubMed

Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

2016-03-01

Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. © 2016 British Society for Neuroendocrinology.

CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy.

PubMed

Guerra, Lorenzo; D'Oria, Susanna; Favia, Maria; Castellani, Stefano; Santostasi, Teresa; Polizzi, Angela M; Mariggiò, Maria A; Gallo, Crescenzio; Casavola, Valeria; Montemurro, Pasqualina; Leonetti, Giuseppina; Manca, Antonio; Conese, Massimo

2017-07-01

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients. Here, we have investigated whether ivacaftor has a clinical impact on non-G551D gating mutations and function of circulating leukocytes as well. Seven patients were treated with ivacaftor and evaluated at baseline, and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters, circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry and HVCN1 mRNA expression by real time PCR. Ivacaftor determined a significant decrease in sweat chloride concentrations at all time points during treatment. Body mass index (BMI), FEV 1 , and FVC showed an increasing trend. While C-reactive protein decreased significantly at 2 months, the opposite behavior was noticed for circulating monocytes. CFTR activity in MNC was found to increase significantly at 3 and 6 months. Neutrophil oxidative burst peaked at 2 months and then decreased to baseline. HVCN1 mRNA expression was significantly higher than baseline at 1-3 months and decreased after 6 months of treatment. The chloride efflux in MNC correlated positively with both FEV 1 and FVC. On the other hand, sweat chloride correlated positively with CRP and WBC, and negatively with both respiratory function tests. A cluster analysis confirmed that sweat chloride, FEV 1 , FVC, BMI, and MNC chloride efflux behaved as a single entity over time. In patients with non-G551D mutations, ivacaftor improved both chloride transport in sweat ducts and chloride efflux in MNC, that is, functions directly imputed to CFTR. © 2017 Wiley Periodicals, Inc.

The leading mode of observed and CMIP5 ENSO-residual sea surface temperatures and associated changes in Indo-Pacific climate

USGS Publications Warehouse

Funk, Christopher C.; Hoell. Andrew,

2015-01-01

WPWM circulation changes appear consistent with a Matsuno–Gill-like atmospheric response associated with an ocean–atmosphere dipole structure contrasting increased (decreased) western (eastern) Pacific precipitation, SSHs, and ocean temperatures. These changes have enhanced the Walker circulation and modulated weather on a global scale. An AGCM experiment and the WPWM of global boreal spring precipitation indicate significant drying across parts of East Africa, the Middle East, the southwestern United States, southern South America, and Asia. Changes in the WPWM have tracked closely with precipitation and the increase in drought frequency over the semiarid and water-insecure areas of East Africa, the Middle East, and southwest Asia.

Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development.

PubMed

Anuradha; Krishna, Amitabh

2017-07-01

The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November-December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx. Copyright © 2017 Elsevier Inc. All rights reserved.

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

PubMed

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

2015-07-01

Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

PubMed

Santi, A; Genis, L; Torres Aleman, I

2018-06-01

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus.

PubMed

Kang, Seung-Ji; Jin, Hye-Mi; Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung-Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung; Park, Yong-Wook

2017-07-01

Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus. This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase. This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus

PubMed Central

Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung-Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung

2017-01-01

Background Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus. Methodology/Principal findings This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase. Conclusions This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients. PMID:28750012

Future changes in tropospheric ozone under Representative Concentration Pathways (RCPs)

NASA Astrophysics Data System (ADS)

Kawase, Hiroaki; Nagashima, Tatsuya; Sudo, Kengo; Nozawa, Toru

2011-03-01

We consider future changes in tropospheric ozone based on the Representative Concentration Pathways (RCPs), which are new emission and concentration scenarios for the 5th coupled model intercomparison project. In contrast to the SRES scenarios, all the RCP scenarios assume an emission reduction of NOx by the late 21st Century that has the potential to achieve tropospheric ozone reduction. However, increasing radiative forcing (RF) due to greenhouse gases and changes in CH4 concentration also contribute to differences in the tropospheric ozone distribution among RCP scenarios. In the RCP4.5 and RCP6.0, assuming the stabilization of RF, the increase in tropospheric ozone due to enhanced residual circulation is cancelled out by the ozone reduction due to ozone precursor reductions. In contrast, in the RCP8.5, assuming increasing RF even after 2100, further enhanced residual circulation and significant increase in CH4 cause a dramatic increase in tropospheric ozone.

Role of dust direct radiative effect on the tropical rain belt over Middle East and North Africa: A high-resolution AGCM study

NASA Astrophysics Data System (ADS)

Bangalath, Hamza Kunhu; Stenchikov, Georgiy

2015-05-01

To investigate the influence of direct radiative effect of dust on the tropical summer rain belt across the Middle East and North Africa (MENA), the present study utilizes the high-resolution capability of an Atmospheric General Circulation Model, the High-Resolution Atmospheric Model. Ensembles of Atmospheric Model Intercomparison Project style simulations have been conducted with and without dust radiative impacts, to differentiate the influence of dust on the tropical rain belt. The analysis focuses on summer season. The results highlight the role of dust-induced responses in global- and regional-scale circulations in determining the strength and the latitudinal extent of the tropical rain belt. A significant response in the strength and position of the local Hadley circulation is predicted in response to meridionally asymmetric distribution of dust and the corresponding radiative effects. Significant responses are also found in regional circulation features such as African Easterly Jet and West African Monsoon circulation. Consistent with these dynamic responses at various scales, the tropical rain belt across MENA strengthens and shifts northward. Importantly, the summer precipitation over the semiarid strip south of Sahara, including Sahel, increases up to 20%. As this region is characterized by the "Sahel drought," the predicted precipitation sensitivity to the dust loading over this region has a wide range of socioeconomic implications. Overall, the study demonstrates the extreme importance of incorporating dust radiative effects and the corresponding circulation responses at various scales, in the simulations and future projections of this region's climate.

Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

PubMed Central

Rinaldi, Arturo Ottavio; Sanseverino, Isabella; Purificato, Cristina; Cortese, Antonio; Mechelli, Rosella; Francisci, Silvia; Salvetti, Marco; Millefiorini, Enrico; Gessani, Sandra; Gauzzi, Maria Cristina

2015-01-01

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. PMID:25590278

Changing monsoon and midlatitude circulation interactions over the Western Himalayas and possible links to occurrences of extreme precipitation

NASA Astrophysics Data System (ADS)

Priya, P.; Krishnan, R.; Mujumdar, Milind; Houze, Robert A.

2017-10-01

Historical rainfall records reveal that the frequency and intensity of extreme precipitation events, during the summer monsoon (June-September) season, have significantly risen over the Western Himalayas (WH) and adjoining upper Indus basin since 1950s. Using multiple datasets, the present study investigates the possible coincidences between an increasing trend of precipitation extremes over WH and changes in background flow climatology. The present findings suggest that the combined effects of a weakened southwest monsoon circulation, increased activity of transient upper-air westerly troughs over the WH region, enhanced moisture supply by southerly winds from the Arabian Sea into the Indus basin have likely provided favorable conditions for an increased frequency of certain types of extreme precipitation events over the WH region in recent decades.

Adiposity associated changes in serum glucose and adiponectin levels modulate ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2018-06-01

The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased circulating blood cell counts in combat-related PTSD: Associations with inflammation and PTSD severity.

PubMed

Lindqvist, Daniel; Mellon, Synthia H; Dhabhar, Firdaus S; Yehuda, Rachel; Grenon, S Marlene; Flory, Janine D; Bierer, Linda M; Abu-Amara, Duna; Coy, Michelle; Makotkine, Iouri; Reus, Victor I; Aschbacher, Kirstin; Bersani, F Saverio; Marmar, Charles R; Wolkowitz, Owen M

2017-12-01

Inflammation is reported in post-traumatic stress disorder (PTSD). Few studies have investigated circulating blood cells that may contribute to inflammation. We assessed circulating platelets, white blood cells (WBC) and red blood cells (RBC) in PTSD and assessed their relationship to inflammation and symptom severity. One-hundred and sixty-three male combat-exposed veterans (82 PTSD, 81 non-PTSD) had blood assessed for platelets, WBC, and RBC. Data were correlated with symptom severity and inflammation. All cell counts were significantly elevated in PTSD. There were small mediation effects of BMI and smoking on these relationships. After adjusting for these, the differences in WBC and RBC remained significant, while platelet count was at trend level. In all subjects, all of the cell counts correlated significantly with inflammation. Platelet count correlated with inflammation only in the PTSD subjects. Platelet count, but none of the other cell counts, was directly correlated with PTSD severity ratings in the PTSD group. Combat PTSD is associated with elevations in RBC, WBC, and platelets. Dysregulation of all three major lineages of hematopoietic cells in PTSD, as well as their significant correlation with inflammation, suggest clinical significance of these changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Orography and the Boreal Winter Stratosphere: The Importance of the Mongolian Mountains

NASA Astrophysics Data System (ADS)

White, R. H.; Battisti, D. S.; Sheshadri, A.

2018-02-01

The impact of mountains on stratospheric circulation is explored using the Whole Atmosphere Community Climate Model. The "Mongolian mountains" decrease the boreal winter stratospheric jet strength by ˜1/3 and increase the frequency of major sudden stratospheric warmings from 0.08 year-1 to the observed 0.60 year-1. These changes are twice the magnitude of the impacts of the Tibetan plateau and Himalayas. Consistent with the decrease in the zonal jet, there is enhanced Eliassen-Palm flux convergence; this is predominantly from changes in wave propagation pathways through changes to the upper troposphere circulation, not from an increased amplitude of planetary waves reaching the stratosphere. The Mongolian mountains have the greater impact on upper tropospheric circulation due to their meridional location. The Rocky Mountains have no significant impact on the stratospheric jet. Changes in wave propagation in response to the Mongolian mountains are similar to those associated with major sudden stratospheric warming events in observations.

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

PubMed

Stárka, L; Hill, M; Havlíková, H; Kancheva, L; Sobotka, V

2006-01-01

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

Stable isotopes of fossil teeth corroborate key general circulation model predictions for the Last Glacial Maximum in North America

NASA Astrophysics Data System (ADS)

Kohn, Matthew J.; McKay, Moriah

2010-11-01

Oxygen isotope data provide a key test of general circulation models (GCMs) for the Last Glacial Maximum (LGM) in North America, which have otherwise proved difficult to validate. High δ18O pedogenic carbonates in central Wyoming have been interpreted to indicate increased summer precipitation sourced from the Gulf of Mexico. Here we show that tooth enamel δ18O of large mammals, which is strongly correlated with local water and precipitation δ18O, is lower during the LGM in Wyoming, not higher. Similar data from Texas, California, Florida and Arizona indicate higher δ18O values than in the Holocene, which is also predicted by GCMs. Tooth enamel data closely validate some recent models of atmospheric circulation and precipitation δ18O, including an increase in the proportion of winter precipitation for central North America, and summer precipitation in the southern US, but suggest aridity can bias pedogenic carbonate δ18O values significantly.

Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2

NASA Astrophysics Data System (ADS)

Skinner, L. C.; Primeau, F.; Freeman, E.; de La Fuente, M.; Goodwin, P. A.; Gottschalk, J.; Huang, E.; McCave, I. N.; Noble, T. L.; Scrivner, A. E.

2017-07-01

While the ocean's large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean-atmosphere radiocarbon disequilibrium estimates to demonstrate a ~689+/-53 14C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial-interglacial CO2 change.

Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria.

PubMed

Riera, Marta; Anguiano, Lidia; Clotet, Sergi; Roca-Ho, Heleia; Rebull, Marta; Pascual, Julio; Soler, Maria Jose

2016-03-15

Circulating and renal activity of angiotensin-converting enzyme 2 (ACE2) is increased in non-obese diabetic (NOD) mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17, a metalloprotease implied in ACE2 shedding, was assessed. NOD female and non-diabetic control mice were studied for 21 days after diabetes onset and divided into various treatment groups. Diabetic animals received either vehicle; 0.4 or 0.8 μg/kg paricalcitol, aliskiren, or a combination of paricalcitol and aliskiren. We then studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren resulted in significantly reduced circulating ACE2 activity in NOD mice but there were no changes in urinary albumin excretion. Serum renin activity was significantly decreased in mice that received aliskiren but no effect was found when paricalcitol was used alone. Renal content of ADAM17 was significantly decreased in animals that received a high dose of paricalcitol. Renal and circulating oxidative stress (quantified by plasma H2O2 levels and immunolocalization of nitrotyrosine) were reduced in high-dose paricalcitol-treated mice compared with non-treated diabetic mice. In culture, paricalcitol incubation resulted in a significant increase in ACE2 expression compared with nontreated cells. In NOD mice with type 1 diabetes, paricalcitol modulates ACE2 activity, ADAM17, and oxidative stress renal content independently from the glycemic profile and urinary albumin excretion. In tubular cells, paricalcitol may modulate ACE2 by blocking its shedding. In the early stage of diabetic nephropathy, paricalcitol treatment counterbalances the effect of diabetes on circulating ACE2 activity. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies. Copyright © 2016 the American Physiological Society.

Chronic alcohol consumption is associated with changes in the distribution, immunophenotype, and the inflammatory cytokine secretion profile of circulating dendritic cells.

PubMed

Laso, Francisco Javier; Vaquero, José Miguel; Almeida, Julia; Marcos, Miguel; Orfao, Alberto

2007-05-01

Alcoholism is frequently associated with altered immune responses, limited information being available on its effects on dendritic cells (DC). In the present study we analyze the effects of chronic alcoholism on circulating DC. For the first time we studied the numerical distribution of DC in peripheral blood (PB), their immunophenotype, and their ex vivo pattern of spontaneous cytokine secretion, in chronic alcoholic patients without liver disease (AWLD group; n=17) and active ethanol (EtOH) intake, as well as in subjects with alcohol liver cirrhosis (ALC group; n=21). A significantly decreased HLADR expression and an increased reactivity for CD123 was observed on PB DC from AWLD patients; additionally, increased secretion of interleukin (IL) 1beta, IL6, IL12, and tumor necrosis factor-alpha (TNFalpha) by DC was also noted in this group. Conversely, patients with ALC and at least 1 year of alcohol withdrawal (ALCAW group) showed a decreased number of total circulating DC, whereas ALC patients with active EtOH intake (ALCET group) had an abnormally low production of IL1beta and TNFalpha by PB DC. Chronic alcoholism in the absence of liver disease is associated with an increased secretion of inflammatory cytokines by PB DC, whereas ALCAW and ALCET patients show decreased numbers of circulating DC and reduced secretion of these cytokines, respectively.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy.

PubMed

Olszanecka-Glinianowicz, Magdalena; Owczarek, Aleksander; Bożentowicz-Wikarek, Maria; Brzozowska, Aniceta; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Grodzicki, Tomasz; Więcek, Andrzej; Chudek, Jerzy

2014-11-01

Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of Tumour Epithelial Subtype on Circulating microRNAs in Breast Cancer Patients

PubMed Central

Brougham, Cathy; Glynn, Claire L.; Wall, Deirdre; Hyland, Peter; Duignan, Maria; McLoughlin, Mark; Newell, John; Kerin, Michael J.

2014-01-01

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients. PMID:24626163

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

PubMed

Tayebjee, Muzahir H; Nadar, Sunil; Blann, Andrew D; Gareth Beevers, D; MacFadyen, Robert J; Lip, Gregory Y H

2004-09-01

Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =.0041 and P =.0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =.035 and P =.005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =.007) and HDL cholesterol (r = -0.237, P =.022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension. Copyright 2004 American Journal of Hypertension, Ltd.

Age-dependent Impairment of HIF-1α̣Expression in Diabetic Mice: Correction with Electroporation-facilitated Gene Therapy Increases Wound Healing, Angiogenesis, and Circulating Angiogenic Cells

PubMed Central

Liu, Lixin; Marti, Guy P.; Wei, Xiaofei; Zhang, Xianjie; Zhang, Huafeng; Liu, Ye V.; Nastai, Manuel; Semenza, Gregg L.; Harmon, John W.

2009-01-01

Wound healing is impaired in elderly patients with diabetes mellitus. We hypothesized that age-dependent impairment of cutaneous wound healing in db/db diabetic mice: (a) would correlate with reduced expression of the transcription factor hypoxia-inducible factor 1α (HIF-1α) as well as its downstream target genes; and (b) could be overcome by HIF-1α replacement therapy. Wound closure, angiogenesis, and mRNA expression in excisional skin wounds were analyzed and circulating angiogenic cells were quantified in db/db mice that were untreated or received electroporation-facilitated HIF-1α gene therapy. HIF-1α mRNA levels in wound tissue were significantly reduced in older (4–6 months) as compared to younger (1.5–2 months) db/db mice. Expression of mRNAs encoding the angiogenic cytokines vascular endothelial growth factor (VEGF), angiopoietin 1 (ANGPT1), ANGPT2, platelet derived growth factor B (PDGF-B), and placental growth factor (PLGF) was also impaired in wounds of older db/db mice. Intradermal injection of plasmid gWIZ-CA5, which encodes a constitutively active form of HIF-1α, followed by electroporation, induced increased levels of HIF-1α mRNA at the injection site on day 3 and increased levels of VEGF, PLGF, PDGF-B, and ANGPT2 mRNA on day 7. Circulating angiogenic cells in peripheral blood increased 10-fold in mice treated with gWIZ-CA5. Wound closure was significantly accelerated in db/db mice treated with gWIZ-CA5 as compared to mice treated with empty vector. Thus, HIF-1α gene therapy corrects the age-dependent impairment of HIF-1α expression, angiogenic cytokine expression, and circulating angiogenic cells that contribute to the age-dependent impairment of wound healing in db/db mice. PMID:18506785

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

PubMed

Emanueli, Costanza; Shearn, Andrew I U; Laftah, Abas; Fiorentino, Francesca; Reeves, Barnaby C; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D

2016-01-01

Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage. The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Liver-derived IGF-I contributes to GH-dependent increases in lean mass and bone mineral density in mice with comparable levels of circulating GH.

PubMed

Nordstrom, Sarah M; Tran, Jennifer L; Sos, Brandon C; Wagner, Kay-Uwe; Weiss, Ethan J

2011-07-01

The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

PubMed Central

Emanueli, Costanza; Fiorentino, Francesca; Reeves, Barnaby C.; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D.

2016-01-01

Introduction Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current “gold standard” surrogate biomarker of myocardial damage. Methods and Results The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. Conclusions The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients. PMID:27128471

Blood circulation under conditions of weightlessness

NASA Technical Reports Server (NTRS)

Kastyan, I. I.; Kopanev, V. I.

1980-01-01

Experimental materials and published data on the problem of blood circulation in man and animals under conditions of short and long term weightlessness are summarized. The data obtained allow the conclusion, that when humans spent 5 days in a weightless state their blood circulation was not essentially distributed. Some features of the functioning of the cardiovascular system are pointed out: delay of adaptation rate, increase in lability, etc. There is a discussion of the physiological mechanisms for the direct and indirect effect of weightlessness. The direct effect comprise the complex of reactions caused by the significant fall in hydrostatic pressure and the indirect embraces all the reactions arising in the organism resulting from disturbance of the systematic character of the analyzers that take part in the analysis of space realtions and the body's orientation in space.

Long-term trend in ground-based air temperature and its responses to atmospheric circulation and anthropogenic activity in the Yangtze River Delta, China

NASA Astrophysics Data System (ADS)

Peng, Xia; She, Qiannan; Long, Lingbo; Liu, Min; Xu, Qian; Zhang, Jiaxin; Xiang, Weining

2017-10-01

The Yangtze River Delta (YRD), including Shanghai City, Jiangsu and Zhejiang Provinces, is the largest metropolitan region in China. In the past decades, the region has experienced massive urbanization and detrimentally affected the environment in the region. Identifying the spatio-temporal variations of climate change and its influencing mechanism in the YRD is an important task for assessing their impacts on the local society and ecosystem. Based on long-term (1958-2014) observation data of meteorological stations, three temperature indices, i.e. extreme maximum temperature (TXx), extreme minimum temperature (TNn), and mean temperature (TMm), were selected and spatialized with climatological calculations and spatial techniques. Evolution and spatial heterogeneity of three temperature indices over YRD as well as their links to atmospheric circulation and anthropogenic activity were investigated. In the whole YRD, a statistically significant overall uptrend could be detected in three temperature indices with the Mann-Kendall (M-K) trend test method. The linear increasing trend for TMm was 0.31 °C/10 a, which was higher than the global average (0.12 °C/10 a during 1951-2012). For TXx and TNn, the increasing rates were 0.41 °C/10 a and 0.52 °C/10 a. Partial correlation analysis indicated that TMm was more related with TXx (rp = 0.68, p < 0.001) than TNn (rp = 0.48, p < 0.001). Furthermore, it was detected with M-K analysis at pixel scale that 62.17%, 96.75% and 97.05% of the areas in the YRD showed significant increasing trends for TXx, TNn and TMm, respectively. The increasing trend was more obvious in the southern mountainous areas than the northern plains areas. Further analysis indicated that the variation of TXx over YRD was mainly influenced by anthropogenic activities (e.g. economic development), while TNn was more affected by atmospheric circulations (e.g., the Eurasian zonal circulation index (EAZ) and the cold air activity index (CA)). For TMm, it was a result of comprehensive effects of both atmospheric circulations and anthropogenic activities. On the whole, the northern plain areas was mainly dominated by atmospheric circulations, while the southern mountain areas of YRD was more affected by anthropogenic activities. The findings of this study might help to build a better understanding of the mechanics of temperature variations, and assess the potentially influencing factors on temperature changes.

Regional drought shifts (1710-2010) in East Central Asia and linkages with atmospheric circulation recorded in tree-ring δ18O

NASA Astrophysics Data System (ADS)

Xu, Guobao; Liu, Xiaohong; Trouet, Valerie; Treydte, Kerstin; Wu, Guoju; Chen, Tuo; Sun, Weizhen; An, Wenling; Wang, Wenzhi; Zeng, Xiaomin; Qin, Dahe

2018-04-01

Drought occurrence and duration in central Asia are of important socioeconomic, ecological, and geophysical significance and have received increasing research attention in recent years. Understanding long-term drought trends and their driving forces require reliable records of past drought variability with broad spatial representativeness. Here, we compiled four tree-ring δ18O records from eastern central Asia (ECA) and composited them into a drought-sensitive proxy to explore regional ECA moisture variations over the past 301 years (1710-2010 CE). A robust regional standardized precipitation-evapotranspiration index (SPEI) reconstruction was established based on the tree-ring cellulose δ18O fractionation mechanism and statistically significant proxy-climate relationships. We identified prominent droughts in 1710-1770, 1810-1830, and the beginning of the twenty-first century, and a regime shift to a persistently wet period from the 1880s to 2000. Our reconstruction reveals the impact of drought and pluvial patterns on the decline of Zhungar Empire, and on historical agricultural and socio-economical activities, including increased migration into ECA during the 1770-1800 pluvial. Our findings also suggest that wet conditions in the twentieth century in ECA were related to a strengthening of the westerly circulation and thus shed light on large-scale atmospheric circulation dynamics in central Asia.

Changes in Microbial Plankton Assemblages Induced by Mesoscale Oceanographic Features in the Northern Gulf of Mexico.

PubMed

Williams, Alicia K; McInnes, Allison S; Rooker, Jay R; Quigg, Antonietta

2015-01-01

Mesoscale circulation generated by the Loop Current in the Northern Gulf of Mexico (NGOM) delivers growth-limiting nutrients to the microbial plankton of the euphotic zone. Consequences of physicochemically driven community shifts on higher order consumers and subsequent impacts on the biological carbon pump remain poorly understood. This study evaluates microbial plankton <10 μm abundance and community structure across both cyclonic and anti-cyclonic circulation features in the NGOM using flow cytometry (SYBR Green I and autofluorescence parameters). Non-parametric multivariate hierarchical cluster analyses indicated that significant spatial variability in community structure exists such that stations that clustered together were defined as having a specific 'microbial signature' (i.e. statistically homogeneous community structure profiles based on relative abundance of microbial groups). Salinity and a combination of sea surface height anomaly and sea surface temperature were determined by distance based linear modeling to be abiotic predictor variables significantly correlated to changes in microbial signatures. Correlations between increased microbial abundance and availability of nitrogen suggest nitrogen-limitation of microbial plankton in this open ocean area. Regions of combined coastal water entrainment and mesoscale convergence corresponded to increased heterotrophic prokaryote abundance relative to autotrophic plankton. The results provide an initial assessment of how mesoscale circulation potentially influences microbial plankton abundance and community structure in the NGOM.

The importance of planetary rotation period for ocean heat transport.

PubMed

Cullum, J; Stevens, D; Joshi, M

2014-08-01

The climate and, hence, potential habitability of a planet crucially depends on how its atmospheric and ocean circulation transports heat from warmer to cooler regions. However, previous studies of planetary climate have concentrated on modeling the dynamics of atmospheres, while dramatically simplifying the treatment of oceans, which neglects or misrepresents the effect of the ocean in the total heat transport. Even the majority of studies with a dynamic ocean have used a simple so-called aquaplanet that has no continental barriers, which is a configuration that dramatically changes the ocean dynamics. Here, the significance of the response of poleward ocean heat transport to planetary rotation period is shown with a simple meridional barrier--the simplest representation of any continental configuration. The poleward ocean heat transport increases significantly as the planetary rotation period is increased. The peak heat transport more than doubles when the rotation period is increased by a factor of ten. There are also significant changes to ocean temperature at depth, with implications for the carbon cycle. There is strong agreement between the model results and a scale analysis of the governing equations. This result highlights the importance of both planetary rotation period and the ocean circulation when considering planetary habitability.

Insulin regulates the novel adipokine adipolin/CTRP12: in vivo and ex vivo effects.

PubMed

Tan, Bee K; Lewandowski, Krzysztof C; O'Hare, Joseph Paul; Randeva, Harpal S

2014-04-01

There has been intense interest in the adipokines of the C1q complement/TNF-related protein (CTRP) superfamily. Adipolin (CTRP12) has been described as a novel adipokine, abundantly expressed in adipose tissue with insulin-sensitising and anti-inflammatory effects. We wanted to investigate the effects of acute and chronic hyperinsulinaemia on circulating adipolin concentrations (ELISA) via a prolonged insulin-glucose infusion in humans. We also examined the effects of insulin and the insulin sensitiser, rosiglitazone, on adipolin concentrations (western blotting) in human adipose tissue explants. We found that hyperinsulinaemic induction in healthy lean human subjects significantly increased circulating levels of adipolin (P<0.05 and P<0.01). Furthermore, in subcutaneous adipose tissue explants, insulin significantly increased adipolin protein expression and secretion (P<0.05 and P<0.01). This effect was attenuated by the phosphatidylinositol 3-kinase inhibitor, LY294002 (P<0.05). Moreover, the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) agonist, rosiglitazone, significantly increased adipolin protein expression and secretion in subcutaneous adipose tissue explants (P<0.05 and P<0.01). This effect was inhibited by the PPARγ antagonist, GW9662 (P<0.05). Our data provide novel insights into adipolin physiology in human subjects.

Influence of Idealized Heterogeneity on Wet and Dry Planetary Boundary Layers Coupled to the Land Surface. 1; Instantaneous Fields and Statistics

NASA Technical Reports Server (NTRS)

Houser, Paul (Technical Monitor); Patton, Edward G.; Sullivan, Peter P.; Moeng, Chin-Hoh

2003-01-01

This is the first in a two-part series of manuscripts describing numerical experiments on the influence of 2-30 km striplike heterogeneity on wet and dry boundary layers coupled to the land surface. The strip-like heterogeneity is shown to dramatically alter the structure of the free-convective boundary layer by inducing significant organized circulations that modify turbulent statistics. The coupling with the land-surface modifies the circulations compared to previous studies using fixed surface forcing. Total boundary layer turbulence kinetic energy increases significantly for surface heterogeneity at scales between Lambda/z(sub i) = 4 and 9, however entrainment rates for all cases are largely unaffected by the strip-like heterogeneity.

Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA

PubMed Central

Haber, Daniel A.; Velculescu, Victor E.

2015-01-01

The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell–derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. PMID:24801577

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia.

PubMed

Tian, Huaiyu; Sun, Zhe; Faria, Nuno Rodrigues; Yang, Jing; Cazelles, Bernard; Huang, Shanqian; Xu, Bo; Yang, Qiqi; Pybus, Oliver G; Xu, Bing

2017-08-01

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia

PubMed Central

Sun, Zhe; Faria, Nuno Rodrigues; Yang, Jing; Cazelles, Bernard; Huang, Shanqian; Xu, Bo; Yang, Qiqi; Pybus, Oliver G.; Xu, Bing

2017-01-01

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation. PMID:28771468

Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent.

PubMed

Kapoor, Vaishali; Singh, Abhay K; Dey, Sharmistha; Sharma, Suresh C; Das, Satya N

2010-12-01

The aim of this study was to quantitate circulating COX-2 levels in patients with tobacco-related intraoral cancer and to evaluate antitumor activities of COX-2 peptide inhibitors in vitro on KB cell lines. We used a novel biosensor-based surface plasmon resonance (SPR) technique for estimation of circulating COX-2 levels in 76 patients with oral cancer and 43 normal individuals. Antitumor activities of five COX-2 inhibitory peptides were evaluated using propidium iodide labeling and flow cytometry, alamar blue, MTS, and annexin-V binding assays. Patients with oral cancer showed threefold increase in serum COX-2 level when compared to normal controls (P < 0.0001). Further, late-stage tumors and lymph node metastasis were associated with significant increase in serum COX-2 levels. Patients with higher circulating COX-2 also showed higher immunoreactivity to anti-COX-2 antibody in the lesions. The peptides significantly reduced viability and inhibited growth/proliferation, induced cytotoxicity and apoptosis in tumor cells. However, no such effect was observed either on normal human leukocytes or on MCF-7 cell line that did not over express COX-2. Our results indicate that SPR may be a useful proteomic technique for quantitative assessment of COX-2 and to identify patients with high-risk oral premalignant or occult cancer, as well as in monitoring response to novel COX-2 targeting strategies. Furthermore, COX-2 peptide inhibitors appear to be a new class of potent anticancer agent for human oral carcinoma.

Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker

PubMed Central

Burock, Susen; Herrmann, Pia; Wendler, Ina; Niederstrasser, Markus; Wernecke, Klaus-Dieter; Stein, Ulrike

2015-01-01

AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer patients. METHODS: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients, either newly diagnosed with gastric cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well as follow-up patients. Findings were controlled by using plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR. RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumor-free volunteers and gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage, compared to tumor-free volunteers: patients with tumors without metastasis (P = 0.005), with synchronous metastasis (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival when compared with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore, gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated (P = 0.001). CONCLUSION: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study. PMID:25574109

Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways

USDA-ARS?s Scientific Manuscript database

Increases in adipose tissue weight positively correlates with increased circulating inflammatory cytokines such as interleukin-6 (IL-6). We previously have shown that adipose stem cell produce significantly higher levels of IL-6 when compared to other cell types in the adipose tissue in genetically ...

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood–brain barrier: [17O]H2O JJVCPE MRI study

PubMed Central

Huber, Vincent J.; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L.

2018-01-01

The blood–brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow–Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow–Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [17O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [17O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB. PMID:29481527

Up-regulation of NKG2A inhibitory receptor on circulating NK cells contributes to transfusion-induced immunodepression in patients with β-thalassemia major.

PubMed

Zou, Yong; Song, Zhi-Xing; Lu, Ying; Liang, Xiao-Li; Yuan, Qing; Liao, Si-Hong; Bao, Jun-Jie

2016-08-01

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.

Association between circulating specific leukocyte types and incident chronic kidney disease: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Tian, Niu; Penman, Alan D; Manning, R Davis; Flessner, Michael F; Mawson, Anthony R

2012-01-01

Progressive renal fibrosis is a characteristic of all the diseases that cause renal failure and is invariably accompanied by a prominent leukocyte infiltration in the kidney. The goal of this study was to determine the association between the circulating specific leukocyte types and incident chronic kidney disease (CKD). In a cohort of 10,056 middle-aged white and African American adults, levels of circulating neutrophils, lymphocytes, and monocytes were measured at baseline; blood pressure (BP) and serum creatinine were measured and estimated glomerular filtration rate (eGFR) was calculated at baseline and 3 and 9 years later; and surveillance for first hospitalization or death with CKD was carried out over a mean follow-up of 7.4 years (maximum, 11.9 years). Increased neutrophil levels and decreased lymphocyte levels were significantly associated with greater CKD incidence after adjustment for covariates. African Americans tended to have similar but stronger patterns of association between circulating leukocytes and CKD incidence than whites, although the differences between race groups were not statistically significant. We also found that eGFR and BP were higher at each visit in African Americans than whites between ages 45 and 65. These findings support a potential role for circulating specific leukocytes in the pathogenesis of kidney dysfunction, especially in African Americans, indicating the leukocyte-related renal mechanism of essential hypertension (HT). Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

The strengthening relationship between Eurasian snow cover and December haze days in central North China after the mid-1990s

NASA Astrophysics Data System (ADS)

Yin, Zhicong; Wang, Huijun

2018-04-01

The haze pollution in December has become increasingly serious over recent decades and imposes damage on society, ecosystems, and human health. In addition to anthropogenic emissions, climate change and variability were conducive to haze in China. In this study, the relationship between the snow cover over eastern Europe and western Siberia (SCES) and the number of haze days in December in central North China was analyzed. This relationship significantly strengthened after the mid-1990s, which is attributed to the effective connections between the SCES and the Eurasian atmospheric circulations. During 1998-2016, the SCES significantly influenced the soil moisture and land surface radiation, and then the combined underlying drivers of enhanced soil moisture and radiative cooling moved the the East Asia jet stream northward and induced anomalous, anti-cyclonic circulation over central North China. Modulated by such atmospheric circulations, the local lower boundary layer, the decreased surface wind, and the more humid air were conducive to the worsening dispersion conditions and frequent haze occurrences. In contrast, from 1979 to 1997, the linkage between the SCES and soil moisture was negligible. Furthermore, the correlated radiative cooling was distributed narrowly and far from the key area of snow cover. The associated atmospheric circulations with the SCES were not significantly linked with the ventilation conditions over central North China. Consequently, the relationship between the SCES and the number of hazy days in central North China was insignificant before the mid-1990s but has strengthened and has become significant since then.

Effect of the tropical Pacific and Indian Ocean warming since the late 1970s on wintertime Northern Hemispheric atmospheric circulation and East Asian climate interdecadal changes

NASA Astrophysics Data System (ADS)

Chu, Cuijiao; Yang, Xiu-Qun; Sun, Xuguang; Yang, Dejian; Jiang, Yiquan; Feng, Tao; Liang, Jin

2018-04-01

Observation reveals that the tropical Pacific-Indian Ocean (TPIO) has experienced a pronounced interdecadal warming since the end of the 1970s. Meanwhile, the wintertime midlatitude Northern Hemispheric atmospheric circulation and East Asian climate have also undergone substantial interdecadal changes. The effect of the TPIO warming on these interdecadal changes are identified by a suite of AMIP-type atmospheric general circulation model experiments in which the model is integrated from September 1948 to December 1999 with prescribed historical, observed realistic sea surface temperature (SST) in a specific region and climatological SST elsewhere. Results show that the TPIO warming reproduces quite well the observed Northern Hemispheric wintertime interdecadal changes, suggesting that these interdecadal changes primarily originate from the TPIO warming. However, each sub-region of TPIO has its own distinct contribution. Comparatively, the tropical central-eastern Pacific (TCEP) and tropical western Pacific (TWP) warming makes dominant contributions to the observed positive-phase PNA-like interdecadal anomaly over the North Pacific sector, while the tropical Indian Ocean (TIO) warming tends to cancel these contributions. Meanwhile, the TIO and TWP warming makes dominant contributions to the observed positive NAO-like interdecadal anomaly over the North Atlantic sector as well as the interdecadal anomalies over the Eurasian sector, although the TWP warming's contribution is relatively small. These remote responses are directly attributed to the TPIO warming-induced tropical convection, rainfall and diabatic heating increases, in which the TIO warming has the most significant effect. Moreover, the TPIO warming excites a Gill-type pattern anomaly over the tropical western Pacific, with a low-level anticyclonic circulation anomaly over the Philippine Sea. Of three sub-regions, the TIO warming dominates such a pattern, although the TWP warming tends to cancel this effect. The anticyclonic circulation anomaly intensifies the southwesterly flow that transfers more moisture from the Bay of Bengal to East Asia and considerably increases the winter precipitation over the southern East Asia. This is strongly supported by the observational fact that there has been a significant interdecadal increase of winter precipitation over the southern China since the end of the 1970s.

An increase level of acylation stimulating protein is correlated with metabolic risk markers in North Indian obese women.

PubMed

Mishra, Supriya; Gupta, Vani; Mishra, Sameeksha; Gupta, Vandana; Mahdi, Abbas Ali; Sachan, Rekha

2017-12-01

The present study was to investigate the association between serum acylation stimulating protein (ASP) level with metabolic risk factors in North Indian obese women. This is a case control study, total n=322 women aged between 20 and 45 years (n=162 with metabolic syndrome & n=160 without metabolic syndrome) were recruited for the study according to National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Serum ASP level were determined by enzyme linked immunosorbent assay. Results indicated that circulating ASP and other metabolic risk factors (waist circumference, triglycerides, fasting plasma glucose etc) were significantly higher in women with metabolic syndrome (WmetS) than in women without syndrome (WometS) (p<0.001). Furthermore circulating ASP was significantly higher possitively correlated with waist circumference (r=0.51, p<0.001), triglyceride (r=0.56, p<0.001), glucose (r=0.70, p<0.001), and negatively correlated with high density lipoprotein(r=-0.56, p<0.001) in women with metabolic syndrome. Conclusively circulating ASP was found to be significantly associated with hyperlipidemia, obesity and obesity related disorders in North Indian obese women. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Changing monsoon and midlatitude circulation interactions over the Western Himalayas and possible links to occurrences of extreme precipitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Priya, P.; Krishnan, R.; Mujumdar, Milind

Historical rainfall records reveal that the frequency and intensity of extreme precipitation events, during the summer monsoon (June to September) season, have significantly risen over the Western Himalayas (WH) and adjoining upper Indus basin since 1950s. Using multiple datasets, the present study investigates the possible coincidences between an increasing trend of precipitation extremes over WH and changes in background flow climatology. The present findings suggest that the combined effects of a weakened southwest monsoon circulation, increased activity of transient upper-air westerly troughs over the WH region, enhanced moisture supply by southerly winds from the Arabian Sea into the Indus basinmore » have likely provided favorable conditions for an increased frequency of certain types of extreme precipitation events over the WH region in recent decades.« less

Effects of thyroxin therapy on different analytes related to obesity and inflammation in dogs with hypothyroidism.

PubMed

Tvarijonaviciute, A; Jaillardon, L; Cerón, J J; Siliart, B

2013-04-01

Hypothyroidism in dogs is accompanied by changes in intermediary metabolism including alterations in bodyweight (BW), insulin resistance, and lipid profile. In this study, changes in selected adipokines (adiponectin, leptin), butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with hypothyroidism under thyroxin therapy. Blood samples were collected when hypothyroidism was diagnosed (before treatment) and after treatment with thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group A), whereas the remainder were considered to have been insufficiently treated (group B). Following treatment, group A dogs demonstrated a statistically significant decrease in canine thyroid stimulating hormone (c-TSH) (P<0.001) and an increase in free thyroxine (fT4) (P<0.001) concentrations, associated with a significant decrease in BW (P<0.05), leptin (P<0.01), and adiponectin, (P<0.001) and an increase in BChE (P<0.01) and Hp (P<0.05). Group B dogs showed no statistically significant changes in c-TSH, but had a significant increase in fT4 (P<0.001) accompanied by a significant decrease in adiponectin (P<0.05) of lower magnitude than group A. No significant changes in the mean circulating levels of APPs were observed in both groups, with the exception of an increase in Hp (P<0.05) in group A. In summary, the successful treatment of hypothyroidism reduces circulating levels of adiponectin and leptin, while increasing BChE activity in dogs. The mean increase in Hp values and decrease in SAA for some of the dogs after treatment warrants further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dengue in Rio Grande do Sul, Brazil: 2014 to 2016.

