Serum calprotectin levels correlate with biochemical and histological markers of disease activity in TNBS colitis

PubMed Central

Cury, Didia Bismara; Mizsputen, Sender Jankiel; Versolato, Clara; Miiji, Luciana Odashiro; Pereira, Edson; Delboni, Maria Aparecida; Schor, Nestor; Moss, Alan C.

2014-01-01

Background and aim Serum calprotectin is elevated in patients with inflammatory bowel disease (IBD). Whether it correlates other markers of disease activity is unknown. The aim of this study was to correlate serum calprotectin with biochemical and histological measures of intestinal inflammation. Materials and methods TNBS colitis was induced in wistar rats, and serial blood samples were collected at 0, 3, and 12 days. Animals were subsequently sacrificed for pathological evaluation at day 12. Serum calprotectin and cytokines were measured by ELISA. Pathologic changes were classified at the macroscopic and microscopic levels. Results TNBS colitis induced elevated serum calprotectin, TNF and IL-6 within 24 h. Levels of serum calprotectin remained elevated in parallel to persistence of loose stool and weight loss to day 12. Serum calprotectin levels correlated with serum levels of TNF-α and IL6 (p < 0.001), but not CRP. Animals with liquid stool had significantly higher levels of serum calprotectin than control animals. There was a correlation between macroscopic colitis scores, and levels of serum calprotectin. Conclusion Serum calprotectin levels correlate with biochemical and histological markers of inflammation in TNBS colitis. This biomarker may have potential for diagnostic use in patients with IBD. PMID:23685388

Caribbean mangroves adjust to rising sea level through biotic controls on change in soil elevation

USGS Publications Warehouse

McKee, K.L.; Cahoon, D.R.; Feller, Ilka C.

2007-01-01

Aim The long-term stability of coastal ecosystems such as mangroves and salt marshes depends upon the maintenance of soil elevations within the intertidal habitat as sea level changes. We examined the rates and processes of peat formation by mangroves of the Caribbean Region to better understand biological controls on habitat stability. Location Mangrove-dominated islands on the Caribbean coasts of Belize, Honduras and Panama were selected as study sites. Methods Biological processes controlling mangrove peat formation were manipulated (in Belize) by the addition of nutrients (nitrogen or phosphorus) to Rhizophora mangle (red mangrove), and the effects on the dynamics of soil elevation were determined over a 3-year period using rod surface elevation tables (RSET) and marker horizons. Peat composition and geological accretion rates were determined at all sites using radiocarbon-dated cores. Results The addition of nutrients to mangroves caused significant changes in rates of mangrove root accumulation, which influenced both the rate and direction of change in elevation. Areas with low root input lost elevation and those with high rates gained elevation. These findings were consistent with peat analyses at multiple Caribbean sites showing that deposits (up to 10 m in depth) were composed primarily of mangrove root matter. Comparison of radiocarbon-dated cores at the study sites with a sea-level curve for the western Atlantic indicated a tight coupling between peat building in Caribbean mangroves and sea-level rise over the Holocene. Main conclusions Mangroves common to the Caribbean region have adjusted to changing sea level mainly through subsurface accumulation of refractory mangrove roots. Without root and other organic inputs, submergence of these tidal forests is inevitable due to peat decomposition, physical compaction and eustatic sea-level rise. These findings have relevance for predicting the effects of sea-level rise and biophysical processes on tropical mangrove ecosystems.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

Uric Acid Level and Elevated Blood Pressure in U.S. Adolescents

PubMed Central

Loeffler, Lauren F.; Navas-Acien, Ana; Brady, Tammy M.; Miller, Edgar R.; Fadrowski, Jeffrey J.

2012-01-01

Uric acid is associated with cardiovascular disease (CVD) and CVD risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of U.S. adolescents, a population with a relatively low prevalence of CVD and CVD risk factors. Among 6,036 adolescents 12-17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) the mean age was 14.5 years, 17% were obese (body mass index [BMI] ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity and BMI percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex and height, for each 0.1 mg/dL increase in uric acid level was 1.38 (95% confidence interval [CI], 1.16 to 1.65). Compared to <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI, 1.38 to 3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy U.S. adolescents. Additional prospective studies and clinical trials are needed to determine if uric acid is merely a marker in a complex metabolic pathway, or causal of hypertension and thus a potential screening and therapeutic target. PMID:22353609

B Lymphocyte Stimulator Levels in Systemic Lupus Erythematosus: Higher Circulating Levels in African American Patients and Increased Production after Influenza Vaccination in Patients with Low Baseline Levels

PubMed Central

Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.

2011-01-01

Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709

Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions

PubMed Central

Jeon, Yejoo; Choi, Yun Suk; Jang, Eun Sun; Kim, Jin Wook; Jeong, Sook-Hyang

2017-01-01

Background/Aims α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. Methods Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. Results One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. Conclusions Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed. PMID:27609486

The magnitude of elevated maternal serum human chorionic gonadotropin and pregnancy complications.

PubMed

Sharony, Reuven; Zipper, Oren; Amichay, Keren; Wiser, Amir; Kidron, Debora; Biron-Shental, Tal; Maymon, Ron

2017-07-01

This study assessed the correlation between the magnitude of the elevation in maternal serum human chorionic gonadotropin (MShCG) levels and pregnancy complications. Among 80,716 screened pregnancies, 120 with moderately elevated MShCG (3.00-5.99 MoM) were compared to 84 with extremely elevated MShCG >6.00 MoM. A control series of 120 women with normal MShCG (<3.00 MoM) were matched. Rates of intrauterine growth restriction, preterm labour, antepartum foetal death (APFD), pre-eclampsia, and placental abruption were analysed. We found that the study group had more adverse outcomes than the control group (73/204 [36%] vs. 18/120 [15%]; p < .0001). The rate was higher in the extremely elevated group than in the moderately elevated group (43/84 [51%] vs. 30/120 [25%]; p < .0001). All 12 cases of APFD (14%) occurred among the extremely elevated series. In conclusion, adverse pregnancy outcomes are more common in women with extremely elevated MShCG. The patients should receive counselling regarding this trend and undergo close pregnancy monitoring. Impact statement • What is already known on this subject?In addition to its contribution to Down syndrome (DS) screening, maternal serum human chorionic gonadotropin (MShCG) levels are a marker for pregnancy complications such as intrauterine growth restriction (IUGR), preterm labour (PTL), antepartum fatal death (APFD), pre-eclampsia (PE), placental abruption (PA) and fetal malformations with or without chromosomal aberrations. • What the results of this study add? We found that in the presence of elevated MShCG levels, the incidence of IUGR and PTL increased. PE increased clinically, but statistical significance was seen only when MShCG was extremely elevated (≥ 6.00 MoM). APFD and PA were associated with very high MShCG levels only. • What the implications are of these findings for clinical practice and/or further research? Women with high MShCG levels should be counselled. In case of very high levels (≥ 6.00 MoM), the risk of APFD and PA should be discussed. The pregnancy should be monitored for IUGR, PTL and PE. In view of the limited number of enrolled patients with very high levels of MShCG, the experience of other institutions is needed to corroborate these findings.