PubMed

Gregianini, Tatiana Schaffer; Tumioto-Giannini, Gabriela Luchiari; Favreto, Cátia; Plentz, Luciana Ciarelli; Ikuta, Nilo; da Veiga, Ana B Gorini

2018-01-01

The first autochthonous dengue case in Rio Grande do Sul (RS), Southern Brazil, occurred in 2007. In 2008 and 2009, only imported cases were reported in RS, but from 2010 to 2013, reports of autochthonous infections increased significantly. This study analyzes and discusses laboratory, demographic, and clinical data regarding dengue cases in RS, from 2014 to 2016. This study analyzed 13,420 serum samples from notified patients with suspicion of dengue fever in RS from 2014 to 2016. Seasonality of positive cases, viral serotypes, and clinical and epidemiological aspects were analyzed. There was no difference in gender (P = .4); dengue fever occurred mainly in adults, with similar distribution among age groups. The number of dengue virus (DENV) cases increased from 89 cases in 2014 to 2518 in 2016. Dengue virus 1 was the most prevalent circulating serotype during this period (97.5% of cases). Dengue virus infections show peaks in March and April (late summer and early autumn), after periods of high temperatures and rainfall. In 2014, dengue cases were concentrated in the northwestern and eastern regions of RS, and in 2015 and 2016, the northern region also confirmed a high number of cases. With increase in DENV circulation in RS, a rise in the number of autochthonous infections was also observed, mainly in highly urbanized areas. This study revealed that circulation of DENV in RS increased significantly in 2015 and 2016, with a rise in the number of autochthonous infections and cocirculation with Chikungunya and Zika viruses, recently introduced into RS. Copyright © 2017 John Wiley & Sons, Ltd.

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.

PubMed

DeJarnett, Natasha; Yeager, Ray; Conklin, Daniel J; Lee, Jongmin; O'Toole, Timothy E; McCracken, James; Abplanalp, Wes; Srivastava, Sanjay; Riggs, Daniel W; Hamzeh, Ihab; Wagner, Stephen; Chugh, Atul; DeFilippis, Andrew; Ciszewski, Tiffany; Wyatt, Brad; Becher, Carrie; Higdon, Deirdre; Ramos, Kenneth S; Tollerud, David J; Myers, John A; Rai, Shesh N; Shah, Jasmit; Zafar, Nagma; Krishnasamy, Sathya S; Prabhu, Sumanth D; Bhatnagar, Aruni

2015-11-01

Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways. © 2015 American Heart Association, Inc.

The impact of oceanic heat transport on the atmospheric circulation

NASA Astrophysics Data System (ADS)

Lucarini, Valerio; Lunkeit, Frank

2017-04-01

A general circulation model of intermediate complexity with an idealized Earth-like aquaplanet setup is used to study the impact of changes in the oceanic heat transport on the global atmospheric circulation. Focus is on the atmospheric mean meridional circulation and global thermodynamic properties. The atmosphere counterbalances to a large extent the imposed changes in the oceanic heat transport, but, nonetheless, significant modifications to the atmospheric general circulation are found. Increasing the strength of the oceanic heat transport up to 2.5 PW leads to an increase in the global mean near-surface temperature and to a decrease in its equator-to-pole gradient. For stronger transports, the gradient is reduced further, but the global mean remains approximately constant. This is linked to a cooling and a reversal of the temperature gradient in the tropics. Additionally, a stronger oceanic heat transport leads to a decline in the intensity and a poleward shift of the maxima of both the Hadley and Ferrel cells. Changes in zonal mean diabatic heating and friction impact the properties of the Hadley cell, while the behavior of the Ferrel cell is mostly controlled by friction. The efficiency of the climate machine, the intensity of the Lorenz energy cycle and the material entropy production of the system decline with increased oceanic heat transport. This suggests that the climate system becomes less efficient and turns into a state of reduced entropy production as the enhanced oceanic transport performs a stronger large-scale mixing between geophysical fluids with different temperatures, thus reducing the available energy in the climate system and bringing it closer to a state of thermal equilibrium.

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE.

PubMed

Ason, Brandon; van der Hoorn, José W A; Chan, Joyce; Lee, Edward; Pieterman, Elsbet J; Nguyen, Kathy Khanh; Di, Mei; Shetterly, Susan; Tang, Jie; Yeh, Wen-Chen; Schwarz, Margrit; Jukema, J Wouter; Scott, Rob; Wasserman, Scott M; Princen, Hans M G; Jackson, Simon

2014-11-01

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower risk (47-88%) of experiencing a cardiovascular event. Here, we utilized pcsk9(-/-) mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9(-/-) mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (-45%) and TGs (-36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (-91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Circulating rotavirus-specific T cells have a poor functional profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parra, Miguel; Herrera, Daniel; Jácome, María Fernanda

Frequencies of circulating T cells producing IFN-γ, TNF-α, and IL-2, and percentages of T cells proliferating after stimulation with rotavirus (RV), tetanus toxoid, and influenza were evaluated in PBMC derived from healthy adults and children. In addition, the potential anergic state of RV-specific T cells was analyzed by stimulation of PBMC with RV antigen in the presence of three anergy inhibitors (rIL-2, rIL-12, or DGKα-i). The quality and magnitude of RV-T cell responses were significantly lower than those of tetanus toxoid and influenza antigens. RV-CD4 T cell response was enriched in monofunctional IFN-γ{sup +} cells, while influenza-CD4 and tetanus toxoid-CD4more » T cell responses were enriched in multifunctional T cells. Moreover, rIL-2 – unlike rIL-12 or DGKα-i – increased the frequencies of RV-CD4 TNF-α{sup +}, CD4 IFN-γ{sup +}, and CD8 IFN-γ{sup +} cells. Thus, circulating RV-T cells seem to have a relatively poor functional profile that may be partially reversed in vitro by the addition of rIL-2. - Highlights: • The quality and magnitude of circulating RV-T cell responses are relatively poor. • Circulating RV-CD4 T cells are enriched in monofunctional IFN-γ+ cells. • Treatment with rIL-2 increased the frequencies of cytokine secreting RV-T cells.« less

Effect of increased exercise in school children on physical fitness and endothelial progenitor cells: a prospective randomized trial.

PubMed

Walther, Claudia; Gaede, Luise; Adams, Volker; Gelbrich, Götz; Leichtle, Alexander; Erbs, Sandra; Sonnabend, Melanie; Fikenzer, Kati; Körner, Antje; Kiess, Wieland; Bruegel, Mathias; Thiery, Joachim; Schuler, Gerhard

2009-12-01

The aim of this prospective, randomized study was to examine whether additional school exercise lessons would result in improved peak oxygen uptake (primary end point) and body mass index-standard deviation score, motor and coordinative abilities, circulating progenitor cells, and high-density lipoprotein cholesterol (major secondary end points). Seven sixth-grade classes (182 children, aged 11.1+/-0.7 years) were randomized to an intervention group (4 classes with 109 students) with daily school exercise lessons for 1 year and a control group (3 classes with 73 students) with regular school sports twice weekly. The significant effects of intervention estimated from ANCOVA adjusted for intraclass correlation were the following: increase of peak o(2) (3.7 mL/kg per minute; 95% confidence interval, 0.3 to 7.2) and increase of circulating progenitor cells evaluated by flow cytometry (97 cells per 1 x 10(6) leukocytes; 95% confidence interval, 13 to 181). No significant difference was seen for body mass index-standard deviation score (-0.08; 95% confidence interval, -0.28 to 0.13); however, there was a trend to reduction of the prevalence of overweight and obese children in the intervention group (from 12.8% to 7.3%). No treatment effect was seen for motor and coordinative abilities (4; 95% confidence interval, -1 to 8) and high-density lipoprotein cholesterol (0.03 mmol/L; 95% confidence interval, -0.08 to 0.14). Regular physical activity by means of daily school exercise lessons has a significant positive effect on physical fitness (o(2)max). Furthermore, the number of circulating progenitor cells can be increased, and there is a positive trend in body mass index-standard deviation score reduction and motor ability improvement. Therefore, we conclude that primary prevention by means of increasing physical activity should start in childhood. URL: http://www.clinicaltrials.gov. Identifier: NCT00176371.

The efficiency of a dedicated staff on operating room turnover time in hand surgery.

PubMed

Avery, Daniel M; Matullo, Kristofer S

2014-01-01

To evaluate the effect of orthopedic and nonorthopedic operating room (OR) staff on the efficiency of turnover time in a hand surgery practice. A total of 621 sequential hand surgery cases were retrospectively reviewed. Turnover times for sequential cases were calculated and analyzed with regard to the characteristics of the OR staff being primarily orthopedic or nonorthopedic. A total of 227 turnover times were analyzed. The average turnover time with all nonorthopedic staff was 31 minutes, for having only an orthopedic surgical technician was 32 minutes, for having only an orthopedic circulator was 25 minutes, and for having both an orthopedic surgical technician and a circulator was 20 minutes. Statistical significance was seen when comparing only an orthopedic surgical technician versus both an orthopedic circulator and a surgical technician and when comparing both nonorthopedic staff versus both an orthopedic circulator and a surgical technician. OR efficiency is being increasingly evaluated for its effect on hospital revenue and OR staff costs. Reducing turnover time is one aspect of a multifaceted solution in increasing efficiency. Our study showed that, for hand surgery, orthopedic-specific staff can reduce turnover time. Economic/Decision Analysis III. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Association between thyroid hormones and TRAIL.

PubMed

Bernardi, Stella; Bossi, Fleur; Toffoli, Barbara; Giudici, Fabiola; Bramante, Alessandra; Furlanis, Giulia; Stenner, Elisabetta; Secchiero, Paola; Zauli, Giorgio; Carretta, Renzo; Fabris, Bruno

2017-11-01

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels. TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells. Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro. Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Preparation, pharmacokinetics and tumour-suppressive activity of berberine liposomes.

PubMed

Wang, Xinghui; Wang, Qiong; Liu, Zhihui; Zheng, Xiao

2017-06-01

Berberine (BBR) has shown promising antitumour effects in vitro. However, intravenous administration of BBR solution is complicated by lethal adverse cardiovascular effects. The aim of this study was to prepare common and polyethylene glycol (PEG)-modified long-circulating BBR liposomes and evaluate their efficacy and safety as potential antitumour agents. Physiochemical properties of common and long-circulating BBR liposomes were characterized including particle size, Zeta potential and thermal stability. Pharmacokinetic and tissue distribution study of liposomal BBR was performed in rats and tumour-bearing nude mice, respectively. Antitumour efficacy and safety were observed in SGC-7901 tumour-xenografted mice. Berberine liposomes showed homogenous morphology, storage stability and sustained-releasing behaviour in vitro. BBR liposomes led to significantly increased circulation retention of BBR in comparison with BBR solution. In tumour-bearing mice, BBR liposomes selectively increased BBR concentrations in the liver, spleen, lung and tumour, while conferred lower distribution to the heart and kidney. Importantly, chronic administration of BBR liposomes proved effective and safe in suppressing the tumour growth in nude mice, especially the PEG-modified long-circulating liposomes. Our study suggested that BBR liposomes may provide a safe form of intravenous drug therapy for strengthening the antitumour effects of BBR. © 2017 Royal Pharmaceutical Society.

α1-Adrenergic receptor downregulates hepatic FGF21 production and circulating FGF21 levels in mice.

PubMed

Nonogaki, Katsunori; Kaji, Takao

2017-01-18

Fibroblast growth factor 21 (FGF21) is primarily secreted by the liver as an endocrine hormone and is suggested as a promising target for the treatment of metabolic diseases. FGF21 acts centrally to exert its effects on energy expenditure and body weight via the sympathetic nervous system in mice. Here we show that intraperitoneal injection of phentolamine (an α-adrenergic receptor antagonist, 5mg/kg) significantly increased plasma FGF21 levels compared with the saline controls in C57BL6J mice, whereas alprenolol (a β-adrenergic receptor antagonist, 6mg/kg) had no effect. In addition, intraperitoneal injection of prazosin (an α1-adrenergic receptor antagonist, 5mg/kg) significantly increased plasma FGF21 levels compared with the controls, whereas yohimbine (an α2-adrenergic receptor antagonist, 5mg/kg) had no effect. Moreover, the treatment with prazosin significantly increased the expression of hepatic FGF21, while having no effect on the expression of hepatic PPARα and PPARγ. After a 5-h fast, intraperitoneal injection of prazosin significantly increased plasma FGF21 levels and impaired glucose tolerance compared with controls. These findings suggest that α1-adrenergic receptor downregulates the expression of hepatic FGF21 and plasma FGF21 levels independently of feeding and hepatic PPARα and PPARγ expression in mice, and that the increases in circulating FGF21 levels might be related to impaired glucose tolerance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A comparison of whole body vibration and moist heat on lower extremity skin temperature and skin blood flow in healthy older individuals.

PubMed

Lohman, Everett B; Sackiriyas, Kanikkai Steni Balan; Bains, Gurinder S; Calandra, Giovanni; Lobo, Crystal; Nakhro, Daniel; Malthankar, Gauri; Paul, Sherwine

2012-07-01

Tissue healing is an intricate process that is regulated by circulation. Heat modalities have been shown to improve skin circulation. Recent research supports that passive vibration increases circulation without risk of burns. Study purpose is to compare and determine effects of short duration vibration, moist heat, and a combination of the two on skin blood flow (SBF) and skin temperature (ST) in elderly, non-diabetic individuals following short-term exposure. Ten subjects, 3 female and 7 male (55-73 years of age), received two interventions over three days: 1--Active vibration, 2--passive vibration, 3--moist heat, 4--moist heat combined with passive vibration (MHPV), 5--a commercial massaging heating pad, and 6--no intervention. SBF and ST were measured using a MOOR Laser Doppler before and after the intervention and the third measurement were taken 10 minutes following. Mean SBF following a ten-minute intervention were significantly different in the combination of moist heat and passive vibration from the control, active vibration, and the commercial massaging heating pad. Compared to baseline measurements, this resulted in mean SBF elevation to 450% (at conclusion of 10 minutes of intervention) and 379% (10 minutes post). MHPV (p=0.02) showed significant changes in ST from the commercial massaging heating pad, passive vibration, and active vibration interventions. SBF in the lower legs showed greatest increase with MHPV. Interventions should be selected that are low risk while increasing lower extremity skin blood flow.

Is Kinesio Taping to Generate Skin Convolutions Effective for Increasing Local Blood Circulation?

PubMed Central

Yang, Jae-Man; Lee, Jung-Hoon

2018-01-01

Background It is unclear whether traditional application of Kinesio taping, which produces wrinkles in the skin, is effective for improving blood circulation. This study investigated local skin temperature changes after the application of an elastic therapeutic tape using convolution and non-convolution taping methods (CTM/NCTM). Material/Methods Twenty-eight pain-free men underwent CTM and NCTM randomly applied to the right and left sides of the lower back. Using infrared thermography, skin temperature was measured before, immediately after application, 5 min later, 15 min later, and after the removal of the tape. Results Both CTM and NCTM showed a slight, but significant, decrease in skin temperature for up to 5 min. The skin temperature at 15 min and after the removal of the tape was not significantly different from the initial temperature for CTM and NCTM. There were also no significant differences in the skin temperatures between CTM and NCTM. Conclusions Our findings do not support a therapeutic effect of wrinkling the skin with elastic tape application as a technique to increase local blood flow. PMID:29332101

Is Kinesio Taping to Generate Skin Convolutions Effective for Increasing Local Blood Circulation?

PubMed

Yang, Jae-Man; Lee, Jung-Hoon

2018-01-14

BACKGROUND It is unclear whether traditional application of Kinesio taping, which produces wrinkles in the skin, is effective for improving blood circulation. This study investigated local skin temperature changes after the application of an elastic therapeutic tape using convolution and non-convolution taping methods (CTM/NCTM). MATERIAL AND METHODS Twenty-eight pain-free men underwent CTM and NCTM randomly applied to the right and left sides of the lower back. Using infrared thermography, skin temperature was measured before, immediately after application, 5 min later, 15 min later, and after the removal of the tape. RESULTS Both CTM and NCTM showed a slight, but significant, decrease in skin temperature for up to 5 min. The skin temperature at 15 min and after the removal of the tape was not significantly different from the initial temperature for CTM and NCTM. There were also no significant differences in the skin temperatures between CTM and NCTM. CONCLUSIONS Our findings do not support a therapeutic effect of wrinkling the skin with elastic tape application as a technique to increase local blood flow.

Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.

PubMed

Rodriguez-Mateos, Ana; Rendeiro, Catarina; Bergillos-Meca, Triana; Tabatabaee, Setareh; George, Trevor W; Heiss, Christian; Spencer, Jeremy Pe

2013-11-01

There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.

A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging.

PubMed

Yang, Shanshan; Gerow, Kenneth G; Huber, Hillary F; Considine, McKenna M; Li, Cun; Mattern, Vicki; Comuzzie, Anthony G; Ford, Stephen P; Nathanielsz, Peter W

2017-05-09

Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

RAFT-synthesized Graft Copolymers that Enhance pH-dependent Membrane Destabilization and Protein Circulation Times

PubMed Central

Crownover, Emily; Duvall, Craig L.; Convertine, Anthony; Hoffman, Allan S.; Stayton, Patrick S.

2012-01-01

Here we describe a new graft copolymer architecture of poly(propylacrylic acid) (polyPAA) that displays potent pH-dependent, membrane-destabilizing activity and in addition is shown to enhance protein blood circulation kinetics. PolyPAA containing a single telechelic alkyne functionality was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization with an alkyne-functional chain transfer agent (CTA) and coupled to RAFT polymerized poly(azidopropyl methacrylate) (polyAPMA) through azide-alkyne [3+2] Huisgen cycloaddition. The graft copolymers become membrane destabilizing at endosomal pH values and are active at significantly lower concentrations than the linear polyPAA. A biotin terminated polyPAA graft copolymer was prepared by grafting PAA onto polyAPMA polymerized with a biotin functional RAFT CTA. The blood circulation time and biodistribution of tritium labeled avidin conjugated to the polyPAA graft copolymer was characterized along with a clinically utilized 40 kDa branched polyethylene glycol (PEG) also possessing biotin functionalization. The linear and graft polyPAA increase the area under the curve (AUC) over avidin alone by 9 and 12 times, respectively. Furthermore, polyPAA graft copolymer conjugates accumulated in tumor tissue significantly more than the linear polyPAA and the branched PEG conjugates. The collective data presented in this report indicate that the polyPAA graft copolymers exhibit robust pH-dependent, membrane-destabilizing activity, low cytotoxicity and significantly enhance blood circulation time and tumor accumulation. PMID:21699931

Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery.

PubMed

Ejarque, Miriam; Borlaug, Marianne; Vilarrasa, Nuria; Martinez-Perez, Bruno; Llauradó, Gemma; Megía, Ana; Helland, Thomas; Gutierrez, Cristina; Serena, Carolina; Folkestad, Oddry; Nuñez-Roa, Catalina; Roche, Kelly; Casajoana, Ana; Fradera, Rosa; González-Clemente, José Miguel; López, Miguel; Mohn, Arne C; Nedrebø, Bjørn G; Nogueiras, Ruben; Mellgren, Gunnar; Fernø, Johan; Fernández-Veledo, Sonia; Vendrell, Joan

2017-06-01

This work aimed to explore the link between angiopoietin-like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross-sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.

PubMed

van der Post, J A; van Buul, B J; Hart, A A; van Heerikhuize, J J; Pesman, G; Legros, J J; Steegers, E A; Swaab, D F; Boer, K

1997-03-01

Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 < P < 0.98) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P < 0.0001 to P < 0.005). Platelet-bound AVP decreased and Np-OT increased during pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy, whether or not in combination with severe sodium restriction, support the absence of significant non-osmotic stimulation of AVP during pregnancy.

Increased numbers of circulating ICOS⁺ follicular helper T and CD38⁺ plasma cells in patients with newly diagnosed primary biliary cirrhosis.

PubMed

Wang, Li; Sun, Xiguang; Qiu, Jinpeng; Cai, Yanjun; Ma, Liang; Zhao, Pingwei; Jiang, Yanfang

2015-02-01

Aberrant activation of follicular helper T (TFH) and B cells is associated with the development of autoimmune diseases. However, little is known about the potential role of these cells in the development of primary biliary cirrhosis (PBC). This study aimed at characterizing the numbers of different subsets of circulating Tfh and B cells as well as evaluating their potential association with the levels of immunoglobulins and autoantibodies in newly diagnosed PBC patients. The numbers of circulating CD27(+), CD38(+), CD86(+) and CD95(+) B cells as well as inducible T cell costimulator (ICOS)(+) and programmed death-1 (PD-1)(+), IL-21(+) TFH cells were examined in 58 patients with newly diagnosed PBC and 30 matched healthy controls (HCs). The numbers of circulating CD38(+)CD19(+), CD86(+)CD19(+), and CD95(+)CD19(+) B cells; CD3(+)CD4(+)CXCR5(+)ICOS(+) and CD3(+)CD4(+)CXCR5(+)PD-1(+) Tfh cells; and the levels of serum IL-21 in the PBC patients were significantly greater, but the numbers of CD27(+)CD19(+) B cells were significantly less than those in the HCs (p < 0.05). The numbers of CD3(+)CD4(+)CXCR5(+)ICOS(+) Tfh cells were positively correlated with the numbers of CD38(+)CD19(+) and CD86(+)CD38(+)CD19(+) B cells and the levels of serum anti-mitochondrial antibodies against M2 antigen (AMA-M2), AMA and immunolgubin M (IgM) in the PBC patients. The levels of serum IL-21 were positively correlated with the levels of serum AMA-M2, AMA, IgG and IgM, but negatively with the numbers of CD27(+)CD19(+) B cells in the PBC patients. Increased numbers of circulating ICOS(+) and IL-21(+) Tfh and CD38(+) plasma cells may be exhibited by patients with recent diagnoses of PBC.

Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

PubMed

Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

2015-07-01

Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial growth factor (VEGF) inside the liver and in the portal circulation. Pharmacological manipulation of AA metabolites may be beneficial for cirrhotic portal hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.

Circulating soluble LIGHT/TNFSF14 is increased and associated with IL-8 concentration in chronic spontaneous urticaria.

PubMed

Kasperska-Zając, Alicja; Damasiewicz-Bodzek, Aleksandra; Grzanka, Ryszard; Skrzypulec-Frankel, Agnieszka; Bieniek, Katarzyna; Sikora-Żydek, Agnieszka; Jochem, Jerzy

2018-01-01

LIGHT (homologous to lymphotoxins, exhibiting inducible expression, and competing with herpes simplex virus (HSV) glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) has been involved in various autoimmune and inflammatory disorders. LIGHT induces the expression of interleukin-8 (IL-8), which is up-regulated in chronic spontaneous urticaria (CSU). To determine circulating soluble LIGHT concentration and its relationship with IL-8 concentration in patients with CSU. Concentrations of LIGHT, IL-8, and C-reactive protein (CRP) were determined in plasma or serum of CSU patients by an enzyme-linked immunosorbent assay. LIGHT plasma concentration was significantly higher in moderate-severe CSU patients as compared with the healthy subjects, but not with mild CSU patients. There were significant correlations between increased LIGHT and IL-8 concentrations, but not with increased CRP in CSU patients. Enhanced plasma concentrations of soluble LIGHT and its association with IL-8 concentration suggest the role of LIGHT in systemic inflammatory activation in CSU patients. We hypothesize that LIGHT-mediated immune-inflammatory response plays a role in severe phenotypes of the disease.

Circulating erythroblasts in maternal blood are not elevated before onset of preterm labor.

PubMed

Hoesli, Irene; Danek, Milan; Lin, Dexin; Li, Ying; Hahn, Sinuhe; Holzgreve, Wolfgang

2002-11-01

Preterm labor has recently been reported to be associated with an increased release of cell free fetal deoxyribonucleic acid (DNA) into the maternal circulation. We have previously observed increases in both fetal cell traffic and cell free fetal DNA in preeclamptic pregnancies. In this study, we investigated whether fetal cell traffic is also disturbed in pregnancies with preterm labor. In a case-control study, we examined 47 pregnancies complicated by preterm contractions that occurred between 20 and 34 weeks' gestation and an equal number of matched controls. Erythroblasts were enriched for by magnetic cell sorting and enumerated. These values were then correlated with subsequent pregnancy outcome. In the study group 16 patients delivered prematurely (subgroup A). The other 31 (subgroup B) delivered at term, as did all those in the control group. No significant difference was noted in erythroblast numbers between either one of the subgroups and the controls. Contrary to the reported increased levels of free fetal DNA in maternal serum, erythroblasts in maternal blood are not elevated significantly in pregnancies with threatened premature labor or in those that deliver preterm.

Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners.

PubMed

Rehm, K; Sunesara, I; Marshall, G D

2015-10-01

Exercise training can alter immune function. Marathon training has been associated with an increased susceptibility to infectious diseases and an increased activity of inflammatory-based diseases, but the precise mechanisms are unknown. The purpose of this study was to compare levels of circulating CD4+  T cell subsets in the periphery of marathon-trained runners and matched non-marathon controls. 19 recreational marathoners that were 4 weeks from running a marathon and 19 demographically-matched healthy control subjects had the percentage of CD4+ T cell subpopulations (T helper 1, T helper 2, T helper 1/T helper 2 ratio, regulatory T cells, CD4+ IL10+, and CD4+ TGFβ+ (Transforming Growth Factor-beta) measured by flow cytometry. Marathon-trained runners had significantly less T helper 1 and regulatory T cells and significantly more T helper 2, CD4+ IL10+, and TGFβ+ cells than the control subjects. The alterations in the percentage of T helper 1 and T helper 2 cells led to a significantly lower T helper 1/T helper 2 ratio in the marathon-trained runners. These data suggest that endurance-based training can increase the number of anti-inflammatory cells. This may be a potential mechanism for the increased incidence of both infectious and inflammatory diseases observed in endurance athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

Major surgical trauma induces proteolysis of insulin-like growth factor binding protein-3 in transgenic mice and is associated with a rapid increase in circulating levels of matrix metalloproteinase-9.

PubMed

Belizon, A; Kirman, I; Balik, E; Karten, M; Jain, S; Whelan, R L

2007-04-01

The authors previously demonstrated a significant decrease in plasma levels of intact insulin-like growth factor binding protein-3 (IGFBP-3) after major open but not after laparoscopic-assisted surgery in humans. They postulated that this decrease may have an effect on postoperative tumor growth. It also has been shown that plasma levels of matrix metalloproteinase-9 (MMP-9), a protease capable of degrading IGFBP-3, are transiently increased after open colectomy in humans. The authors aimed to develop an animal model that would allow further study of the effect that surgical trauma has on plasma levels IGFBP-3 and MMP-9. In addition, they set out to assess the concentration of MMP-9 in circulating monocytes before and after surgery. The 30 mice included in this study were divided into three groups: sham laparotomy, carbon dioxide (CO2) pneumoperitoneum, and anesthesia control. All mice were IGFBP-3 transgenics (overexpressing human IGFBP-3) on a CD1 background. The mice were anesthetized using ketamine and xylazine. Blood was drawn retroorbitally 48 h before the procedure. The duration of the procedure was 30 min. The animals were killed 24 h postoperatively and blood was drawn. Intact IGFBP-3 levels were measured using a combination of Western blot analysis and enzyme-linked immunoassay (ELISA) at the two time points: before and after the operation. Plasma and peripheral blood mononuclear cell levels of MMP-9 were measured at each time point using zymography. Mononuclear cell lysates were used to determine intracellular MMP-9 levels. Plasma levels of intact IGFBP-3 were significantly lower than preoperative levels after sham laparotomy. A mean decrease of 76.6% was noted (p < 0.05). Zymography demonstrated significantly higher plasma MMP-9-related proteolytic activity than observed preoperatively after sham laparotomy (78.5 vs 42.3 Relative Units [RU]; p < 0.05). In the pneumoperitoneum group, no significant decrease was found between the pre- and postoperative levels of intact IGFBP-3. A nonsignificant increase in MMP-9 was noted after CO2 pneumoperitoneum (38 RU preoperatively vs. 46.4 RU postoperatively; p > 0.05). The anesthesia control group did not demonstrate a significant change in either circulating intact IGFBP-3 levels or MMP-9 levels. Mononuclear intracellular levels of MMP-9 were significantly lower after laparotomy than the preoperative levels (3 vs 37 RU). The postprocedure intracellular levels of MMP-9 were not significantly decreased in the pneumoperitoneum or anesthesia control group. Plasma levels of intact IGFBP-3, a cell growth regulating factor, were found to be decreased significantly after laparotomy. This decrease was not seen after pneumoperitoneum. Depletion of intact IGFBP-3 after laparotomy correlated with a rapid release of MMP-9 from mononuclear cells and an increase in circulating plasma MMP-9 levels. Matrix metalloproteinase-9 may play an important role in IGFBP-3 proteolysis after surgical trauma. Furthermore, circulating mononuclear cells are one source of MMP-9 after surgery. Finally, the model used reproduces events in humans after surgery, and thus should permit further study on the mechanism of IGFBP-3 proteolysis after surgical trauma.

Overexpression of porcine lipoprotein-associated phospholipase A2 in swine.

PubMed

Tang, Xiaochun; Wang, Gangqi; Liu, Xingxing; Han, Xiaolei; Li, Zhuang; Ran, Guangyao; Li, Zhanjun; Song, Qi; Ji, Yuan; Wang, Haijun; Wang, Yuhui; Ouyang, Hongsheng; Pang, Daxin

2015-09-25

Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse circulation, it predominantly binds to high-density lipoprotein cholesterol (HDL-C) and exhibits anti-inflammatory properties. To further investigate the effects of Lp-PLA2 in the circulation, we generated over-expressed Lp-PLA2 transgenic swine. The eukaryotic expression plasmid of porcine Lp-PLA2 which driven by EF1α promoter was constructed and generate transgenic swine via SCNT. The expression and activity of Lp-PLA2 in transgenic swine were evaluated, and the total cholesterol (TC), HDL-C, LDL-C and triglyceride (TG) levels in the fasting and fed states were also assessed. Compared with wild-type swine controls, the transgenic swine exhibited elevated Lp-PLA2 mRNA levels and activities, and the activity did not depend on the feeding state. The TC, HDL-C and LDL-C levels were not significantly increased. There was no change in the TG levels in the fasting state between transgenic and control pigs. However, in the fed state, the TG levels of transgenic swine were slightly increased compared with the control pigs and were significantly elevated compared with the fasting state. In addition, inflammatory gene (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1 and tumor necrosis factor [TNF]-α) mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly increased. The results demonstrated that Lp-PLA2 is associated with triglycerides which may be helpful for understanding the relationship of this protein with cardiovascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

PubMed Central

Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S. Ananth; Hennessy, Annemarie

2016-01-01

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia due to endothelial dysfunction. Circulating sFLT-1 (soluble fms-like tyrosine kinase 1) increases and PlGF (placental growth factor) reduces prior to and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of an 182 day pregnancy). Two weeks after uteroplacental ischemia (UPI), rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100μg/kg/day) for 5 days. Blood pressure (BP) was monitored by intra-arterial radiotelemetry, sFLT-1 and PlGF by ELISA. UPI resulted in experimental preeclampsia evidenced by increased BP, proteinuria and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after UPI. rhPlGF reduced SBP in the treated group (-5.2mmHg+0.8mmHg;from 132.6+6.6mmHg to 124.1+7.6mmHg) compared to an increase in SBP in controls (6.5mmHg+3mmHg; from 131.3+1.5mmHg to 138.6+1.5mmHg). Proteinuria reduced in the treated group (-72.7±55.7mg/mmol) but increased in the control group. Circulating sFLT-1 was not affected by the administration of PlGF, however a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference in the weights or lengths of the neonates in the rhPlGF or control group, however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. PMID:27091894

Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

PubMed

Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S Ananth; Hennessy, Annemarie

2016-06-01

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 μg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. © 2016 American Heart Association, Inc.

Perioperative circulating tumor cell detection: Current perspectives

PubMed Central

Kaifi, Jussuf T.; Li, Guangfu; Clawson, Gary; Kimchi, Eric T.; Staveley-O'Carroll, Kevin F.

2016-01-01

ABSTRACT Primary cancer resections and in selected cases surgical metastasectomies significantly improve survival, however many patients develop recurrences. Circulating tumor cells (CTCs) function as an independent marker that could be used in the prognostication of different cancers. Sampling of blood and bone marrow compartments during cancer resections is a unique opportunity to increase individual tumor cell capture efficiency. This review will address the diagnostic and therapeutic potentials of perioperative tumor isolation and highlight the focus of future studies on characterization of single disseminated cancer cells to identify targets for molecular therapy and immune escape mechanisms. PMID:27045201

[Effect of a drug composition containing pyroglutamic acid and pyrrolidone on the cerebral circulation].

PubMed

Lun'shina, E V; Gan'shina, T S; Mirzoian, R S

2002-01-01

A drug composition containing pyroglutamic acid and pyrrolidone produces a significant effect on the cerebral circulation in rats and cats, which is manifested by increased cerebral blood flow and by a dose-independent improvement of the microcirculation. The cerebrovascular effects were similarly pronounced in both rats and cats which indicates that the drug action is independent of the animal species. The drug combination studied did not exhibit antiserotonin activity. The data obtained show evidence of a substantial contribution of the cerebrovascular component to the neuroprotector action of the drug composition studied.

Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction

PubMed Central

Panikkar, Archana; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A.; Wykes, Michelle; Moss, Denis J.; Rickinson, Alan; Balfour, Henry H.

2015-01-01

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. PMID:26109734

Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs

PubMed Central

Fain, John N.; Company, Joseph M.; Booth, Frank W.; Laughlin, M. Harold; Padilla, Jaume; Jenkins, Nathan T.; Bahouth, Suleiman W.; Sacks, Harold S.

2013-01-01

Background Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin. Methods Castrated male pigs of the Rapacz familial hypercholesterolemic (FHM) strain and normal (Yucatan miniature) pigs were sacrificed after 16–20 weeks of exercise training. Samples of cardiac muscle, deltoid and triceps brachii muscle, subcutaneous and epicardial fat were obtained and FNDC5 mRNA, along with that of 6 other genes, was measured in all tissues of FHM pigs by reverse transcription polymerase chain reaction. FNDC protein in deltoid and triceps brachii was determined by Western blotting in both FHM and normal pigs. Citrate synthase activity was measured in the muscle samples of all pigs as an index of exercise training. Irisin was measured by an ELISA assay. Results There was no statistically significant effect of exercise training on FNDC5 gene expression in epicardial or subcutaneous fat, deltoid muscle, triceps brachii muscle or heart muscle. Exercise-training elevated circulating levels of irisin in the FHM pigs and citrate synthase activity in deltoid and triceps brachii muscle. A similar increase in citrate synthase activity was seen in muscle extracts of exercise-trained normal pigs but there was no alteration in circulating irisin. Conclusion Exercise training in pigs does not increase FNDC5 mRNA or protein in the deltoid or triceps brachii of FHM or normal pigs while increasing circulating irisin only in the FHM pigs. These data indicate that the response to exercise training in normal pigs is not comparable to that seen in mice. PMID:23831442

Performance and stability analysis of gas-injection enhanced natural circulation in heavy-liquid-metal-cooled systems

NASA Astrophysics Data System (ADS)

Yoo, Yeon-Jong

The purpose of this study is to investigate the performance and stability of the gas-injection enhanced natural circulation in heavy-liquid-metal-cooled systems. The target system is STAR-LM, which is a 400-MWt-class advanced lead-cooled fast reactor under development by Argonne National Laboratory and Oregon State University. The primary loop of STAR-LM relies on natural circulation to eliminate main circulation pumps for enhancement of passive safety. To significantly increase the natural circulation flow rate for the incorporation of potential future power uprates, the injection of noncondensable gas into the coolant above the core is envisioned ("gas lift pump"). Reliance upon gas-injection enhanced natural circulation raises the concern of flow instability due to the relatively high temperature change in the reactor core and the two-phase flow condition in the riser. For this study, the one-dimensional flow field equations were applied to each flow section and the mixture models of two-phase flow, i.e., both the homogeneous and drift-flux equilibrium models were used in the two-phase region of the riser. For the stability analysis, the linear perturbation technique based on the frequency-domain approach was used by employing the Nyquist stability criterion and a numerical root search method. It has been shown that the thermal power of the STAR-LM natural circulation system could be increased from 400 up to 1152 MW with gas injection under the limiting void fraction of 0.30 and limiting coolant velocity of 2.0 m/s from the steady-state performance analysis. As the result of the linear stability analysis, it has turned out that the STAR-LM natural circulation system would be stable even with gas injection. In addition, through the parametric study, it has been found that the thermal inertia effects of solid structures such as fuel rod and heat exchanger tube should be considered in the stability analysis model. The results of this study will be a part of the optimized stable design of the gas-injection enhanced natural circulation of STAR-LM with substantially improved power level and economical competitiveness. Furthermore, combined with the parametric study, this research could contribute a guideline for the design of other similar heavy-liquid-metal-cooled natural circulation systems with gas injection.

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

PubMed

Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

2017-05-01

Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). Our results suggest that higher BCAA levels do not have a causal effect on insulin resistance while increased insulin resistance drives higher circulating fasting BCAA levels.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evidence for Interannual to Decadal Variations in Hadley and Walker Circulations and Links to Water and Energy Fluxes

NASA Technical Reports Server (NTRS)

Robertson, Franklin; Bosilovich, Michael; Miller, Timothy

2007-01-01

Mass and energy transports associated with the Hadley and Walker circulations are important components of the earth s climate system and are strongly linked to hydrologic processes. Interannual to decadal variation in these flows likely signify a combination of natural climate noise as well as a response to anthropgenic forcing. There remains considerable uncertainty in quantifying variations in these flows. Evidence in the surface pressure record supports a weakening of the Walker circulation over the Pacific in recent decades. Conversely the NCEP / NCAR and ERA 40 reanalyses indicate that the Hadley circulation has increased in strength over the last two decades, though these analyses depict significantly different mass circulation changes. Interestingly, the NCEP - II / DOE reanalysis contains essentially no Hadley circulation changes. Most climate model integrations anticipate a weakening of both tropical circulations associated with stronger static stability. Clearly there is much uncertainty not only with the mass transports, but also how they are linked to water and energy balance of the planet through variations in turbulent heat and radiative fluxes and horizontal exports / imports of energy. Here we examine heat and water budget variations from a number of reanalysis products and focus on the linear and nonlinear response of ENSO warm and cold events as opportunities to study budget variations over the past 15-20 years. Our analysis addresses such questions as To what extent do Hadley and Walker Cell variations compensate each other on mass and energy transport? Do static stability adjustments appear to constrain fractional precipitation response vs. fractional water vapor response? We appeal to constraints offered by GPCP precipitation, SSWI ocean evaporation estimates, and ISCCP-FD radiative fluxes, and other satellite data sets to interpret and confirm reanalysis-based diagnostics. Using our findings we also attempt to place in context the recent findings that tropical ocean evaporation increased by order 5% or more during the 1990s, reconciling this with GPCP precipitation variations.

Increased body fat mass explains the positive association between circulating estradiol and insulin resistance in postmenopausal women.