Hyperuricemia in the inhabitants of the Marshall Islands

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

Adams, W.H.; Harper, J.A.; Heotis, P.M.

1984-06-01

Annual medical examinations are conducted by Brookhaven National Laboratory (BNL) for a population of Marshallese who were accidentally exposed to radioactive fallout in 1954, for a comparison population, and for all inhabitants of the atolls of Rongelap and Utirik. Disease surveillance includes analysis of serum samples. Elevated serum uric acid (SUA) levels are common along Pacific populations, and modifying environmental factors have been investigated as a cause for this finding. The authors have studied SUA levels of people living in the Marshall Islands, and have found elevated values similar to those reported for other Micronesian populations. The nearly Gaussian distributionmore » of individual serum uric acid values for men, and for women less than or equal to45 years of age, indicates that the elevation is due to a regularized increase in serum uric acid rather than to a subpopulation that has pathologic hyperuricemia. The higher serum uric acid levels appear, therefore, to be normal for the Marshallese, a conclusion supported by the infrequency of clinical gout in the population tested.« less

C-reactive protein levels: a prognostic marker for patients with head and neck cancer?

PubMed Central

2010-01-01

Background Recent advances in understanding complex tumor interactions have led to the discovery of an association between inflammation and cancer, in particular for colon and lung cancer, but only a very few have dealt with oral cancer. Therefore, the aim of the current study was to investigate the significance of preoperative C-reactive protein (CRP) levels as a parameter for development of lymph node metastases or recurrence. Materials and methods In 278 patients with oral cancer, preoperative CRP levels were compared with development of recurrence and metastasis. Results In 27 patients from the normal CRP group, and in 21 patients from the elevated CRP group, local recurrence was observed. Concerning lymph node metastases, 37 patients were in the normal group and 9 patients in the elevated CRP group. No significant correlation could be found between elevated CRP levels and metastasis (p = 0.468) or recurrence (p = 0.137). Conclusion Our findings do not appear to support a correlation between preoperative CRP levels and development of recurrence or metastases. In further studies, CRP levels in precancerous lesions and in Human Papilloma Virus (HPV) positive patients with oral squamous cell carcinoma (SCC) should be studied. PMID:20673375

Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

PubMed Central

Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

2012-01-01

Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

Short-Term Moderately Elevated Intraocular Pressure Is Associated With Elevated Scotopic Electroretinogram Responses

PubMed Central

Choh, Vivian; Gurdita, Akshay; Tan, Bingyao; Prasad, Ratna C.; Bizheva, Kostadinka; Joos, Karen M.

2016-01-01

Purpose Moderately elevated intraocular pressure (IOP) is a risk factor for open-angle glaucoma. Some patients suffer glaucoma despite clinically measured normal IOPs. Fluctuations in IOP may have a significant role since IOPs are higher during sleep and inversion activities. Controlled transient elevations of IOPs in rats over time lead to optic nerve structural changes that are similar to the early changes observed in constant chronic models of glaucoma. Because early intervention decreases glaucoma progression, this study was done to determine if early physiological changes to the retina could be detected with noninvasive electrophysiological and optical imaging tests during moderately elevated IOP. Methods Intraocular pressures were raised to moderately high levels (35 mm Hg) in one eye of Sprague-Dawley rats while the other (control) eye was untreated. One group of rats underwent scotopic threshold response (STR) and electroretinogram (ERG) testing, while another 3 groups underwent optical coherence tomography (OCT) imaging, Western blot, or histologic evaluation. Results The amplitudes of the STR and ERG responses in eyes with moderately elevated IOPs were enhanced compared to the values before IOP elevation, and compared to untreated contralateral eyes. Structural changes to the optic nerve also occurred during IOP elevation. Conclusions Although ischemic IOP elevations are well-known to globally reduce components of the scotopic ERG, acute elevation in rats to levels often observed in untreated glaucoma patients caused an increase in these parameters. Further exploration of these phenomena may be helpful in better understanding the mechanisms mediating early retinal changes during fluctuating or chronically elevated IOP. PMID:27100161

Relationship between inflammation, insulin resistance and type 2 diabetes: 'cause or effect'?

PubMed

Greenfield, Jerry R; Campbell, Lesley V

2006-05-01

Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.

Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

PubMed Central

Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Ma, Xinlong; Liu, Zhongjun; Liu, Xiaoguang

2014-01-01

Background Dickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma. Methods The mRNA and protein levels of DKK1 and β-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results Both DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions Elevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma. PMID:25144498

Tumor Necrosis Factor-Alpha Stimulates Cytokine Expression and Transient Sensitization of Trigeminal Nociceptive Neurons

PubMed Central

Durham, Zachary L.; Hawkins, Jordan L.; Durham, Paul L.

2016-01-01

Objective Elevated levels of tumor necrosis factor-alpha (TNF-α) in the capsule of the temporomandibular joint (TMJ) are implicated in the underlying pathology of temporomandibular disorders (TMD). TMD are a group of conditions that result in pain in the TMJ and/or muscles of mastication, and are associated with significant social and economic burdens. The goal of this study was to investigate the effect of elevated TNF-α levels in the TMJ capsule on nocifensive behavioral response to mechanical stimulation of trigeminal neurons and regulation of cytokines within the trigeminal ganglion. Design Male Sprague-Dawley rats were injected bilaterally in the TMJ capsule with TNF-α and changes in nocifensive head withdrawal responses to mechanical stimulation of cutaneous tissue directly over the capsule was determined using von Frey filaments. Cytokine levels in trigeminal ganglia were determined by protein array analysis at several time points post injection and correlated to nocifensive behavior. Results TNF-α caused a significant increase in the average number of nocifensive responses when compared to naive and vehicle treated animals 2 hours post injection, but levels returned to control levels at 24 hours. Based on array analysis, the levels of eight cytokines were significantly elevated above vehicle control levels at 2 hours following TNF-α injection, but all eight had returned to the vehicle control levels after 24 hours. Conclusions Our findings provide evidence that elevated levels of TNF-α in the joint capsule, which is reported to occur in TMD, promotes nociception in trigeminal ganglia neurons via a mechanism that temporally correlates with differential regulation of several cytokines. PMID:27836101

Global DEM Errors Underpredict Coastal Vulnerability to Sea Level Rise and Flooding

NASA Astrophysics Data System (ADS)

Kulp, Scott; Strauss, Benjamin

2016-04-01

Elevation data based on NASA's Shuttle Radar Topography Mission (SRTM) have been widely used to evaluate threats from global sea level rise, storm surge, and coastal floods. However, SRTM data are known to include large vertical errors in densely urban or densely vegetated areas. The errors may propagate to derived land and population exposure assessments. We compare assessments based on SRTM data against references employing high-accuracy bare-earth elevation data generated from lidar data available for coastal areas of the United States. We find that both 1-arcsecond and 3-arcsecond horizontal resolution SRTM data systemically underestimate exposure across all assessed spatial scales and up to at least 10m above the high tide line. At 3m, 1-arcsecond SRTM underestimates U.S. population exposure by more than 60%, and under-predicts population exposure in 90% of coastal states, 87% of counties, and 83% of municipalities. These fractions increase with elevation, but error medians and variability fall to lower levels, with national exposure underestimated by just 24% at 10m. Results using 3-arcsecond SRTM are extremely similar. Coastal analyses based on SRTM data thus appear to greatly underestimate sea level and flood threats, especially at lower elevations. However, SRTM-based estimates may usefully be regarded as providing lower bounds to actual threats. We additionally assess the performance of NOAA's Global Land One-km Base Elevation Project (GLOBE), another publicly-available global DEM, but do not reach any definitive conclusion because of the spatial heterogeneity in its quality.

Early Elevation of Serum TNFα is Associated with Poor Outcome in Subarachnoid Hemorrhage

PubMed Central

Chou, Sherry HY.; Feske, Steven K.; Atherton, Juli; Konigsberg, Rachael G.; De Jager, Philip L.; Du, Rose; Lo, Eng H.; Ning, MingMing

2013-01-01

Objective Subarachnoid hemorrhage (SAH) is associated with inflammation which may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6) are associated with vasospasm and poor outcome in SAH. Methods In 52 consecutive SAH subjects, we compared TNFα and IL-6 levels on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to poor outcome at 3- and 6-months. Vasospasm was defined as >50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score >2. Results Elevated TNFα on post-SAH days 2–3 was associated with poor 3-month outcome (p=0.0004). Global elevation of TNFα over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (p=0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNFα nor IL-6 levels were associated with vasospasm. Conclusions Elevation in serum TNFα on post-SAH days 2–3 and global elevation of TNFα over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNFα in SAH-related brain injury and its potential as a SAH outcome biomarker. PMID:22918199

Three Gorges Dam: Impact of Water Level Changes on the Density of Schistosome-Transmitting Snail Oncomelania hupensis in Dongting Lake Area, China

PubMed Central

Wu, Jin-Yi; Zhou, Yi-Biao; Chen, Yue; Liang, Song; Li, Lin-Han; Zheng, Sheng-Bang; Zhu, Shao-ping; Ren, Guang-Hui; Song, Xiu-Xia; Jiang, Qing-Wu

2015-01-01

Background Schistosomiasis remains an important public health issue in China and worldwide. Oncomelania hupensis is the unique intermediate host of schistosoma japonicum, and its change influences the distribution of S. japonica. The Three Gorges Dam (TGD) has substantially changed the ecology and environment in the Dongting Lake region. This study investigated the impact of water level and elevation on the survival and habitat of the snails. Methods Data were collected for 16 bottomlands around 4 hydrological stations, which included water, density of living snails (form the Anxiang Station for Schistosomiasis Control) and elevation (from Google Earth). Based on the elevation, sixteen bottomlands were divided into 3 groups. ARIMA models were built to predict the density of living snails in different elevation areas. Results Before closure of TGD, 7 out of 9 years had a water level beyond the warning level at least once at Anxiang hydrological station, compared with only 3 out of 10 years after closure of TGD. There were two severe droughts that happened in 2006 and 2011, with much fewer number of flooding per year compared with other study years. Overall, there was a correlation between water level changing and density of living snails variation in all the elevations areas. The density of living snails in all elevations areas was decreasing after the TGD was built. The relationship between number of flooding per year and the density of living snails was more pronounced in the medium and high elevation areas; the density of living snails kept decreasing from 2003 to 2014. In low elevation area however, the density of living snails decreased after 2003 first and turned to increase after 2011. Our ARIMA prediction models indicated that the snails would not disappear in the Dongting Lake region in the next 7 years. In the low elevation area, the density of living snails would increase slightly, and then stabilize after the year 2017. In the medium elevation region, the change of the density of living snails would be more obvious and would increase till the year 2020. In the high elevation area, the density of living snails would remain stable after the year 2015. Conclusion The TGD influenced water levels and reduced the risk of flooding and the density of living snails in the study region. Based on our prediction models, the density of living snails in all elevations tends to be stabilized. Control of S. japonica would continue to be an important task in the study area in the coming decade. PMID:26114956

Low cortisol levels in blood from dairy cows with ketosis: a field study

PubMed Central

2010-01-01

Background An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Methods Cortisol, insulin, β-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. Results No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). Conclusions The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research. PMID:20487518

B cell-stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B cell lymphoma

PubMed Central

Breen, Elizabeth Crabb; Hussain, Shehnaz K.; Magpantay, Larry; Jacobson, Lisa P.; Detels, Roger; Rabkin, Charles S.; Kaslow, Richard A.; Variakojis, Daina; Bream, Jay H.; Rinaldo, Charles R.; Ambinder, Richard F.; Martínez-Maza, Otoniel