PubMed

Marchand, Geneviève B; Carreau, Anne-Marie; Weisnagel, S John; Bergeron, Jean; Labrie, Fernand; Lemieux, Simone; Tchernof, André

2018-05-01

The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E 2 ) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m 2 ) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E 2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E 2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P < 0.02). With adjustments for percent body fat, correlations between E 2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E 1 ) and estrone-sulfate (E 1 -S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity.

Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease.

PubMed

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Clotet, Sergi; Mojal, Sergi; Fernández, Elvira; Soler, María José

2016-10-01

Circulating Angiotensin Converting Enzyme 2 (ACE2) activity in chronic kidney disease (CKD) patients without previous history of cardiovascular disease (CVD) has been associated with classical risk factors (older age, diabetes and male gender). Furthermore, silent atherosclerosis has been described as a pathological link between CKD and CVD. We analyzed baseline ACE2 activity in non-dialysis CKD stages 3-5 (CKD3-5) patients as a biomarker of renal progression, silent atherosclerosis and CV events after 2 years of follow-up. Prospective study of 1458 CKD3-5 subjects without any previous CV event included in the Spanish multicenter NEFRONA study. Association between baseline circulating ACE2 activity and renal parameters, carotid/femoral echography, atheromatous disease, ankle-brachial index, intima-media thickness, need of renal replacement therapy, cardiovascular events and mortality at 24 months of follow-up were analyzed. Patients with an increase in the number of territories with plaques at 24 months showed significantly higher levels of baseline ACE2 activity as compared to stable patients (29.6 (20.6-47.6)RFU/μL/h versus 35.7 (24.5-56), p < 0.001). Multivariate linear regression analysis showed that male gender, pathological ankle-brachial index and progressive silent atherosclerosis defined as an increased number of territories with plaques at 24 months were associated with increased baseline ACE2 activity. Male gender, older age, diabetes, smoking and increased baseline circulating ACE2 were independent predictors of atherosclerosis at 24 months of follow-up. In CKD3-5 patients, higher circulating ACE2 activity at baseline is associated with higher risk for silent atherosclerosis, suggesting that ACE2 may serve as a biomarker to predict CV risk before CVD is established. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short-term effects of an intensive lifestyle modification program on lipid peroxidation and antioxidant systems in patients with coronary artery disease.

PubMed

Jatuporn, Srisakul; Sangwatanaroj, Somkiat; Saengsiri, Aem-Orn; Rattanapruks, Sopida; Srimahachota, Suphot; Uthayachalerm, Wasan; Kuanoon, Wanpen; Panpakdee, Orasa; Tangkijvanich, Pisit; Tosukhowong, Piyaratana

2003-01-01

The purpose of this study was to compare the short-term effects of an intensive lifestyle modification (ILM) program on lipid peroxidation and antioxidant systems in patients with coronary artery disease (CAD). Twenty-two patients in the control group continued to receive their conventional treatment with lipid-lowering drugs, whereas 22 patients in the experimental group were assigned to intensive lifestyle modification (ILM) without taking any lipid-lowering agent. The ILM program comprised dietary advice on low-fat diets, high antioxidants and high fiber intakes, yoga exercise, stress management and smoking cessation. After 4 months of intervention, patients in the experimental group revealed a statistically significant increase in plasma total antioxidants, plasma vitamin E and erythrocyte glutathione (GSH) compared to patients in the control group. There was no significant change in plasma malondialdehyde (MDA), a circulating product of lipid peroxidation, in either group. We concluded that the ILM program increased circulating antioxidants and reduced oxidative stress in patients with CAD.

Immunoconjugates and long circulating systems: Origins, current state of the art and future directions☆

PubMed Central

Koshkaryev, Alexander; Sawant, Rupa; Deshpande, Madhura; Torchilin, Vladimir

2012-01-01

Significant progress has been made recently in the area of immunoconjugated drugs and drug delivery systems (DDS). The immuno-modification of either the drug or DDS has proven to be a very promising approach that has significantly improved the targeted accumulation in pathological sites while decreasing its undesirable side effects in healthy tissues. The arrangement for both prolonged life in the circulation and specific target recognition represents another potent strategy in the development of immuno-targeted systems. The longevity of immuno-targeted DDS such as immunoliposomes and immunomicelles improves their targetability even in the presence of the additional passive accumulation in areas with a compromised vasculature. The added use of the immuno-targeted systems takes advantage of the specific microenvironment of pathological sites including lowered pH, increased temperature, and variation in the enzymatic activity. “Smart” stimulus-responsive systems combine different valuable functionalities including PEG-protection, targeting antibody, cell-penetration, and stimulus-sensitive functions. In this review we examined the evolution, current status and future directions in the area of therapeutical immunoconjugates and long-circulating immuno-targeted DDS. PMID:22964425

Pro- and antiinflammatory cytokines in threatened miscarriages.

PubMed

Calleja-Agius, Jean; Muttukrishna, Shanthi; Pizzey, Arnold R; Jauniaux, Eric

2011-07-01

The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatened miscarriage (TM) and subsequent outcome. Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNFα, interferon gamma (IFNγ), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. Monocyte expression of TNFα and circulating levels of TNFα, IFNγ, IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNFα/IL-10, IFNγ/IL-10, and TNFα/IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage. Copyright © 2011. Published by Mosby, Inc.

Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeys.

PubMed

Kavanagh, K; Flynn, D M; Jenkins, K A; Wilson, M D; Chilton, F H

2013-07-01

Echium oil (EO) contains stearidonic acid (18:4), a n-3 polyunsaturated fatty acids (PUFAs), and gamma-linolenic acids (18:3), a n-6 PUFA that can be converted to long chain (LC)-PUFAs. We aimed to compare a safflower oil (SO)-enriched diet to EO- and fish oil (FO)-enriched diets on circulating and tissue PUFAs levels and glycemic, inflammatory, and cardiovascular health biomarkers in insulin resistant African green monkeys. In a Latin-square cross-over study, eight monkeys consumed matched diets for 6 weeks with 3-week washout periods. Monkeys consuming FO had significantly higher levels of n-3 LC-PUFAs and EO supplementation resulted in higher levels of circulating n-3 LC-PUFAs and a significant increase in dihomo-gamma linolenic acid (DGLA) in red blood cells and muscle. Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys. Copyright © 2013 Elsevier Ltd. All rights reserved.

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Calkins, Dick S.; Waligora, James M.; Gilbert, John H., III; Powell, Michael R.

1992-01-01

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95 percent confidence interval (95 percent CI) = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (greater than 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95 percent CI = 0.89-0.95), compared to those with early onset (equal to or less than 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Does Formaldehyde Increase Cell Free DNA in Maternal Plasma Specimens?

PubMed

Jacob, Rintu R; Saxena, Renu; Verma, Ishwar C

2016-11-01

There have been conflicting observations reported in the literature regarding the effects of formaldehyde in the recovery of cell free fetal DNA (CFF DNA) from maternal plasma. The aim of the present study was to assess the effect of formaldehyde treatment on circulating cell free DNA. We conducted this study using blood specimens collected from 11 pregnant women, each of whom was carrying a male fetus. DYS14 and HBB real time assays were performed to quantify fetal and total circulating cell free DNA from formaldehyde treated and untreated maternal plasma specimens, respectively. The concentration of total circulating cell free DNA in formaldehyde-treated maternal plasma was reduced, compared with untreated maternal plasma (n = 11; P = .02). The percentage of CFF DNA between formaldehyde-treated and untreated maternal plasma specimens did not differ significantly (n = 11; P = .15). Addition of formaldehyde does not significantly enhance the proportion of cell free fetal DNA when blood specimens are processed without delay. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The relationship between hypertensive disorders in pregnancy and placental maternal and fetal vascular circulation.

PubMed

Kovo, Michal; Bar, Jacob; Schreiber, Letizia; Shargorodsky, Marina

2017-11-01

We examined the impact of chronic hypertension (HTN), gestational HTN, and preeclampsia on placental maternal and fetal vascular circulation. Of the 1047 women who gave birth and underwent a placental histopathologic examination between 2007 and 2013 at Wolfson Medical Center, 140 women were included in the present study: 34 women with preeclampsia, 25 women with chronic HTN, 28 women with gestational HTN, and 53 women without hypertensive disorder, matched by age, gravidity, parity, and mode of delivery.Placental lesions related to maternal vascular malperfusion (MVM) differed significantly across groups (P < .0001) and were highest in subjects with chronic HTN and preeclampsia (72% and 65%, respectively) and lowest in women without hypertensive disorder (26%). Placental fetal vascular malperfusion rate did not differ significantly between groups (P = .767). In the logistic regression analysis, chronic HTN emerged as a significant predictor of placental MVM and increased the risk of this outcome more than sixfold (odds ratio 6.614, 95% confidence interval 2.047-21.37, P = .002). Preeclampsia emerged as a significant predictor of MVM and more than tripled the risk of this outcome (odds ratio 3.468, 95% confidence interval 1.083-11.103, P = .036). Gestational HTN was not significantly associated with increased MVM rate. We demonstrated that chronic HTN and preeclampsia were associated with an increased rate of vascular placental maternal malperfusion and emerged as significant independent predictors of this outcome. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

PubMed

Warburton, Elizabeth M; Kam, Michael; Bar-Shira, Enav; Friedman, Aharon; Khokhlova, Irina S; Koren, Lee; Asfur, Mustafa; Geffen, Eli; Kiefer, Daniel; Krasnov, Boris R; Degen, A Allan

2016-09-01

Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.

Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.

PubMed

Puyo, A M; Vega, G W; Pellegrino de Iraldi, A; Albornoz, L E; Rosón, M I; Scaglia, P; Celentano, M M; Corazza, J P; Palumbo, E L; Fernández, B E; de la Riva, I J

1998-01-01

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Association between circulating microRNA-208a and severity of coronary heart disease.

PubMed

Zhang, Yao; Li, Hai-Hong; Yang, Rui; Yang, Bai-Jing; Gao, Zhao-Yu

2017-09-01

Circulating microRNA (miR)-208a is specifically expressed in the heart muscle, which is involved in the regulation of myosin during cardiac development. Previous studies reported that cardiac-specific miR-208a level is significantly higher in plasma of coronary heart disease (CHD) patients. However, whether it correlates with severity of CHD, has never been elucidated before. The aim of this study was to explore the association between miR-208a and the presence and severity of CHD. Samples were collected from 290 CHD patients and 110 subjects with angiographic exclusion of CHD. Circulating miRNA-208a expression was detected using quantitative real-time PCR. The Gensini score was used to evaluate the severity of coronary stenotic lesions. Expression of miRNA-208a was identified on the basis of the quartiles of the Gensini score, and association between the miRNA-208a levels and CHD was analyzed. Diagnostic potential of miR-208a of CHD was performed by ROC analysis. CHD patients had higher miRNA-208a expression (1.61, 0.45-3.86 vs. 0.66, 0.11-1.42, p < .001), and the biomarker level significantly increased following an increasing the Gensini score (p < .001). Gensini score was significantly associated with miRNA-208a expression (r = 0.8525, p < .001). The optimal cut-off value of the relative level of miR-208a was with a specificity of 93.6% and a sensitivity of 75.5%. The AUC of miR-208a was 0.919 (95% CI, 0.893-0.945; p < .001). These preliminary results suggest that the expression of miR-208a may be associated with atherogenesis. The level of circulating miR-208a in predicting the severity of coronary atherosclerosis may have a relatively certain value.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2

PubMed Central

Skinner, L. C.; Primeau, F.; Freeman, E.; de la Fuente, M.; Goodwin, P. A.; Gottschalk, J.; Huang, E.; McCave, I. N.; Noble, T. L.; Scrivner, A. E.

2017-01-01

While the ocean’s large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean–atmosphere radiocarbon disequilibrium estimates to demonstrate a ∼689±53 14C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial–interglacial CO2 change. PMID:28703126

A numerical modeling study of the physical mechanisms causing radiation to promote the genesis of a tropical cyclone

NASA Astrophysics Data System (ADS)

Nicholls, M.; Pielke, R., Sr.; Smith, W. H.; Saleeby, S. M.; Wood, N.

2016-12-01

Several cloud-resolving numerical modeling results indicate that radiative forcing significantly accelerates tropical cyclogenesis. The primary mechanism appears to be differential radiative forcing between a relatively cloud-free environment and a developing tropical disturbance that generates circulations that influence convective activity in the core of the system, a mechanism first suggested by Gray and Jacobson. A dynamical perspective of this mechanism is taken by viewing it in terms of the lateral propagation of thermally driven gravity wave circulations. Numerical model experiments indicate that as an expansive stratiform cloud layer forms aloft the long wave cooling is reduced at low and mid levels. During the daytime there is not a very large differential radiative forcing between the environment and the cloud system, but it becomes significant at night when there is strong radiative clear sky cooling of the environment. Thermally driven circulations, are induced characterized by relatively weak subsidence in the environment but considerably stronger upward motion in the system core. This leads to a cooling tendency and increased relative humidity at night which appears to be a major factor in enhancing convective activity thereby leading in the mean to an increased rate of genesis. The increased upward motion and relative humidity that occurs throughout a deep layer is likely to aid in the triggering of convection, and provide a more favorable local environment at mid-levels for maintenance of buoyancy in convective cells due to a reduction of the detrimental effects of dry air entrainment. In order to clarify the effects of radiation the radiative forcing occurring in a fully physics simulation is imposed as a forcing term on the thermodynamic equation in a simulation without microphysics or radiation included to examine the induced circulations and the resultant thermodynamic changes that can influence convective development.

Endotoxin-induced shock in the rat. A role for C5a.

PubMed Central

Smedegård, G.; Cui, L. X.; Hugli, T. E.

1989-01-01

Administration of endotoxin from gram-negative bacteria to rats results in systemic hypotension, an increased hematocrit, and decreased numbers of circulating leukocytes (polymorphonuclear), monocytes, and platelets. These potentially lethal physiologic changes may be partially attributed to complement activation and generation of anaphylatoxins by the endotoxin (LPS). We demonstrated an elevation in the plasma levels of both C3a and C5a in LPS-treated rats. Injection of 5 micrograms C5ades Arg (rat) into rats produced effects similar to those induced by LPS, including decreased mean arterial pressure (systemic hypotension) and decreased numbers of circulating polymorphonuclear leukocytes, monocytes, and platelets. Unlike the response to LPS, C5a did not increase the hematocrit, indicating little effect on vascular permeability at the doses used. When LPS-treated animals were pretreated with F(ab')2 fragments of rabbit anti-rat C5a, no changes were measured in the circulating cell counts compared with LPS alone; however a significant improvement in the mean arterial pressure and a decrease in hematocrit was observed. We conclude that LPS-induced (septic) shock in the rat may result, in part, from the effects of complement activation and particularly from the generation of C5a. The influence of C5a on the LPS effect in the rat appears to enhance both the hypotensive (mean arterial pressure) and vascular permeability (hematocrit) responses. These results appear to support and confirm earlier observations that anti-human C5a increased survival in a septic-shock monkey model by eliminating circulating C5a and presumably thereby reducing the effects of endotoxin on blood pressure. Our results demonstrate that C5a plays a significant role in the hemodynamic changes associated with endotoxin-induced shock. Neutralization of C5a with specific antibodies may reduce the hypotensive response to endotoxin sufficiently to prevent lethal septic shock both in animals and in man. PMID:2789475

Activation of UCPs gene expression in skeletal muscle can be independent on both circulating fatty acids and food intake. Involvement of ROS in a model of mouse cancer cachexia.

PubMed

Busquets, Sílvia; Almendro, Vanessa; Barreiro, Esther; Figueras, Maite; Argilés, Josep M; López-Soriano, Francisco J

2005-01-31

Implantation of a fast growing tumour to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. This was accompanied by a significant increase in both UCP2 and UCP3 gene expression in skeletal muscle and heart. Interestingly, this increase in gene expression was not linked to a rise in circulating fatty acids or in a decrease in food intake, as previously reported in other pathophysiological states. These results question the concept that hyperlipaemia is the only factor controlling UCP gene expression in different pathophysiological conditions. In addition, the present work suggests that UCPs might participate in a counter-regulatory mechanism to lower the production of ROS.

Carbon Emission Flow in Networks

PubMed Central

Kang, Chongqing; Zhou, Tianrui; Chen, Qixin; Xu, Qianyao; Xia, Qing; Ji, Zhen

2012-01-01

As the human population increases and production expands, energy demand and anthropogenic carbon emission rates have been growing rapidly, and the need to decrease carbon emission levels has drawn increasing attention. The link between energy production and consumption has required the large-scale transport of energy within energy transmission networks. Within this energy flow, there is a virtual circulation of carbon emissions. To understand this circulation and account for the relationship between energy consumption and carbon emissions, this paper introduces the concept of “carbon emission flow in networks” and establishes a method to calculate carbon emission flow in networks. Using an actual analysis of China's energy pattern, the authors discuss the significance of this new concept, not only as a feasible approach but also as an innovative theoretical perspective. PMID:22761988

Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults.

PubMed

Forti, Louis Nuvagah; Van Roie, Evelien; Njemini, Rose; Coudyzer, Walter; Beyer, Ingo; Delecluse, Christophe; Bautmans, Ivan

2015-10-01

BDNF is known to induce neuroplasticity and low circulating levels have been related to neuronal loss in older persons. Physical exercise is thought to trigger BDNF-induced neuroplasticity, but conflicting observations have been reported regarding the effects of resistance training on circulating BDNF in the elderly. These conflicting observations might reflect dose-and gender-specific differences. Fifty-six apparently healthy elderly (68 ± 5 years) participants were randomized to 12 weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 Males, 10 Females, 2 × 10-15 repetitions at 80% 1 RM), low-resistance (LOW, 9 Males, 10 Females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was collected for BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training). 12 weeks of LOW+ exercise significantly increased BDNF levels in male (from 34.9 ± 10.7 ng/mL to 42.9 ± 11.9 ng/mL, time × group interaction p=0.013), but not in female participants. No significant change was observed in HIGH or LOW, neither in male nor female subjects. Our results show that only the mixed-low-resistance training program with a very high number of repetitions at a sufficiently high external resistance was able to increase circulating BDNF in older male participants. Training to volitional fatigue might be necessary to obtain optimal results. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed gender difference. Copyright © 2015 Elsevier Inc. All rights reserved.

Two-year changes in circulating adiponectin, ectopic fat distribution and body composition in response to weight-loss diets: the POUNDS Lost Trial.

PubMed

Ma, W; Huang, T; Wang, M; Zheng, Y; Wang, T; Heianza, Y; Sun, D; Smith, S R; Bray, G A; Sacks, F M; Qi, L

2016-11-01

Adiponectin has a pivotal role in linking fat distribution with cardiometabolic disorders. We investigated the associations of long-term changes in circulating adiponectin with body composition and fat distribution at different abdominal depots in response to weight-loss dietary interventions, as well as the modification effect of sex. In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial, 811 overweight or obese adults were randomly assigned to one of four diets varying in macronutrient intakes. Circulating concentrations of adiponectin were repeatedly measured at baseline, 6 months and 2 years. Body composition and fat distribution were repeatedly measured by dual-energy X-ray absorptiometry scan (n=424) and computed tomography (n=195). Over the 2-year intervention, after adjustment for age, sex, ethnicity, follow-up time, diet group, baseline body mass index and baseline level of respective outcome trait, increase of adiponectin was significantly associated with reduction of total fat mass (FM), total fat-free mass (FFM), whole body total percentage of fat mass (FM%), percentage of trunk fat (TF%), total adipose tissue (TAT), and adipose tissue mass at different depots including visceral (VAT), deep subcutaneous (DSAT) and superficial subcutaneous (SSAT; P<0.03 for each). The relations with FM, FM%, TF%, VAT and DSAT were significantly modified by sex (P for interaction=0.02, 0.005 and <0.001, 0.002, 0.03, respectively) with greater reductions associated with increase of adiponectin in men than in women. Long-term changes in circulating adiponectin were differentially associated with improvement of body composition and abdominal fat distribution in men and women.

Circulating dendritic cell precursors in chronic kidney disease: a cross-sectional study.

PubMed

Paul, Katharina; Kretzschmar, Daniel; Yilmaz, Atilla; Bärthlein, Barbara; Titze, Stephanie; Wolf, Gunter; Busch, Martin

2013-12-10

Dendritic cells (DC) are professional antigen-presenting cells in the immune system. They patrol the blood as circulating dendritic cell precursors (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic plaque burden. Since chronic kidney disease (CKD) is associated with chronic inflammation and increased cardiovascular risk, the aim of our study was to investigate a potential effect of CKD on circulating DCP numbers especially in patients with a history of cardiovascular disease. The number of circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was analysed by flow cytometry in 245 patients with CKD stage 3 (with and without known cardiovascular events) and 85 coronary healthy controls. In addition, data were compared with a historical group of 130 patients with known coronary artery disease (CAD). Compared to controls, patients with CKD 3 revealed a significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P < 0.001, respectively). Compared with CAD-patients, the decrease in circulating DCP in CKD was comparable or even more pronounced indicating a potential role for DCP in cardiovascular risk potentiation due to CKD. Based on previous findings in CAD, the marked decrease of DCP in CKD implicates a potential role for DCP as a mediator of cardiovascular disease. Whether DCP in CKD may act as new cardiovascular biomarkers needs to be established in future prospective trials.

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Relationship among circulating anti-Müllerian hormone, insulin like growth factor 1, cadmium and superovulatory response in dairy cows.

PubMed

Abdel Aziz, R L; Khalil, A A Y; Abdel-Wahab, A; Hassan, N Y; Abdel-Hamied, E; Kasimanickam, R K

2017-09-15

The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P < 0.05). There was no correlation between circulating concentrations of AMH and IGF1. The number of corpus luteum (r = 0.71), total embryo (r = 0.67), total transferable embryo (r = 0.51) and total grade 1 embryo (r = 0.5) were positively correlated to AMH concentrations (P < 0.05). There was a trend for negative correlation found between circulating cadmium concentrations and total grade 1 embryo yield (P < 0.1). When cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced. Published by Elsevier Inc.

Residual Circulation and Temperature Changes during the Evolution of Stratospheric Sudden Warmings Revealed in MERRA

NASA Astrophysics Data System (ADS)

Song, Byeong-Gwon; Chun, Hye-Yeong; Kim, Young-Ha

2015-04-01

A composite analysis for 21 stratospheric sudden warming (SSW) cases in 1979-2012 northern winter is performed using the MERRA reanalysis in order to investigate the changes in residual circulation and temperature during the SSW evolution. The SSW cases are classified as Type-1 and Type-2, based on the relative amplitude of planetary waves with zonal wavenumbers 1 and 2. The residual circulation induced by each forcing term in the transformed Eulerian mean (TEM) equation and the temperature advection associated with the circulation are calculated for both types of SSW. It is found that strong poleward and downward motion exists in the polar stratosphere just before the central date of SSW, which is induced primarily by the Eliassen-Palm flux divergence forcing (EPD). Gravity-wave drag (GWD) induces strong poleward and downward motion in the lower mesosphere. The temperature advection is significantly increased in the stratosphere before the central date of the SSW, as a result of the strong downward motion due to the EPD. However, the temperature change in the lower mesosphere is small despite the strong downward motion, because the vertical gradient of the potential temperature is relatively small at these altitudes. The temperature change in the stratosphere before the SSW is more rapid for Type-2 than Type-1. After the central date of SSW, the polar stratospheric temperature is recovered primarily by diabatic heating rather than by the residual circulation associated with wave forcing. Difference in the speed of temperature recovery between the two types of SSW is not significant.

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

PubMed

Minich, L L; Tani, L Y; Hawkins, J A; Bartkowiak, R R; Royall, M L; Pantalos, G M

2001-04-01

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

Changes in Microbial Plankton Assemblages Induced by Mesoscale Oceanographic Features in the Northern Gulf of Mexico

PubMed Central

Williams, Alicia K.; McInnes, Allison S.; Rooker, Jay R.; Quigg, Antonietta

2015-01-01

Mesoscale circulation generated by the Loop Current in the Northern Gulf of Mexico (NGOM) delivers growth-limiting nutrients to the microbial plankton of the euphotic zone. Consequences of physicochemically driven community shifts on higher order consumers and subsequent impacts on the biological carbon pump remain poorly understood. This study evaluates microbial plankton <10 μm abundance and community structure across both cyclonic and anti-cyclonic circulation features in the NGOM using flow cytometry (SYBR Green I and autofluorescence parameters). Non-parametric multivariate hierarchical cluster analyses indicated that significant spatial variability in community structure exists such that stations that clustered together were defined as having a specific ‘microbial signature’ (i.e. statistically homogeneous community structure profiles based on relative abundance of microbial groups). Salinity and a combination of sea surface height anomaly and sea surface temperature were determined by distance based linear modeling to be abiotic predictor variables significantly correlated to changes in microbial signatures. Correlations between increased microbial abundance and availability of nitrogen suggest nitrogen-limitation of microbial plankton in this open ocean area. Regions of combined coastal water entrainment and mesoscale convergence corresponded to increased heterotrophic prokaryote abundance relative to autotrophic plankton. The results provide an initial assessment of how mesoscale circulation potentially influences microbial plankton abundance and community structure in the NGOM. PMID:26375709

Metalloproteinase Inhibition Protects against Reductions in Circulating Adrenomedullin during Lead-induced Acute Hypertension.

PubMed

Nascimento, Regina A; Mendes, Gabryella; Possomato-Vieira, Jose S; Gonçalves-Rizzi, Victor Hugo; Kushima, Hélio; Delella, Flavia K; Dias-Junior, Carlos A

2015-06-01

Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP-2) seems to cleave vasoactive peptides. This study examined whether MMP-2 and MMP-9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin-1 or with reductions in circulating adrenomedullin and calcitonin gene-related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 μg/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 μg/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole-blood lead levels (9 μg/dL) were found in lead-exposed rats treated with either doxycycline or water. Lead-induced increases in systolic blood pressure (from 143 ± 2 to 167 ± 3 mmHg) and gelatin zymography of plasma samples showed that lead increased MMP-9 (but not MMP-2) levels. Both lead-induced increased MMP-9 activity and hypertension were blunted by doxycycline. Doxycycline also prevented lead-induced reductions in circulating adrenomedullin. No significant changes in plasma levels of endothelin-1 or CGRP were found. Lead-induced decreases in nitric oxide markers and antioxidant status were not prevented by doxycycline. In conclusion, acute lead exposure increases blood pressure and MMP-9 activity, which were blunted by doxycycline. These findings suggest that MMP-9 may contribute with lead-induced hypertension by cleaving the vasodilatory peptide adrenomedullin, thereby inhibiting adrenomedullin-dependent lowering of blood pressure. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Circulating osteoprotegerin is associated with chronic kidney disease in hypertensive patients.

PubMed

Bernardi, Stella; Toffoli, Barbara; Bossi, Fleur; Candido, Riccardo; Stenner, Elisabetta; Carretta, Renzo; Barbone, Fabio; Fabris, Bruno

2017-07-06

Osteoprotegerin (OPG) is a glycoprotein that plays an important regulatory role in the skeletal, vascular, and immune system. It has been shown that OPG predicts chronic kidney disease (CKD) in diabetic patients. We hypothesized that OPG could be a risk marker of CKD development also in non-diabetic hypertensive patients. A case-control study was carried out to measure circulating OPG levels in 42 hypertensive patients with CKD and in 141 hypertensive patients without CKD. A potential relationship between OPG and the presence of CKD was investigated and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of OPG that best explained the presence of CKD. Secondly, to evaluate whether OPG increase could affect the kidney, 18 C57BL/6J mice were randomized to be treated with saline or recombinant OPG every 3 weeks for 12 weeks. Circulating OPG levels were significantly higher in hypertensive patients with CKD, and there was a significant inverse association between OPG and renal function, that was independent from other variables. ROC analysis showed that OPG levels had a high statistically predictive value on CKD in hypertensive patients, which was greater than that of hypertension. The OPG best cut-off value associated with CKD was 1109.19 ng/L. In the experimental study, OPG delivery significantly increased the gene expression of pro-inflammatory and pro-fibrotic mediators, as well as the glomerular nitrosylation of proteins. This study shows that OPG is associated with CKD in hypertensive patients, where it might have a higher predictive value than that of hypertension for CKD development. Secondly, we found that OPG delivery significantly increased the expression of molecular pathways involved in kidney damage. Further longitudinal studies are needed not only to evaluate whether OPG predicts CKD development but also to clarify whether OPG should be considered a risk factor for CKD.

Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

PubMed Central

Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

2016-01-01

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

Recent changes in the summer monsoon circulation and their impact on dynamics and thermodynamics of the Arabian Sea

NASA Astrophysics Data System (ADS)

Pratik, Kad; Parekh, Anant; Karmakar, Ananya; Chowdary, Jasti S.; Gnanaseelan, C.

2018-05-01

The present study examines changes in the low-level summer monsoon circulation over the Arabian Sea and their impact on the ocean dynamics using reanalysis data. The study confirms intensification and northward migration of low-level jet during 1979 to 2015. Further during the study period, an increase in the Arabian Sea upper ocean heat content is found in spite of a decreasing trend in the net surface heat flux, indicating the possible role of ocean dynamics in the upper ocean warming. Increase in the anti-cyclonic wind stress curl associated with the change in the monsoon circulation induces downwelling over the central Arabian Sea, favoring upper ocean warming. The decreasing trend of southward Ekman transport, a mechanism transporting heat from the land-locked north Indian Ocean to southern latitudes, also supports increasing trend of the upper ocean heat content. To reinstate and quantify the role of changing monsoon circulation in increasing the heat content over the Arabian Sea, sensitivity experiment is carried out using ocean general circulation model. In this experiment, the model is forced by inter-annual momentum forcing while rest of the forcing is climatological. Experiment reveals that the changing monsoon circulation increases the upper ocean heat content, effectively by enhancing downwelling processes and reducing southward heat transport, which strongly endorses our hypothesis that changing ocean dynamics associated with low-level monsoon circulation is causing the increasing trend in the heat content of the Arabian Sea.

The Importance of Planetary Rotation Period for Ocean Heat Transport

PubMed Central

Stevens, D.; Joshi, M.

2014-01-01

Abstract The climate and, hence, potential habitability of a planet crucially depends on how its atmospheric and ocean circulation transports heat from warmer to cooler regions. However, previous studies of planetary climate have concentrated on modeling the dynamics of atmospheres, while dramatically simplifying the treatment of oceans, which neglects or misrepresents the effect of the ocean in the total heat transport. Even the majority of studies with a dynamic ocean have used a simple so-called aquaplanet that has no continental barriers, which is a configuration that dramatically changes the ocean dynamics. Here, the significance of the response of poleward ocean heat transport to planetary rotation period is shown with a simple meridional barrier—the simplest representation of any continental configuration. The poleward ocean heat transport increases significantly as the planetary rotation period is increased. The peak heat transport more than doubles when the rotation period is increased by a factor of ten. There are also significant changes to ocean temperature at depth, with implications for the carbon cycle. There is strong agreement between the model results and a scale analysis of the governing equations. This result highlights the importance of both planetary rotation period and the ocean circulation when considering planetary habitability. Key Words: Exoplanet—Oceans—Rotation—Climate—Habitability. Astrobiology 14, 645–650. PMID:25041658

Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention.

PubMed

Párrizas, Marcelina; Brugnara, Laura; Esteban, Yaiza; González-Franquesa, Alba; Canivell, Sílvia; Murillo, Serafín; Gordillo-Bastidas, Elizabeth; Cussó, Roser; Cadefau, Joan A; García-Roves, Pablo M; Servitja, Joan-Marc; Novials, Anna

2015-03-01

Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies. Here we set to describe the profile of circulating microRNAs (miRNAs) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools. We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance, as well as newly diagnosed diabetic patients. We validated the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention, as well as in a mouse model of glucose intolerance. We identified two miRNAs, miR-192 and miR-193b, whose abundance is significantly increased in the prediabetic state but not in diabetic patients. Strikingly, these miRNAs are also increased in plasma of glucose-intolerant mice. Moreover, circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise, which succeeded in normalizing metabolic parameters. Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans. This circulating miRNA signature for prediabetes could be used as a new diagnostic tool, as well as to monitor response to intervention.

Pattern of maternal circulating CRH in laboratory-housed squirrel and owl monkeys

PubMed Central

Power, ML; Williams, LE; Gibson, SV; Schulkin, J; Helfers, J; Zorrilla, EP

2010-01-01

The anthropoid primate placenta appears to be unique in producing corticotropin-releasing hormone (CRH). Placental CRH is involved in an endocrine circuit key to the production of estrogens during pregnancy. CRH induces cortisol production by the maternal and fetal adrenal glands, leading to further placental CRH production. CRH also stimulates the fetal adrenal glands to produce dehydroepiandrostendione sulfate (DHEAS) which the placenta converts into estrogens. There are at least two patterns of maternal circulating CRH across gestation among anthropoids. Monkeys examined to date (Papio and Callithrix) have an early-to-mid gestational peak of circulating CRH, followed by a steady decline to a plateau level, with a possible rise near parturition. In contrast, humans and great apes have an exponential rise in circulating CRH peaking at parturition. To further document and compare patterns of maternal circulating CRH in anthropoid primates, we collected monthly blood samples on 14 squirrel monkeys (Saimiri boliviensis) and 10 owl monkeys (Aotus nancymaae) during pregnancy. CRH immunoreactivity was measured from extracted plasma by solid-phase RIA. Both squirrel and owl monkeys displayed a mid-gestational peak in circulating CRH: days 45–65 of the 152-day gestation for squirrel monkeys (mean±SEM CRH = 2694±276 pg/ml) and days 60–80 of the 133-day gestation for owl monkeys (9871±974 pg/ml). In squirrel monkeys, circulating CRH declined to 36% of mean peak value by two weeks before parturition and then appeared to increase; the best model for circulating CRH over gestation in squirrel monkeys was a cubic function, similar to previous results for baboons and marmosets. In owl monkeys, circulating CRH appeared to plateau with no subsequent significant decline approaching parturition, although a cubic function was the best fit. This study provides additional evidence for a mid-gestational peak of maternal circulating CRH in ancestral anthropoids that has been lost in the hominoid lineage. PMID:20872786

A comparison of the effect of a variety of thermal and vibratory modalities on skin temperature and blood flow in healthy volunteers

PubMed Central

Lohman, Everett B.; Bains, Gurinder S.; Lohman, Trevor; DeLeon, Michael; Petrofsky, Jerrold Scott

2011-01-01

Summary Background Circulation plays an essential role in tissue healing. Moist heat and warm water immersion have been shown to increase skin circulation; however, these heating modalities can cause burns. Recent research has shown that passive vibration can also increase circulation but without the risk of burns. Material/Methods The aim of this study is to compare the effects of short-duration vibration, moist heat, and a combination of the two on skin blood flow (SBF) and skin temperature (ST). Ten (10) subjects, 5 female and 5 male, aged 20–30 years of age, received two interventions a day for 3 consecutive days: Intervention 1 – Active vibration only (vibration exercise), Intervention 2 – passive vibration only, Intervention 3 – moist heat only, Intervention 4 – passive vibration combined with moist heat, Intervention 5 – a commercial massaging heating pad, and Intervention 6 – no intervention, resting in supine only (control). SBF and ST were measured using a laser Doppler imager during the 10 minute intervention and then throughout the nine minute recovery period. Results The mean skin blood flow following a ten-minute intervention of the combination of passive vibration and moist heat was significantly different from the control, active vibration, and the commercial massaging heating pad. Skin temperature following the ten-minute interventions of moist heat alone and passive vibration alone were both significantly different from the commercial massaging heating pad and active vibration interventions. Conclusions The combination of passive vibration and moist heat produced the greatest increase in skin blood flow and the second highest increase in skin blood flow nine minutes post application. PMID:21873956

Six months training alone or combined with diet alters HOMA-AD, HOMA-IR and plasma and adipose tissue adiponectin in obese women.

PubMed

Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

2014-01-01

We investigate the effect of 6 months aerobic training alone or in combination with diet on adiponectin in circulation and in adipose abdominal tissue (AT) in obese women. Twenty obese subjects were randomized into a 24 weeks intervention: 1) training (TR) and 2) training and diet (TRD). Blood samples were collected at baseline, after 12 wk and 24 wk. AT biopsies were obtained only at baseline and after 24 wk. In the TRD group the fat loss was after 12 wk -13.74% (p<0.01) and after 24 wk -21.82% (p<0.01) with no changes in the TR group. After 12 and 24 wk, VO2max was increased by 21.81-39.54% (p<0.05) in the TRD group and 18.09-40.95% in the TR group (p<0.05). After 12 wk, plasma adiponectin was raised only in the TRD group (55.8%, p<0.05). After 24 weeks, circulating adiponectin was elevated by 110.4% (p<0.01) in the TRD group and by 27% (p<0.05) in the TR group. In AT biopsies, subjects in the TRD and TR groups exhibited a significant increase in adiponectin (p<0.05 and p<0.01, respectively). The two indices HOMA-IR and HOMA-AD for assessing insulin resistance were strongly affected by protocols. HOMA-IR decreased (p<0.05) only after 24 wk in the TRD group. HOMA-AD increased in both groups after 12 (p<0.05) and 24 wk (p<0.01). Six months chronic aerobic exercise alone or combined with diet result in a significant increase in circulating and adipose tissue adiponectin levels in obese women independent of changes in body composition and/or in HOMA-IR.

Effects of urban land-use change in East China on the East Asian summer monsoon based on the CAM5.1 model

NASA Astrophysics Data System (ADS)

Ma, Hongyun; Jiang, Zhihong; Song, Jie; Dai, Aiguo; Yang, Xiuqun; Huo, Fei

2016-05-01

The effects of urban land-use change in East China on the East Asian summer monsoon (EASM) are investigated using a Community Atmosphere Model Version 5.1. The results show that the urban land-use change in East China causes spatially-varying changes in surface net radiation and heat fluxes, atmospheric circulation, and water budgets. It results in significant surface warming (cooling) and precipitation decrease (increase) in a large region north (south) of 30°N. Urban expansion agglomerated in (29°-41°N, 110°-122°E) alters the surface energy budget and warms the surface, resulting in strengthened southwesterly airflow south of 25°N and increased convergence below the mid-troposphere between 20° and 30°N. A concomitant northward downdraft associated with the increased convection generates an anomalous high pressure north of 30°N. Meanwhile, the downdraft not only produces adiabatic warming but also inhibits the dynamic condition for precipitation formation. The anomalous high pressure formed in North China prevents the southwesterly airflow from advancing northward, leading to increase the convergence and precipitation in South China. These changes reduce the meridional temperature gradient in the mid-lower troposphere and weaken the westerly airflow near 30°N. In addition, horizontal transport of vorticity north of 35°N weakens significantly, which leads to an anomalous barotropic structure of anticyclonic there. As a result, the anomalous anticyclonic circulation and descent north of 30°N are strengthened. At the same time, the anomalous cyclonic circulation and ascent south of 30°N are enhanced. These process induced by the thermal state changes due to urbanization weakens the EASM.

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

PubMed

Christenson, W R; Becker, B D; Wahle, B S; Moore, K D; Dass, P D; Lake, S G; Van Goethem, D L; Stuart, B P; Sangha, G K; Thyssen, J H

1996-02-01

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Efficacy of an extract from garlic, Allium sativum, against infection with the furunculosis bacterium, Aeromonas salmonicida, in rainbow trout, Oncorhynchus mykiss

USGS Publications Warehouse

Breyer, Kate E.; Getchell, Rodman G.; Cornwell, Emily R.; Wooster, Gregory A.; Ketola, H. George; Bowser, Paul R.