2011-01-01

Background The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine if elevated serum levels of molecules associated with B cell activation precede the diagnosis of AIDS-associated NHL. Methods Serum levels of B cell activation-associated molecules, interleukin-6 (IL6), interleukin-10 (IL10), soluble CD23 (sCD23), soluble CD27 (sCD27), soluble CD30 (sCD30), C-reactive protein (CRP), and IgE were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to three time points per subject, 0–5 years prior to AIDS-NHL diagnosis. Results Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared to HIV+ controls or to AIDS controls, after adjusting for CD4 T cell number. Elevated serum levels of B cell activation-associated molecules were seen to be associated with the development of systemic (non-CNS) NHL, but not with the development of primary CNS lymphoma. Conclusions Levels of certain B cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B cell activation contributes to the development of these hematologic malignancies. Impact Marked differences in serum levels of several molecules are seen for several years pre-diagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL. PMID:21527584

Relations of Depressive Symptoms and Antidepressant Use to Body Mass Index and Selected Biomarkers for Diabetes and Cardiovascular Disease

PubMed Central

Balasubramanian, Raji; Pagoto, Sherry L.; Schneider, Kristin L.; Hébert, James R.; Phillips, Lawrence S.; Goveas, Joseph S.; Culver, Annie L.; Olendzki, Barbara C.; Beck, James; Smoller, Jordan W.; Sepavich, Deidre M.; Ockene, Judith K.; Uebelacker, Lisa; Zorn, Martha; Liu, Simin

2013-01-01

Objectives. We investigated whether depressive symptoms and antidepressant use are associated with biomarkers for glucose dysregulation and inflammation, body mass index (BMI), and waist circumference. Methods. Postmenopausal women were recruited into the Women’s Health Initiative from 1993 to 1998, and data were collected at regular intervals through 2005. We used multiple linear regression models to examine whether depressive symptoms and antidepressant use are associated with BMI, waist circumference, and biomarkers. Results. Analysis of data from 71 809 women who completed all relevant baseline and year 3 assessments showed that both elevated depressive symptoms and antidepressant use were significantly associated with higher BMI and waist circumference. Among 1950 women, elevated depressive symptoms were significantly associated with increased insulin levels and measures of insulin resistance. Analyses of baseline data from 2242 women showed that both elevated depressive symptoms and antidepressant use were associated with higher C-reactive protein levels. Conclusions. Monitoring body habitus and other biomarkers among women with elevated depression symptoms or taking antidepressant medication may be prudent to prevent diabetes and cardiovascular disease. PMID:23763394

In-vitro Wound Healing Effect of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor from Plant

PubMed Central

Karna, Sandeep

2017-01-01

Background: Prostaglandins (PGs) have short existence in vivo because they are rapidly metabolized by NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) to 15-ketoprostaglandins. Inhibition of 15-PGDH causes elevated level of PGE2 in cellular system. It will be valuable for the therapeutic management of diseases requiring elevated PGE2 levels, like wound healing. Objective: Ninety-eight plant samples were screened for the discovery of potent 15-PGDH inhibitor. Among them, top five plant extracts as potent 15-PGDH inhibitor were chosen to determine PGE2 release from HaCaT (Keratinocyte cell line) cell line. Finally, top 15-PGDH inhibitor was selected to evaluate in vitro wound healing effect on HaCaT scratch model. Method: The inhibitory activity for 15-PGDH inhibitors was evaluated using fluorescence spectrophotometer by measuring the formation of NADH at 468 nm following excitation at 340 nm. Cell viability assay and PGE2 release was evaluated in HaCaT cell line after treatment of 15-PGDH inhibitors. Scratches were made using sterile 200 μL on HaCaT cell and wound-healing effect was evaluated after treatment of 15-PGDH inhibitor. Results: 15-PGDH inhibitors elevated PGE2 levels in concentration-dependent manner. Ethanol extract of Artocarpus heterophyllus (EEAH), the most potent 15-PGDH inhibitor (IC50 = 0.62 µg/mL) with least cytotoxicity (IC50 = 670 µg/ml), elevated both intracellular and extracellular PGE2 levels. EEAH facilitated in-vitro wound healing in a HaCaT (Keratinocyte cell line) scratch model. Conclusion: EEAH might apply to treat dermal wounds by elevating PGE2 levels via COX-1 induction and 15-PGDH inhibition. SUMMARY Biological inactivation of 15-PGDH causes elevated level of PGE2 which will be useful for the management of disease that requires elevated level of PGE2. Abbreviations used: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase, COX: Cyclooxygenase, DTT: Dithiothreitol, DMEM: Dulbecco's modified Eagle's media, EEAH: Ethanol extract of Artocarpus heterophyllus, MRP4: Multidrug resistance 4, PGs: Prostaglandins, PGT: Prostaglandin transporter, SDS: Sodium dodecylsulfate PMID:28479736

Quantification of extracellular levels of corticosterone in the basolateral amygdaloid complex of freely-moving rats: a dialysis study of circadian variation and stress-induced modulation.

PubMed

Bouchez, Gaëlle; Millan, Mark J; Rivet, Jean-Michel; Billiras, Rodolphe; Boulanger, Raphaël; Gobert, Alain

2012-05-03

Corticosterone influences emotion and cognition via actions in a diversity of corticolimbic structures, including the amygdala. Since extracellular levels of corticosterone in brain have rarely been studied, we characterized a specific and sensitive enzymatic immunoassay for microdialysis quantification of corticosterone in the basolateral amygdaloid complex of freely-moving rats. Corticosterone levels showed marked diurnal variation with an evening (dark phase) peak and stable, low levels during the day (light phase). The "anxiogenic agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in dialysis levels of corticosterone in basolateral amygdaloid complex. They likewise increased dialysis levels of dopamine and noradrenaline, but not serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml, the elevation provoked by forced-swim was ca. 20-fold and this increase was abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone levels in basolateral amygdaloid complex were abrogated by combined but not separate administration of the corticotrophin releasing factor(1) (CRF(1)) receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor antagonist, SSR149,415. Underpinning their specificity, they did not block forced-swim-induced elevations in dopamine and noradrenaline. In conclusion, extracellular levels of corticosterone in the basolateral amygdaloid complex display marked diurnal variation. Further, they are markedly elevated by acute stressors, the effects of which are mediated (in contrast to concomitant elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b) receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

PubMed Central

Shantha Kumara, H M C; Gaita, David; Miyagaki, Hiromichi; Yan, Xiaohong; Hearth, Sonali AC; Njoh, Linda; Cekic, Vesna; Whelan, Richard L

2016-01-01

AIM To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). METHODS CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis. PMID:27574553

Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

TRPV1: Contribution to Retinal Ganglion Cell Apoptosis and Increased Intracellular Ca2+ with Exposure to Hydrostatic Pressure

PubMed Central

Sappington, Rebecca M.; Sidorova, Tatiana; Long, Daniel J.; Calkins, David J.

2013-01-01

Purpose Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to pressure sensing and Ca2+-dependent cell death in other systems, also contributes to pressure-induced RGC death and whether this contribution involves Ca2+. Methods trpv1 mRNA expression in RGCs was probed with the use of PCR and TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin) and agonism (capsaicin) were used to probe how TRPV1 activation affects the survival of isolated RGCs at ambient and elevated hydrostatic pressure (+70 mm Hg). Finally, for RGCs under pressure, the authors tested whether EGTA chelation of Ca2+ improves survival and whether, with the Ca2+ dye Fluo-4 AM, TRPV1 contributes to increased intracellular Ca2+. Results RGCs express trpv1 mRNA, with robust TRPV1 protein localization to the cell body and axon. For isolated RGCs under pressure, TRPV1 antagonism increased cell density and reduced apoptosis to ambient levels (P ≤ 0.05), whereas for RGCs at ambient pressure, TRPV1 agonism reduced density and increased apoptosis to levels for elevated pressure (P ≤ 0.01). Chelation of extracellular Ca2+ reduced RGC apoptosis at elevated pressure by nearly twofold (P ≤ 0.01). Exposure to elevated hydrostatic pressure induced a fourfold increase in RGC intracellular Ca2+ that was reduced by half with TRPV1 antagonism. Finally, in the DBA/2 mouse model of glaucoma, levels of TRPV1 in RGCs increased with elevated IOP. Conclusions RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca2+. PMID:18952924

Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Sin, Don D.; Miller, Bruce E.; Duvoix, Annelyse; Man, S. F. Paul; Zhang, Xuekui; Silverman, Edwin K.; Connett, John E.; Anthonisen, Nicholas A.; Wise, Robert A.; Tashkin, Donald; Celli, Bartolome R.; Edwards, Lisa D.; Locantore, Nicholas; MacNee, William; Tal-Singer, Ruth; Lomas, David A.

2011-01-01

Rationale: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. Objectives: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. Methods: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Measurements and Main Results: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Conclusions: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:21216880

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo*

PubMed Central

Cuevas-Gonzalez, Juan Carlos; Lievanos-Estrada, Zahide; Vega-Memije, Maria Elisa; Hojyo-Tomoka, Maria Teresa; Dominguez-Soto, Luciano

2016-01-01

BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate. PMID:26982774

Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder

PubMed Central

Olsson, Sara K.; Samuelsson, Martin; Saetre, Peter; Lindström, Leif; Jönsson, Erik G.; Nordin, Conny; Engberg, Göran; Erhardt, Sophie; Landén, Mikael

2010-01-01

Background Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder. Methods We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography. Results Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers. Limitations The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease. Conclusion Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder. PMID:20420770

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries

PubMed Central

Rosenfield, Robert L.; Wroblewski, Kristen; Padmanabhan, Vasantha; Littlejohn, Elizabeth; Mortensen, Monica; Ehrmann, David A.

2013-01-01

Objective To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Design Prospective case-control study. Setting General clinical research center. Participant(s) Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Intervention(s) Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Main Outcome Measure(s) Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. Result(s) AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. Conclusion(s) AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool. PMID:22541936

Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide

PubMed Central

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J.; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A.; Taylor, Matthew R. G.; Lowes, Brian D.; Fuller, Maria; Benjamin, Elfrida R.; Sweetman, Lawrence

2014-01-01

Background Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X‐linked lysosomal disorder that is a risk factor for most types of heart disease. Methods and Results We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α‐galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow‐up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). Conclusions In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near‐term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. Clinical Trial Registration URL: clinicaltrials.gov. Unique Identifier: NCT01019629. PMID:24496231

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity.

PubMed

Nishijima, Tsuguo; Tajima, Kazuki; Yamashiro, Yoshihiro; Hosokawa, Keisuke; Suwabe, Akira; Takahashi, Kazuhiro; Sakurai, Shigeru

2016-04-01

(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) < 15 events/h), moderate (15 ≤ AHI < 30), and severe OSAS (AHI ≥ 30). Plasma s(P)RR levels were significantly elevated in all three OSAS groups compared to non-OSAS control subjects (AHI < 5) in the entire cohort and male subjects, whereas in female subjects, the significant elevation was found only in severe OSAS. Plasma s(P)RR levels were significantly correlated with AHI in both sexes, with a higher r value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients

PubMed Central

Kwon, Soon Hyo; Woollard, John R.; Saad, Ahmed; Garovic, Vesna D.; Zand, Ladan; Jordan, Kyra L.; Textor, Stephen C.

2017-01-01

ABSTRACT Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin—angiotensin blockade). After isolation from urine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.4 ± 6.4, 6.8 ± 3.4 and 6.3 ± 3.7%, respectively; P < 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target. PMID:27190371

Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants.

PubMed

Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

2016-01-01

Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa.

Elevated circulating endothelial cell-derived microparticle levels in patients with liver cirrhosis: a preliminary report

PubMed Central

Simon, Krzysztof Adam; Pazgan-Simon, Monika

2015-01-01

Aim of the study To determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites. Material and methods Sixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31+ CD42b– AN-V–) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31+ CD42b– AN-V+). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NOx–) levels were determined using a Greiss reaction method. Results Compared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher (p < 0.01), as well as NOx– (p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels. Conclusions Elevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients. PMID:28856256

Macrophage Migration Inhibitory Factor for the Early Prediction of Infarct Size

PubMed Central

Chan, William; White, David A.; Wang, Xin‐Yu; Bai, Ru‐Feng; Liu, Yang; Yu, Hai‐Yi; Zhang, You‐Yi; Fan, Fenling; Schneider, Hans G.; Duffy, Stephen J.; Taylor, Andrew J.; Du, Xiao‐Jun; Gao, Wei; Gao, Xiao‐Ming; Dart, Anthony M.