2015-01-01

Juvenile rainbow trout, Oncorhynchus mykiss, were fed diets containing 0, 0.5, 1.0, and 2.0% of a garlic extract, challenged with a modified 50% lethal dose of Aeromonas salmonicida and monitored for 28 d. There were significant increases in survival of trout fed 0.5 and 1.0% garlic extract as compared to the control and 2.0% garlic extract groups. A target animal safety study was performed at varying increments using the target dose of 0.5% garlic extract at 0× (0% garlic extract), 1× (0.5% garlic extract), 3× (1.5% garlic extract), and 5× (2.5% garlic extract) for 3× (6 wk) the duration of the original study. There was a significant increase in the level of circulating lymphocytes and a significant decrease in the level of circulating monocytes. The latter correlated to an increased level of pigment-containing macrophage centers within the renal tissue as garlic extract dosing increased, denoting a potential deleterious inflammatory effect as macrophage infiltration became severe at the highest dose. These studies suggest that feeding low-dose (0.5% or 1.0%) garlic extract improves survivability in rainbow trout when challenged with A. salmonicida and appears safe; however, higher levels do not appear to be effective and may cause deleterious effects on health.

Impact of fluorescent silicon nanoparticles on circulating hemolymph and hematopoiesis in an invertebrate model organism.

PubMed

Xing, Rui; Li, Kai-Le; Zhou, Yan-Feng; Su, Yuan-Yuan; Yan, Si-Qi; Zhang, Kai-Long; Wu, Si-Cong; Sima, Yang-Hu; Zhang, Ke-Qin; He, Yao; Xu, Shi-Qing

2016-09-01

Silicon nanoparticles (SiNPs) have attractive potential applications in biological and medical fields, and yet their impact on animals is still controversial, and there have been no reports of their effects on hematopoiesis. In this study, the effects of SiNPs on hemocytes and hematopoiesis were investigated by administering SiNPs via a vascular injection into an invertebrate model, the silkworm. Our results show that the ability of SiNPs to enter different types of circulating hemocytes and their impact on those hemocytes differed significantly. Rapid accumulation of SiNPs was observed in granulocytes, oenocytoids, and spherulocytes, which have immune functions in the circulating hemolymph, whereas SiNPs did not easily enter prohemocytes, which can differentiate into granulocytes, oenocytoids, and spherulocytes and replenish them. The SiNPs that entered the hemocytes initiated autophagy and apoptosis via the lysosomal/mitochondrial pathway. High-dose SiNPs weakly stimulated lysosomal activity in hematopoietic organs, but did not lead to a significant increase in reactive oxygen species or severe autophagy or apoptosis in the organ tissues. We suggest that the damage caused by high-dose SiNPs to hematopoiesis is self-healing, because few SiNPs entered the hematopoietic stem cells in the circulating hemolymph, so the damage to the hematopoietic tissues was limited. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of circulating granulocytes in sheep lung injury produced by phorbol myristate acetate.

PubMed

Dyer, E L; Snapper, J R

1986-02-01

Phorbol myristate acetate (PMA) and endotoxin cause pulmonary granulocyte sequestration and alteration in lung fluid and solute exchange in awake sheep that are felt to be analogous to the adult respiratory distress syndrome in humans. The basic hypothesis that PMA causes lung injury by activating circulating granulocytes has never been tested. The effects of infused PMA on lung mechanics and the cellular constituents of lung lymph have also not been reported. We therefore characterized the effects of intravenous PMA, 5 micrograms/kg, on lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, blood and lymph leukocyte counts, and plasma and lymph cyclooxygenase products of arachidonate metabolism in 10 awake sheep with normal granulocyte counts and after granulocyte depletion with hydroxyurea. PMA significantly altered lung mechanics from base line in both nongranulocyte depleted and granulocyte-depleted sheep. Dynamic compliance decreased by over 50% and resistance to airflow across the lungs increased over threefold acutely following PMA infusion in both sets of experiments. Changes in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, and plasma and lymph arachidonate metabolites were not significantly affected by greater than 99% depletion of circulating granulocytes. We conclude that the lung injury caused by PMA in chronically instrumented awake sheep probably is not a result of activation of circulating granulocytes.

Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome.

PubMed

Torre, Donato; Tambini, Roberto; Manfredi, Mariangela; Mangani, Valerio; Livi, Paola; Maldifassi, Viviana; Campi, Paolo; Speranza, Filippo

2003-04-01

Resolution of inflammation/infection involves removal of neutrophils and other inflammatory cells by the induction of apoptosis. Fas/Apo-1 is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form. In this study we investigated the role of circulating Fas/Apo-1 in patients with systemic inflammatory response syndrome (SIRS). We evaluated 57 critically ill patients, 34 with infectious SIRS (sepsis and septic shock), and 23 patients with noninfectious SIRS. Circulating Fas/Apo-1 was determined by a commercially available immunoassay. Our results clearly show that levels of Fas/Apo-1 were significantly elevated in patients with infectious and noninfectious SIRS (10.4 +/- 8.1 pg/mL, controls: 5.0 +/- 0.7 pg/mL; p < 0.0001). In addition, Fas/Apo-1 levels were not able in predicting in predicting poor outcome of patients with SIRS. In conclusion, these results show that increased levels of Fas/Apo-1 from patients with SIRS is a mechanism which contribute to inflammatory response through accumulation of neutrophils at sites of inflammation/infection.

Flow structure and vorticity transport on a plunging wing

NASA Astrophysics Data System (ADS)

Eslam Panah, Azar

The structure and dynamics of the flow field created by a plunging flat plate airfoil are investigated at a chord Reynolds number of 10,000 while varying plunge amplitude and Strouhal number. Digital particle image velocimetry measurements are used to characterize the shedding patterns and the interactions between the leading and trailing edge vortex structures (LEV and TEV), resulting in the development of a wake classification system based on the nature and timing of interactions between the leading- and trailing-edge vortices. The convection speed of the LEV and its resulting interaction with the TEV is primarily dependent on reduced frequency; however, at Strouhal numbers above approximately 0.4, a significant influence of Strouhal number (or plunge amplitude) is observed in which LEV convection is retarded, and the contribution of the LEV to the wake is diminished. It is shown that this effect is caused by an enhanced interaction between the LEV and the airfoil surface, due to a significant increase in the strength of the vortices in this Strouhal number range, for all plunge amplitudes investigated. Comparison with low-Reynolds-number studies of plunging airfoil aerodynamics reveals a high degree of consistency and suggests applicability of the classification system beyond the range examined in the present work. Some important differences are also observed. The three-dimensional flow field was characterized for a plunging two-dimensional flat-plate airfoil using three-dimensional reconstructions of planar PIV data. Whereas the phase-averaged description of the flow field shows the secondary vortex penetrating the leading-edge shear layer to terminate LEV formation on the airfoil, time-resolved, instantaneous PIV measurements show a continuous and growing entrainment of secondary vorticity into the shear layer and LEV. A planar control volume analysis on the airfoil indicated that the generation of secondary vorticity produced approximately one half the circulation, in magnitude, as the leading-edge shear layer flux. A small but non-negligible vorticity source was also attributed to spanwise flow toward the end of the downstroke. Preliminary measurements of the structure and dynamics of the leading-edge vortex (LEV) are also investigated for plunging finite-aspect-ratio wings at a chord Reynolds number of 10,000 while varying aspect ratio and root boundary condition. Stereoscopic particle image velocimetry (SPIV) measurements are used to characterize LEV dynamics and interactions with the plate in multiple chordwise planes. The relationship between the vorticity field and the spanwise flow field over the wing, and the influence of root boundary conditions on these quantities has been investigated. The viscous symmetry plane is found to influence this flow field, in comparison to other studies YiRo:2010,Vi:2011b,CaWaGuVi:2012, by influencing tilting of the LEV near the symmetry wall, and introducing a corewise root-to-tip flow near the symmetry plane. Modifications in the root boundary conditions are found to significantly affect this. LEV circulations for the different aspect ratio plates are also compared. At the bottom of the downstroke, the maximum circulation is found at the middle of the semi-span in each case. The circulation of the sAR=2 wing is found to significantly exceed that of the sAR=1 wing and, surprisingly, the maximum circulation value is found to be independent of root boundary conditions for thesAR=2 case and also closely matched that of the quasi-2D case. Furthermore, the 3-D flow field of a finite wing ofsAR=2 was characterized using three-dimensional reconstructions of planar PIV data after minimizing the gap between the plunging plate and the top stationary wall. The LEV on the finite wing rapidly evolved into an arch structure centered at approximately the 50% spanwise position, similar to previous observations by Calderon et al., and Yilmaz and Rockwell. At that location, the circulation contribution due to spanwise flow was approximately half that of the shear layer flux because of the significantly greater three-dimensionality in the flow. Increased tilting at the 25% and 75% spanwise locations suggests increasing three-dimensionality at those locations compared to the symmetry plane of the arch (50% spanwise location). The deviation between the LEV circulation and integrated convective vorticity fluxes at the 50% spanwise location suggests that entrainment of secondary vorticity plays a similar role in regulating LEV circulation as in the 2D case. While the wing surface flux of vorticity could not be measured in that case, the significant difference between LEV circulation and the known integrated fluxes is comparable to that for the 2D plate, suggesting that a significant boundary flux of secondary vorticity may exist.

Acute Stress Facilitates Trace Eyeblink Conditioning in C57BL/6 Male Mice and Increases the Excitability of Their CA1 Pyramidal Neurons

ERIC Educational Resources Information Center

Weiss, Craig; Sametsky, Evgeny; Sasse, Astrid; Spiess, Joachim; Disterhoft, John F.

2005-01-01

The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned…

Circulating resistin is a significant predictor of mortality independently from cardiovascular comorbidities in elderly, non-diabetic subjects with chronic kidney disease.

PubMed

Marouga, Anna; Dalamaga, Maria; Kastania, Anastasia N; Kroupis, Christos; Lagiou, Maria; Saounatsou, Koralia; Dimas, Kleanthi; Vlahakos, Demetrios V

2016-01-01

Resistin is associated with inflammation, atherosclerosis and cardiovascular (CV) disease. To associate circulating resistin with all-cause and CV mortality in chronic kidney disease (CKD) patients. Serum resistin was determined in a cohort of 80 elderly, non-diabetic patients with stable CKD at different stages in a follow-up period of 5 years. Circulating resistin was significantly elevated in deceased compared to alive patients. Resistin emerged as an independent biomarker of all-cause and CV mortality after a 5-year follow-up period. Elevated circulating resistin was a significant independent predictor of CV and all-cause mortality in elderly, non-diabetic CKD patients.

Spatiotemporal variability of temperature and precipitation in Gansu Province (Northwest China) during 1951-2015

NASA Astrophysics Data System (ADS)

Wen, Xiaohu; Wu, Xiaoqing; Gao, Meng

2017-11-01

Climate change is potentially challenging the sustainable development in many parts of the world, especially the semi-arid and arid regions on the earth. Northwest China (NWC) is one of the most arid areas in East Asia, and Gansu Province is located at the important climate transition zone in NWC. Spatiotemporal variability of both temperature and precipitation were analyzed based on the daily observation dataset at 29 meteorological stations over Gansu during 1951-2015. The Mann-Kendall trend test was utilized to detect monotonic trends in extreme climate indices, mean temperature, and total precipitation. The results revealed that the warming trends were statistically significant at most stations in Gansu, especially at the high altitude stations; however, the change trends in annual and seasonal precipitation over Gansu were not significant as expected. Furthermore, the 29 stations were spatially grouped using hierarchical clustering method. The regional-averaged temperature anomalies also showed a significant warming trend beginning at the end of 1970s. Spatial variations were also observed in the annual and seasonal precipitation over Gansu. In general, precipitation increased in the western part of Gansu while decreased in the eastern part. Additionally, the wavelet analyses revealed that the teleconnection between large scale circulation and summer precipitation varied not only from region to region, but also was different at different time scale and different time periods. Analysis of large-scale atmospheric circulation changes showed that a strengthening anticyclonic circulation, increasing geopotential height and rapid warming over the Eurasian continent were considered to be attributable to climate change in Gansu and even in NWC.

Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep Apnea: Links to Cancer Comorbidity.

PubMed

Gaoatswe, Gadintshware; Kent, Brian D; Corrigan, Michelle A; Nolan, Geraldine; Hogan, Andrew E; McNicholas, Walter T; O'Shea, Donal

2015-10-01

Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA. We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production. Teaching hospital based sleep unit and research laboratory. Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035). Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA. © 2015 Associated Professional Sleep Societies, LLC.

Responses of estuarine circulation and salinity to the loss of intertidal flats – A modeling study

DOE PAGES

Yang, Zhaoqing; Wang, Taiping

2015-08-25

Intertidal flats in estuaries are coastal wetlands that provide critical marine habitats to support wide ranges of marine species. Over the last century many estuarine systems have experienced significant loss of intertidal flats due to anthropogenic impacts. This paper presents a modeling study conducted to investigate the responses of estuarine hydrodynamics to the loss of intertidal flats caused by anthropogenic actions in Whidbey Basin of Puget Sound on the northwest coast of North America. Changes in salinity intrusion limits in the estuaries, salinity stratification, and circulation in intertidal flats and estuaries were evaluated by comparing model results under the existingmore » baseline condition and the no-flat condition. Model results showed that loss of intertidal flats results in an increase in salinity intrusion, stronger mixing, and a phase shift in salinity and velocity fields in the bay front areas. Model results also indicated that loss of intertidal flats enhances two-layer circulation, especially the bottom water intrusion. Loss of intertidal flats increases the mean salinity but reduces the salinity range in the subtidal flats over a tidal cycle because of increased mixing. Salinity intrusion limits extend upstream in all three major rivers discharging into Whidbey Basin when no intertidal flats are present. Changes in salinity intrusion and estuarine circulation patterns due to loss of intertidal flats affect the nearshore habitat and water quality in estuaries and potentially increase risk of coastal hazards, such as storm surge and coastal flooding. Furthermore, model results suggested the importance of including intertidal flats and the wetting-and-drying process in hydrodynamic simulations when intertidal flats are present in the model domain.« less

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model

NASA Astrophysics Data System (ADS)

Boulton, Chris A.; Allison, Lesley C.; Lenton, Timothy M.

2014-12-01

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached.

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model

PubMed Central

Boulton, Chris A.; Allison, Lesley C.; Lenton, Timothy M.

2014-01-01

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached. PMID:25482065

Early warning signals of Atlantic Meridional Overturning Circulation collapse in a fully coupled climate model.

PubMed

Boulton, Chris A; Allison, Lesley C; Lenton, Timothy M

2014-12-08

The Atlantic Meridional Overturning Circulation (AMOC) exhibits two stable states in models of varying complexity. Shifts between alternative AMOC states are thought to have played a role in past abrupt climate changes, but the proximity of the climate system to a threshold for future AMOC collapse is unknown. Generic early warning signals of critical slowing down before AMOC collapse have been found in climate models of low and intermediate complexity. Here we show that early warning signals of AMOC collapse are present in a fully coupled atmosphere-ocean general circulation model, subject to a freshwater hosing experiment. The statistical significance of signals of increasing lag-1 autocorrelation and variance vary with latitude. They give up to 250 years warning before AMOC collapse, after ~550 years of monitoring. Future work is needed to clarify suggested dynamical mechanisms driving critical slowing down as the AMOC collapse is approached.

Studies of Current Circulation at Ocean Waste Disposal Sites

NASA Technical Reports Server (NTRS)

Klemas, V. (Principal Investigator); Davis, G.; Henry, R.

1976-01-01

The author has identified the following significant results. Acid waste plume was observed in LANDSAT imagery fourteen times ranging from during dump up to 54 hours after dump. Circulation processes at the waste disposal site are highly storm-dominated, with the majority of the water transport occurring during strong northeasterlies. There is a mean flow to the south along shore. This appears to be due to the fact that northeasterly winds produce stronger currents than those driven by southeasterly winds and by the thermohaline circulation. During the warm months (May through October), the ocean at the dump site stratifies with a distinct thermocline observed during all summer cruising at depths ranging from 10 to 21 m. During stratified conditions, the near-bottom currents were small. Surface currents responded to wind conditions resulting in rapid movement of surface drogues on windy days. Mid-depth drogues showed an intermediate behavior, moving more rapidly as wind velocities increased.

Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility.

PubMed

Liu, Hao; Chen, Wei; Zhi, Xiao; Chen, En-Jiang; Wei, Tao; Zhang, Jian; Shen, Jian; Hu, Li-Qiang; Zhao, Bin; Feng, Xin-Hua; Bai, Xue-Li; Liang, Ting-Bo

2018-05-22

Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells.

Dynamical significance of tides over the Bay of Bengal

NASA Astrophysics Data System (ADS)

Bhagawati, Chirantan; Pandey, Suchita; Dandapat, Sumit; Chakraborty, Arun

2018-06-01

Tides play a significant role in the ocean surface circulations and vertical mixing thereby influencing the Sea Surface Temperatures (SST) as well. This, in turn, plays an important role in the global circulation when used as a lower boundary condition in a global atmospheric general circulation model. Therefore in the present study, the dynamics of tides over the Bay of Bengal (BoB) is investigated through numerical simulations using a high resolution (1/12°) Regional Ocean Modeling System (ROMS). Based on statistical analysis it is observed that incorporation of explicit tidal forcing improves the model performance in simulating the basin averaged monthly surface circulation features by 64% compared to the simulation without tides. The model simulates also Mixed Layer Depth (MLD) and SST realistically. The energy exchange between tidal oscillations and eddies leads to redistribution of surface kinetic energy density with a net decrease of 0.012 J m-3 in the western Bay and a net increase of 0.007 J m-3 in the eastern Bay. The tidal forcing also affects the potential energy anomaly and vertical mixing thereby leading to a fall in monthly MLD over the BoB. The mixing due to tides leads to a subsequent reduction in monthly SST and a corresponding reduction in surface heat exchange. These results from the numerical simulation using ROMS reveal that tides have a significant influence over the air-sea heat exchange which is the most important parameter for prediction of Tropical Cyclone frequency and its future variability over the BoB.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

PubMed

Toro, Luis; Barrientos, Víctor; León, Pablo; Rojas, Macarena; Gonzalez, Magdalena; González-Ibáñez, Alvaro; Illanes, Sebastián; Sugikawa, Keigo; Abarzúa, Néstor; Bascuñán, César; Arcos, Katherine; Fuentealba, Carlos; Tong, Ana María; Elorza, Alvaro A; Pinto, María Eugenia; Alzamora, Rodrigo; Romero, Carlos; Michea, Luis

2018-05-01

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease.

PubMed

He, Zhangping; Tang, Yanyan; Qin, Chao

2017-06-01

Circulating leukocyte-derived microparticles act as proinflammatory mediators that reflect vascular inflammation. In this study, we examined the hypothesis that the quantity of leukocyte-derived microparticles is increased in patients with ischemic cerebrovascular diseases, and investigated utility of various phenotypes of leukocyte-derived microparticles as specific biomarkers of vascular inflammation injury. Additionally we focused on identifying leukocyte-derived microparticles that may be correlated with stroke severity in acute ischemic stroke patients. The plasma concentration of leukocyte-derived microparticles obtained by a series of centrifugations of 76 consecutive patients with ischemic cerebrovascular diseases and 70 age-, sex-, and race-matched healthy controls were determined by flow cytometry. Significantly elevated numbers of leukocyte (CD45+), monocyte (CD14+), lymphocyte (CD4+), granulocyte (CD15+) derived microparticles were found in the plasma samples of patients ischemic cerebrovascular diseases, compared to healthy controls (p<0.05). Furthermore, the plasma levels of CD14+ microparticles were significantly correlated with stroke severity (r=0.355, p=0.019), cerebral vascular stenosis severity (r=0.255, p=0.025) and stroke subtype (r=0.242, p=0.036). No association with stroke was observed for other leukocyte-derived phenotypes. These results demonstrate that circulating leukocyte-derived microparticles amounts are increased in patients with ischemic cerebrovascular diseases, compared with healthy controls. As proinflammatory mediators, leukocyte-derived microparticles may contribute to vascular inflammatory and the inflammatory process in acute ischemic stroke. Levels of CD14+ microparticles may be a promising biomarker of ischemic severity and outcome of stroke in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparison of whole body vibration and moist heat on lower extremity skin temperature and skin blood flow in healthy older individuals

PubMed Central

Lohman, Everett B.; Sackiriyas, Kanikkai Steni Balan; Bains, Gurinder S.; Calandra, Giovanni; Lobo, Crystal; Nakhro, Daniel; Malthankar, Gauri; Paul, Sherwine

2012-01-01

Summary Background Tissue healing is an intricate process that is regulated by circulation. Heat modalities have been shown to improve skin circulation. Recent research supports that passive vibration increases circulation without risk of burns. Study purpose is to compare and determine effects of short duration vibration, moist heat, and a combination of the two on skin blood flow (SBF) and skin temperature (ST) in elderly, non-diabetic individuals following short-term exposure. Material/Methods Ten subjects, 3 female and 7 male (55–73 years of age), received two interventions over three days: 1 – Active vibration, 2 – passive vibration, 3 – moist heat, 4 – moist heat combined with passive vibration (MHPV), 5 – a commercial massaging heating pad, and 6 – no intervention. SBF and ST were measured using a MOOR Laser Doppler before and after the intervention and the third measurement were taken 10 minutes following. Results Mean SBF following a ten-minute intervention were significantly different in the combination of moist heat and passive vibration from the control, active vibration, and the commercial massaging heating pad. Compared to baseline measurements, this resulted in mean SBF elevation to 450% (at conclusion of 10 minutes of intervention) and 379% (10 minutes post). MHPV (p=0.02) showed significant changes in ST from the commercial massaging heating pad, passive vibration, and active vibration interventions. Conclusions SBF in the lower legs showed greatest increase with MHPV. Interventions should be selected that are low risk while increasing lower extremity skin blood flow. PMID:22739731

Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms.

PubMed

Godoy, Jaime; Mellado, Patricio; Tapia, Jorge; Santín, Julia

2009-03-01

Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.

Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction.

PubMed

Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

2015-09-01

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Decreased eicosapentaenoic acid levels in acne vulgaris reveals the presence of a proinflammatory state.

PubMed

Aslan, İbrahim; Özcan, Filiz; Karaarslan, Taner; Kıraç, Ebru; Aslan, Mutay

2017-01-01

This study aimed to determine circulating levels of polyunsaturated fatty acids (PUFAs), secretory phospholipase A2 (sPLA2), lipoprotein lipase (LPL) and measure circulating protein levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4, cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with acne vulgaris. Serum from 21 control subjects and 31 acne vulgaris patients were evaluated for levels of arachidonic acid (AA, C20:4n- 6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). PUFA levels were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods Serum EPA levels were significantly decreased while AA/EPA and DGLA/EPA ratio were significantly increased in acne vulgaris patients compared to controls. Serum levels of AA, DGLA and DHA showed no significant difference while activity of sPLA2 and LPL were significantly increased in acne vulgaris compared to controls. Results of this study reveal the presence of a proinflammatory state in acne vulgaris as shown by significantly decreased serum EPA levels and increased activity of sPLA2, AA/EPA and DGLA/EPA ratio. Increased LPL activity in the serum of acne vulgaris patients can be protective through its anti-dyslipidemic actions. This is the first study reporting altered EPA levels and increased sPLA2 activity in acne vulgaris and supports the use of omega-3 fatty acids as adjuvant treatment for acne patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Circulating microparticles from obstructive sleep apnea syndrome patients induce endothelin-mediated angiogenesis.

PubMed

Tual-Chalot, Simon; Gagnadoux, Frédéric; Trzepizur, Wojciech; Priou, Pascaline; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2014-02-01

Microparticles are deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating microparticles are associated with endothelial dysfunction by reducing endothelial-derived nitric oxide production. Here, we have analyzed the potential role of circulating microparticles from OSAS patients on the regulation of angiogenesis and the involved pathway. VEGF content carried by circulating microparticles from OSAS patients was increased when compared with microparticles from non-OSAS patients. Circulating microparticles from OSAS patients induced an increase of angiogenesis that was abolished in the presence of the antagonist of endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased in human endothelial cells treated by OSAS microparticles. We highlight that circulating microparticles from OSAS patients can modify the secretome of endothelial cells leading to angiogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

Stressed lungs: unveiling the role of circulating stress ...

EPA Pesticide Factsheets

Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

Circulatory response and autonomic nervous activity during gum chewing.

PubMed

Hasegawa, Yoko; Sakagami, Joe; Ono, Takahiro; Hori, Kazuhiro; Zhang, Min; Maeda, Yoshinobu

2009-08-01

Mastication has been proven to enhance the systemic circulation, with circulatory responses seeming to be largely regulated by autonomic nervous activity via a more complex regulatory system than those of other activities. However, few studies have examined the relationships between changes in autonomic nervous activity and the systemic circulation that are induced by masticatory movement. We investigated changes in the systemic circulation and autonomic nervous activity during gum chewing to clarify the influence of mastication. Electrocardiograms, arterial blood pressure, and masseter electromyograms were taken while chewing gum continuously as indicators of systemic circulation in 10 healthy subjects with normal dentition. Cardiac sympathetic activity and vagus nervous activity, as well as vasomotor sympathetic nervous activity, were evaluated by fluctuation analysis of heart rate and blood pressure. Repeated analysis of variance and multiple comparisons were performed to determine chronological changes in each indicator during gum chewing. Gum chewing increased the heart rate and the mean arterial pressure. Although cardiac sympathetic activity and vagus nervous activity showed significant changes, vasomotor sympathetic nervous activity did not. These results suggest that changes in the autonomic nervous activity of the heart are mainly involved in the enhancement of systemic circulation with gum chewing. This explains some characteristics of autonomic nervous regulation in masticatory movement.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

PubMed Central

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

Metformin and insulin receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vigneri, R.; Gullo, D.; Pezzino, V.

The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitromore » to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.« less

The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6.

PubMed

Ide, Mark; Jagdev, Daljit; Coward, Paula Y; Crook, Martin; Barclay, G Robin; Wilson, Ron F

2004-03-01

The acute-phase response involves molecules including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). This study aimed to determine whether subgingival scaling resulted in rapid changes in plasma concentrations of these molecules. Twenty-three non-smoking adults with chronic periodontitis received subgingival scaling for 60 minutes. Venous blood samples were taken at 0, 15, 30, 60, and 120 minutes. TNF-alpha and IL-6 were assayed from all samples and CRP from the baseline and final samples. Lipopolysaccharide (LPS) was assayed at 0, 15, and 30 minutes using limulus lysate assay (LAL) and EndoCAb Ig assays. LPS assays were suggestive of a transient low-grade bacteremia, but changes in LPS approaching significance (P=0.061) were seen with LAL only. There was a significant increase in circulating TNF-alpha (P=0.0387) and IL-6 (P<0.0001), and the degree of change in TNF-alpha was correlated with the severity of periodontal breakdown (P=0.001). There was also a significant correlation between levels of IL-6 and TNF-alpha (P<0.001). Chronic periodontitis patients undergoing an episode of subgingival scaling show a significant elevation in circulating TNF-alpha and IL-6. This may account for anecdotal reports of pyrexia following treatment and may be significant in terms of the relationship between periodontal disease, bacteremia, and cardiovascular disease.

Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma.

PubMed

Gong, Fang; Zhu, Hua-Yan; Zhu, Jie; Dong, Qiao-Jing; Huang, Xuan; Jiang, Dong-Jin

2018-05-01

The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5 + CD4 + T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5 + CD4 + T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5 + CD4 + T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5 + CD4 + T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4 + -, IL-21 + -producing CXCR5 + CD4 + T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5 + CD4 + T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4 + -, IL-21 + -CXCR5 + CD4 + T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5 + CD4 + T cells may have a significant role in facilitating IgE production in allergic asthma patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

[Effect of gas-lift device on the morphology and performance of ANAMMOX sludge].

PubMed

Li, Xiang; Huang, Yong; Yuan, Yi; Zhou, Cheng; Chen, Zong-Heng; Zhang, Da-Lin

2014-12-01

The upflow reactor with gas-lift device was started up by inoculating ANAMMOX sludge granules of less than 0.9 mm. The effects of gas lift device system on the morphology and performance of ANAMMOX sludge were studied by using the nitrogen gas produced in ANAMMOX to drive the effluent circulation in the reactor. The results showed that, the airlift circulation function was not clear in the startup stage of the reactor, because the nitrogen gas production was very low. At the same time, the ANAMMOX granular sludge was easy to condensate. When the load rate of nitrogen removal reached 3.4 kg x (m3 x d)(-1), the function of gas lift was significant, resulting in gradually increased effluent self-circulation, and the granules were dispersed and grew gradually. After 183d of operation, the granular sludge was dominated by the granules with sizes of 1.6-2.5 mm, which accounted for 53.2% of the total sludge volume. The MLVSS content increased with the increase of sludge particle size. The gas lift device had the same function as the external reflux pump, and was helpful for sludge granulation in the ANAMMOX reactor, while reducing power consumption and the cost of the equipment.

Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

PubMed

Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

2015-01-01

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

Circulating levels of hydrogen sulfide and substance P in patients with sepsis.

PubMed

Gaddam, Ravinder Reddy; Chambers, Stephen; Murdoch, David; Shaw, Geoffrey; Bhatia, Madhav

2017-10-01

To determine alterations of circulating levels of hydrogen sulfide and substance P in patients with sepsis compared to non-sepsis patients with similar disease severity and organ dysfunction. This study included 23 septic and 14 non-septic patients during 2015-16 study period at the Christchurch Hospital Intensive Care Unit, Christchurch, New Zealand. Blood samples were collected from the time of admission to 96 h, with collection at different time points (0 h, 12 h, 24 h, 48 h, 72 h and 96 h) and subjected to measurement of hydrogen sulfide, substance P, procalcitonin, C-reactive protein, interleukin-6 and lactate levels. Patients with sepsis showed higher circulating hydrogen sulfide and substance P levels compared to patients without sepsis. Hydrogen sulfide levels were significantly higher at 12 h (1.45 vs 0.75 μM; p < 0.05) and 24 h (1.11 vs 0.72 μM; p < 0.01), whereas substance P levels were higher at 48 h (0.55 vs 0.31 ng/mL; p < 0.05). Increased hydrogen sulfide and substance P levels in septic patients were associated with increased levels of inflammatory mediators - procalcitonin, C-reactive protein and interleukin-6. These results provide evidence that higher circulating levels of hydrogen sulfide and substance P are associated with increased inflammatory response in patients with sepsis. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Physiological, Pharmacological, and Nutritional Regulation of Circulating Adiponectin Concentrations in Humans

PubMed Central

Swarbrick, Michael M.

2008-01-01

Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434

Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

PubMed

Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

2004-10-15

Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

PubMed

Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D

1996-01-01

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

The Role of Gravity Waves in Generating Equatorial Oscillations in Modulating Atmospheric Tides

NASA Technical Reports Server (NTRS)

Mayr, H. G.; Mengel, J. G.; Chan, K. L.; Porter, H. S.; Reddy, C. A.

1999-01-01

We discuss a Numerical Spectral Mode (NSM) that extends from the ground up into the thermosphere and incorporates Hines' Doppler spread parameterization (DSP) for small scale gravity waves (GW). This model is applied to describe the seasonal variations in the mean zonal circulation, the semi-annual and quasi-biennial oscillations (SAO and QBO), as well as the tides and planetary waves in the middle atmosphere. Initial results showed that this model can reproduce the salient features observed, including the QBO extending into the upper mesosphere inferred from UARS measurements. The model has now been extended to simulate also: (a) the zonal circulation of the lower stratosphere and upper troposphere, and (b) the upwelling at equatorial latitudes associated with the Brewer Dobsen circulation that affects the dynamics significantly as pointed out by Dunkerton. Upward vertical winds increase the period of the QBO observed from the ground. To compensate for that, one needs to increase in the model the eddy diffusivity and the GW momentum flux, bringing the latter closer to values recommended in the DSP. This development is conducive to extending the QBO and SAO to higher latitudes through global scale momentum redistribution. Multi-year interannual oscillations are generated through wave filtering by the solar driven annual oscillation in the zonal circulation. In a 3D version of the model, wave momentum is absorbed and dissipated by tides and planetary waves. A somewhat larger GW source (well within the DSP range) is then required to generate realistic QBO and SAO amplitudes. Since GW momentum is deposited in the altitude regime of increasing winds, the amplitude of the diurnal tide is amplified and its vertical wavelength is reduced at altitudes between 70 and 120 km. Wave filtering by the mean zonal circulation causes the GW flux to peak during equinox, and this produces a large semi-annual variation in the tide that has been observed on UARS. Without the diurnal tide, the semidiurnal tide would also be modulated in this way. But the diurnal tide filters out the GW preferentially during equinox, so that the semidiurnal tide tends to peak during solstice. Under the influence of GW, the tides are modulated significantly by planetary waves that are generated preferentially during solstice in part due to baroclinic instability.

Mixing parametrizations for ocean climate modelling

NASA Astrophysics Data System (ADS)

Gusev, Anatoly; Moshonkin, Sergey; Diansky, Nikolay; Zalesny, Vladimir

2016-04-01

The algorithm is presented of splitting the total evolutionary equations for the turbulence kinetic energy (TKE) and turbulence dissipation frequency (TDF), which is used to parameterize the viscosity and diffusion coefficients in ocean circulation models. The turbulence model equations are split into the stages of transport-diffusion and generation-dissipation. For the generation-dissipation stage, the following schemes are implemented: the explicit-implicit numerical scheme, analytical solution and the asymptotic behavior of the analytical solutions. The experiments were performed with different mixing parameterizations for the modelling of Arctic and the Atlantic climate decadal variability with the eddy-permitting circulation model INMOM (Institute of Numerical Mathematics Ocean Model) using vertical grid refinement in the zone of fully developed turbulence. The proposed model with the split equations for turbulence characteristics is similar to the contemporary differential turbulence models, concerning the physical formulations. At the same time, its algorithm has high enough computational efficiency. Parameterizations with using the split turbulence model make it possible to obtain more adequate structure of temperature and salinity at decadal timescales, compared to the simpler Pacanowski-Philander (PP) turbulence parameterization. Parameterizations with using analytical solution or numerical scheme at the generation-dissipation step of the turbulence model leads to better representation of ocean climate than the faster parameterization using the asymptotic behavior of the analytical solution. At the same time, the computational efficiency left almost unchanged relative to the simple PP parameterization. Usage of PP parametrization in the circulation model leads to realistic simulation of density and circulation with violation of T,S-relationships. This error is majorly avoided with using the proposed parameterizations containing the split turbulence model. The high sensitivity of the eddy-permitting circulation model to the definition of mixing is revealed, which is associated with significant changes of density fields in the upper baroclinic ocean layer over the total considered area. For instance, usage of the turbulence parameterization instead of PP algorithm leads to increasing circulation velocity in the Gulf Stream and North Atlantic Current, as well as the subpolar cyclonic gyre in the North Atlantic and Beaufort Gyre in the Arctic basin are reproduced more realistically. Consideration of the Prandtl number as a function of the Richardson number significantly increases the modelling quality. The research was supported by the Russian Foundation for Basic Research (grant № 16-05-00534) and the Council on the Russian Federation President Grants (grant № MK-3241.2015.5)

Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

PubMed Central

Ferreira, Diego dos Santos; Boratto, Fernanda Alves; Cardoso, Valbert Nascimento; Serakides, Rogéria; Fernandes, Simone Odília; Ferreira, Lucas Antônio Miranda; Oliveira, Mônica Cristina

2015-01-01

Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly high. These results show that long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime have a tropism for infectious foci. PMID:25848262

Nanotechnology for Synthetic High Density Lipoproteins

PubMed Central

Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

2014-01-01

Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients

PubMed Central

Batchelor, Tracy T.; Sorensen, A. Gregory; di Tomaso, Emmanuelle; Zhang, Wei-Ting; Duda, Dan G.; Cohen, Kenneth S.; Kozak, Kevin R.; Cahill, Daniel P.; Chen, Poe-Jou; Zhu, Mingwang; Ancukiewicz, Marek; Mrugala, Maciej M.; Plotkin, Scott; Drappatz, Jan; Louis, David N.; Ivy, Percy; Scadden, David T.; Benner, Thomas; Loeffler, Jay S.; Wen, Patrick Y.; Jain, Rakesh K.

2009-01-01

SUMMARY Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171—an oral tyrosine kinase inhibitor of VEGF receptors—has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1α, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor. PMID:17222792

The relationship between a Mediterranean diet and circulating adiponectin levels is influenced by cigarette smoking.

PubMed

Al-Attas, Omar Salem; Hussain, Tajamul; Al-Daghri, Nasser Mohammad; De Rosas, Edgard; Kazmi, Usamah; Vinodson, Benjamin

2013-01-01

Adherence to a Mediterranean diet has been shown to lower the risk of developing several chronic diseases. The ability to augment circulating adiponectin levels is proposed as an underlying mechanism mediating the beneficial effects of this diet. We aimed to examine whether the positive relationship between the Mediterranean diet and adiponectin is altered by cigarette smoking, taking potential confounders into consideration. Plasma adiponectin levels were enzymatically measured in 45 never smokers, 61 smokers and 34 ex-smokers who adhered to a Mediterranean style diet and in 41 never smokers who did not adhere to the diet. Plasma adiponectin levels increased significantly in nonsmoking diet adherents compared to nonsmoking non-diet adherents. Among the diet adherents adiponectin decreased significantly in both moderate and heavy smokers compared to never smokers and significantly increased in quitters compared to smokers. Multiple regression analysis, controlling for age, obesity, Mediterranean diet and insulin resistance revealed an independent inverse association of smoking with adiponectin. Adiponectin levels remained significant and similar in subjects stratified according to age (50 years), BMI (25 kg/m(2)) and HOMA-IR (1.6). Despite its positive effects on adiponectin, the Mediterranean diet failed to negate the adiponectin-lowering effect of cigarette smoking, demonstrating the profound and independent capacity of cigarette smoke to negatively influence human health.

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

PubMed

O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

2013-01-01

Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non-healing diabetic foot ulcers in humans.

Mid-latitude afforestation shifts general circulation and tropical precipitation.

PubMed

Swann, Abigail L S; Fung, Inez Y; Chiang, John C H

2012-01-17

We show in climate model experiments that large-scale afforestation in northern mid-latitudes warms the Northern Hemisphere and alters global circulation patterns. An expansion of dark forests increases the absorption of solar energy and increases surface temperature, particularly in regions where the land surface is unable to compensate with latent heat flux due to water limitation. Atmospheric circulation redistributes the anomalous energy absorbed in the northern hemisphere, in particular toward the south, through altering the Hadley circulation, resulting in the northward displacement of the tropical rain bands. Precipitation decreases over parts of the Amazon basin affecting productivity and increases over the Sahel and Sahara regions in Africa. We find that the response of climate to afforestation in mid-latitudes is determined by the amount of soil moisture available to plants with the greatest warming found in water-limited regions. Mid-latitude afforestation is found to have a small impact on modeled global temperatures and on global CO(2), but regional heating from the increase in forest cover is capable of driving unintended changes in circulation and precipitation. The ability of vegetation to affect remote circulation has implications for strategies for climate mitigation.

12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake.

PubMed

Stanford, Kristin I; Lynes, Matthew D; Takahashi, Hirokazu; Baer, Lisa A; Arts, Peter J; May, Francis J; Lehnig, Adam C; Middelbeek, Roeland J W; Richard, Jeffrey J; So, Kawai; Chen, Emily Y; Gao, Fei; Narain, Niven R; Distefano, Giovanna; Shettigar, Vikram K; Hirshman, Michael F; Ziolo, Mark T; Kiebish, Michael A; Tseng, Yu-Hua; Coen, Paul M; Goodyear, Laurie J

2018-05-01

Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors.

PubMed

Ajabnoor, Ghada M A; Bahijri, Suhad; Shaik, Noor Ahmad; Borai, Anwar; Alamoudi, Aliaa A; Al-Aama, Jumana Y; Chrousos, George P

2017-01-01

During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance. To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1α in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors. Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 +1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (±1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1α was evaluated in circulating leukocytes. Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/ HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1α mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan. Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1α mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus.

Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-01-01

In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Hydrothermal systems are a sink for dissolved black carbon in the deep ocean

NASA Astrophysics Data System (ADS)

Niggemann, J.; Hawkes, J. A.; Rossel, P. E.; Stubbins, A.; Dittmar, T.

2016-02-01

Exposure to heat during fires on land or geothermal processes in Earth's crust induces modifications in the molecular structure of organic matter. The products of this thermogenesis are collectively termed black carbon. Dissolved black carbon (DBC) is a significant component of the oceanic dissolved organic carbon (DOC) pool. In the deep ocean, DBC accounts for 2% of DOC and has an apparent radiocarbon age of 18,000 years. Thus, DBC is much older than the bulk DOC pool, suggesting that DBC is highly refractory. Recently, it has been shown that recalcitrant deep-ocean DOC is efficiently removed during hydrothermal circulation. Here, we hypothesize that hydrothermal circulation is also a net sink for deep ocean DBC. We analyzed DBC in samples collected at different vent sites in the Atlantic, Pacific and Southern oceans. DBC was quantified in solid-phase extracts as benzenepolycarboxylic acids (BPCAs) following nitric acid digestion. Concentrations of DBC were much lower in hydrothermal fluids than in surrounding deep ocean seawater, confirming that hydrothermal circulation acts as a net sink for oceanic DBC. The relative contribution of DBC to bulk DOC did not change during hydrothermal circulation, indicating that DBC is removed at similar rates as bulk DOC. The ratio of the oxidation products benzenehexacarboxylic acid (B6CA) to benzenepentacarboxylic acid (B5CA) was significantly higher in hydrothermally altered samples compared to ratios typically found in the deep ocean, reflecting a higher degree of condensation of DBC molecules after hydrothermal circulation. Our study identified hydrothermal circulation as a quantitatively important sink for refractory DBC in the deep ocean. In contrast to photodegradation of DBC at the sea surface, which is more efficient for more condensed DBC, i.e. decreasing the B6CA/B5CA ratio, hydrothermal processing increases the B6CA/B5CA ratio, introducing a characteristic hydrothermal DBC signature.

A Preliminary Study on the Circulation of an ocean covering a Synchronously Rotating Planet

NASA Astrophysics Data System (ADS)

Matsuo, H.; Ishiwatari, M.; Takehiro, S.; Hayashi, Y.; Nakajima, K.

2012-12-01

Recently, nearly 800 extrasolar planets have been detected. It seems that some of them present into habitable zone, in which planets can have ocean, and such planets rotate synchronously with their central stars. Ocean is necessary for life, and the circulation makes climate mild by heat transport on the earth. The earth is the only planet that has ocean in the solar system so that it has not been understood what oceanic circulation is like in another planets. The purpose of this study is prediction of oceanic circulation on extrasolar planets by using numerical simulation. As a first step, elementary consideration is made. The planet is almost entirely covered with ocean and whose rotation period corresponds with its orbital period. On synchronously rotating planets, the thermal contrast between day-hemisphere and night-hemisphere would be extreme. However, it may be lessend if there is significant zonal heat transport. The circulation in such conditions has not been known well. We performed a numerical experiment based on the linear shallow water equation, assuming that both the evaporation and the precipitation occur only on day-hemisphere (Noda et al., 2011). With these distributions of the evaporation and the precipitation, one may anticipate the circulation occurs in only day-hemisphere. However, the resulting calculation is characterized with zonally uniform zonal flow, which also covers night hemisphere. In addition, the intensity of the flow increases with time. That behavior can be understood by constructing asymptotic solution which is first degree in time. The importance of Coriolis force, which bends meridional flow to zonal flow, is identified. It is implied that, even when only day-hemisphere has the evaporation and precipitation, there may be significant amount of heat can be transported from the day-hemisphere to the night-hemisphere by the strong zonal flow. The growth of zonal flow would be stopped when the evaporation and the precipitation are balanced with mass transport in the bottom Ekman layer.

Evidence for functional heterogeneity of circulating B-type natriuretic peptide.

PubMed

Liang, Faquan; O'Rear, Jessica; Schellenberger, Ute; Tai, Lungkuo; Lasecki, Michael; Schreiner, George F; Apple, Fred S; Maisel, Alan S; Pollitt, N Stephen; Protter, Andrew A

2007-03-13

These studies describe molecular forms of circulating B-type natriuretic peptide (BNP) as well as their biological activity. Increased circulating levels of immunoreactive BNP correlate with the severity of heart failure and are considered a sensitive biomarker. However, little is known about the molecular forms of circulating BNP and their biological activity. Western blot analysis was used to characterize immunoreactive BNP species in heart failure plasma. Recombinant proBNP was assessed for reactivity in commercially available BNP assays and cell activity by cyclic guanosine monophosphate production in vascular cells. Heart failure plasma contained both low- (LMW-BNP) and high-molecular-weight (HMW-BNP) forms. The LMW-BNP migrated similarly to a 32-amino acid BNP standard, whereas HMW-BNP, when deglycosylated, was similar to deglycosylated recombinant proBNP. Recombinant proBNP and BNP were equally recognized by the Triage BNP assay (Biosite, San Diego, California). Furthermore, recombinant proBNP and BNP were both recognized by the Advia Centaur BNP test (Bayer Diagnostics, Tarrytown, New York), but only recombinant proBNP was recognized by the Elecsys NTproBNP assay (Roche Diagnostics, Indianapolis, Indiana). Recombinant proBNP exerted significantly less biological activity than BNP on human endothelial and vascular smooth muscle cells. Comparison of effective concentration (50%) values indicates that proBNP is 6- to 8-fold less potent than BNP in these human cells. This study demonstrates that proBNP, constituting a substantial portion of immunoreactive BNP in heart failure plasma, possesses significantly lower biological activity than the processed 32-amino acid hormone. These results implicate a discordance in heart failure between the high circulating levels of immunoreactive BNP and hormone activity, suggesting that some patients may be in a state of natriuretic peptide deficiency.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

PubMed

Arumugam, Paritha I; Mullins, Eric S; Shanmukhappa, Shiva Kumar; Monia, Brett P; Loberg, Anastacia; Shaw, Maureen A; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L; Malik, Punam

2015-10-08

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ∼10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. © 2015 by The American Society of Hematology.

Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome.

PubMed

Bicer, M; Alan, M; Alarslan, P; Guler, A; Kocabas, G U; Imamoglu, C; Aksit, M; Bozkaya, G; Isil, A M; Baloglu, A; Aslanipoiur, B; Calan, Mehmet

2018-06-28

Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member of relaxin/insulin superfamily. Growing evidence implicates the crucial role of the peptide in some metabolisms including food intake, glucose homeostasis and reproductive system. Polycystic ovary syndrome (PCOS) is involved in both reproductive and metabolic issues. The aim of the study was determination of circulating levels of INSL5 alteration in women with PCOS and evaluation of the relationship between INSL5 and hormonal-metabolic parameters as well as carotid intima media thickness (cIMT). A total of 164 subjects were recruited in this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched controls). Circulating INSL5 levels were assessed via ELISA method. High-resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic parameters of the recruited subjects were determined. Circulating INSL5 levels were significantly elevated in women with PCOS compared to controls (27.63 ± 7.74 vs. 19.90 ± 5.85 ng/ml, P < 0.001). The mean values of INSL5 were significantly higher in overweight subjects compared to lean weight subjects in both groups. The women with PCOS having insulin resistance have increased INSL5 compared to those of PCOS subjects without insulin resistance. INSL5 is associated with insulin resistance, BMI, luteinizing hormone and free androgen index. Multivariate logistic regression analyses revealed that the odds ratio for having PCOS in the highest tertile of INSL5 was higher than in the lowest tertile. PCOS subjects exhibited an elevation in circulating INSL5 levels along with a link between INSL5 level induction and metabolic-hormonal parameters.

Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

PubMed

Chiva-Blanch, Gemma; Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Peña, Esther; Ybarra, Juan; Pou, Jose M; Badimon, Lina

2016-07-01

Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Increased Levels of Calprotectin in Obesity Are Related to Macrophage Content: Impact on Inflammation and Effect of Weight Loss

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Fernández-Real, José Manuel; Salvador, Javier; Frühbeck, Gema

2011-01-01

Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage–related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities. PMID:21738950

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

PubMed Central

Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

2014-01-01

Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels less than 7.0 mmol/l should be preferred in this setting. PMID:24271038

Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

PubMed Central

Stawski, Robert; Walczak, Konrad; Kosielski, Piotr; Meissner, Pawel; Budlewski, Tomasz; Padula, Gianluca; Nowak, Dariusz

2017-01-01

Objective Acute single strenuous exercise increases circulating cell free DNA (cf DNA). We tested whether three repeated bouts of exhaustive exercise induced the cf DNA response without development of tolerance in healthy men. Methods Eleven average-trained men (age 34.0±5.2 years, body mass index 26.2±3.1 kg/m2, maximal oxygen consumption—VO2max 49.6±4.5 ml/kg*min) performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 hours of resting. Blood was collected before and after each bout of exercise for determination of cell free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, selected markers of muscle damage, and blood cell count. Results Each bout induced the increase (p<0.05) in plasma cf n-DNA: from 3.4±1.4 to 38.5±27.5, from 4.1±3.3 to 48.5±26.2, and 3.1±1.6 to 53.8±39.9 ng/mL after the first, second, and third exercise, respectively. In a congruent way, cf mt-DNA rose significantly after the second (from 229±216 to 450±228*103 GE/mL) and third bout of exercise (from 173±120 to 462±314*103 GE/mL). Pre-exercise cf mt-DNA decreased (p<0.05) by 2-times (from 355±219 before the first bout to 173±120*103 GE/mL before the third bout) over the study period and were accompanied by significant increase in white blood cells, platelets, creatine kinase, creatinine and lactate after each bout. However, the exercise induced percentage increment of cf n-DNA was always many times higher than corresponding increments of the afore-mentioned markers at any occasion. Conclusions Repeated bouts of exhaustive exercise induced remarkable increase in circulating cf n-DNA without signs of tolerance development. Baseline cf mt-DNA decreased in response to series of strenuous exercise. Since percentage increments of cf n-DNA in response to exercise were many times higher than those observed for other markers, measurement of circulating cf n-DNA could be a sensitive tool for monitoring acute exercise effects in human body. PMID:28542490

Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet

PubMed Central

Stewart, Laura K.; Soileau, Jeff L.; Ribnicky, David; Wang, Zhong Q.; Raskin, Ilya; Poulev, Alexander; Majewski, Martin; Cefalu, William T.; Gettys, Thomas W.

2008-01-01

Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-γ, interleukin-1α, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating markers of inflammation observed in animals on an HF diet at 8W. PMID:18555853

Strong and deep Atlantic meridional overturning circulation during the last glacial cycle.

PubMed

Böhm, E; Lippold, J; Gutjahr, M; Frank, M; Blaser, P; Antz, B; Fohlmeister, J; Frank, N; Andersen, M B; Deininger, M

2015-01-01

Extreme, abrupt Northern Hemisphere climate oscillations during the last glacial cycle (140,000 years ago to present) were modulated by changes in ocean circulation and atmospheric forcing. However, the variability of the Atlantic meridional overturning circulation (AMOC), which has a role in controlling heat transport from low to high latitudes and in ocean CO2 storage, is still poorly constrained beyond the Last Glacial Maximum. Here we show that a deep and vigorous overturning circulation mode has persisted for most of the last glacial cycle, dominating ocean circulation in the Atlantic, whereas a shallower glacial mode with southern-sourced waters filling the deep western North Atlantic prevailed during glacial maxima. Our results are based on a reconstruction of both the strength and the direction of the AMOC during the last glacial cycle from a highly resolved marine sedimentary record in the deep western North Atlantic. Parallel measurements of two independent chemical water tracers (the isotope ratios of (231)Pa/(230)Th and (143)Nd/(144)Nd), which are not directly affected by changes in the global cycle, reveal consistent responses of the AMOC during the last two glacial terminations. Any significant deviations from this configuration, resulting in slowdowns of the AMOC, were restricted to centennial-scale excursions during catastrophic iceberg discharges of the Heinrich stadials. Severe and multicentennial weakening of North Atlantic Deep Water formation occurred only during Heinrich stadials close to glacial maxima with increased ice coverage, probably as a result of increased fresh-water input. In contrast, the AMOC was relatively insensitive to submillennial meltwater pulses during warmer climate states, and an active AMOC prevailed during Dansgaard-Oeschger interstadials (Greenland warm periods).

Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance.

PubMed

Jia, Yanjun; Luo, Xiaohe; Ji, Ying; Xie, Jingwen; Jiang, Han; Fu, Mao; Li, Xiaoqiang

2017-09-01

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Subjects with normal glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationships between hormones and aggressive behavior in green anole lizards: an analysis using structural equation modeling.

PubMed

Yang, Eun-Jin; Wilczynski, Walter

2002-09-01

We investigated the relationship between aggressive behavior and circulating androgens in the context of agonistic social interaction and examined the effect of this interaction on the androgen-aggression relationship in response to a subsequent social challenge in male Anolis carolinensis lizards. Individuals comprising an aggressive encounter group were exposed to an aggressive conspecific male for 10 min per day during a 5-day encounter period, while controls were exposed to a neutral stimulus for the same period. On the sixth day, their responses to an intruder test were observed. At intervals, individuals were sacrificed to monitor plasma androgen levels. Structural equation modeling (SEM) was used to test three a priori interaction models of the relationship between social stimulus, aggressive behavior, and androgen. Model 1 posits that exposure to a social stimulus influences androgen and aggressive behavior independently. In Model 2, a social stimulus triggers aggressive behavior, which in turn increases circulating levels of androgen. In Model 3, exposure to a social stimulus influences circulating androgen levels, which in turn triggers aggressive behavior. During the 5 days of the encounter period, circulating testosterone (T) levels of the aggressive encounter group followed the same pattern as their aggressive behavioral responses, while the control group did not show significant changes in their aggressive behavior or T level. Our SEM results supported Model 2. A means analysis showed that during the intruder test, animals with 5 days of aggressive encounters showed more aggressive responses than did control animals, while their circulating androgen levels did not differ. This further supports Model 2, suggesting that an animal's own aggressive behavior may trigger increases in levels of plasma androgen. Copyright 2002 Elsevier Science (USA)

Investigating the Climatic Impacts of Globally Shifted Anthropogenic Emissions

NASA Astrophysics Data System (ADS)

Wang, Y.; Jiang, J. H.; Su, H.

2014-12-01

With a quasi-exponential growth in industrialization since the mid-1990s, Asia has undergone a dramatic increase in anthropogenic emissions of aerosol and precursor gases to the atmosphere. Meanwhile, such emissions have been stabilized or reduced over North America and Europe. This geographical shift of global emission sources could potentially perturb the regional and global climate due to impact of aerosols on cloud properties, precipitation, and large-scale circulation. We use an atmospheric general circulation model (AGCM) with different aerosol scenarios to investigate the radiative and microphysical effects of anthropogenic aerosols on the large-scale circulation and regional climate over the globe. We conduct experiments to simulate the continental shift of aerosol distribution by contrasting two simulations using 1970 and 2010 anthropogenic emission sources. We found the elevation of aerosol concentrations in East and South Asia results in regional surface temperature cooling of -0.10° to -0.17°C, respectively, due to the enhanced solar extinction by aerosols and cloud reflectivity. The reduction of the local aerosol loadings in Europe causes a significant warming of +0.4°C. However, despite recent decreasing in aerosol emission, North America shows a cooling of -0.13°C, likely caused by increasing of cloudiness under the influence of modulated general circulation. These aerosol induced temperature changes are consistent with the observed temperature trends from 1980 to 2013 in the reanalysis data. Our study also predicts weaker East/South Asia summer monsoons due to strong regional aerosol forcing. Moreover, the ascending motion in the northern tropics is found to be weakened by asymmetrical aerosol forcing, resulting in the cross-equatorial shift of Hadley Circulation.

The chemical and radiative effects of the Mount Pinatubo eruption

NASA Technical Reports Server (NTRS)

Kinneson, Douglas E.; Grant, Keith E.; Connell, Peter S.; Rotman, Douglas A.; Wuebbles, Donald J.

1994-01-01

To clarify the mechanisms leading to effects on stratospheric ozone, time-dependent stratospheric aerosol and gas experiment II (SAGE II) and cryogenic limb array elaton spectrometer (CLAES) aerosol optical extinction data and SAGE II surface area density are used as parameters in a two-dimensional (2-D) zonally averaged chemical radiative transport model. The model was integrated with time from before the eruption through December 1993. The modeled impact on global ozone results from increased rates of heterogeneous reactions on sulfate aerosols and from the increased radiative heating and scattering caused by these aerosols. When the aerosol heating is allowed to modify the temperature distribution, the maximum change calculated in equatorial column ozone is -1.6%. The calculated equatorial temperature change and peak local ozone change in October 1991 are +6K and -4%, respectively. When aerosol heating perturbs the circulation in the model, the maximum change in equatorial column ozone is -6%. Increased heterogeneous processing on sulfate aerosols is calculated to have changed equatorial column ozone in late 1991 by -1.5%. Global column ozone in the model in 1992 and 1993 changed by -2.8% and -2.4%, respectively. The relationship of ozone-controlling processes in the lower stratosphere is altered as well; HO(x) becomes the most important catalytic cycle, followed by ClO(x) and NO(x). This is driven by significant changes in trace gas concentrations. In October 1991, lower stratospheric, equatorial NO(x) decreased by 40%, ClO(x) increased by 60%, and HO(x) increased by 25%. When the effect of heterogeneous chemical processing on sulfate aerosols is combined with aerosol heating, modifying either circulation or temperature, dramatically different ozone fingerprints with time and latitude are predicted. Model-derived changes in the equatorial region in column ozone best represented the observed data when perturbed circulation was combined with heterogeneous chemical effects. However, at high latitudes, the increased ozone production from the strengthening of the mean circulation tends to cancel the heterogeneous reduction of ozone. This is not in good agreement with observed data, especially in 1992 and 1993. When the circulation is held fixed and the temperature allowed to change, and heterogeneous chemical effects are included, the equatorial ozone decrease predicted was too small for 1991. However, the mid- to high-latitude decrease in 1992 and 1993 is in better agreement with observed data.

Irisin in response to acute and chronic whole-body vibration exercise in humans.

PubMed

Huh, Joo Young; Mougios, Vassilis; Skraparlis, Athanasios; Kabasakalis, Athanasios; Mantzoros, Christos S

2014-07-01

Irisin is a recently identified myokine, suggested to mediate the beneficial effects of exercise by inducing browning of white adipocytes and thus increasing energy expenditure. In humans, the regulation of irisin by exercise is not completely understood. We investigated the effect of acute and chronic whole-body vibration exercise, a moderate-intensity exercise that resembles shivering, on circulating irisin levels in young healthy subjects. Healthy untrained females participated in a 6-week program of whole-body vibration exercise training. Blood was drawn before and immediately after an acute bout of exercise at baseline (week 0) and after 6 weeks of training. The resting irisin levels were not different at baseline (week 0) and after 6 weeks of training. At both 0 and 6 weeks of training, an acute bout of vibration exercise significantly elevated circulating irisin levels by 9.5% and 18.1%, respectively (p=0.05 for the percent change of irisin levels). Acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Measurements of the Early Development of Trailing Vorticity from a Rotor

NASA Technical Reports Server (NTRS)

McAlister, Kenneth W.; Heineck, James T.

2002-01-01

The wake behind a two-bladed model rotor in light climb was measured using particle image velocimetry, with particular emphasis on the development of the trailing vortex during the first revolution of the rotor. The distribution of vorticity was distinguished from the slightly elliptical swirl pattern. Peculiar dynamics within the "void" region may explain why the peak vorticity appeared to shift away from the center as the vortex aged, suggesting the onset of instability. The swirl and axial velocities (which reached 44% and 12% of the rotor tip speed, respectively) were found to be asymmetric relative to the vortex center. In particular, the axial flow was composed of two concentrated zones moving in opposite directions. The radial distribution of the circulation rapidly increased in magnitude until reaching a point just beyond the core radius, after which the rate of growth decreased significantly. The core-radius circulation increased slightly with wake age, but the large-radius circulation appeared to remain relatively constant. The radial distributions of swirl velocity and vorticity exhibit self-similar behaviors, especially within the core. The diameter of the vortex core was initially about 10% of the rotor-blade chord, but more than doubled its size after one revolution of the rotor.

Clinical significance of detecting circulating tumor cells in colorectal cancer using subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH)

PubMed Central

Shen, Zhen; Jing, Yan; Lu, Haibo; Li, Heng; Yang, Xiaoye; Cui, Xiangbin; Li, Yuqing; Lou, Zheng; Liu, Peng; Zhang, Cun; Zhang, Wei

2017-01-01

Circulating tumor cells (CTC) are useful in early detection of colorectal cancer. This study described a newly developed platform, integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033). No significant association was found between tumor stage, survival and preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one week after surgery; seven patients with decreased CTC numbers (compared with preoperative CTC number) were free of recurrence; whereas two of the three patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were detected in 34 colorectal cancer patients three months after surgery; patients with CTC<2 at three months after surgery had significantly longer Progression Free Survival than those with CTC>=2 (P=0.019); patients with decreased CTC number (compared with preoperative CTC number) had significantly longer Progression Free Survival than those with increased CTC number (P=0.003). In conclusion, CTCs could be detected in various stages of colorectal cancer using SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and prognosis. PMID:28423493

Correlations between the modelled potato crop yield and the general atmospheric circulation

NASA Astrophysics Data System (ADS)

Sepp, Mait; Saue, Triin

2012-07-01

Biology-related indicators do not usually depend on just one meteorological element but on a combination of several weather indicators. One way to establish such integral indicators is to classify the general atmospheric circulation into a small number of circulation types. The aim of present study is to analyse connections between general atmospheric circulation and potato crop yield in Estonia. Meteorologically possible yield (MPY), calculated by the model POMOD, is used to characterise potato crop yield. Data of three meteorological stations and the biological parameters of two potato sorts were applied to the model, and 73 different classifications of atmospheric circulation from catalogue 1.2 of COST 733, domain 05 are used to qualify circulation conditions. Correlation analysis showed that there is at least one circulation type in each of the classifications with at least one statistically significant (99%) correlation with potato crop yield, whether in Kuressaare, Tallinn or Tartu. However, no classifications with circulation types correlating with MPY in all three stations at the same time were revealed. Circulation types inducing a decrease in the potato crop yield are more clearly represented. Clear differences occurred between the observed geographical locations as well as between the seasons: derived from the number of significant circulation types, summer and Kuressaare stand out. Of potato varieties, late 'Anti' is more influenced by circulation. Analysis of MSLP maps of circulation types revealed that the seaside stations (Tallinn, Kuressaare) suffer from negative effects of anti-cyclonic conditions (drought), while Tartu suffers from the cyclonic activity (excessive water).

Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome.

PubMed

Xi, Wenyan; Yang, Yongkang; Mao, Hui; Zhao, Xiuhua; Liu, Ming; Fu, Shengyu

2016-02-11

To investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This prospective cohort observational study included 81 anovulatory women with PCOS who underwent 213 cycles of CC ovarian stimulation. Serum AMH concentrations were measured on cycle day 3 before the commencement of CC in the first cycle, which were compared between responders and CC-resistant anovulation (CRA). Logistic regression analysis was applied to study the value of serum AMH for the prediction of ovarian responsiveness to CC stimulation. The receiver-operating characteristic (ROC) curve was used to evaluate the prognostic value of circulating AMH. Serum AMH levels. Women who ovulated after CC therapy had a significantly lower AMH compared with the CRA (5.34 ± 1.97 vs.7.81 ± 3.49, P < 0.001). There was a significant gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation (P < 0.05). In multivariate logistic regression analysis, AMH was an independent predictor of ovulation induction by CC in PCOS patients. ROC curve analysis showed AMH to be a useful predictor of ovulation induction by CC in PCOS patients, having 92 % specificity and 65 % sensitivity when the threshold AMH concentration was 7.77 ng/ml. Serum AMH may be clinically useful to predict which PCOS women are more likely to respond to CC treatment and thus to direct the selection of protocols of ovulation induction.

Opposing actions of TRPV4 channel activation in the lung vasculature.

PubMed

Ke, Sun-Kui; Chen, Lan; Duan, Hong-Bing; Tu, Yuan-Rong

2015-12-01

Transient receptor potential vanilloid 4 (TRPV4) calcium channels are known to promote endothelium-dependent relaxation of mouse mesenteric arteries but TRPV4's role in the pulmonary vasculature is uncertain. Thus, we characterized TRPV4 channel vascular tone regulation in mouse main pulmonary artery rings and in the isolated perfused pulmonary circulation and studied possible mechanisms behind these characterizations. Using myography and a TRPV4 specific agonist GSK1016790A in a C57BL/6 WT mouse model of isolated constant-flow lung perfusion, we studied vascular tone regulation in arterial rings from the main left and right pulmonary arteries and vascular resistance of the intra-pulmonary circulation beyond the second branches of the pulmonary arteries. Removal of the endothelium confirmed endothelial dependence. GSK1016790A relaxed the main pulmonary artery (EC50 4 × 10(-8)mol/L), which was inhibited by removal of the endothelium from main pulmonary artery rings. GSK1016790A significantly increased vascular resistance of the pulmonary circulation in isolated perfused lungs, but these effects were inhibited by a TRPV4 antagonist AB159908. A nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and K(+) channel blockers apamin plus charybdotoxin (ChTx) significantly inhibited GSK1016790A in the main pulmonary artery and in an isolated perfused lung in vitro. Activated TRPV4 channels increase pulmonary vascular resistance and vasodilate the main pulmonary artery. Copyright © 2015 Elsevier B.V. All rights reserved.

The impact of resolution on the dynamics of the martian global atmosphere: Varying resolution studies with the MarsWRF GCM

NASA Astrophysics Data System (ADS)

Toigo, Anthony D.; Lee, Christopher; Newman, Claire E.; Richardson, Mark I.

2012-09-01

We investigate the sensitivity of the circulation and thermal structure of the martian atmosphere to numerical model resolution in a general circulation model (GCM) using the martian implementation (MarsWRF) of the planetWRF atmospheric model. We provide a description of the MarsWRF GCM and use it to study the global atmosphere at horizontal resolutions from 7.5° × 9° to 0.5° × 0.5°, encompassing the range from standard Mars GCMs to global mesoscale modeling. We find that while most of the gross-scale features of the circulation (the rough location of jets, the qualitative thermal structure, and the major large-scale features of the surface level winds) are insensitive to horizontal resolution over this range, several major features of the circulation are sensitive in detail. The northern winter polar circulation shows the greatest sensitivity, showing a continuous transition from a smooth polar winter jet at low resolution, to a distinct vertically “split” jet as resolution increases. The separation of the lower and middle atmosphere polar jet occurs at roughly 10 Pa, with the split jet structure developing in concert with the intensification of meridional jets at roughly 10 Pa and above 0.1 Pa. These meridional jets appear to represent the separation of lower and middle atmosphere mean overturning circulations (with the former being consistent with the usual concept of the “Hadley cell”). Further, the transition in polar jet structure is more sensitive to changes in zonal than meridional horizontal resolution, suggesting that representation of small-scale wave-mean flow interactions is more important than fine-scale representation of the meridional thermal gradient across the polar front. Increasing the horizontal resolution improves the match between the modeled thermal structure and the Mars Climate Sounder retrievals for northern winter high latitudes. While increased horizontal resolution also improves the simulation of the northern high latitudes at equinox, even the lowest model resolution considered here appears to do a good job for the southern winter and southern equinoctial pole (although in detail some discrepancies remain). These results suggest that studies of the northern winter jet (e.g., transient waves and cyclogenesis) will be more sensitive to global model resolution that those of the south (e.g., the confining dynamics of the southern polar vortex relevant to studies of argon transport). For surface winds, the major effect of increased horizontal resolution is in the superposition of circulations forced by local-scale topography upon the large-scale surface wind patterns. While passive predictions of dust lifting are generally insensitive to model horizontal resolution when no lifting threshold is considered, increasing the stress threshold produces significantly more lifting in higher resolution simulations with the generation of finer-scale, higher-stress winds due primarily to better-resolved topography. Considering the positive feedbacks expected for radiatively active dust lifting, we expect this bias to increase when such feedbacks are permitted.

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

PubMed

Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.

An extreme event of sea-level rise along the Northeast Coast of North America in 2009-2010.

PubMed

Goddard, Paul B; Yin, Jianjun; Griffies, Stephen M; Zhang, Shaoqing

2015-02-24

The coastal sea levels along the Northeast Coast of North America show significant year-to-year fluctuations in a general upward trend. The analysis of long-term tide gauge records identified an extreme sea-level rise (SLR) event during 2009-10. Within this 2-year period, the coastal sea level north of New York City jumped by 128 mm. This magnitude of interannual SLR is unprecedented (a 1-in-850 year event) during the entire history of the tide gauge records. Here we show that this extreme SLR event is a combined effect of two factors: an observed 30% downturn of the Atlantic meridional overturning circulation during 2009-10, and a significant negative North Atlantic Oscillation index. The extreme nature of the 2009-10 SLR event suggests that such a significant downturn of the Atlantic overturning circulation is very unusual. During the twenty-first century, climate models project an increase in magnitude and frequency of extreme interannual SLR events along this densely populated coast.

Patterns of bleaching and mortality following widespread warming events in 2014 and 2015 at the Hanauma Bay Nature Preserve, Hawai'i.

PubMed

Rodgers, Ku'ulei S; Bahr, Keisha D; Jokiel, Paul L; Richards Donà, Angela

2017-01-01

Drastic increases in global carbon emissions in the past century have led to elevated sea surface temperatures that negatively affect coral reef organisms. Worldwide coral bleaching-related mortality is increasing and data has shown even isolated and protected reefs are vulnerable to the effects of global climate change. In 2014 and 2015, coral reefs in the main Hawaiian Islands (MHI) suffered up to 90% bleaching, with higher than 50% subsequent mortality in some areas. The location and severity of bleaching and mortality was strongly influenced by the spatial and temporal patterns of elevated seawater temperatures. The main objective of this research was to understand the spatial extent of bleaching mortality in Hanauma Bay Nature Preserve (HBNP), O'ahu, Hawai'i to gain a baseline understanding of the physical processes that influence localized bleaching dynamics. Surveys at HBNP in October 2015 and January 2016 revealed extensive bleaching (47%) and high levels of coral mortality (9.8%). Bleaching was highly variable among the four HBNP sectors and ranged from a low of ∼31% in the central bay at Channel (CH) to a high of 57% in the area most frequented by visitors (Keyhole; KH). The highest levels of bleaching occurred in two sectors with different circulation patterns: KH experienced comparatively low circulation velocity and a low temperature increase while Witches Brew (WB) and Backdoors (BD) experienced higher circulation velocity and higher temperature increase. Cumulative mortality was highest at WB (5.0%) and at BD (2.9%) although WB circulation velocity is significantly higher. HBNP is minimally impacted by local factors that can lead to decline such as high fishing pressure or sedimentation although human use is high. Despite the lack of these influences, high coral mortality occurred. Visitor impacts are strikingly different in the two sectors that experienced the highest mortality evidenced by the differences in coral cover associated with visitor use however, coral mortality was similar. These results suggest that elevated temperature was more influential in coral bleaching and the associated mortality than high circulation or visitor use.

Patterns of bleaching and mortality following widespread warming events in 2014 and 2015 at the Hanauma Bay Nature Preserve, Hawai‘i

PubMed Central

2017-01-01

Drastic increases in global carbon emissions in the past century have led to elevated sea surface temperatures that negatively affect coral reef organisms. Worldwide coral bleaching-related mortality is increasing and data has shown even isolated and protected reefs are vulnerable to the effects of global climate change. In 2014 and 2015, coral reefs in the main Hawaiian Islands (MHI) suffered up to 90% bleaching, with higher than 50% subsequent mortality in some areas. The location and severity of bleaching and mortality was strongly influenced by the spatial and temporal patterns of elevated seawater temperatures. The main objective of this research was to understand the spatial extent of bleaching mortality in Hanauma Bay Nature Preserve (HBNP), O‘ahu, Hawai‘i to gain a baseline understanding of the physical processes that influence localized bleaching dynamics. Surveys at HBNP in October 2015 and January 2016 revealed extensive bleaching (47%) and high levels of coral mortality (9.8%). Bleaching was highly variable among the four HBNP sectors and ranged from a low of ∼31% in the central bay at Channel (CH) to a high of 57% in the area most frequented by visitors (Keyhole; KH). The highest levels of bleaching occurred in two sectors with different circulation patterns: KH experienced comparatively low circulation velocity and a low temperature increase while Witches Brew (WB) and Backdoors (BD) experienced higher circulation velocity and higher temperature increase. Cumulative mortality was highest at WB (5.0%) and at BD (2.9%) although WB circulation velocity is significantly higher. HBNP is minimally impacted by local factors that can lead to decline such as high fishing pressure or sedimentation although human use is high. Despite the lack of these influences, high coral mortality occurred. Visitor impacts are strikingly different in the two sectors that experienced the highest mortality evidenced by the differences in coral cover associated with visitor use however, coral mortality was similar. These results suggest that elevated temperature was more influential in coral bleaching and the associated mortality than high circulation or visitor use. PMID:28584703

Which way will the circulation shift in a changing climate? Possible nonlinearity of extratropical cloud feedbacks

NASA Astrophysics Data System (ADS)

Tandon, Neil F.; Cane, Mark A.

2017-06-01

In a suite of idealized experiments with the Community Atmospheric Model version 3 coupled to a slab ocean, we show that the atmospheric circulation response to CO2 increase is sensitive to extratropical cloud feedback that is potentially nonlinear. Doubling CO2 produces a poleward shift of the Southern Hemisphere (SH) midlatitude jet that is driven primarily by cloud shortwave feedback and modulated by ice albedo feedback, in agreement with earlier studies. More surprisingly, for CO2 increases smaller than 25 %, the SH jet shifts equatorward. Nonlinearities are also apparent in the Northern Hemisphere, but with less zonal symmetry. Baroclinic instability theory and climate feedback analysis suggest that as the CO2 forcing amplitude is reduced, there is a transition from a regime in which cloud and circulation changes are largely decoupled to a regime in which they are highly coupled. In the dynamically coupled regime, there is an apparent cancellation between cloud feedback due to warming and cloud feedback due to the shifting jet, and this allows the ice albedo feedback to dominate in the high latitudes. The extent to which dynamical coupling effects exceed thermodynamic forcing effects is strongly influenced by cloud microphysics: an alternate model configuration with slightly increased cloud liquid (LIQ) produces poleward jet shifts regardless of the amplitude of CO2 forcing. Altering the cloud microphysics also produces substantial spread in the circulation response to CO2 doubling: the LIQ configuration produces a poleward SH jet shift approximately twice that produced under the default configuration. Analysis of large ensembles of the Canadian Earth System Model version 2 demonstrates that nonlinear, cloud-coupled jet shifts are also possible in comprehensive models. We still expect a poleward trend in SH jet latitude for timescales on which CO2 increases by more than 25 %. But on shorter timescales, our results give good reason to expect significant equatorward deviations. We also discuss the implications for understanding the circulation response to small external forcings from other sources, such as the solar cycle.

Circulating androgens in women: exercise-induced changes.

PubMed

Enea, Carina; Boisseau, Nathalie; Fargeas-Gluck, Marie Agnès; Diaz, Véronique; Dugué, Benoit

2011-01-01

Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance.

Effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation.

PubMed

Masuda, Yoshiki; Tatsumi, Hiroomi; Imaizumi, Hitoshi; Gotoh, Kyoko; Yoshida, Shinichiro; Chihara, Shinya; Takahashi, Kanako; Yamakage, Michiaki

2014-03-01

Prone ventilation is an effective method for improving oxygenation in patients with acute respiratory failure. However, in extracorporeal circulation, there is a risk of cannula-related complications when changing the position. In this study, we investigated cannula-related complications when changing position for prone ventilation and the effect of prone ventilation on impaired oxygenation in patients who underwent extracorporeal membrane oxygenation (ECMO). The study subjects were patients who underwent prone ventilation during ECMO in the period from 2004 to 2011. Indication for prone ventilation was the presence of dorsal infiltration shown by lung computed tomography. Factors investigated were cannula insertion site, dislodgement or obstruction of the cannula, malfunction of vascular access and unplanned dislodgement of the catheters when changing position. Mean arterial pressure, PaO2/FiO2, PEEP level, blood flow and rotation speed of the pump were also determined before and after position change. Five patients were selected as study subjects. The mean duration of prone positioning was 15.3 ± 0.5 h. Strict management during position changes prevented cannula-related complications in the patients who underwent extracorporeal circulation. There were no significant changes in mean arterial pressure, PEEP level, blood flow and rotation speed of the pump when changing position. Low PaO2/FiO2 prior to prone ventilation was significantly increased after supine to prone and then prone to supine position. Prone positioning to improve impaired oxygenation is a safe procedure and not a contraindication in patients receiving extracorporeal circulation.

Effects of Hypoglycemia on Circulating Stem and Progenitor Cells in Diabetic Patients.

PubMed

Fadini, Gian Paolo; Boscari, Federico; Cappellari, Roberta; Galasso, Silvia; Rigato, Mauro; Bonora, Benedetta Maria; D'Anna, Marianna; Bruttomesso, Daniela; Avogaro, Angelo

2018-03-01

Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2). Tertiary referral inpatient clinic. Type 1 diabetic patients (Study 1, n = 19); diabetic patients hospitalized for severe iatrogenic hypoglycemia, matched inpatient and outpatient controls (Study 2, n = 22/group). Type 1 diabetic patients underwent two in-hospital sessions of glucose monitoring during a breakfast meal with or without induction of hypoglycemia in random order. In Study 2, patients hospitalized for hypoglycemia and matched controls were compared. Circulating stem cells and EPCs were measured by flow cytometry based on the expression of CD34 and kinase insert domain receptor (KDR). In Study 1, the physiologic decline of CD34+KDR+ EPCs from 8 am to 2 pm was abolished by insulin-induced hypoglycemia in type 1 diabetic patients. In Study 2, diabetic patients hospitalized for severe iatrogenic hypoglycemia had significantly lower levels of CD34+ stem cells and CD34+KDR+ EPCs compared with diabetic inpatients or outpatient controls. In diabetic patients, a single mild hypoglycemic episode can compromise the physiologic EPC fluctuation, whereas severe hypoglycemia is associated with a marked reduction in stem cells and EPCs. These data provide a possible link between hypoglycemia and adverse outcomes of diabetes.

Interleukin-20 circulating levels in obese women: effect of weight loss.

PubMed

Maiorino, M I; Schisano, B; Di Palo, C; Vietri, M T; Cioffi, M; Giugliano, G; Giugliano, D; Esposito, K

2010-03-01

Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight. Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P=0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r=0.35; P=0.02) and visceral fat (waist-hip ratio; r=0.32; P=0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153)pg/ml (median and 25%/75%; P=0.03), and it was positively associated with changes in body mass index and waist-hip ratio. In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist-hip ratio, and are reduced by weight loss. (c) 2009 Elsevier B.V. All rights reserved.