2013-01-01

Background Early diagnosis and knowledge of infarct size is critical for the management of acute myocardial infarction (MI). We evaluated whether early elevated plasma level of macrophage migration inhibitory factor (MIF) is useful for these purposes in patients with ST‐elevation MI (STEMI). Methods and Results We first studied MIF level in plasma and the myocardium in mice and determined infarct size. MI for 15 or 60 minutes resulted in 2.5‐fold increase over control values in plasma MIF levels while MIF content in the ischemic myocardium reduced by 50% and plasma MIF levels correlated with myocardium‐at‐risk and infarct size at both time‐points (P<0.01). In patients with STEMI, we obtained admission plasma samples and measured MIF, conventional troponins (TnI, TnT), high sensitive TnI (hsTnI), creatine kinase (CK), CK‐MB, and myoglobin. Infarct size was assessed by cardiac magnetic resonance (CMR) imaging. Patients with chronic stable angina and healthy volunteers were studied as controls. Of 374 STEMI patients, 68% had elevated admission MIF levels above the highest value in healthy controls (>41.6 ng/mL), a proportion similar to hsTnI (75%) and TnI (50%), but greater than other biomarkers studied (20% to 31%, all P<0.05 versus MIF). Only admission MIF levels correlated with CMR‐derived infarct size, ventricular volumes and ejection fraction (n=42, r=0.46 to 0.77, all P<0.01) at 3 day and 3 months post‐MI. Conclusion Plasma MIF levels are elevated in a high proportion of STEMI patients at the first obtainable sample and these levels are predictive of final infarct size and the extent of cardiac remodeling. PMID:24096574

RNA/DNA ratio and LPL and MyoD mRNA expressions in muscle of Oreochromis niloticus fed with elevated levels of palm oil

NASA Astrophysics Data System (ADS)

Ayisi, Christian Larbi; Zhao, Jinliang

2016-02-01

Palm oil is of great potential as one of the sustainable alternatives to fish oil (FO) in aquafeeds. In this present study, five isonitrogenous diets (32% crude protein) with elevated palm oil levels of 0%, 2%, 4%, 6% and 8% were used during an 8-week feeding trial to evaluate its effects on RNA/DNA ratio and lipoprotein lipase (LPL) and MyoD mRNA expressions in muscle of Oreochromis niloticus. The results showed that RNA, DNA content as well as ratio of RNA to DNA were significantly affected ( P < 0.05), in each case the highest was recorded in fish group subjected to 6% palm oil level. There was a strong positive correlation between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and specific growth rate (SGR), protein efficiency ratio (PER), while a negative correlation existed between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and feed conversion ratio (FCR). The mRNA expressions of LPL and MyoD in muscle were not significantly affected by the different palm oil levels, although the highest expression was observed in fish fed with 6% palm oil level. There also existed a strong positive correlation between the mRNA expression of LPL, MyoD and SGR, PER, while their correlation with FCR was negative. In conclusion, elevated palm oil affected the RNA, DNA concentration as well as RNA/DNA ratio significantly, although the mRNA expression of LPL and MyoD were not affected significantly by elevated palm oil levels.

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

PubMed Central

2011-01-01

Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment. PMID:22029888

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

PubMed Central

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia

2017-01-01

Background In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value. PMID:28562682

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

PubMed Central

Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

2015-01-01

Background. Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61–2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61–2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma. PMID:26618165

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

PubMed Central

Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1–4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis.

PubMed

Alcalai, Ronny; Planer, David; Culhaoglu, Afsin; Osman, Aydin; Pollak, Arthur; Lotan, Chaim

2007-02-12

Although troponin is considered a specific marker for the diagnosis of acute coronary syndrome (ACS), recent studies have shown troponin elevation in a variety of nonischemic conditions. Our aim was to determine the predictors for the diagnosis of ACS in the presence of an abnormal troponin level. All patients with abnormal troponin T levels were analyzed. Demographic and clinical data were collected and death was recorded. The study group was divided into 2 subgroups: ACS vs nonthrombotic troponin elevation. A multivariate logistic regression analysis was performed to define variables that predict the diagnosis of ACS. The positive predictive value (PPV) for ACS diagnosis was calculated, and a survival analysis was performed. During the study period, 615 patients had elevated troponin T levels. Only 326 patients (53%) received a main diagnosis of ACS, while 254 (41%) had nonthrombotic troponin elevation; for 35 patients (6%), the diagnosis was not conclusive. Positive predictors for the diagnosis of ACS were age between 40 and 70 years, history of hypertension or ischemic heart disease, normal renal function, and a troponin T level higher than 1.0 ng/mL. The overall PPV of troponin T for ACS diagnosis was only 56% (95% CI, 52%-60%). The PPV of troponin T level higher than 1.0 ng/mL in the presence of normal renal function was 90% but was as low as 27% for values of 0.1 to 1.0 ng/mL for elderly patients with renal failure. In-hospital and long-term survival rates were significantly better (P<.001) for patients with ACS. Nonspecific troponin elevation is a common finding among hospitalized patients and correlates with worse prognosis. The diagnosis of myocardial infarction should still mostly be based on the clinical presentation. The predictors and algorithm suggested in this study might increase the diagnostic accuracy of ACS and direct the appropriate treatment.

Association Between Concussion and Lower Extremity Injuries in Collegiate Athletes

PubMed Central

Gilbert, Frances C.; Burdette, G. Trey; Joyner, A. Barry; Llewellyn, Tracy A.; Buckley, Thomas A.