Modeling circulation patterns induced by spatial cross-shore wind variability in a small-size coastal embayment

NASA Astrophysics Data System (ADS)

Cerralbo, Pablo; Espino, Manuel; Grifoll, Manel

2016-08-01

This contribution shows the importance of the cross-shore spatial wind variability in the water circulation in a small-sized micro-tidal bay. The hydrodynamic wind response at Alfacs Bay (Ebro River delta, NW Mediterranean Sea) is investigated with a numerical model (ROMS) supported by in situ observations. The wind variability observed in meteorological measurements is characterized with meteorological model (WRF) outputs. From the hydrodynamic simulations of the bay, the water circulation response is affected by the cross-shore wind variability, leading to water current structures not observed in the homogeneous-wind case. If the wind heterogeneity response is considered, the water exchange in the longitudinal direction increases significantly, reducing the water exchange time by around 20%. Wind resolutions half the size of the bay (in our case around 9 km) inhibit cross-shore wind variability, which significantly affects the resultant circulation pattern. The characteristic response is also investigated using idealized test cases. These results show how the wind curl contributes to the hydrodynamic response in shallow areas and promotes the exchange between the bay and the open sea. Negative wind curl is related to the formation of an anti-cyclonic gyre at the bay's mouth. Our results highlight the importance of considering appropriate wind resolution even in small-scale domains (such as bays or harbors) to characterize the hydrodynamics, with relevant implications in the water exchange time and the consequent water quality and ecological parameters.

Neurokinin 3 receptor and phosphocholine transferase: missing factors for pathogenesis of C-reactive protein in preeclampsia.

PubMed

Parchim, Nicholas F; Wang, Wei; Iriyama, Takayuki; Ashimi, Olaide A; Siddiqui, Athar H; Blackwell, Sean; Sibai, Baha; Kellems, Rodney E; Xia, Yang

2015-02-01

C-reactive protein (CRP), an innate immune mediator, is elevated in the circulation before symptoms in patients with preeclampsia, a severe hypertensive pregnancy disorder with high mortality and morbidity. However, the specific sources underlying increased CRP and the role of elevated CRP in preeclampsia are undefined. Here, we report that circulating CRP levels are significantly increased in a large cohort of normotensive pregnant individuals when compared with nulligravid women and is further increased in patients with preeclampsia. These findings led us to discover further that placental syncytiotrophoblasts are previously unrecognized cellular sources of CRP and underlie elevated CRP in normotensive pregnant women and the additional increase in patients with preeclampsia. Next, we demonstrated that injection of CRP induces preeclampsia features, including hypertension (157 mm Hg CRP treated versus 119 mm Hg control), proteinuria (35.0 mg/μg CRP treated versus 14.1 mg/μg control), kidney, and placental damage and increased levels of sFlt-1 in pregnant mice but not in nonpregnant mice. Our study implicates that phosphocholine transferase, a placental-specific enzyme post-translationally modifying neurokinin B, is essential for the pathogenic role of CRP in preeclampsia through activation of the neurokinin 3 receptor. Overall, our studies have provided significant new insight on the pathogenic role of CRP in preeclampsia and highlighted innovative therapeutic strategies. © 2014 American Heart Association, Inc.

[Effect of urapidil combined with phentolamine on hypertension during extracorporeal circulation].

PubMed

Wang, Fangjun; Chen, Bin; Liu, Yang; Tu, Faping

2014-08-01

To study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation. Ninety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded. There was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation. Urapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

Low Cerebral Blood Volume Identifies Poor Outcome in Stent Retriever Thrombectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Protto, Sara, E-mail: sara.protto@pshp.fi; Pienimäki, Juha-Pekka; Seppänen, Janne

BackgroundMechanical thrombectomy (MT) is an efficient treatment of acute stroke caused by large-vessel occlusion. We evaluated the factors predicting poor clinical outcome (3-month modified Rankin Scale, mRS >2) although MT performed with modern stent retrievers.MethodsWe prospectively collected the clinical and imaging data of 105 consecutive anterior circulation stroke patients who underwent MT after multimodal CT imaging. Patients with occlusion of the internal carotid artery and/or middle cerebral artery up to the M2 segment were included. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome and the clinical outcome. Differences between the groups were studied with appropriatemore » statistical tests and binary logistic regression analysis.ResultsLow cerebral blood volume Alberta stroke program early CT score (CBV-ASPECTS) was associated with poor clinical outcome (median 7 vs. 9, p = 0.01). Lower collateral score (CS) significantly predicted poor outcome in regression modelling with CS = 0 increasing the odds of poor outcome 4.4-fold compared to CS = 3 (95% CI 1.27–15.5, p = 0.02). Lower CBV-ASPECTS significantly predicted poor clinical outcome among those with moderate or severe stroke (OR 0.82, 95% CI 0.68–1, p = 0.05) or poor collateral circulation (CS 0–1, OR 0.66, 95% CI 0.48–0.90, p = 0.009) but not among those with mild strokes or good collaterals.ConclusionsCBV-ASPECTS estimating infarct core is a significant predictor of poor clinical outcome among anterior circulation stroke patients treated with MT, especially in the setting of poor collateral circulation and/or moderate or severe stroke.« less

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Mumps outbreaks in a highly vaccinated population: Investigation of a neutralization titre against the current circulating wildtype genotype G5 mumps virus.

PubMed

Kenny, Lena; O'Kelly, Edwin; Connell, Jeff; De Gascun, Cillian; Hassan, Jaythoon

2016-01-01

Mumps outbreaks continue to occur globally, despite high levels of uptake of the mumps vaccine. In order to address immunity to the current circulating wildtype virus, we sought to determine a mumps G5 specific IgG quantitative value which correlates with genotype G5 specific neutralization ability in vitro. Sera from 199 individuals including controls and acute mumps cases were assessed for mumps specific IgG titres using five different enzyme immunoassays coated with antigen from different mumps virus strains. A subset of 66 sera was also assessed for in vitro neutralizing antibody against a contemporary circulating genotype G5 mumps virus. For all the different antigenic targets, mumps specific IgG titres were higher in patients following acute mumps infection compared to controls. In acute mumps infected patients, females showed significantly higher serum titres of anti-G5 IgG compared to males (p<0.05). Furthermore, control males did not show any change in G5 specific IgG with increasing age whereas females show a progressive rise in titre. Linear regression analysis revealed a significant association between the mumps G5 specific IgG levels in the EIA and the in vitro neutralization titres (r(2)=0.59). Specific IgG to the current circulating genotype G5 mumps strain showed significantly lower titres in males which supports our previous observation that there is a male gender bias in cases of acute mumps infection. Furthermore, in this preliminary study, the data indicate that genotype G5 specific IgG levels of >40 RU/ml are required for neutralization capability to be observed in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

Intrapulpal Temperature Increases Caused by 445-nm Diode Laser-Assisted Debonding of Self-Ligating Ceramic Brackets During Simulated Pulpal Fluid Circulation.

PubMed

Stein, Steffen; Wenzler, Johannes; Hellak, Andreas; Schauseil, Michael; Korbmacher-Steiner, Heike; Braun, Andreas

2018-04-01

This study investigated temperature increases in dental pulp resulting from laser-assisted debonding of ceramic brackets using a 445-nm diode laser. Eighteen ceramic brackets were bonded in standardized manner to 18 caries-free human third molars. Pulpal fluid circulation was simulated by pumping distilled water at 37°C through the pulp chamber. The brackets were irradiated with a 445-nm diode laser. Temperatures were measured using a thermal camera at points P1 (center of the pulp) and P2 (in the hard dental tissue) at the baseline (T0), at the start and end of laser application (T1 and T2), and the maximum during the sequence (T max ). Significant differences in the temperatures measured at P1 and P2 were observed among T0, T1, T2, and T max . Significant increases in temperature were noted at points P1 and P2, between T1 and T2, T1 and T max , and T2 and T max . The maximum P2 values were significantly higher than at P1. The maximum temperature increase measured in the pulp was 2.23°C, lower than the critical threshold of 5.5°C. On the basis of the laser settings used, there is no risk to the vitality of dental pulp during laser-assisted debonding of ceramic brackets with a 445-nm diode laser.

Simple and rapid LC-MS method for the determination of circulating albumin microheterogeneity in veal calves exposed to heat stress.

PubMed

Baldassarre, Maurizio; Naldi, Marina; Domenicali, Marco; Volo, Sabrina; Pietra, Marco; Dondi, Francesco; Caraceni, Paolo; Peli, Angelo

2017-09-10

Heat stress has a major impact on veal calves welfare and productivity. Prolonged exposure to warm temperature is associated with several alterations of physiologic processes and increased systemic inflammation and oxidative stress. Bovine serum albumin (BSA) is the most abundant plasma protein and, besides the regulation of osmotic pressure, carries several additional functions, including antioxidant, immunomodulatory, binding and transport activities. Such non-oncotic properties are closely related to structural integrity of the circulating molecule and may be compromised in stressful microenvironments as it occurs in heat stressed animals. Thus, in the present study we developed and validated an LC-MS analytical technique for the characterization of circulating BSA microheterogeneity in veal calves exposed to heat stress. The method was specifically tailored to the structural characteristics of the BSA molecule as well as to the complexity of the biological samples, allowing the identification of several BSA isoforms, each characterized by a specific structural defect. The mass spectrometry based approach enabled the identification of BSA isoforms with reversible and irreversible oxidation and/or glycation and the native BSA, the only isoform endowed with structural and functional integrity. We found that, in veal calves, heat stress is associated to a significant reduction of the native BSA and to a significant increment of the reversibly and irreversibly oxidized BSA. Then, by monitoring the BSA microheterogeneity over a period of moderate heat stress, we found that the native BSA as well as the glycated BSA increased significantly during the recovery period. Based on our results the analysis of the BSA microheterogeneity could represent a novel biomarker for the assessment of animal welfare during environmental stressful conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children.

PubMed

Kilian, Yvonne; Wehmeier, Udo F; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

2016-01-01

The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min(-1)·kg(-1) peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90-95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30', 60', 180') and HVT (d3, 0', 60'). RESULTS of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

Elevated levels of endothelial cell-derived microparticles following short-term withdrawal of continuous positive airway pressure in patients with obstructive sleep apnea: data from a randomized controlled trial.

PubMed

Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Stradling, John; Kohler, Malcolm

2013-01-01

Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation. Copyright © 2012 S. Karger AG, Basel.

Circulating innate lymphoid cells are unchanged in response to DAC HYP therapy.

PubMed

Gillard, Geoffrey O; Saenz, Steven A; Huss, David J; Fontenot, Jason D

2016-05-15

Innate lymphoid cells (ILCs) play an important role in immunity, inflammation, and tissue remodeling and their dysregulation is implicated in autoimmune and inflammatory disorders. We analyzed the impact of daclizumab, a humanized monoclonal anti-CD25 antibody, on circulating natural killer (NK) cells and ILCs in a cohort of multiple sclerosis patients. An increase in CD56(bright) NK cells and CD56(hi)CD16(intermediate) transitional NK cells was observed. No significant change in total ILCs or major ILC subpopulations was observed. These results refine our understanding of the impact of daclizumab on innate lymphoid cell populations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

High Versus Low Load Resistance Training: The Effect of 24 Weeks Detraining on Serum Brain Derived-Neurotrophic Factor (BDNF) in Older Adults.

PubMed

Nuvagah Forti, L; Van Roie, E; Njemini, R; Coudyzer, W; Beyer, I; Delecluse, C; Bautmans, I

2017-01-01

Previously we showed that 12 weeks of mixed-low resistance training (LOW+) significantly increased circulating BDNF in older male individuals. To examine the impact of 24 weeks detraining on circulating BDNF. Randomized intervention study. Community-dwelling older adults. Forty-seven out of 56 participants stopped training (detraining) after 12 weeks of resistance exercise (3x/week) at either HIGH-resistance (5 Males, 5 Females, 2x10-15 repetitions at 80%1RM), LOW-resistance (6 Males, 7 Females, 1x80-100 repetitions at 20%1RM), or mixed-low LOW+-resistance (6 Males, 8 Females, 1x60 repetitions at 20%1RM followed by 1x10-20 repetitions at 40%1RM), of whom 37 (aged 68±5 years) provided sufficient serum samples for BDNF analysis at baseline, 12 week and at 36 weeks (24 weeks detraining). BDNF had initially increased by 31% (from 33.4±10.9 ng/mL to 44.5±13.2 ng/mL, p=0.005) after 12 weeks in the LOW+ exercise group in males and decreased by 26% (from 44.5±13.2 ng/mL to 32.9±10.7 ng/mL) after detraining, though not statistically significant (p=0.082). In females, no significant change in BDNF was found in any of the intervention groups (p>0.05), neither after training, nor detraining. At 36 weeks all of the subgroups showed BDNF levels comparable (all p>0.10) to baseline (before the exercise intervention). Our results show that a 12-weeks LOW+ resistance exercise increases circulating BDNF in older male subjects but that this reduces back to baseline levels after 24 weeks of detraining. Continuous exercise adherence seems to be needed to sustain the training-induced effects on BDNF in older persons. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed sex difference.

Understanding variability of the Southern Ocean overturning circulation in CORE-II models

NASA Astrophysics Data System (ADS)

Downes, S. M.; Spence, P.; Hogg, A. M.

2018-03-01

The current generation of climate models exhibit a large spread in the steady-state and projected Southern Ocean upper and lower overturning circulation, with mechanisms for deep ocean variability remaining less well understood. Here, common Southern Ocean metrics in twelve models from the Coordinated Ocean-ice Reference Experiment Phase II (CORE-II) are assessed over a 60 year period. Specifically, stratification, surface buoyancy fluxes, and eddies are linked to the magnitude of the strengthening trend in the upper overturning circulation, and a decreasing trend in the lower overturning circulation across the CORE-II models. The models evolve similarly in the upper 1 km and the deep ocean, with an almost equivalent poleward intensification trend in the Southern Hemisphere westerly winds. However, the models differ substantially in their eddy parameterisation and surface buoyancy fluxes. In general, models with a larger heat-driven water mass transformation where deep waters upwell at the surface ( ∼ 55°S) transport warmer waters into intermediate depths, thus weakening the stratification in the upper 2 km. Models with a weak eddy induced overturning and a warm bias in the intermediate waters are more likely to exhibit larger increases in the upper overturning circulation, and more significant weakening of the lower overturning circulation. We find the opposite holds for a cool model bias in intermediate depths, combined with a more complex 3D eddy parameterisation that acts to reduce isopycnal slope. In summary, the Southern Ocean overturning circulation decadal trends in the coarse resolution CORE-II models are governed by biases in surface buoyancy fluxes and the ocean density field, and the configuration of the eddy parameterisation.

Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

PubMed

Nicholls, D P; Riley, M; Elborn, J S; Stanford, C F; Shaw, C; McKillop, J M; Buchanan, K D

1992-10-01

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Competing influences of greenhouse warming and aerosols on Asian summer monsoon circulation and rainfall

NASA Astrophysics Data System (ADS)

Lau, William Ka-Ming; Kim, Kyu-Myong

2017-05-01

In this paper, we have compared and contrasted competing influences of greenhouse gases (GHG) warming and aerosol forcing on Asian summer monsoon circulation and rainfall based on CMIP5 historical simulations. Under GHG-only forcing, the land warms much faster than the ocean, magnifying the pre-industrial climatological land-ocean thermal contrast and hemispheric asymmetry, i.e., warmer northern than southern hemisphere. A steady increasing warm-ocean-warmer-land (WOWL) trend has been in effect since the 1950's substantially increasing moisture transport from adjacent oceans, and enhancing rainfall over the Asian monsoon regions. However, under GHG warming, increased atmospheric stability due to strong reduction in mid-tropospheric and near surface relative humidity coupled to an expanding subsidence areas, associated with the Deep Tropical Squeeze (DTS, Lau and Kim, 2015b) strongly suppress monsoon convection and rainfall over subtropical and extratropical land, leading to a weakening of the Asian monsoon meridional circulation. Increased anthropogenic aerosol emission strongly masks WOWL, by over 60% over the northern hemisphere, negating to a large extent the rainfall increase due to GHG warming, and leading to a further weakening of the monsoon circulation, through increasing atmospheric stability, most likely associated with aerosol solar dimming and semi-direct effects. Overall, we find that GHG exerts stronger positive rainfall sensitivity, but less negative circulation sensitivity in SASM compared to EASM. In contrast, aerosols exert stronger negative impacts on rainfall, but less negative impacts on circulation in EASM compared to SASM.

Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association.

PubMed

Schairer, Catherine; Fuhrman, Barbara J; Boyd-Morin, Jennifer; Genkinger, Jeanine M; Gail, Mitchell H; Hoover, Robert N; Ziegler, Regina G

2016-01-01

Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER(+)) tumors. Higher BMI also increases estrogen production. We estimated the proportion of the BMI-ER(+) breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER(+) breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER(+) breast cancer association using Aalen additive hazards and Cox regression models. All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Further research is required to identify mechanisms underlying the BMI-breast cancer association. ©2015 American Association for Cancer Research.

How much rainfall sustained a Green Sahara during the mid-Holocene?

NASA Astrophysics Data System (ADS)

Hopcroft, Peter; Valdes, Paul; Harper, Anna

2016-04-01

The present-day Sahara desert has periodically transformed to an area of lakes and vegetation during the Quaternary in response to orbitally-induced changes in the monsoon circulation. Coupled atmosphere-ocean general circulation model simulations of the mid-Holocene generally underestimate the required monsoon shift, casting doubt on the fidelity of these models. However, the climatic regime that characterised this period remains unclear. To address this, we applied an ensemble of dynamic vegetation model simulations using two different models: JULES (Joint UK Land Environment Simulator) a comprehensive land surface model, and LPJ (Lund-Potsdam-Jena model) a widely used dynamic vegetation model. The simulations are forced with a number of idealized climate scenarios, in which an observational climatology is progressively altered with imposed anomalies of precipitation and other related variables, including cloud cover and humidity. The applied anomalies are based on an ensemble of general circulation model simulations, and include seasonal variations but are spatially uniform across the region. When perturbing precipitation alone, a significant increase of at least 700mm/year is required to produce model simulations with non-negligible vegetation coverage in the Sahara region. Changes in related variables including cloud cover, surface radiation fluxes and humidity are found to be important in the models, as they modify the water balance and so affect plant growth. Including anomalies in all of these variables together reduces the precipitation change required for a Green Sahara compared to the case of increasing precipitation alone. We assess whether the precipitation changes implied by these vegetation model simulations are consistent with reconstructions for the mid-Holocene from pollen samples. Further, Earth System models predict precipitation increases that are significantly smaller than that inferred from these vegetation model simulations. Understanding this difference presents an ongoing challenge.

Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.

PubMed

Popoff, S N; Osier, L K; Zerwekh, J E; Marks, S C

1994-01-01

Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Hughes, David J; Duarte-Salles, Talita; Hybsier, Sandra; Trichopoulou, Antonia; Stepien, Magdalena; Aleksandrova, Krasimira; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Affret, Aurélie; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kaaks, Rudolf; Boeing, Heiner; Bamia, Christina; Lagiou, Pagona; Peppa, Eleni; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, Hendrik Bastiaan; Peeters, Petra H; Engeset, Dagrun; Weiderpass, Elisabete; Lasheras, Cristina; Agudo, Antonio; Sánchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Hemmingsson, Oskar; Wareham, Nicholas J; Khaw, Kay-Tee; Bradbury, Kathryn E; Cross, Amanda J; Gunter, Marc; Riboli, Elio; Romieu, Isabelle; Schomburg, Lutz; Jenab, Mazda

2016-08-01

Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-μg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. © 2016 American Society for Nutrition.

In Vitro Study of Flow Regulation for Pulmonary Insufficiency

PubMed Central

Camp, T. A.; Stewart, K. C.; Figliola, R. S.; McQuinn, T.

2007-01-01

Given the tolerance of the right heart circulation to mild regurgitation and gradient, we study the potential of using motionless devices to regulate the pulmonary circulation. In addition, we document the flow performance of two mechanical valves. A motionless diode, a nozzle, a mechanical bileaflet valve, and a tilting disk valve were tested in a pulmonary mock circulatory system over the normal human range of pulmonary vascular resistance (PVR). For the mechanical valves, regurgitant fractions (RFs) and transvalvular pressure gradients were found to be weak functions of PVR. On the low end of normal PVR, the bileaflet and tilting disk valves fluttered and would not fully close. Despite this anomaly, the regurgitant fraction of either valve did not change significantly. The values for RF and transvalvular gradient measured varied from 4 to 7% and 4 to 7 mm Hg, respectively, at 5 lpm for all tests. The diode valve was able to regulate flow with mild regurgitant fraction and trivial gradient but with values higher than either mechanical valve tested. Regurgitant fraction ranged from 2 to 17% in tests extending from PVR values of 1 to 4.5 mm Hg/lpm at 5 lpm and with concomitant increases in gradient up to 17 mm Hg. The regurgitant fraction for the nozzle increased from 2 to 23% over the range of PVR with gradients increasing to 18 mm Hg. The significant findings were: (1) the mechanical valves controlled regurgitation at normal physiological cardiac output and PVR even though they failed to close at some normal values of PVR and showed leaflet flutter; and (2) it may be possible to regulate the pulmonary circulation to tolerable levels using a motionless pulmonary valve device. PMID:17408334

Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease.

PubMed

Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S; Natarajan, Mohan; Aravindan, Natarajan

2016-04-05

Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression.

The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death.

PubMed

Zazueta, Oscar E; Preston, Sara E; Moniodis, Anna; Fried, Sabrina; Kim, Miae; Townsend, Keri; Wood, Isabelle; Boukedes, Steve; Guleria, Indira; Camp, Phillip; El-Chemaly, Souheil; Rosas, Ivan O; Chandraker, Anil; Milford, Edgar; Goldberg, Hilary J

2017-09-01

Development of donor-specific antibodies (DSA) after lung transplantation is associated with antibody mediated rejection, acute cellular rejection, and bronchiolitis obliterans syndrome; however, the significance of circulating antibodies before transplant remains unclear. We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012. We assessed the impact of circulating HLA and noncytotoxic DSA detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD-related death. 30% of subjects had circulating class I antibodies alone, 4% Class II, and 14.4% class I and class II at mean fluorescent intensity greater than 1000. Nine percent of the subjects had DSA class I, 9% class II, and 2.4% both DSA classes 1 and 2. Neither the presence of circulating antibodies (adjusted hazard ratio, 0.87; 95% confidence interval, 0.50-1.54) nor the presence of DSA (adjusted hazard ratio, 1.56; 95% confidence interval, 0.77-3.18) before transplant at mean fluorescent intensity greater than 1000 was associated with the development of CLAD or CLAD-related death. Although in previous studies we have shown an increased incidence of antibody-mediated rejection in patients with pretransplant DSA, neither the presence of HLA antibodies nor DSA translated to an increased risk of allograft dysfunction or death if prospective crossmatch testing was negative. Prospective studies are needed to define the impact of pretransplant sensitization on lung transplant recipients.

Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure.

PubMed

Dickinson, Brent A; Semus, Hillary M; Montgomery, Rusty L; Stack, Christianna; Latimer, Paul A; Lewton, Steven M; Lynch, Joshua M; Hullinger, Thomas G; Seto, Anita G; van Rooij, Eva

2013-06-01

Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease. In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression. Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.

High salt intake increases blood pressure via BDNF-mediated downregulation of KCC2 and impaired baroreflex inhibition of vasopressin neurons.

PubMed

Choe, Katrina Y; Han, Su Y; Gaub, Perrine; Shell, Brent; Voisin, Daniel L; Knapp, Blayne A; Barker, Philip A; Brown, Colin H; Cunningham, J Thomas; Bourque, Charles W

2015-02-04

The mechanisms by which dietary salt promotes hypertension are unknown. Previous work established that plasma [Na(+)] and osmolality rise in proportion with salt intake and thus promote release of vasopressin (VP) from the neurohypophysis. Although high levels of circulating VP can increase blood pressure, this effect is normally prevented by a potent GABAergic inhibition of VP neurons by aortic baroreceptors. Here we show that chronic high salt intake impairs baroreceptor inhibition of rat VP neurons through a brain-derived neurotrophic factor (BDNF)-dependent activation of TrkB receptors and downregulation of KCC2 expression, which prevents inhibitory GABAergic signaling. We show that high salt intake increases the spontaneous firing rate of VP neurons in vivo and that circulating VP contributes significantly to the elevation of arterial pressure under these conditions. These results provide the first demonstration that dietary salt can affect blood pressure through neurotrophin-induced plasticity in a central homeostatic circuit. Copyright © 2015 Elsevier Inc. All rights reserved.

Suppressed midlatitude summer atmospheric warming by Arctic sea ice loss during 1979-2012

NASA Astrophysics Data System (ADS)

Wu, Qigang; Cheng, Luyao; Chan, Duo; Yao, Yonghong; Hu, Haibo; Yao, Ying

2016-03-01

Since the 1980s, rapid Arctic warming, sea ice decline, and weakening summer circulation have coincided with an increasing number of extreme heat waves and other destructive weather events in the Northern Hemisphere (NH) midlatitudes in summer. Recent papers disagree about whether such high-impact events are related to Arctic warming and/or ice loss. Here we use atmospheric model ensemble simulations to attribute effects of sea ice loss and other factors on observed summer climate trends during 1979-2012. The ongoing greenhouse gas buildup and resulting sea surface temperature warming outside the Arctic explains nearly all land warming and a significant portion of observed weakening zonal winds in the NH midlatitudes. However, sea ice loss has induced a negative Arctic Oscillation(AO)-type circulation with significant summer surface and tropospheric cooling trends over large portions of the NH midlatitudes, which reduce the warming and might reduce the probability of regional severe hot summers.

Reduced interdecadal variability of Atlantic Meridional Overturning Circulation under global warming.

PubMed

Cheng, Jun; Liu, Zhengyu; Zhang, Shaoqing; Liu, Wei; Dong, Lina; Liu, Peng; Li, Hongli

2016-03-22

Interdecadal variability of the Atlantic Meridional Overturning Circulation (AMOC-IV) plays an important role in climate variation and has significant societal impacts. Past climate reconstruction indicates that AMOC-IV has likely undergone significant changes. Despite some previous studies, responses of AMOC-IV to global warming remain unclear, in particular regarding its amplitude and time scale. In this study, we analyze the responses of AMOC-IV under various scenarios of future global warming in multiple models and find that AMOC-IV becomes weaker and shorter with enhanced global warming. From the present climate condition to the strongest future warming scenario, on average, the major period of AMOC-IV is shortened from ∼50 y to ∼20 y, and the amplitude is reduced by ∼60%. These reductions in period and amplitude of AMOC-IV are suggested to be associated with increased oceanic stratification under global warming and, in turn, the speedup of oceanic baroclinic Rossby waves.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China.

PubMed

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b- EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b- EMPs among lean, overweight, and obese subjects.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China

PubMed Central

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b− EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b− EMPs among lean, overweight, and obese subjects. PMID:27314039

The influence of tropical heating displacements on the extratropical climate

NASA Technical Reports Server (NTRS)

Hou, Arthur Y.

1993-01-01

The hypothesis is advanced that a latitudinal shift in the tropical convective heating pattern can significantly alter temperatures in the extratropics. Results of a simplified general circulation model (GCM) show that the shift of a prescribed tropical heating toward the summer pole, on time scales longer than a few weeks, leads to a more intense cross-equatorial 'winter' Hadley circulation, enhanced upper-level tropical easterlies, and a slightly stronger subtropical winter jet, accompanied by warming at the winter middle and high latitudes as a result of increased dynamical heating. The indications are that there is a robust connection between the net dynamic heating in the extratropics and the implied changes in the subtropical wind shear resulting from adjustments in the Hadley circulation associated with convective heating displacements in the tropics. The implications are that (1) the low-frequency temporal variability in the Hadley circulation may play an important role in modulating wave transport in the winter extratropics, (2) the global climate may be sensitive to those processes that control deep cumulus convection in the tropics, and (3) systematic temperature biases in GCMs may be reduced by improving the tropical rainfall simulation.

Effect of Whey Supplementation on Circulating C-Reactive Protein: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Zhou, Ling-Mei; Xu, Jia-Ying; Rao, Chun-Ping; Han, Shufen; Wan, Zhongxiao; Qin, Li-Qiang

2015-01-01

Whey supplementation is beneficial for human health, possibly by reducing the circulating C-reactive protein (CRP) level, a sensitive marker of inflammation. Thus, a meta-analysis of randomized controlled trials was conducted to evaluate their relationship. A systematic literature search was conducted in July, 2014, to identify eligible studies. Either a fixed-effects model or a random-effects model was used to calculate pooled effects. The meta-analysis results of nine trials showed a slight, but no significant, reduction of 0.42 mg/L (95% CI −0.96, 0.13) in CRP level with the supplementation of whey protein and its derivates. Relatively high heterogeneity across studies was observed. Subgroup analyses showed that whey significantly lowered CRP by 0.72 mg/L (95% CI −0.97, −0.47) among trials with a daily whey dose ≥20 g/day and by 0.67 mg/L (95% CI −1.21, −0.14) among trials with baseline CRP ≥3 mg/L. Meta-regression analysis revealed that the baseline CRP level was a potential effect modifier of whey supplementation in reducing CRP. In conclusion, our meta-analysis did not find sufficient evidence that whey and its derivates elicited a beneficial effect in reducing circulating CRP. However, they may significantly reduce CRP among participants with highly supplemental doses or increased baseline CRP levels. PMID:25671415

Influence of the direct NO-donor SIN-1 on the interaction between platelets and stainless steel stents under dynamic conditions.

PubMed

Jung, F; Mrowietz, C; Seyfert, U T; Grewe, R; Franke, R P

2003-01-01

It was investigated whether the NO-donor SIN-1, the active metabolite of molsidomine, influenced the activation of platelets, the formation of circulating platelet aggregates, the spontaneous aggregation of platelets and the activation of the clotting system triggered by a body foreign surface in an in vitro closed-loop perfusion model. With human platelet-rich plasma at micromolar concentrations SIN-1 exerted pronounced effects on the interaction between platelets and an exogenous surface. In the absence of SIN-1, the number of circulating single platelets decreased significantly, which could be due either to the formation of circulating platelet aggregates or to the adhesion of platelets to the stent. Both these processes were blocked by the addition of SIN-1. Moreover, the platelets exhibited hyperaggregability in the absence of SIN-1 whereas the NO-donor was able to completely inhibit spontaneous platelet aggregation. Similar results were obtained in flow cytometry experiments. Without SIN-1, high platelet surface densities of both the GPIb/IX and GPIIb/IIIa receptors were observed. In addition, the density of the fibrinogen receptor increased significantly with the number of perfusion cycles. SIN-1 was able to suppress the augmented GPIIb/IIIa receptor expression significantly. Molsidomine seemed to have the potential to reduce the incidence of thrombotic processes triggered by the exogenous surface of the stent.

Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients

PubMed Central

Liu, Wei; Ling, Shukuan; Sun, Weijia; Liu, Tong; Li, Yuheng; Zhong, Guohui; Zhao, Dingsheng; Zhang, Pengfei; Song, Jinping; Jin, Xiaoyan; Xu, Zi; Song, Hailin; Li, Qi; Liu, Shujuan; Chai, Meng; Dai, Qinyi; He, Yi; Fan, Zhanming; Zhou, Yu Jie; Li, Yingxian

2015-01-01

The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with the severity of coronary artery calcification (CAC), and testify whether the selected miRNAs could reflect the obstructive coronary artery disease in symptomatic patients. Patients with chest pain and moderated risk for coronary artery disease (CAD) were characterized with coronary artery calcium score (CACS) from cardiac computed tomography (CT). We analyzed plasma miRNA levels of clinical matched 11 CAC (CACS > 100) and 6 non-CAC (CACS = 0) subjects by microarray profile. Microarray analysis identified 34 differentially expressed miRNAs between CAC and non CAC groups. Eight miRNAs (miR-223, miR-3135b, miR-133a-3p, miR-2861, miR-134, miR-191-3p, miR-3679-5p, miR-1229 in CAC patients) were significantly increased in CAC plasma in an independent clinical matched cohort. Four miRNAs (miR-2861, 134, 1229 and 3135b) were correlated with the degree of CAC. Validation test in angiographic cohort showed that miR-134, miR-3135b and miR-2861 were significantly changed in patients with obstructive CAD . We identified three significantly upregulated circulating miRNAs (miR-134, miR-3135b and 2861) correlated with CAC while detected obstructive coronary disease in symptomatic patients. PMID:26537670

Effect of wave-current interaction on wind-driven circulation in narrow, shallow embayments

USGS Publications Warehouse

Signell, Richard P.; Beardsley, Robert C.; Graber, H. C.; Capotondi, A.

1990-01-01

The effect of wind waves on the steady wind-driven circulation in a narrow, shallow bay is investigated with a two-dimensional (y, z) circulation model and the Grant and Madsen [1979] bottom-boundary layer model, which includes wave-current interaction. A constant wind stress is applied in the along-channel x direction to a channel with a constant cross-sectional profile h(y). The wind-induced flushing of shallow bays is shown to be sensitive to both the shape of the cross section and the effects of surface waves. The flushing increases with increasing , where h′ is the standard deviation of cross-channel depth and  is the mean depth. This is consistent with the findings of Hearn et al. [1987]. The flushing decreases, however, with the inclusion of surface wave effects which act to increase the bottom drag felt by the currents. Increasing effective bottom friction reduces the strength of the circulation, while the along-bay surface slope, bottom stress and the structure of current profiles remain nearly unchanged. An implication of the circulation dependence on wave-current interaction is that low-frequency oscillatory winds may drive a mean circulation when the wave field changes with wind direction.x

Apoptosis of circulating lymphocytes during pediatric cardiac surgery

NASA Astrophysics Data System (ADS)

Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.

2006-02-01

There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

PubMed

Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

2014-07-03

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

Connections of urban and rural mortality with daily weather in Hungary (1971-2005)

NASA Astrophysics Data System (ADS)

Mika, J.; Fülöp, A.; Dunkel, Z.

2009-04-01

Possible effects of weather anomalies on mortality in cardiovascular and respiratory illnesses are investigated in Hungary. Long-term (1971-2005) archives of ca. 2.8 million fatalities are analysed. The mortality data are compared with seven diurnal meteorological parameters. They are the mean, maxima and minima of temperature, cloudiness, wind speed, relative humidity and sea-level pressure. Since the statistical connections between the mortality frequencies and the latter variables are weak and non-linear in some cases, we also applied four different circulation types in comparison with the diurnal fatalities. All investigations are performed for Budapest, with its ca. 2 million urban dwellers (the 'city') and for the other parts of the county (the ‘rural control'), populated by over 8 million inhabitants. Our results support the well-known decreasing effect of temperature in winter) and increasing effect (in summer) on cardiovascular mortality in the rural environment. On the other hand, however, this latter effect for summer is not at all evident in Budapest. Higher temperature in winter statistically coincides with lower number of respiratory fatalities both in the urban and the rural communities. Connections with the different circulation types are less unequivocal, but proportion of significant effects is 2-3 times higher than a random occurrence. Majority of these significant connections fit our a priori guess relations, but it is still not clear why these significant effects of macro-circulation are so hectically changing between significant and non-significant effects, both in the city and out of it. Key words: mortality, cardiovascular and respiratory illnesses, weather effect, macro-synoptic types, Hungary

48-hours administration of fenoterol in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

PubMed

Grzesiak, Mariusz; Hincz, Piotr; Forys, Sebastian; Ahmed, Rehana B; Wilczynski, Jan

2013-01-01

The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy. Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower. Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow.

Immunoglobulins against Tyrosine Nitrated Epitopes in Coronary Artery Disease

PubMed Central

Thomson, Leonor; Tenopoulou, Margarita; Lightfoot, Richard; Tsika, Epida; Parastatidis, Ioannis; Martinez, Marissa; Greco, Todd M.; Doulias, Paschalis-Thomas; Wu, Yuping; Tang, W. H. Wilson; Hazen, Stanley L.; Ischiropoulos, Harry

2012-01-01

Background Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine nitrated proteins, a footprint of oxygen and nitrogen derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of coronary artery disease (CAD) subjects. However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. Methods and Results Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of CAD subjects. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in CAD patients (n=374) and subjects without CAD (non CAD controls, n=313). A ten-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in the CAD subjects (3.75 ± 1.8 μg antibody Eq/mL plasma vs. 0.36 ± 0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. Conclusions The results of this cross sectional study suggest that post-translational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neoepitopes for elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD. PMID:23081989

Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial12

PubMed Central

Samavat, Hamed; Newman, April R; Wang, Renwei; Yuan, Jian-Min; Wu, Anna H; Kurzer, Mindy S

2016-01-01

Background: Green tea has been suggested to improve cardiovascular disease risk factors, including circulating lipid variables. However, current evidence is predominantly based on small, short-term randomized controlled trials conducted in diverse populations. Objective: The aim of this study was to examine the efficacy and impact of green tea extract (GTE) supplementation high in epigallocatechin gallate (EGCG) on blood lipids in healthy postmenopausal women. Design: This was an ancillary study of a double-blind, randomized, placebo-controlled, parallel-arm trial investigating the effects of a GTE supplement containing 1315 mg catechins (843 mg EGCG) on biomarkers of breast cancer risk. Participants were randomly assigned to receive GTE (n = 538) or placebo (n = 537) and were stratified by catechol-O-methyltransferase (COMT) genotype activity (high COMT compared with low or intermediate COMT genotype activity). They consumed either 4 GTE or identical placebo capsules daily for 12 mo. A total of 936 women completed this substudy. Circulating lipid panels including total cholesterol (TC), HDL cholesterol, and triglycerides were measured at baseline and at months 6 and 12. Results: Compared with placebo, 1-y supplementation with GTE capsules resulted in a significant reduction in circulating TC (−2.1% compared with 0.7%; P = 0.0004), LDL cholesterol (−4.1% compared with 0.9%; P < 0.0001) and non-HDL cholesterol (−3.1% compared with 0.4%; P = 0.0032). There was no change in HDL-cholesterol concentration, but triglyceride concentrations increased by 3.6% in the GTE group, whereas they decreased by 2.5% in the placebo group (P = 0.046). A significant reduction in TC was observed only among women with high (i.e., ≥200 mg/dL) baseline TC concentrations (P-interaction = 0.01) who consumed GTE capsules. The effect of GTE on the increase in triglycerides was mainly observed among obese women and statin users (P-interaction = 0.06). Conclusion: Supplementation with GTE significantly reduced circulating TC and LDL-cholesterol concentrations, especially in those with elevated baseline TC concentrations. This trial was registered at clinicaltrials.gov as NCT00917735. PMID:27806972

Significant Weakening of Brewer-Dobson Circulation Trends Over the 21st Century as a Consequence of the Montreal Protocol

NASA Astrophysics Data System (ADS)

Polvani, Lorenzo M.; Abalos, Marta; Garcia, Rolando; Kinnison, Doug; Randel, William J.

2018-01-01

It is well established that increasing greenhouse gases, notably CO2, will cause an acceleration of the stratospheric Brewer-Dobson circulation (BDC) by the end of this century. We here present compelling new evidence that ozone depleting substances are also key drivers of BDC trends. We do so by analyzing and contrasting small ensembles of "single-forcing" integrations with a stratosphere resolving atmospheric model with interactive chemistry, coupled to fully interactive ocean, land, and sea ice components. First, confirming previous work, we show that increasing concentrations of ozone depleting substances have contributed a large fraction of the BDC trends in the late twentieth century. Second, we show that the phasing out of ozone depleting substances in coming decades—as a consequence of the Montreal Protocol—will cause a considerable reduction in BDC trends until the ozone hole is completely healed, toward the end of the 21st century.

Mendelian Randomization Studies Do Not Support a Role for Raised Circulating Triglyceride Levels Influencing Type 2 Diabetes, Glucose Levels, or Insulin Resistance

PubMed Central

De Silva, N. Maneka G.; Freathy, Rachel M.; Palmer, Tom M.; Donnelly, Louise A.; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice A.; Ward, Kirsten J.; Sandhu, Manjinder S.; Harbord, Roger M.; McCarthy, Mark I.; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T.; Wareham, Nicholas; Lawlor, Debbie A.; Morris, Andrew D.; Palmer, Colin N.A.; Frayling, Timothy M.