2016-01-01

Background: Concussions have been associated with elevated musculoskeletal injury risk; however, the influence of unreported and unrecognized concussions has not been investigated. Hypothesis: The purpose of this study was to examine the association between concussion and lower extremity musculoskeletal injury rates across a diverse array of sports among collegiate student-athletes at the conclusion of their athletic career. The hypothesis was that there will be a positive association between athletes who reported a history of concussions and higher rates of lower extremity injuries. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Student-athletes (N = 335; 62.1% women; mean age, 21.2 ± 1.4 years) from 13 sports completed a reliable injury history questionnaire. Respondents indicated the total number of reported, unreported, and potentially unrecognized concussions as well as lower extremity injuries including ankle sprains, knee injuries, and muscle strains. Chi-square analyses were performed to identify the association between concussion and lower extremity injuries. Results: There were significant associations between concussion and lateral ankle sprain (P = 0.012), knee injury (P = 0.002), and lower extremity muscle strain (P = 0.031). There were also significant associations between reported concussions and knee injury (P = 0.003), unreported concussions and knee injury (P = 0.002), and unrecognized concussions and lateral ankle sprain (P = 0.001) and lower extremity muscle strains (P = 0.006), with odds ratios ranging from 1.6 to 2.9. Conclusion: There was a positive association between concussion history and lower extremity injuries (odds ratios, 1.6-2.9 elevated risk) among student-athletes at the conclusion of their intercollegiate athletic careers. Clinical Relevance: Clinicians should be aware of these elevated risks when making return-to-participation decisions and should incorporate injury prevention protocols. PMID:27587598

Lead exposure and the 2010 achievement test scores of children in New York counties

PubMed Central

2012-01-01

Background Lead is toxic to cognitive and behavioral functioning in children even at levels well below those producing physical symptoms. Continuing efforts in the U.S. since about the 1970s to reduce lead exposure in children have dramatically reduced the incidence of elevated blood lead levels (with elevated levels defined by the current U.S. Centers for Disease Control threshold of 10 μg/dl). The current study examines how much lead toxicity continues to impair the academic achievement of children of New York State, using 2010 test data. Methods This study relies on three sets of data published for the 57 New York counties outside New York City: school achievement data from the New York State Department of Education, data on incidence of elevated blood lead levels from the New York State Department of Health, and data on income from the U.S. Census Bureau. We studied third grade and eighth grade test scores in English Language Arts and mathematics. Using the county as the unit of analysis, we computed bivariate correlations and regression coefficients, with percent of children achieving at the lowest reported level as the dependent variable and the percent of preschoolers in the county with elevated blood lead levels as the independent variable. Then we repeated those analyses using partial correlations to control for possible confounding effects of family income, and using multiple regressions with income included. Results The bivariate correlations between incidence of elevated lead and number of children in the lowest achievement group ranged between 0.38 and 0.47. The partial correlations ranged from 0.29 to 0.40. The regression coefficients, both bivariate and partial (both estimating the increase in percent of children in the lowest achievement group for every percent increase in the children with elevated blood lead levels), ranged from 0.52 to 1.31. All regression coefficients, when rounded to the nearest integer, were approximately 1. Thus, when the percent of children showing elevated lead increases by one percent, the percent of children in the lowest achievement group, according to the regression equations generated, also increases by about one percent. All associations were significant at the 0.05 level. Conclusion Despite public health advances, and despite the imprecision of measures, an association between the incidence of elevated blood lead and achievement in New York counties is still apparent, not attributable to confounding by income. Efforts to reduce lead exposure should persist with vigor. PMID:22269775

Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical Illness.

PubMed

Leaf, David E; Jacob, Kirolos A; Srivastava, Anand; Chen, Margaret E; Christov, Marta; Jüppner, Harald; Sabbisetti, Venkata S; Martin, Aline; Wolf, Myles; Waikar, Sushrut S

2017-06-01

Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort ( n =131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients. Copyright © 2017 by the American Society of Nephrology.

Elevated Serum Gastrin Is Associated With a History of Advanced Neoplasia in Barrett’s Esophagus

PubMed Central

Wang, Judy S.; Varro, Andrea; Lightdale, Charles J.; Lertkowit, Nantaporn; Slack, Kristen N.; Fingerhood, Michael L.; Tsai, Wei Yann; Wang, Timothy C.; Abrams, Julian A.

2011-01-01

OBJECTIVES Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett’ s esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS A total of 95 patients were enrolled. The mean age was 64.7 (±10.0) years, and 70.5 % were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P = 0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95 % confidence interval (CI): 1.20–24.8). CONCLUSIONS In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression. PMID:19904251

Environmental pesticide exposure in Honduras following hurricane Mitch.

PubMed Central

Balluz, L.; Moll, D.; Diaz Martinez, M. G.; Merida Colindres, J. E.; Malilay, J.

2001-01-01

OBJECTIVE: To investigate whether environmental contamination occurred in the wake of hurricane Mitch (30-31 October 1998), we conducted a population-based cross-sectional household survey in the barrio of Istoca, Department of Choluteca, Honduras. The goals were to evaluate chemical contamination of potable water and the extent of human exposure to chemicals as a result of extensive flooding. METHODS: The survey consisted of an environmental exposure assessment, which included assaying water and soil samples for contaminants, and taking blood and urine samples from 45 adolescents aged 15-18 years. We also made a subjective questionnaire assessment of 155 households. FINDINGS: There was significant contamination of the soil in Istoca, but no water contamination in the aftermath of hurricane Mitch. The soil levels of chlopyrifos and parathion were 30- and 1000-times higher, respectively, than the Environmental Data Quality Level. However, the most striking finding was the detection of elevated levels of chlorinated and organophosphate pesticides in adolescents. Toxicological analyses of serum specimens showed that 51% of the samples had elevated levels of 1,1-dichloro-2,2-bis-(p-chlorophenyl) ethylene (p,p-DDE) (range, 1.16-96.9 ng/ml) (US reference mean = 3.5 ng/ml) in adults). Dieldrin levels > 0.2 ng/ml were also present in 23% of the serum specimens (serum levels of this analyte in US adolescents are < 0.2 ng/ml). Of 43 urine samples analysed for organophosphate metabolites, 18.6% contained diethyl phosphate (DEP) at levels which were greater that the reference mean of 6.45 micrograms/g creatinine. We also detected elevated levels of p-nitrophenol (p-NP) and of 3,5,6-trichloro-2-pyridinol (3,5,6-TCPY) in 91% and 42% of the samples, respectively. CONCLUSIONS: The elevated levels of chlorinated pesticides were surprising, since although these substances were banned in Honduras 15 years ago it appears that they are still being used in the country. Moreover, elevated levels of organophosphates were detected in the study adolescents even three weeks after the hurricane. Since these chemicals are usually cleared from the body quickly, our data suggest that the adolescents face an ongoing threat from pesticide exposure. PMID:11357206

Generalized Anxiety and Major Depressive syndrome ...