2011-01-01

OBJECTIVE The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. RESEARCH DESIGN AND METHODS We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. RESULTS Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52–0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97–1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI −0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [−0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log10 triglycerides: 0.61 [95% CI 0.45–0.83]; P = 0.002). CONCLUSIONS Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal. PMID:21282362

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

PubMed

De Silva, N Maneka G; Freathy, Rachel M; Palmer, Tom M; Donnelly, Louise A; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N; Shields, Beverley; Knight, Beatrice A; Ward, Kirsten J; Sandhu, Manjinder S; Harbord, Roger M; McCarthy, Mark I; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T; Wareham, Nicholas; Lawlor, Debbie A; Morris, Andrew D; Palmer, Colin N A; Frayling, Timothy M

2011-03-01

The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52-0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97-1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI -0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [-0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log(10) triglycerides: 0.61 [95% CI 0.45-0.83]; P = 0.002). Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal.

Multiple states in the late Eocene ocean circulation

NASA Astrophysics Data System (ADS)

Baatsen, M. L. J.; von der Heydt, A. S.; Kliphuis, M.; Viebahn, J.; Dijkstra, H. A.

2018-04-01

The Eocene-Oligocene Transition (EOT) marks a major step within the Cenozoic climate in going from a greenhouse into an icehouse state, with the formation of a continental-scale Antarctic ice sheet. The roles of steadily decreasing CO2 concentrations versus changes in ocean circulation at the EOT are still debated and the threshold for Antarctic glaciation is obscured by uncertainties in global geometry. Here, a detailed study of the late Eocene ocean circulation is carried out using an ocean general circulation model under two slightly different geography reconstructions of the middle-to-late Eocene (38 Ma). Using the same atmospheric forcing, both geographies give a profoundly different equilibrium ocean circulation state. The underlying reason for this sensitivity is the presence of multiple equilibria characterised by either North or South Pacific deep water formation. A possible shift from a southern towards a northern overturning circulation would result in significant changes in the global heat distribution and consequently make the Southern Hemisphere climate more susceptible for significant cooling and ice sheet formation on Antarctica.

Changes in circulating microRNA levels can be identified as early as day 8 of pregnancy in cattle.

PubMed

Ioannidis, Jason; Donadeu, F Xavier

2017-01-01

Poor reproductive performance remains a major issue in the dairy industry, with low conception rates having a significant impact on milk production through extended calving intervals. A major limiting factor is the lack of reliable methods for early pregnancy diagnosis. Identification of animals within a herd that fail to conceive within 3 weeks after insemination would allow early re-insemination and shorten calving intervals. In a previous study, we found an increase in plasma miR-26a levels in Day 16-pregnant relative to non-pregnant heifers, however changes in miRNA levels that early during pregnancy were very small which likely prevented the identification of robust biomarkers. In this study, we extended our analyses to a wider interval during pregnancy (Days 8 to 60, n = 11 heifers) with the rationale that this may facilitate the identification of additional early pregnancy miRNA biomarkers. Using small RNA sequencing we identified a total of 77 miRNAs that were differentially expressed on Day 60 relative to Day 0 of pregnancy. We selected 14 miRNAs for validation by RT-qPCR and confirmed significant differences in the expression of let-7f, let-7c, miR-30c, miR-101, miR-26a, miR-205 and miR-143 between Days 0 and 60. RT-qPCR profiling throughout Days 0, 8, 16 and 60 of pregnancy showed a distinct increase in circulating levels of miR-26a (3.1-fold, P = 0.046) as early as Day 8 of pregnancy. In summary, in contrast to earlier stages of pregnancy (≤ Day 24), marked differences in the levels of multiple miRNAs can be detected in circulation by Day 60 in cattle. Retrospective analyses showed miR-26a levels to be increased in circulation as early as Day 8, sooner than previously reported in any species, suggesting a biological role for this miRNA in the very early events of pregnancy.

Circulating asymmetric dimethylarginine and the risk of preeclampsia: a meta-analysis based on 1338 participants.

PubMed

Yuan, Jing; Wang, Xinguo; Xie, Yudou; Wang, Yuzhi; Dong, Lei; Li, Hong; Zhu, Tongyu

2017-07-04

Patients with preeclampsia have higher circulating asymmetric dimethylarginine (ADMA). However, whether circulating ADMA is elevated before the diagnosis of preeclampsia has not been determined. A meta-analysis of observational studies that reported circulating ADMA level before the onset of preeclampsia was performed. Pubmed and Embase were searched. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the differences in circulating ADMA. A random effect model or a fixed effect model was applied depending on the heterogeneity. The predictive efficacy of circulating ADMA for the incidence of preeclampsia was also explored. Eleven comparisons with 1338 pregnant women were included. The pooled results showed that the circulating ADMA was significantly higher in women who subsequently developed preeclampsia as compared with those did not (SMD: 0.71, p < 0.001) with a moderate heterogeneity (I2 = 43%). Stratified analyses suggested elevation of circulating ADMA is more remarkable in studies with GA of ADMA sampling ≥ 20 weeks (SMD: 0.89, p < 0.01) as compared those with GA of ADMA sampling < 20 weeks (SMD: 0.56, p < 0.01; p for subgroup interaction = 0.03). Differences of maternal age, study design, and ADMA measurement methods did not significantly affect the results. Only two studies evaluated the potential predicting ability of circulating ADMA for subsequent preeclampsia, and retrieved moderate predictive efficacy. Circulating ADMA is elevated before the development of preeclampsia. Studies are needed to evaluate the predictive efficacy of ADMA for the incidence of preeclampsia.

Investigation of corrosion caused by constituents of refinery wastewater effluent used as circulating cooling water.

PubMed

Zhang, Zhongzhi; Song, Shaofu; Huang, Jie; Ji, Lin; Wu, Fangyun

2003-01-01

The corrosion rate of steel plate using single-factor, multifactor, and complex water systems was investigated via refinery wastewater effluents used as circulating cooling water. The results show that the primary corrosion factors of steel depend on the characteristics of the ions, the formation of the oxidized coating, the diffusion of dissolved oxygen, and other complex factors, although ions such as chloride, calcium, and carbonate play an important role. The corrosion rate of carbon steel exhibits two trends: The corrosion rate is high at low conductivity, increases to a maximum, and then decreases and becomes stable with increasing conductivity, as is the case with chloride, sulfate, nitrate and calcium ions. On the other hand, the corrosion rate is highest at low conductivity and then decreases and becomes stable with increasing conductivity, as is the case with carbonate, silicate, and sodium nitrate ions. Research results indicate that the anticorrosive ability is minimal at low conductivity; but is excellent at high conductivity. Pretreatment of low-conductivity water using air flotation and clarification to decrease the concentrations of chloride, calcium, and carbonate ions to a suitable level to satisfy the anticorrosion requirements is required. However, it is not necessary to significantly reduce the salt concentration or conductivity of the water by osmosis or ion exchange to obtain an anticorrosion effect when reusing wastewater effluents as circulating cooling water.

Development of a multichannel optical system for differential cortical measurement

NASA Astrophysics Data System (ADS)

Maki, Atsushi; Yamashita, Yuichi; Watanabe, Eiju; Koizumi, Hideaki

1997-08-01

A prototype system based on intensity-modulation spectroscopy (IMS) was produced with the goal of developing 'optoencephalography' as a new instrument for clinical application and for investigating human brain functions. This system can use dual wavelengths (787 and 827 nm) to simultaneously measure reflectances at 8 measurement positions on the human head. Using the system, we measured the changes in blood circulation and oxygenation changes caused by epileptic seizures and specific brain functions. The former measurements were made simultaneously with tests to determine the epileptic focus by using single-photon-emission computed tomography (SPECT) and electrodes set in the brian. Four measurement positions were fixed in each temporal region. The areas where cerebral blood flow increased, as observed by SPECT, corresponded to the positions where the regional cerebral blood volume (rCBV) increased, as measured by the IMS system. Furthermore, the timing of the epileptic seizures, as measured by the depth-electrodes, corresponded to the timing of the increase in rCBV measured by the prototype system. Our measurements of changes in blood circulation as a result of brain functions were made for motor functions to compare the differences between the right and left hemisphere in how they respond to specific functions. Four measurement positions were set in bilateral motor areas. Significant differences in blood circulation in connection with brain activities were observed between the right and left hemispheres.

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

PubMed Central

Perrotta, Silverio; Cucciolla, Valeria; Ferraro, Marcella; Ronzoni, Luisa; Tramontano, Annunziata; Rossi, Francesca; Scudieri, Anna Chiara; Borriello, Adriana; Roberti, Domenico; Nobili, Bruno; Cappellini, Maria Domenica; Oliva, Adriana; Amendola, Giovanni; Migliaccio, Anna Rita; Mancuso, Patrizia; Martin-Padura, Ines; Bertolini, Francesco; Yoon, Donghoon; Prchal, Josef T.; Della Ragione, Fulvio

2010-01-01

Background Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. Methodology/Principal Findings We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G→T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34+ cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Conclusions/Significance Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis. PMID:20700488

Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells

PubMed Central

Chen, Peng; Huang, Yu-Yen; Bhave, Gauri; Hoshino, Kazunori; Zhang, Xiaojing

2015-01-01

We report an inkjet-printed microscale magnetic structure that can be integrated on regular glass slides for the immunomagnetic screening of rare Circulating Tumor Cells (CTCs). CTCs detach from the primary tumor site, circulate with the bloodstream, and initiate the cancer metastasis process. Therefore, a liquid biopsy in the form of capturing and analyzing CTCs may provide key information for cancer prognosis and diagnosis. Inkjet printing technology provides a non-contact, layer-by-layer and mask-less approach to deposit defined magnetic patterns on an arbitrary substrate. Such thin film patterns, when placed in an external magnetic field, significantly enhance the attractive force in the near-field close to the CTCs to facilitate the separation. We demonstrated the efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in separating COLO205 (human colorectal cancer cell line) from whole blood samples. The micromagnets increased the capture efficiency by 26% compared with using plain glass slide as the substrate. PMID:26289942

An analysis of the relationship between cloud anomalies and sea surface temperature anomalies in a global circulation model

NASA Technical Reports Server (NTRS)

Peterson, Thomas C.; Barnett, Tim P.; Roeckner, Erich; Vonder Haar, Thomas H.

1992-01-01

The relationship between the sea surface temperature anomalies (SSTAs) and the anomalies of the monthly mean cloud cover (including the high-level, low-level, and total cloud cover), the outgoing longwave radiation, and the reflected solar radiation was analyzed using a least absolute deviations regression at each grid point over the open ocean for a 6-yr period. The results indicate that cloud change in association with a local 1-C increase in SSTAs cannot be used to predict clouds in a potential future world where all the oceans are 1-C warmer than at present, because much of the observed cloud changes are due to circulation changes, which in turn are related not only to changes in SSTAs but to changes in SSTA gradients. However, because SSTAs are associated with changes in the local ocean-atmosphere moisture and heat fluxes as well as significant changes in circulation (such as ENSO), SSTAs can serve as a surrogate for many aspects of global climate change.

Probability of US Heat Waves Affected by a Subseasonal Planetary Wave Pattern

NASA Technical Reports Server (NTRS)

Teng, Haiyan; Branstator, Grant; Wang, Hailan; Meehl, Gerald A.; Washington, Warren M.

2013-01-01

Heat waves are thought to result from subseasonal atmospheric variability. Atmospheric phenomena driven by tropical convection, such as the Asian monsoon, have been considered potential sources of predictability on subseasonal timescales. Mid-latitude atmospheric dynamics have been considered too chaotic to allow significant prediction skill of lead times beyond the typical 10-day range of weather forecasts. Here we use a 12,000-year integration of an atmospheric general circulation model to identify a pattern of subseasonal atmospheric variability that can help improve forecast skill for heat waves in the United States. We find that heat waves tend to be preceded by 15-20 days by a pattern of anomalous atmospheric planetary waves with a wavenumber of 5. This circulation pattern can arise as a result of internal atmospheric dynamics and is not necessarily linked to tropical heating.We conclude that some mid-latitude circulation anomalies that increase the probability of heat waves are predictable beyond the typical weather forecast range.

Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.

PubMed

Rao, Rajesh R; Long, Jonathan Z; White, James P; Svensson, Katrin J; Lou, Jesse; Lokurkar, Isha; Jedrychowski, Mark P; Ruas, Jorge L; Wrann, Christiane D; Lo, James C; Camera, Donny M; Lachey, Jenn; Gygi, Steven; Seehra, Jasbir; Hawley, John A; Spiegelman, Bruce M

2014-06-05

Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses. Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Release of sulfur and chlorine during cofiring RDF and coal in an internally circulating fluidized bed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiaolin Wei; Yang Wang; Dianfu Liu

2009-03-15

An internally circulating fluidized bed (ICFB) was applied to investigate the behavior of chlorine and sulfur during cofiring RDF and coal. The pollutant emissions in the flue gas were measured by Fourier transform infrared (FTIR) spectrometry (Gasmet DX-3000). In the tests, the concentrations of the species CO, CO{sub 2}, HCl, and SO{sub 2} were measured online. Results indicated when cofiring RDF and char, due to the higher content of chlorine in RDF, the formation of HCl significantly increases. The concentration of SO{sub 2} is relatively low because alkaline metal in the fuel ash can absorb SO{sub 2}. The concentration ofmore » CO emission during firing pure RDF is relatively higher and fluctuates sharply. With the CaO addition, the sulfur absorption by calcium quickly increases, and the desulfurization ratio is bigger than the dechlorination ratio. The chemical equilibrium method is applied to predict the behavior of chlorine. Results show that gaseous HCl emission increases with increasing RDF fraction, and gaseous KCl and NaCl formation might occur. 35 refs., 18 figs., 2 tabs.« less

Insulin-like growth factor-1 and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration.

PubMed

Prahalada, S; Block, G; Handt, L; DeBurlet, G; Cahill, M; Hoe, C M; van Zwieten, M J

1999-01-01

Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.

CHANGES IN MOUSE CIRCULATING T-LYMPHOCYTE NUMBERS DURING A NORMAL CRYPTOSPORIDIUM MURIS INFECTION AND AFTER A SINGLE INJECTION OF METHYLPREDNISOLONE ACETATE

EPA Science Inventory

Cryptosporidium species are of public health significance in both developing nations and the industrialized nations of the world. Persons with immature or compromised immune systems are said to have increased risk or mortality once infected. The objective of this study was to c...

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

PubMed Central

Liu, Xiaoyu; Li, Changyu; Li, Junhao; Yu, Tianzhu; Zhou, Guofeng; Cheng, Jiemin; Li, Guoping; Zhou, Yang; Lou, Wenhui; Wang, Xiaolin; Gong, Gaoquan; Liu, Lingxiao; Chen, Yi

2018-01-01

Pancreatic cancer is amongst the most lethal malignancies with increasing incidence and mortality worldwide. Distant metastases, especially intrahepatic metastases, is the leading cause of death for pancreatic cancer. Circulating tumor cells (CTCs) are neoplastic cells released from the primary tumor into circulation, and play critical roles in metastases of various types of cancers. Though clinical studies showed that detection of CTCs in peripheral circulation was associated with worse prognosis in patients with breast cancer and hepatocellular carcinoma, detection CTCs in peripheral blood of pancreatic cancer was still challenging due to hepatic filtration and technical limitations. Previous studies have demonstrated that CTCs could be detected in portal vein circulation in patients with pancreaticobiliary carcinoma. In the present study, taking advantage of ultrasonography-guided transhepatic puncture, we analysis CTCs in portal vein blood obtained from patients with advanced pancreatic cancer. CTCs were detected in all 29-portal vein blood of samples, and absolute numbers of circulating pancreatic cancer cells in portal vein was significantly higher than that in peripheral circulation. Furthermore, we found that CTC counts in portal vein was highly associated with intrahepatic metastases and indicated poorer prognosis in patients with advanced pancreatic cancer. Short-term expansion and in vitro drug sensitivity assay showed that CTCs derived from portal vein blood were highly resistant to several chemotherapy regimens. In summary, detection of CTCs in portal vein could be a powerful tool to stratify the risk of intrahepatic metastases of pancreatic cancer, and provided new insight into the biological feature of pancreatic cancer metastases and drug resistance. PMID:29896289

Assessing the impact of total extracorporeal circulation on hemodynamics in an ovine fetal model.

PubMed

Xiao, Fei; Zhuang, Jian; Zhou, Cheng-Bin; Chen, Ji-Mei; Cen, Jian-Zheng; Xu, Gang; Wen, Shu-Sheng

2017-09-01

The present study aimed to evaluate the impact of total extracorporeal circulation on hemodynamics and placental function in an ovine fetal model. Mid-term ovine fetuses (n=6) underwent extracorporeal circulation (30 min), cardioplegic arrest (20 min) and monitoring (120 min). The ascending aorta and umbilical cords of the fetuses were occluded during the bypass and an extracorporeal membrane oxygenator was used as the oxygen source. Biventricular intracardiac pressures, echocardiographic data, blood gas levels and placental function variables were recorded, and statistical analysis was performed using the repeated-measure analysis of variance test. The data indicated that fetal heart rate and blood pressure at 30, 60, 90 and 120 min following the bypass were stable relative to pre-arrest baseline (pre-bypass) values (P>0.05). However, end diastolic pressures in the ovine right ventricles post-bypass were significantly increased at 30, 60, 90 and 120 min relative to pre-bypass pressures (P<0.05). The pulsatility index also increased at 30 min post-bypass relative to the pre-bypass score (0.91±0.06 vs. 0.61±0.14; P=0.007). The mean resistivity index at all time points post-bypass was consistent with the pre-bypass score (P>0.05), while the mean Tei index values for the left and right ventricles post-bypass were significantly higher at all time points relative to pre-bypass values (P<0.05). The pre-bypass fetal blood pH, SaO 2 , base excess and lactate values were maintained during arrest (P>0.05). Fetal hemodynamics and placental function additionally remained stable for up to 2 h upon reperfusion following total extracorporeal circulation and cardioplegic arrest. Collectively these data suggest that the reproducible ovine fetal model may be useful in the evaluation of fetal cardiac surgery.

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

PubMed

McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A

2013-02-01

What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis.

PubMed

Manetti, Mirko; Pratesi, Sara; Romano, Eloisa; Bellando-Randone, Silvia; Rosa, Irene; Guiducci, Serena; Fioretto, Bianca Saveria; Ibba-Manneschi, Lidia; Maggi, Enrico; Matucci-Cerinic, Marco

2017-01-01

The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU) compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC) pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC), and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further studies are required to clarify the function of Tang cells and investigate the mechanisms responsible for their change in SSc.

Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.

PubMed

Almeida, Julia; Polvorosa, Maria Angeles; Gonzalez-Quintela, Arturo; Madruga, Ignacio; Marcos, Miguel; Pérez-Nieto, Maria Angeles; Hernandez-Cerceño, Maria Luisa; Orfao, Alberto; Laso, Francisco Javier

2015-08-01

Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells. Copyright © 2015 by the Research Society on Alcoholism.

Evaluation of hemodynamic and regional tissue perfusion effects of minimized extracorporeal circulation (MECC).

PubMed

Bauer, Adrian; Diez, Claudius; Schubel, Jens; El-Shouki, Nagi; Metz, Dietrich; Eberle, T; Hausmann, Harald

2010-03-01

Minimized extracorporeal circulation (MECC, Maquet, Cardiopulmonary AG, Hirrlingen, Germany) is an established procedure to perform coronary revascularization. Studies showed positive effects of MECC compared to conventional cardiopulmonary bypass (CCPB) procedures in terms of transfusion requirements, less inflammation reactions, and neurological impairments. Recent retrospective studies showed higher mean arterial pressure (MAP) and a lower frequency of vasoactive drug use. We addressed this issue in this study. The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems. We performed a prospective, controlled, randomized trial with 40 patients either assigned to MECC (n = 18) or CCPB (n = 22) undergoing coronary bypass grafting. Primary endpoints were the perioperative course of mean arterial pressure, and the consumption of norepinephrine. Secondary endpoints were the regional cerebral and renal oxygen saturation (rSO2) as an indicator of area perfusion and the course of hematocrit. Clinical and demographic characteristics did not significantly differ between both groups. Thirty-day mortality was 0%. At four of five time points during extracorporeal circulation (ECC) MAP values were significantly higher in the MECC group compared to CCPB patients (after starting the ECC 60 +/- 11 mmHg vs. 49 +/- 10 mmHg, p = .002). MECC patients received significantly less norepinephrine (MECC 22.5 +/- 35 microg vs. CCPB 60.5 +/- 75 microg, p = .045). The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB. Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group. There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group.

Evaluation of Hemodynamic and Regional Tissue Perfusion Effects of Minimized Extracorporeal Circulation (MECC®)

PubMed Central

Bauer, Adrian; Diez, Claudius; Schubel, Jens; El-Shouki, Nagi; Metz, Dietrich; Eberle, T.; Hausmann, Harald

2010-01-01

Abstract: Minimized extracorporeal circulation (MECC®, Maquet, Cardiopulmonary AG, Hirrlingen, Germany) is an established procedure to perform coronary revascularization. Studies showed positive effects of MECC compared to conventional cardiopulmonary bypass (CCPB) procedures in terms of transfusion requirements, less inflammation reactions, and neurological impairments. Recent retrospective studies showed higher mean arterial pressure (MAP) and a lower frequency of vasoactive drug use. We addressed this issue in this study. The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems. We performed a prospective, controlled, randomized trial with 40 patients either assigned to MECC (n = 18) or CCPB (n = 22) undergoing coronary bypass grafting. Primary endpoints were the perioperative course of mean arterial pressure, and the consumption of norepinephrine. Secondary endpoints were the regional cerebral and renal oxygen saturation (rSO2) as an indicator of area perfusion and the course of hematocrit. Clinical and demographic characteristics did not significantly differ between both groups. Thirty-day mortality was 0%. At four of five time points during extracorporeal circulation (ECC) MAP values were significantly higher in the MECC group compared to CCPB patients (after starting the ECC 60 ± 11 mmHg vs. 49 ± 10 mmHg, p = .002). MECC patients received significantly less norepinephrine (MECC 22.5 ± 35 μg vs. CCPB 60.5 ± 75 μg, p = .045). The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB. Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group. There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group. PMID:20437789

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

PubMed Central

Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

2016-01-01

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: the NewGeneris cohort.

PubMed

Merlo, Domenico Franco; Agramunt, Silvia; Anna, Lívia; Besselink, Harrie; Botsivali, Maria; Brady, Nigel J; Ceppi, Marcello; Chatzi, Leda; Chen, Bowang; Decordier, Ilse; Farmer, Peter B; Fleming, Sarah; Fontana, Vincenzo; Försti, Asta; Fthenou, Eleni; Gallo, Fabio; Georgiadis, Panagiotis; Gmuender, Hans; Godschalk, Roger W; Granum, Berit; Hardie, Laura J; Hemminki, Kari; Hochstenbach, Kevin; Knudsen, Lisbeth E; Kogevinas, Manolis; Kovács, Katalin; Kyrtopoulos, Soterios A; Løvik, Martinus; Nielsen, Jeanette K; Nygaard, Unni Cecilie; Pedersen, Marie; Rydberg, Per; Schoket, Bernadette; Segerbäck, Dan; Singh, Rajinder; Sunyer, Jordi; Törnqvist, Margareta; van Loveren, Henk; van Schooten, Frederik J; Vande Loock, Kim; von Stedingk, Hans; Wright, John; Kleinjans, Jos C; Kirsch-Volders, Micheline; van Delft, Joost H M

2014-02-01

Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.

Leisure-time physical activity and circulating 25-hydroxyvitamin D levels in cancer survivors: a cross-sectional analysis using data from the US National Health and Nutrition Examination Survey.

PubMed

Yang, Lin; Toriola, Adetunji T

2017-07-10

Circulating 25-hydroxyvitamin D (25-OHD) is associated with improved cancer prognosis in some studies, yet it may be a surrogate marker for physical activity. We investigated the associations of leisure-time physical activity (LTPA) with circulating 25-OHD levels in cancer survivors, and determined whether associations differ by indoor and outdoor activity. Cross-sectional study. The US National Health and Nutrition Examination Survey (NHANES). Cancer survivors with available data on demographic information, measures of adiposity, smoking history, self-reported LTPA and circulating 25-OHD levels in five waves of NHANES (2001-2010). Circulating 25-OHD levels. Multivariable linear regression and logistic regression models were used to evaluate the associations of self-reported LTPA with 25-OHD, adjusting for potential confounders. Due to the differences in LTPA measure, the analyses were conducted separately for 2001-2006 and 2007-2010 data. We further estimated associations by indoor and outdoor activity in the 2001-2006 data. There were 1530 cancer survivors (mean age=60.5 years, mean body mass index=28.6 kg/m 2 ). The prevalent cancer sites were breast (19.3%), prostate (18.8%), cervix (10.4%) and colon (8.6%). Compared with inactive cancer survivors, being physically active was associated with higher circulating 25-OHD levels (8.07 nmol/L, 95% CI 4.63 to 11.52) for 2001-2006 data. In the mutually adjusted model, higher outdoor activity (5.83 nmol/L, 95% CI 1.64 to 10.01), but not indoor activity (2.93 nmol/L, 95% CI -1.80 to 7.66), was associated with statistically significantly higher 25-OHD levels. The interaction between indoor and outdoor activities was, however, not significant (p=0.29). The only statistically significant association seen in the 2007-2010 data was among obese cancer survivors. Physical activity, particularly outdoor activity, is associated with higher 25-OHD levels in cancer survivors. In view of the possible beneficial effects of vitamin D on cancer prognosis, engaging in outdoor physical activity could provide clinically meaningful increases in 25-OHD levels among cancer survivors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

PubMed

Anderson, Daniel R; Duryee, Michael J; Shurmur, Scott W; Um, John Y; Bussey, Walter D; Hunter, Carlos D; Garvin, Robert P; Sayles, Harlan R; Mikuls, Ted R; Klassen, Lynell W; Thiele, Geoffrey M

2014-01-01

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

PubMed Central

Anderson, Daniel R.; Duryee, Michael J.; Shurmur, Scott W.; Um, John Y.; Bussey, Walter D.; Hunter, Carlos D.; Garvin, Robert P.; Sayles, Harlan R.; Mikuls, Ted R.; Klassen, Lynell W.; Thiele, Geoffrey M.

2014-01-01

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease. PMID:25210746

Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome.

PubMed

Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua

2017-02-01

Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.

Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer

PubMed Central

Takano, S; Sogawa, K; Yoshitomi, H; Shida, T; Mogushi, K; Kimura, F; Shimizu, H; Yoshidome, H; Ohtsuka, M; Kato, A; Ishihara, T; Tanaka, H; Yokosuka, O; Nomura, F; Miyazaki, M

2010-01-01

Background: Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa. Methods: We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients. Results: Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set. Conclusion: The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics. PMID:20551957

Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage.

PubMed

Liao, Yi-Hung; Liao, Kun-Fu; Kao, Chung-Lan; Chen, Chung-Yu; Huang, Chih-Yang; Chang, Wei-Hsiang; Ivy, John L; Bernard, Jeffrey R; Lee, Shin-Da; Kuo, Chia-Hua

2013-01-01

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

Acute Biphasic Effects of Ayahuasca.

PubMed

Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A; da Silveira, Dartiu Xavier

2015-01-01

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered.

Influence of irradiation on release of endothelial microparticles (EMP) in vitro.

PubMed

Neuber, Christin; Pufe, Johanna; Pietzsch, Jens

2015-01-01

Survivors of Hodgkin's disease as well as of breast and lung cancer are at risk of radiation-associated cardiovascular disease. Recent studies demonstrated a correlation between cardiovascular risk factors and circulating endothelial microparticles (EMP) and thereby suggest increased EMP levels in circulation to be an early biomarker of endothelial dysfunction and cardiovascular risk. This prompted us to analyze the amount of EMP released by human aortic endothelial cells (HAEC) after exposure to different doses of X-ray (0.4, 2, 4, 6, and 20 Gy) using antibodies against the endothelial cell markers CD31, CD144, and CD146 by flow cytometry. In this pilot experiment only CD146 proved appropriate for quantification of HAEC-derived EMP. Exposure of HAEC to different doses of X-ray did not significantly influence formation of CD146-positive EMP. However, low doses (0.4 Gy) tended to decrease EMP formation, whereas higher doses (2 or 4 Gy) slightly increased release of CD146-positive EMP. By contrast, inflammatory activation of HAEC by TPA significantly increased EMP release about 15-fold (P <  0.01). In conclusion, under the present experimental conditions EMP did not prove a suitable biomarker for radiation-induced endothelial dysfunction in vitro.

Minimized extracorporeal circulation is improving outcome of coronary artery bypass surgery in the elderly.

PubMed

Freundt, Miriam; Ried, Michael; Philipp, Alois; Diez, Claudius; Kolat, Philipp; Hirt, Stephan W; Schmid, Christof; Haneya, Assad

2016-03-01

Advanced age is a known risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). Minimized extracorporeal circulation (MECC) has been shown to reduce the negative effects associated with conventional extracorporeal circulation (CECC). This trial assesses the impact of MECC on the outcome of elderly patients undergoing CABG. Eight hundred and seventy-five patients (mean age 78.35 years) underwent isolated CABG using CECC (n=345) or MECC (n=530). The MECC group had a significantly shorter extracorporeal circulation time (ECCT), cross-clamp time and reperfusion time and lower transfusion needs. Postoperatively, these patients required significantly less inotropic support, fewer blood transfusions, less postoperative hemodialysis and developed less delirium compared to CECC patients. In the MECC group, intensive care unit (ICU) stay was significantly shorter and 30-day mortality was significantly reduced [2.6% versus 7.8%; p<0.001]. In conclusion, MECC improves outcome in elderly patients undergoing CABG surgery. © The Author(s) 2015.

Dynamic Mesoscale Land-Atmosphere Feedbacks in Fragmented Forests in Amazonia

NASA Astrophysics Data System (ADS)

Rastogi, D.; Baidya Roy, S.

2011-12-01

This paper investigates land-atmosphere feedbacks in disturbed rainforests of Amazonia. Deforestation along the rapidly expanding highways and road network has created the unique fishbone land cover pattern in Rondonia, a state in southwestern Amazonia. Numerical experiments and observations show that sharp gradients in land cover due to the fishbone heterogeneity triggers mesoscale circulations. These circulations significantly change the spatial pattern of local hydrometeorology, especially convection, clouds and precipitation. The primary research question now is can these changes in local hydrometeorology affect vegetation growth in the clearings. If so, that would be a clear indication that land-atmosphere feedbacks can affect vegetation recovery in fragmented forests. A computationally-efficient modeling tool consisting of a mesoscale atmospheric model dynamically coupled with a plant growth model has been specifically developed to identify the atmospheric feedback pathways. Preliminary experiments focus on the seasonal-scale feedbacks during the dry season. Results show that temperature, incoming shortwave and precipitation are the three primary drivers through which the feedbacks operate. Increasing temperature increases respiratory losses generating a positive feedback. Increased cloud cover reduces incoming PAR and photosynthesis, resulting in a positive feedback. Increased precipitation reduces water stress and promotes growth resulting in a negative feedback. The net effect is a combination of these 3 feedback loops. These findings can significantly improve our understanding of ecosystem resiliency in disturbed tropical forests.

Association of Circulating Orexin-A Level With Metabolic Risk Factors in North Indian Pre Menopausal Women.

PubMed

Gupta, Vani; Mishra, Sameeksha; Kumar, Sandeep; Mishra, Supriya

2015-01-01

The present study was designed to investigate the association between circulating Orexin-A level with metabolic risk factors in North Indian adult women. 342 women were enrolled for the case-control study, 172 women were with metabolic syndrome (mets) and 170 healthy control women were without metabolic syndrome, (womets) according to (NCEP ATP III criteria). Circulating Orexin-A level was determined by enzyme-linked immunosorbent assay. Observations indicated low levels of orexin-A (26.06 ± 6.09 ng/ml) in women with mets and other metabolic risk factors compared to women without metabolic syndrome (36.50 ± 10.42 ng/ml). Further, in women with metabolic syndrome, circulating Orexin A was significantly associated with waist circumference, triglyceride (negative correlation) and hyperdensity lipoprotein (positive correlation). Our study shows that circulating Orexin A was found to be significantly associated with hyperlipidemia, obesity and obesity-related disorders in North Indian premenopausal women.

Evolving flood patterns in a Mediterranean region (1301-2012) and climatic factors - the case of Catalonia

NASA Astrophysics Data System (ADS)

Barrera-Escoda, A.; Llasat, M. C.

2015-01-01

Data on flood occurrence and flood impacts for the last seven centuries in the northeastern Iberian Peninsula have been analysed in order to characterise long-term trends, anomalous periods and their relationship with different climatic factors such as precipitation, general circulation and solar activity. Catastrophic floods (those that produce complete or partial destruction of infrastructure close to the river, and major damages in the overflowed area, including some zones away from the channels) do not present a statistically significant trend, whereas extraordinary floods (the channel is overflowed and some punctual severe damages can be produced in the infrastructures placed in the rivercourse or near it, but usually damages are slight) have seen a significant rise, especially from 1850 on, and were responsible for the total increase in flooding in the region. This rise can be mainly attributed to small coastal catchments, which have experienced a marked increase in developed land and population, resulting in changes in land use and greater vulnerability. Changes in precipitation alone cannot explain the variation in flood patterns, although a certain increase was shown in late summer-early autumn, when extraordinary floods are most frequently recorded. The relationship between the North Atlantic circulation and floods is not as strong, due to the important role of mesoscale factors in heavy precipitation in the northwest of the Mediterranean region. However, it can explain the variance to some extent, mainly in relation to the catastrophic floods experienced during the autumn. Solar activity has some impact on changes in catastrophic floods, with cycles related to the quasi-biennial oscillation (QBO) and the Gleissberg solar cycle. In addition, anomalous periods of high flood frequency in autumn generally occurred during periods of increased solar activity. The physical influence of the latter in general circulation patterns, the high troposphere and the stratosphere, has been analysed in order to ascertain its role in causing floods.

Arctic Ocean Pathways in the 21st century

NASA Astrophysics Data System (ADS)

Aksenov, Yevgeny; van Gennip, Simon J.; Kelly, Stephen J.; Popova, Ekaterina E.; Yool, Andrew

2017-04-01

In the last three decades, changes in the Arctic environment have been occurring at an increasing rate. The opening up of large areas of previously sea ice-covered ocean affects the marine environment with potential impacts on Arctic ecosystems, including through changes in Arctic access, industries and societies. Changes to sea ice and surface winds result in large-scale shifts in ocean circulation and oceanic pathways. This study presents a high-resolution analysis of the projected ocean circulation and pathways of the Arctic water masses across the 21st century. The analysis is based on an eddy-permitting high-resolution global simulation of the ocean general circulation model NEMO (Nucleus for European Modelling of the Ocean) at the 1/4-degree horizontal resolution. The atmospheric forcing is from HadGEM2-ES model output from IPCC Assessment Report 5 (AR5) simulations performed for Coupled Model Intercomparison Project 5 (CMIP5), and follow the Representative Concentration Pathway 8.5 (RCP8.5) scenario. During the 21st century the AO experiences a significant warming, with sea surface temperature increased by in excess of 4 deg. C. Annual mean Arctic sea ice thickness drops to less than 0.5m, and the Arctic Ocean is ice-free in summer from the mid-century. We use an off-line tracer technique to investigate Arctic pathways of the Atlantic and Pacific waters (AW and PW respectively) under this future climate. The AW tracers have been released in the eastern Fram Strait and in the western Barents Sea, whereas the PW tracer has been seeded in the Bering Strait. In the second half of the century the upper 1000 m ocean circulation shows a reduction in the eastward AW flow along the continental slopes towards the Makarov and Canada basins and a deviation of the PW flow away from the Beaufort Sea towards the Siberian coast. Strengthening of Arctic boundary current and intensification of the cyclonic gyre in the Nansen basin of the Arctic Ocean is accompanied by weakening of the current and an anti-cyclonic gyre spin-up in the Makarov Basin. This presents a shift of the Arctic circulation "dipole" and of the Transpolar Drift, with the consequence that the PW flow towards Fram Strait is significantly reduced by the end of the century, weakening the Pacific-Atlantic connection via the Arctic Ocean, and reducing the Arctic freshwater outflow into the North Atlantic. Examination of the simulations suggests that these circulation changes are primarily due to the shift in the wind.

Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models.

PubMed Central

Webb, M. S.; Harasym, T. O.; Masin, D.; Bally, M. B.; Mayer, L. D.

1995-01-01

This study reports on the development of a liposomal formulation of vincristine with significantly enhanced stability and biological properties. The in vitro and in vivo pharmacokinetic, tumour delivery and efficacy properties of liposomal vincristine formulations based on sphingomyelin (SM) and cholesterol were compared with liposomes composed of distearoylphosphatidylcholine (DSPC) and cholesterol. SM/cholesterol liposomes had significantly greater in vitro stability than did similar DSPC/cholesterol liposomes. SM/cholesterol liposomes also had significantly improved biological properties compared with DSPC/cholesterol. Specifically, SM/cholesterol liposomes administered intravenously retained 25% of the entrapped vincristine after 72 h in the circulation, compared with 5% retention in DSPC/cholesterol liposomes. The improved retention properties of SM/cholesterol liposomes resulted in plasma vincristine levels 7-fold higher than in DSPC/cholesterol liposomes. The improved circulation lifetime of vincristine in SM/cholesterol liposomes correlated with increased vincristine accumulation in peritoneal ascitic murine P388 tumours and in subcutaneous solid A431 human xenograft tumours. Increased vincristine delivery to tumours was also accompanied by increased anti-tumour efficacy. Treatment with SM/cholesterol liposomal formulations of vincristine resulted in greater than 50% cures in mice bearing ascitic P388 tumours, an activity that could not be achieved with the DSPC/cholesterol formulation. Similarly, treatment of mice with severe combined immunodeficiency (SCID) bearing solid human A431 xenograft tumours with SM/cholesterol vincristine formulations delayed the time required for 100% increase in tumour mass to > 40 days, compared with 5 days, 7 days and 14 days for mice receiving no treatment or treatment with free vincristine or DSPC/cholesterol formulations of vincristine respectively. PMID:7547237

Short-term exercise training improves flow-mediated dilation and circulating angiogenic cell number in older sedentary adults.

PubMed

Landers-Ramos, Rian Q; Corrigan, Kelsey J; Guth, Lisa M; Altom, Christine N; Spangenburg, Espen E; Prior, Steven J; Hagberg, James M

2016-08-01

Cardiovascular disease risk increases with age due, in part, to impaired endothelial function and decreased circulating angiogenic cell (CAC) number and function. We sought to determine if 10 days of aerobic exercise training improves endothelial function, CAC number, and intracellular redox balance in older sedentary adults. Eleven healthy subjects (4 men, 7 women), 61 ± 2 years of age participated in 60 min of aerobic exercise at 70% maximal oxygen consumption for 10 consecutive days while maintaining body weight. Before and after training, endothelial function was measured as flow-mediated dilation of the brachial artery and fasting blood was drawn to enumerate 3 CAC subtypes. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) in CD34+ CACs were measured using fluorescent probes and reinforced via real-time quantitative polymerase chain reaction. Flow-mediated dilation improved significantly following training (10% ± 1.3% before vs. 16% ± 1.4% after training; P < 0.05). Likewise, CD34+/KDR+ number increased 104% and KDR+ number increased 151% (P < 0.05 for both), although CD34+ number was not significantly altered (P > 0.05). Intracellular NO and ROS levels in CD34+ CACs were not different after training (P > 0.05 for both). Messenger RNA expression of SOD1, endothelial nitric oxide synthase, and NADPH oxidase 2 and neutrophil cytosolic factor 1 in CD34+ CACs was not significantly altered with training (P > 0.05). In conclusion, 10 consecutive days of aerobic exercise increased flow-mediated dilation and CAC number in older, previously sedentary adults, but did not affect intracellular redox balance in CD34+ CACs. Overall, these data indicate that even short-term aerobic exercise training can have a significant impact on cardiovascular disease risk factors.

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

PubMed Central

Jonsdottir, Ingibjörg H.; Hägg, Daniel A.; Glise, Kristina; Ekman, Rolf

2009-01-01

Background Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. Methodology/Principal Findings Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients. Conclusions/Significance MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured. PMID:19888340

The resolution sensitivity of the South Asian monsoon and Indo-Pacific in a global 0.35° AGCM

NASA Astrophysics Data System (ADS)

Johnson, Stephanie J.; Levine, Richard C.; Turner, Andrew G.; Martin, Gill M.; Woolnough, Steven J.; Schiemann, Reinhard; Mizielinski, Matthew S.; Roberts, Malcolm J.; Vidale, Pier Luigi; Demory, Marie-Estelle; Strachan, Jane

2016-02-01

The South Asian monsoon is one of the most significant manifestations of the seasonal cycle. It directly impacts nearly one third of the world's population and also has substantial global influence. Using 27-year integrations of a high-resolution atmospheric general circulation model (Met Office Unified Model), we study changes in South Asian monsoon precipitation and circulation when horizontal resolution is increased from approximately 200-40 km at the equator (N96-N512, 1.9°-0.35°). The high resolution, integration length and ensemble size of the dataset make this the most extensive dataset used to evaluate the resolution sensitivity of the South Asian monsoon to date. We find a consistent pattern of JJAS precipitation and circulation changes as resolution increases, which include a slight increase in precipitation over peninsular India, changes in Indian and Indochinese orographic rain bands, increasing wind speeds in the Somali Jet, increasing precipitation over the Maritime Continent islands and decreasing precipitation over the northern Maritime Continent seas. To diagnose which resolution-related processes cause these changes, we compare them to published sensitivity experiments that change regional orography and coastlines. Our analysis indicates that improved resolution of the East African Highlands results in the improved representation of the Somali Jet and further suggests that improved resolution of orography over Indochina and the Maritime Continent results in more precipitation over the Maritime Continent islands at the expense of reduced precipitation further north. We also evaluate the resolution sensitivity of monsoon depressions and lows, which contribute more precipitation over northeast India at higher resolution. We conclude that while increasing resolution at these scales does not solve the many monsoon biases that exist in GCMs, it has a number of small, beneficial impacts.

Impacts of large-scale atmospheric circulation changes in winter on black carbon transport and deposition to the Arctic

NASA Astrophysics Data System (ADS)

Pozzoli, Luca; Dobricic, Srdan; Russo, Simone; Vignati, Elisabetta

2017-10-01

Winter warming and sea-ice retreat observed in the Arctic in the last decades may be related to changes of large-scale atmospheric circulation pattern, which may impact the transport of black carbon (BC) to the Arctic and its deposition on the sea ice, with possible feedbacks on the regional and global climate forcing. In this study we developed and applied a statistical algorithm, based on the maximum likelihood estimate approach, to determine how the changes of three large-scale weather patterns associated with increasing temperatures in winter and sea-ice retreat in the Arctic impact the transport of BC to the Arctic and its deposition. We found that two atmospheric patterns together determine a decreasing winter deposition trend of BC between 1980 and 2015 in the eastern Arctic while they increase BC deposition in the western Arctic. The increasing BC trend is mainly due to a pattern characterized by a high-pressure anomaly near Scandinavia favouring the transport in the lower troposphere of BC from Europe and North Atlantic directly into to the Arctic. Another pattern with a high-pressure anomaly over the Arctic and low-pressure anomaly over the North Atlantic Ocean has a smaller impact on BC deposition but determines an increasing BC atmospheric load over the entire Arctic Ocean with increasing BC concentrations in the upper troposphere. The results show that changes in atmospheric circulation due to polar atmospheric warming and reduced winter sea ice significantly impacted BC transport and deposition. The anthropogenic emission reductions applied in the last decades were, therefore, crucial to counterbalance the most likely trend of increasing BC pollution in the Arctic.

Nitrogen removal and power generation from treated municipal wastewater by its circulated irrigation for resource-saving rice cultivation.

PubMed

Watanabe, Toru; Mashiko, Takuma; Maftukhah, Rizki; Kaku, Nobuo; Pham, Dong Duy; Ito, Hiroaki

2017-02-01

This study aims at improving the performance of the cultivating system of rice for animal feed with circulated irrigation of treated municipal wastewater by applying a larger amount of wastewater, as well as adding a microbial fuel cell (MFC) to the system. The results of bench-scale experiments indicate that this modification has increased the rice yield, achieving the target for the rice cultivar used in the experiment. In addition, an assessment of protein content of the harvested rice showed that the value of the rice as animal fodder has improved. Compared with normal one-way irrigation, circulated irrigation significantly enhanced the plant growth and rice production. The direction of the irrigation (bottom-to-top or top-to-bottom) in the soil layer had no significant effect. This modified system demonstrated >96% for nitrogen removal from the treated wastewater used for the irrigation, with approximately 40% of the nitrogen being used for rice plant growth. The MFC installed in the system facilitated power generation comparable with that reported for normal paddy fields. The power generation appeared to be enhanced by bottom-to-top irrigation, which could provide organic-rich treated wastewater directly to the bacterial community living on the anode of the MFC set in the soil layer.

Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise

PubMed Central

Lu, Kim D.; Cooper, Dan; Haddad, Fadia; Zaldivar, Frank; Kraft, Monica; Radom-Aizik, Shlomit

2017-01-01

Background Poor aerobic fitness is associated with worsening of asthma symptoms and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes reflecting a reduced responsiveness to stress. Methods In a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to a brief exercise challenge before and after the training intervention. PBMC gene expression of GR, GRβ, HSP70, and TGFβ1, 2 were determined using RT-PCR. Results Peak V̇O2 increased by 14.6 ± 2.3% indicating an effective training (p<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the training intervention, there was a significant decrease in baseline GR expression (p<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents. Conclusions This is the first study in adolescents to show that exercise training reduces GR expression on circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health. PMID:28796240

Is there really a clinical benefit of using minimized extracorporeal circulation for coronary artery bypass grafting?

PubMed

Schöttler, J; Lutter, G; Böning, A; Soltau, D; Bein, B; Caliebe, D; Haake, N; Schoeneich, F; Cremer, J

2008-03-01

Minimized extracorporeal circulation is intended to reduce the negative effects associated with cardiopulmonary bypass. This prospective study was performed to evaluate whether minimized extracorporeal circulation has a clinical benefit for coronary artery surgery patients compared to standard extracorporeal circulation. Sixty patients were randomized into two study groups: 30 patients underwent coronary artery bypass grafting using minimized extracorporeal circulation and 30 patients were operated using standard extracorporeal circulation. Baseline characteristics, intraoperative details, postoperative data, perioperative blood chemistry determinations of hematocrit, platelets, muscle-brain fraction of the creatine kinase, cardiac troponin T and colloid osmotic pressure as measurements of intrathoracic blood volume index and extravascular lung water index were compared. Baseline characteristics and intraoperative details of both groups were similar. Patients who underwent minimized extracorporeal circulation showed more short-term dependency on norepinephrine ( P < 0.01). Their maximal postoperative muscle-brain fraction of the creatine kinase was lower ( P < 0.05) and their hematocrit on arrival in the intensive care unit was higher ( P < 0.01). No other significant differences were found. In both collectives, values for hematocrit ( P < 0.001), platelets ( P < 0.001), colloid osmotic pressure ( P < 0.001) and intrathoracic blood volume index ( P < 0.05) decreased, while the extravascular lung water index did not change significantly during cardiopulmonary bypass. A clinical advantage of minimized over standard extracorporeal circulation was not found. Furthermore, a higher number of patients in the minimized extracorporeal circulation group required postoperative norepinephrine infusions for hemodynamic stabilization. In summary, the presumed superiority of minimized extracorporeal circulation for coronary artery bypass grafting in standard patients could not be confirmed.

Combined ice core and climate-model evidence for the collapse of the West Antarctic Ice Sheet during Marine Isotope Stage 5e.

NASA Astrophysics Data System (ADS)

Steig, Eric J.; Huybers, Kathleen; Singh, Hansi A.; Steiger, Nathan J.; Frierson, Dargan M. W.; Popp, Trevor; White, James W. C.

2015-04-01

It has been speculated that collapse of the West Antarctic Ice Sheet explains the very high eustatic sea level rise during the last interglacial period, marine isotope stage (MIS) 5e, but the evidence remains equivocal. Changes in atmospheric circulation resulting from a collapse of the West Antarctic Ice Sheet (WAIS) would have significant regional impacts that should be detectable in ice core records. We conducted simulations using general circulation models (GCMs) at varying levels of complexity: a gray-radiation aquaplanet moist GCM (GRaM), the slab ocean version of GFDL-AM2 (also as an aquaplanet), and the fully-coupled version of NCAR's CESM with realistic topography. In all the experiments, decreased elevation from the removal of the WAIS leads to greater cyclonic circulation over the West Antarctic region. This creates increased advection of relatively warm marine air from the Amundsen-Bellingshausen Seas towards the South Pole, and increased cold-air advection from the East Antarctic plateau towards the Ross Sea and coastal Marie Byrd Land. The result is anomalous warming in some areas of the East Antarctic interior, and significant cooling in Marie Byrd Land. Comparison of ice core records shows good agreement with the model predictions. In particular, isotope-paleotemperature records from ice cores in East Antarctica warmed more between the previous glacial period (MIS 6) and MIS 5e than coastal Marie Byrd Land. These results add substantial support to other evidence for WAIS collapse during the last interglacial period.

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses--A Case-Control Study.

PubMed

Gao, Ting; Jin, Kairui; Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. A total of 460 permanent residents of the Fengxian District, aged 40-60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18-28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism.

CIRCULATING MICROPARTICLES IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES: CHARACTERIZATION AND ASSOCIATIONS

PubMed Central

Chaturvedi, Shruti; Cockrell, Erin; Espinola, Ricardo; Hsi, Linda; Fulton, Stacey; Khan, Mohammad; Li, Liang; Fonseca, Fabio; Kundu, Suman; McCrae, Keith R.

2014-01-01

The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte, platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2 hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R = 0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with APS and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies. PMID:25467081

Computational studies of the effects of active and passive circulation enhancement concepts on wind turbine performance

NASA Astrophysics Data System (ADS)

Tongchitpakdee, Chanin

With the advantage of modern high speed computers, there has been an increased interest in the use of first-principles based computational approaches for the aerodynamic modeling of horizontal axis wind turbine (HAWT). Since these approaches are based on the laws of conservation (mass, momentum, and energy), they can capture much of the physics in great detail. The ability to accurately predict the airloads and power output can greatly aid the designers in tailoring the aerodynamic and aeroelastic features of the configuration. First-principles based analyses are also valuable for developing active means (e.g., circulation control), and passive means (e.g., Gurney flaps) of reducing unsteady blade loads, mitigating stall, and for efficient capture of wind energy leading to more electrical power generation. In this present study, the aerodynamic performance of a wind turbine rotor equipped with circulation enhancement technology (trailing edge blowing or Gurney flaps) is investigated using a three-dimensional unsteady viscous flow analysis. The National Renewable Energy Laboratory (NREL) Phase VI horizontal axis wind turbine is chosen as the baseline configuration. Prior to its use in exploring these concepts, the flow solver is validated with the experimental data for the baseline case under yawed flow conditions. Results presented include radial distribution of normal and tangential forces, shaft torque, root flap moment, surface pressure distributions at selected radial locations, and power output. Results show that good agreement has been for a range of wind speeds and yaw angles, where the flow is attached. At high wind speeds, however, where the flow is fully separated, it was found that the fundamental assumptions behind this present methodology breaks down for the baseline turbulence model (Spalart-Allmaras model), giving less accurate results. With the implementation of advanced turbulence model, Spalart-Allmaras Detached Eddy Simulation (SA-DES), the accuracy of the results at high wind speeds are improved. Results of circulation enhancement concepts show that, at low wind speed (attached flow) conditions, a Coanda jet at the trailing edge of the rotor blade is effective at increasing circulation resulting in an increase of lift and the chordwise thrust force. This leads to an increased amount of net power generation compared to the baseline configuration for moderate blowing coefficients. The effects of jet slot height and pulsed jet are also investigated in this study. A passive Gurney flap was found to increase the bound circulation and produce increased power in a manner similar to the Coanda jet. At high wind speed where the flow is separated, both the Coanda jet and Gurney flap become ineffective. Results of leading edge blowing indicate that a leading edge blowing jet is found to be beneficial in increasing power generation at high wind speeds. The effect of Gurney flap angle is also studied. Gurney flap angle has significant influence in power generation. Higher power output is obtained at higher flap angles.

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1990-03-01

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

Influences of biological variables and geographic location on circulating concentrations of thyroid hormones in wild bottlenose dolphins (Tursiops truncatus).

PubMed

Fair, Patricia A; Montie, Eric; Balthis, Len; Reif, John S; Bossart, Gregory D

2011-11-01

Thyroid hormones (TH) are key regulators of metabolism and development, yet our understanding of the variability in serum TH concentrations in free-ranging marine mammals is limited. Thus, we examined the interrelationships between TH and age, sex, reproductive status, geographic location, and ocean temperatures in wild bottlenose dolphins (Tursiops truncatus). Circulating concentrations of TH (total thyroxine (tT(4)), free T(4) (fT(4)), and total triiodothyronine (tT(3))) were determined in a total of 195 dolphins; 80 from the coastal waters of Charleston, South Carolina (CHS) and 115 from the Indian River Lagoon, Florida (IRL). Age had the most influence on circulating TH concentrations in dolphins at both sites with decreasing concentrations (p<0.0001) observed with increasing age for all TH. No significant differences were found between males and non-reproductive females. Geographic location significantly influenced tT(4) and tT(3) concentrations; CHS dolphins had higher concentrations than IRL animals. These TH differences between CHS and IRL dolphins may be attributed to the colder year-round water temperature that CHS dolphins inhabit compared to IRL dolphins and could constitute an adaptive response to their colder environment. Results from this study highlight the importance of establishing reference values for dolphins in different geographic locations to support valid comparisons. This initial assessment provides a foundation of how biological and environmental variables could affect circulating TH in dolphins, which will help to elucidate the impacts of disease, pollution, and climate change on the thyroid hormone system of aquatic mammals. Published by Elsevier Inc.

Circulating microparticle levels are reduced in patients with ARDS.

PubMed

Shaver, Ciara M; Woods, Justin; Clune, Jennifer K; Grove, Brandon S; Wickersham, Nancy E; McNeil, J Brennan; Shemancik, Gregory; Ware, Lorraine B; Bastarache, Julie A

2017-05-25

It is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes. A total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times. ARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50-0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49-0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time. Elevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.

Effect of canagliflozin on circulating active GLP-1 levels in patients with type 2 diabetes: a randomized trial.

PubMed

Takebayashi, Kohzo; Hara, Kenji; Terasawa, Tomoko; Naruse, Rika; Suetsugu, Mariko; Tsuchiya, Takafumi; Inukai, Toshihiko

2017-09-30

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

PubMed Central

Rizk, Nasser M.; Sharif, Elham

2015-01-01

Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin. PMID:26180527

Rapid protein disappearance rates along the small intestine advantage poultry performance and influence the post-enteral availability of amino acids.

PubMed

Truong, Ha H; Chrystal, Peter V; Moss, Amy F; Selle, Peter H; Liu, Sonia Yun

2017-12-01

A foundation diet, an intermediate blend and a summit diet were formulated with different levels of soyabean meal, casein and crystalline amino acids to compare 'slow' and 'rapid' protein diets. The diets were offered to male Ross 308 chicks from 7 to 28 d post-hatch and assessed parameters included growth performance, nutrient utilisation, apparent digestibility coefficients and disappearance rates of starch and protein (N) in four small intestinal segments. Digestibility coefficients and disappearance rates of sixteen amino acids in three small intestinal segments and amino acid concentrations in plasma from portal and systemic circulations from the foundation and summit diets were determined. The dietary transition significantly accelerated protein (N) disappearance rates in the distal jejunum and ileum. The transition from foundation to summit diets significantly increased starch digestibility coefficients in the ileum and disappearance rates in all four small intestinal segments. These starch responses were associated with significant enhancements in nutrient utilisation. The dietary transition linearly increased digestibility coefficients and disappearance rates of amino acids in the majority of cases. The summit diet increased plasma concentrations of five amino acids but decreased those of four amino acids relative to the foundation diet to significant extents. Plasma concentrations of free amino acids were higher in the portal than systemic circulations. Rapid protein disappearance rates advantaged poultry performance and influenced post-enteral availability of amino acids. If the underlying mechanisms are to be identified, further research into the impact of protein digestive dynamics on broiler performance is required but appears justified.

Recent slowing of Atlantic overturning circulation as a recovery from earlier strengthening

NASA Astrophysics Data System (ADS)

Jackson, Laura C.; Peterson, K. Andrew; Roberts, Chris D.; Wood, Richard A.

2016-07-01

The Atlantic meridional overturning circulation (AMOC) has weakened substantially over the past decade. Some weakening may already have occurred over the past century, and global climate models project further weakening in response to anthropogenic climate change. Such a weakening could have significant impacts on the surface climate. However, ocean model simulations based on historical conditions have often found an increase in overturning up to the mid-1990s, followed by a decrease. It is therefore not clear whether the observed weakening over the past decade is part of decadal variability or a persistent weakening. Here we examine a state-of-the-art global-ocean reanalysis product, GloSea5, which covers the years 1989 to 2015 and closely matches observations of the AMOC at 26.5° N, capturing the interannual variability and decadal trend with unprecedented accuracy. The reanalysis data place the ten years of observations--April 2004 to February 2014--into a longer-term context and suggest that the observed decrease in the overturning circulation is consistent with a recovery following a previous increase. We find that density anomalies that propagate southwards from the Labrador Sea are the most likely cause of these variations. We conclude that decadal variability probably played a key role in the decline of the AMOC observed over the past decade.

Measurement of the Rheology of Crude Oil in Equilibrium with CO2 at Reservoir Conditions.

PubMed

Hu, Ruien; Crawshaw, John

2017-06-06

A rheometer system to measure the rheology of crude oil in equilibrium with carbon dioxide (CO2) at high temperatures and pressures is described. The system comprises a high-pressure rheometer which is connected to a circulation loop. The rheometer has a rotational flow-through measurement cell with two alternative geometries: coaxial cylinder and double gap. The circulation loop contains a mixer, to bring the crude oil sample into equilibrium with CO2, and a gear pump that transports the mixture from the mixer to the rheometer and recycles it back to the mixer. The CO2 and crude oil are brought to equilibrium by stirring and circulation and the rheology of the saturated mixture is measured by the rheometer. The system is used to measure the rheological properties of Zuata crude oil (and its toluene dilution) in equilibrium with CO2 at elevated pressures up to 220 bar and a temperature of 50 °C. The results show that CO2 addition changes the oil rheology significantly, initially reducing the viscosity as the CO2 pressure is increased and then increasing the viscosity above a threshold pressure. The non-Newtonian response of the crude is also seen to change with the addition of CO2.

Protective effects of circulating microvesicles derived from myocardial ischemic rats on apoptosis of cardiomyocytes in myocardial ischemia/reperfusion injury.

PubMed

Wang, Yao; Wei, Su; Wang, Yi-Lu; Liu, Miao; Shang, Man; Zhang, Qi; Wu, Yan-Na; Liu, Ming-Lin; Song, Jun-Qiu; Liu, Yan-Xia

2017-08-15

To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats. Treatment with I-MVssignificantly reduced the size of myocardial infarction, the activities of serum CK-MB and LDH, and the number of apoptotic cardiomyocytes. The activities of caspase 3, caspase 9 and caspase 12 in myocardium were also decreased significantly with I-MVs treatment. Moreover, the expression of Bax was decreased but Bcl-2 was increased. The expression of glucose regulated protein 78 (GRP78), sarco/endoplasmic reticulum Ca 2+ -ATPase 2 (SERCA2) and phosphorylated phospholamban (p-PLB) were increased after being treated with I-MVs. I-MVs could protect hearts from I/R injury in rats through SERCA2 and p-PLB of calcium regulatory proteins to alleviate intrinsic myocardial apoptosis including mitochondrial and endoplasmic reticulum pathways.

Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism.

PubMed

Kelly, Tammas; Denmark, Lawrence; Lieberman, Daniel Z

2016-11-03

Clinicians have been reluctant to use high dose thyroid (HDT) to treat affective disorders because high circulating levels of thyroid hormone have traditionally been equated with hyperthyroidism, and understood as the cause of the medical sequelae of hyperthyroidism, such as osteoporosis and cardiac abnormalities. This conclusion is not supported by (HDT) research. A literature review of research related to the morbidity and mortality of HDT treatment was performed. There exists a large body of research involving the use of HDT treatment to prevent the recurrence of differentiated thyroid cancer and to treat affective disorders. A review of this literature finds a lack of support for HDT as a cause of osteoporosis, nor is there support for an increase in morbidity or mortality associated with HDT. This finding contrasts with the well-established morbidity and mortality associated with Graves' disease, thyroiditis, and other endogenous forms of hyperthyroidism. The lack of evidence that exogenous HDT causes osteoporosis, cardiac abnormalities or increases mortality compared with the significant morbidity and mortality of hyperthyroidism requires an alternative cause for the medical sequelae of hyperthyroidism. One possibility is an autoimmune mechanism. High circulating levels of thyroid hormone is not the cause of the sequela of hyperthyroidism. The reluctance to using high dose thyroid is unwarranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiphase groundwater flow near cooling plutons

USGS Publications Warehouse

Hayba, D.O.; Ingebritsen, S.E.

1997-01-01

We investigate groundwater flow near cooling plutons with a computer program that can model multiphase flow, temperatures up to 1200??C, thermal pressurization, and temperature-dependent rock properties. A series of experiments examines the effects of host-rock permeability, size and depth of pluton emplacement, single versus multiple intrusions, the influence of a caprock, and the impact of topographically driven groundwater flow. We also reproduce and evaluate some of the pioneering numerical experiments on flow around plutons. Host-rock permeability is the principal factor influencing fluid circulation and heat transfer in hydrothermal systems. The hottest and most steam-rich systems develop where permeability is of the order of 10-15 m2. Temperatures and life spans of systems decrease with increasing permeability. Conduction-dominated systems, in which permeabilities are ???10-16m2, persist longer but exhibit relatively modest increases in near-surface temperatures relative to ambient conditions. Pluton size, emplacement depth, and initial thermal conditions have less influence on hydrothermal circulation patterns but affect the extent of boiling and duration of hydrothermal systems. Topographically driven groundwater flow can significantly alter hydrothermal circulation; however, a low-permeability caprock effectively decouples the topographically and density-driven systems and stabilizes the mixing interface between them thereby defining a likely ore-forming environment.

Multi-scale coupled modelling of waves and currents on the Catalan shelf.

NASA Astrophysics Data System (ADS)

Grifoll, M.; Warner, J. C.; Espino, M.; Sánchez-Arcilla, A.

2012-04-01

Catalan shelf circulation is characterized by a background along-shelf flow to the southwest (including some meso-scale features) plus episodic storm driven patterns. To investigate these dynamics, a coupled multi-scale modeling system is applied to the Catalan shelf (North-western Mediterranean Sea). The implementation consists of a set of increasing-resolution nested models, based on the circulation model ROMS and the wave model SWAN as part of the COAWST modeling system, covering from the slope and shelf region (~1 km horizontal resolution) down to a local area around Barcelona city (~40 m). The system is initialized with MyOcean products in the coarsest outer domain, and uses atmospheric forcing from other sources for the increasing resolution inner domains. Results of the finer resolution domains exhibit improved agreement with observations relative to the coarser model results. Several hydrodynamic configurations were simulated to determine dominant forcing mechanisms and hydrodynamic processes that control coastal scale processes. The numerical results reveal that the short term (hours to days) inner-shelf variability is strongly influenced by local wind variability, while sea-level slope, baroclinic effects, radiation stresses and regional circulation constitute second-order processes. Additional analysis identifies the significance of shelf/slope exchange fluxes, river discharge and the effect of the spatial resolution of the atmospheric fluxes.

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

PubMed Central

Beer, Sandra; Feihl, François; Ruiz, Juan; Juhan-Vague, Irène; Aillaud, Marie-Françoise; Wetzel, Sandrine Golay; Liaudet, Lucas; Gaillard, Rolf C; Waeber, Bernard

2008-01-01

Aim: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state. PMID:19337558

Analysis of ChimeriVax Japanese Encephalitis Virus envelope for T-cell epitopes and comparison to circulating strain sequences.

PubMed

De Groot, Anne S; Martin, William; Moise, Leonard; Guirakhoo, Farshad; Monath, Thomas

2007-11-19

T-cell epitope variability is associated with viral immune escape and may influence the outcome of vaccination against the highly variable Japanese Encephalitis Virus (JEV). We computationally analyzed the ChimeriVax-JEV vaccine envelope sequence for T helper epitopes that are conserved in 12 circulating JEV strains and discovered 75% conservation among putative epitopes. Among non-identical epitopes, only minor amino acid changes that would not significantly affect HLA-binding were present. Therefore, in most cases, circulating strain epitopes could be restricted by the same HLA and are likely to stimulate a cross-reactive T-cell response. Based on this analysis, we predict no significant abrogation of ChimeriVax-JEV-conferred protection against circulating JEV strains.

Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver failure have an early monocytopenia.

PubMed

Moore, J K; MacKinnon, A C; Man, T Y; Manning, J R; Forbes, S J; Simpson, K J

2017-02-01

Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome. On admission, patients with worst outcomes after POD-ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a 'cytokine storm' and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes. Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non-paracetamol-induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention. © 2016 John Wiley & Sons Ltd.

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

PubMed

Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

1998-08-01

Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Non-extracorporeal circulation for coronary artery bypass graft surgery is more beneficial than extracorporeal circulation.

PubMed

Yang, F-Y; Bao, Y-Z; Liu, F-S; Zhu, Y-C; Zheng, J; Zhang, J-H; Zheng, X-F; Wei, G-C

2015-04-01

The objective of this study was to compare coronary artery bypass graft (CABG) surgery with non-extracorporeal vs. extracorporeal circulation. The study outcomes included operative time, number of graft vessels, pulmonary infection rates, and systemic inflammatory markers. 96 patients received selective CABG, either with non-extracorporeal (study group; n = 48) or extracorporeal circulation (control group; n = 48). Operative time, pulmonary infection rates, and blood levels of inflammatory markers TNF-α, IL-6, and IL-8 before and 4, 24, and 48 hours after the surgery were quantified. Graft vessels were quantified using computed tomography. Operative time was significantly shorter in study group (4.58 ± 0.91 vs. 5.36 ± 1.12 hours in control group; p < 0.05). The number of graft vessels and pulmonary infection rates were comparable between both techniques. However, systemic inflammatory markers were significantly (p < 0.05) lower in study group at 4 and, partly, 24 hours after the surgery. Extracorporeal circulation prolongs operation and can aggravate systemic inflammatory response. Therefore, CABG with non-extracorporeal circulation offers more beneficial outcomes.

Circulating vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D and risk of colorectal cancer

PubMed Central

Ying, Hou-Qun; Sun, Hui-Ling; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Deng, Qi-Wen; Chen, Jie; Liu, Xian; Wang, Shu-Kui

2015-01-01

Epidemiological investigation have suggested that there is a significantly inverse association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk for developing colorectal cancer (CRC) in humans. However, little is known about the role of vitamin D binding protein (VDBP) in colorectal carcinogenesis. Blood samples were collected from 212 CRC patients and 212 controls matched with age, gender and blood collection time. We used logistic regression to calculate the odds ratios and 95% confidence intervals for further estimation of the association of the quartiles of VDBP, total, free and bioavailable 25(OH)D with CRC risk. The results revealed that there was no significant association between circulating VDBP concentrations and CRC in the present study, and that a negative association existed between total 25(OH)D and the risk of CRC, which was unchanged after adjustment for VDBP. Higher levels of free and bioavailable 25(OH)D were significantly associated with decreased risk of CRC. After stratifying by VDBP, high levels of total, free and bioavailable 25(OH)D were associated significantly with decreased CRC risk among participants with circulating VDBP below the median. These findings indicate that VDBP is not directly associated with the risk of CRC, but it modulates circulating free and bioavailable 25(OH)D concentration. PMID:25609140

Impaired Angiogenesis and Mobilization of Circulating Angiogenic Cells in HIF-1α Heterozygous-Null Mice after Burn Wounding

PubMed Central

Zhang, Xianjie; Liu, Lixin; Wei, Xiaofei; Tan, Yee Sun; Tong, Lana; Chang, Ryan; Ghanamah, Mohammed S.; Reinblatt, Maura; Marti, Guy P.; Harmon, John W.; Semenza, Gregg L.

2014-01-01

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that controls vascular responses to hypoxia and ischemia. In this study, mice that were heterozygous for a null allele at the locus encoding the HIF-1α subunit (HET mice) and their wild type (WT) littermates were subjected to thermal injury involving 10% of body surface area. HIF-1α protein levels were increased in burn wounds of WT but not of HET mice on day 2. Serum levels of stromal-derived factor 1α, which binds to CXCR4, were increased on day 2 in WT but not in HET mice. Circulating angiogenic cells were also increased on day 2 in WT but not in HET mice and included CXCR4+Sca1+ cells. Laser Doppler perfusion imaging demonstrated increased blood flow in burn wounds of WT but not HET mice on day 7. Immunohistochemistry on day 7 revealed a reduced number of CD31+ vessels at the healing margin of burn wounds in HET as compared to WT mice. Vessel maturation was also impaired in wounds of HET mice as determined by the number of α-smooth muscle actin-positive vessels on day 21. The remaining wound area on day 14 was significantly increased in HET mice compared to WT littermates. The percentage of healed wounds on day 14 was significantly decreased in HET mice. These data delineate a signaling pathway by which HIF-1 promotes angiogenesis during burn wound healing. PMID:20163569

Changes in ocean circulation and carbon storage are decoupled from air-sea CO2 fluxes

NASA Astrophysics Data System (ADS)

Marinov, I.; Gnanadesikan, A.

2011-02-01

The spatial distribution of the air-sea flux of carbon dioxide is a poor indicator of the underlying ocean circulation and of ocean carbon storage. The weak dependence on circulation arises because mixing-driven changes in solubility-driven and biologically-driven air-sea fluxes largely cancel out. This cancellation occurs because mixing driven increases in the poleward residual mean circulation result in more transport of both remineralized nutrients and heat from low to high latitudes. By contrast, increasing vertical mixing decreases the storage associated with both the biological and solubility pumps, as it decreases remineralized carbon storage in the deep ocean and warms the ocean as a whole.

Changes in ocean circulation and carbon storage are decoupled from air-sea CO2 fluxes

NASA Astrophysics Data System (ADS)

Marinov, I.; Gnanadesikan, A.

2010-11-01

The spatial distribution of the air-sea flux of carbon dioxide is a poor indicator of the underlying ocean circulation and of ocean carbon storage. The weak dependence on circulation arises because mixing-driven changes in solubility-driven and biologically-driven air-sea fluxes largely cancel out. This cancellation occurs because mixing driven increases in the poleward residual mean circulation results in more transport of both remineralized nutrients and heat from low to high latitudes. By contrast, increasing vertical mixing decreases the storage associated with both the biological and solubility pumps, as it decreases remineralized carbon storage in the deep ocean and warms the ocean as a whole.

Visible light optical coherence tomography for microvascular oximetry in ocular circulation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chen, Siyu; Yi, Ji; Zhang, Hao F.

2016-03-01

Visible light optical coherence tomography (vis-OCT) is intrinsically capable of optical determination of blood oxygen saturation (sO2). Thanks to its 3D sectioning ability, confounding factors that plaque multi-wavelength fundus photography can be avoided. We further supplemented it with motion-enhanced angiography (vis-OCTA), which allowed us to resolve retinal micro vessels without losing spectral information. As a result, spectroscopic vis-OCTA can extract microvascular sO2 which are generally inaccessible. Here we extend the theoretical formulation of vis-OCTA oximetry to include optical attenuation, scattering and motion contrast. The model allows robust estimation of sO2, while also promising reduction of illuminating power to 1/3 of current value of ~1 mW. To demonstrate the capability of our approach, we performed oxygen challenge while taking vis-OCTA measurements on rat ocular circulation in vivo. We supplied the experiment animal with the following gas mixture: normal air, 5% CO2 air, pure O2 and 10% O2 air. For each inhalation gas, the OCTA measurements were compared with peripheral capillary sO2 (spO2) provided by a pulse oximeter. The retinal artery sO2 measurements corresponded well with spO2 reading as expected (R2 = 0.87). We found that both retinal and choroidal circulation sO2 moderately increased when we supplied 5% CO2 air. 100% O2 inhalation significantly increased both artery and vein oxygenation. On the contrary, 10% O2 air could deplete the oxygen reservoir in the circulation and lead to low sO2 readings.

Spatial and temporal in vivo analysis of circulating and sessile immune cells in mosquitoes: hemocyte mitosis following infection

PubMed Central

2013-01-01

Background Mosquitoes respond to infection by mounting immune responses. The primary regulators of these immune responses are cells called hemocytes, which kill pathogens via phagocytosis and via the production of soluble antimicrobial factors. Mosquito hemocytes are circulated throughout the hemocoel (body cavity) by the swift flow of hemolymph (blood), and data show that some hemocytes also exist as sessile cells that are attached to tissues. The purpose of this study was to create a quantitative physical map of hemocyte distribution in the mosquito, Anopheles gambiae, and to describe the cellular immune response in an organismal context. Results Using correlative imaging methods we found that the number of hemocytes in a mosquito decreases with age, but that regardless of age, approximately 75% of the hemocytes occur in circulation and 25% occur as sessile cells. Infection induces an increase in the number of hemocytes, and tubulin and nuclear staining showed that this increase is primarily due to mitosis and, more specifically, autonomous cell division, by circulating granulocytes. The majority of sessile hemocytes are present on the abdominal wall, although significant numbers of hemocytes are also present in the thorax, head, and several of the appendages. Within the abdominal wall, the areas of highest hemocyte density are the periostial regions (regions surrounding the valves of the heart, or ostia), which are ideal locations for pathogen capture as these are areas of high hemolymph flow. Conclusions These data describe the spatial and temporal distribution of mosquito hemocytes, and map the cellular response to infection throughout the hemocoel. PMID:23631603

Assessing water quality of the Chesapeake Bay by the impact of sea level rise and warming

NASA Astrophysics Data System (ADS)

Wang, P.; Linker, L.; Wang, H.; Bhatt, G.; Yactayo, G.; Hinson, K.; Tian, R.

2017-08-01

The influence of sea level rise and warming on circulation and water quality of the Chesapeake Bay under projected climate conditions in 2050 were estimated by computer simulation. Four estuarine circulation scenarios in the estuary were run using the same watershed load in 1991-2000 period. They are, 1) the Base Scenario, which represents the current climate condition, 2) a Sea Level Rise Scenario, 3) a Warming Scenario, and 4) a combined Sea Level Rise and Warming Scenario. With a 1.6-1.9°C increase in monthly air temperatures in the Warming Scenario, water temperature in the Bay is estimated to increase by 0.8-1°C. Summer average anoxic volume is estimated to increase 1.4 percent compared to the Base Scenario, because of an increase in algal blooms in the spring and summer, promotion of oxygen consumptive processes, and an increase of stratification. However, a 0.5-meter Sea Level Rise Scenario results in a 12 percent reduction of anoxic volume. This is mainly due to increased estuarine circulation that promotes oxygen-rich sea water intrusion in lower layers. The combined Sea Level Rise and Warming Scenario results in a 10.8 percent reduction of anoxic volume. Global warming increases precipitation and consequently increases nutrient loads from the watershed by approximately 5-7 percent. A scenario that used a 10 percent increase in watershed loads and current estuarine circulation patterns yielded a 19 percent increase in summer anoxic volume, while a scenario that used a 10 percent increase in watershed loads and modified estuarine circulation patterns by the aforementioned sea level rise and warming yielded a 6 percent increase in summer anoxic volume. Impacts on phytoplankton, sediments, and water clarity were also analysed.

Interaction of Hurricane Katrina with Optically Complex Water in the Gulf of Mexico: Interpretation Using Satellite-Derived Inherent Optical Properties and Chlorophyll Concentration

DTIC Science & Technology

2009-04-01

Shelf, and into the Gulf of Mexico, empirically derived chl ; increases were observed in the Tortugas Gyre circulation feature, and in adjacent...Mexico, empirically derived chl a increases were observed in the Tortugas Gyre circulation feature, and in adjacent waters. Analy- sis of the...hurricane interaction also influenced the Tortugas Gyre, a recognized circulation feature in the southern Gulf of Mexico induced by the flow of the

Detection of Galactomannan Antigenemia in Patients Receiving Piperacillin-Tazobactam and Correlations between In Vitro, In Vivo, and Clinical Properties of the Drug-Antigen Interaction

PubMed Central

Walsh, Thomas J.; Shoham, Shmuel; Petraitiene, Ruta; Sein, Tin; Schaufele, Robert; Kelaher, Amy; Murray, Heidi; Mya-San, Christine; Bacher, John; Petraitis, Vidmantas

2004-01-01

Recent case reports describe patients receiving piperacillin-tazobactam who were found to have circulating galactomannan detected by the double sandwich enzyme-linked immunosorbent assay (ELISA) system, leading to the false presumption of invasive aspergillosis. Since this property of piperacillin-tazobactam and galactomannan ELISA is not well understood, we investigated the in vitro, in vivo, and clinical properties of this interaction. Among the 12 reconstituted antibiotics representing four classes of antibacterial compounds that are commonly used in immunocompromised patients, piperacillin-tazobactam expressed a distinctively high level of galactomannan antigen in vitro (P = 0.001). After intravenous infusion of piperacillin-tazobactam into rabbits, the serum galactomannan index (GMI) in vivo changed significantly (P = 0.0007) from a preinfusion mean baseline value of 0.27 to a mean GMI of 0.83 by 30 min to slowly decline to a mean GMI of 0.44 24 h later. Repeated administration of piperacillin-tazobactam over 7 days resulted in accumulation of circulating galactomannan to a mean peak GMI of 1.31 and a nadir of 0.53. Further studies revealed that the antigen reached a steady state by the third day of administration of piperacillin-tazobactam. Twenty-six hospitalized patients with no evidence of invasive aspergillosis who were receiving antibiotics and ten healthy blood bank donors were studied for expression of circulating galactomannan. Patients (n = 13) receiving piperacillin-tazobactam had significantly greater mean serum GMI values (0.74 ± 0.14) compared to patients (n = 13) receiving other antibiotics (0.14 ± 0.08) and compared to healthy blood bank donors (0.14 ± 0.06) (P < 0.001). Five (38.5%) of thirteen patients receiving piperacillin-tazobactam had serum GMI values > 0.5 compared to none of thirteen subjects receiving other antibiotics (P = 0.039) and to none of ten healthy blood bank donors (P = 0.046). These data demonstrate that among antibiotics that are commonly used in immunocompromised patients, only piperacillin-tazobactam contains significant amounts of galactomannan antigen in vitro, that in animals receiving piperacillin-tazobactam circulating galactomannan antigen accumulates in vivo to significantly increased and sustained levels, and that some but not all patients receiving this antibiotic will demonstrate circulating galactomannan above the threshold considered positive for invasive aspergillosis by the recently licensed double sandwich ELISA. PMID:15472335

Elemental maps in human allantochorial placental vessels cells: 1. High K + and acetylcholine effects

NASA Astrophysics Data System (ADS)

Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.

2003-09-01

Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, J.F.; Ebbe, S.N.; Hollander, L.

1982-05-01

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples showmore » a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less