EPA Pesticide Factsheets

Objective: Environmental exposure to manganese (Mn) may cause generalized anxiety (GA) and major depression (MD) in residents living in Mn-exposed areas. Marietta and East Liverpool are two Ohio towns identified as having elevated levels of Mn. The objective was to determine if levels of Mn exposure were associated with levels of GA and MD.Participants and methods: 186 participants (Mean age: 55.0 ± 10.80) were examined. Levels of air-Mn were assessed over a period of ten years using U.S. EPA’s AERMOD dispersion model. Average air-Mn exposure was 0.53 μg/m3 in the two towns. The GA syndrome was comprised of anxiety, obsessive-compulsive, and phobic scales from the Symptom Checklist (SCL-90-R). The MD syndrome was comprised of depression, anxiety, and psychoticism scales also from the SCL-90-R. Linear regression models were used to determine the relationship between Mn and GA, MD and the specific components of each.Results: Elevated air-Mn was associated with GA (β= 0.240, p=0.002), and MD (β= 0.202, p=0.011). Air-Mn was associated with specific components of GA anxiety (β= 0.255, p=0.001), phobic anxiety (β= 0.159, p=0.046), and obsessive-compulsive (β= 0.197, p=0.013). Similarly, components of MD syndrome suggested an association as well: depression (β= 0.180, p=0.023), anxiety (β= 0.255, p=0.001), and psychoticism (β= 0.188, p=0.018). Conclusions: The results suggest that residents with elevated exposure to environmental Mn have elevated levels of

Uric Acid in Pregnancy: New Concepts.

PubMed

Moreno Santillan, Armando Alberto; Briones Garduño, Jesus Carlos; Diaz de Leon Ponce, Manuel Antonio

2018-01-01

The relationship between hyperuricemia and hypertensive disorders is well established; however, until today, the role of uric acid in the clinical course of severe preeclampsia has not been elucidated. Some recent studies suggest that at the time of presentation, subjects with severe preeclampsia frequently have significantly elevated serum uric acid levels, and that the degree of elevation correlates with the severity of the maternal syndrome and fetal morbimortality. In this chapter, we present our workgroup experience. In 2016, we designed a prospective, cross-sectional comparative study. A sample of 200 patients - 100 with severe preeclampsia and 100 with normotensive pregnancy - was obtained. Plasmatic uric acid levels were recorded in units of mg/dL as clinical variables and as laboratory and fetal growth data. We considered uric acid equal to or more than 6.0 mg/dL as the elevated level. To relate the significance of elevated uric acid levels with variables, chi-square tests and Mann-Whitney U test were applied. Any p value equal or <0.05 was accepted as significant. We found significant difference (p = 0.05) between serum uric acid levels among both groups. In comparison with the healthy patients, patients with severe preeclampsia and uric acid greater than 6 mg/dl presented significant differences in relation to fetal complications and maternal laboratory and clinical variables. Our conclusion is that values equal to or greater than 6 mg/dL of serum uric acid in patients with severe preeclampsia may be a valuable biomarker for preeclampsia and an association with the presence of adverse fetal and maternal effects. © 2018 S. Karger AG, Basel.

The Accumulation of Versican in the Nodules of Benign Prostatic Hyperplasia

PubMed Central

True, Lawrence D.; Hawley, Sarah; Norwood, Thomas H.; Braun, Kathleen R.; Evanko, Stephen P.; Chan, Christina K.; LeBaron, Richard C.; Wight, Thomas N.

2014-01-01

Background Proteoglycans, a complex group of extracellular matrix (ECM) molecules, are elevated in benign prostatic hyperplasia (BPH). Versican is a stromal proteoglycan present in prostate tissue. Versican expression is elevated in tissues with increased proliferation. Based on these observations, we determined the extent and distribution of versican expression in prostates with BPH. Methods The involvement of versican in BPH nodules was compared with levels in non-nodular transition (TZ) and peripheral zone (PZ) tissues from 18 human prostate glands using immunohistochemistry, Northern blots and/or QRTPCR to localize versican and quantify versican mRNA transcript levels, and Western blots to assess gene product levels. Results Increased versican immunoreactivity was observed in the stroma of BPH nodules. Higher steady state levels of versican variants V0, V1, and V3 mRNA transcript and gene product were detected in the nodular tissues than in the non-nodular TZ or PZ parenchyma. Conclusions These results suggest that versican may play a role in nodule formation in BPH. PMID:18819099

Anti-citrullinated protein antibodies are associated with neutrophil extracellular traps in the sputum in relatives of rheumatoid arthritis patients

PubMed Central

Demoruelle, M. Kristen; Harrall, Kylie K.; Ho, Linh; Purmalek, Monica M.; Seto, Nickie L.; Rothfuss, Heather M.; Weisman, Michael H.; Solomon, Joshua J.; Fischer, Aryeh; Okamoto, Yuko; Kelmenson, Lindsay B.; Parish, Mark C.; Feser, Marie; Fleischer, Chelsie; Anderson, Courtney; Mahler, Michael; Norris, Jill M.; Kaplan, Mariana J.; Cherrington, Brian D.; Holers, V. Michael; Deane, Kevin D.

2017-01-01

Objectives Studies suggest that rheumatoid arthritis (RA)-related autoimmunity is initiated at a mucosal site. However, the factors associated with the mucosal generation of this autoimmunity are unknown, especially in individuals who are at-risk for future RA. Therefore, we tested anti-cyclic citrullinated peptide (anti-CCP) antibodies in the sputum of RA-free first-degree relatives (FDRs) of RA patients and patients with classifiable RA. Methods We evaluated induced sputum and serum from 67 FDRs and 20 RA subjects for anti-CCP-IgA and anti-CCP-IgG, with cut-off levels for positivity determined in a control population. Sputum was also evaluated for cell counts, neutrophil extracellular traps (NETs) using sandwich ELISAs for protein/nucleic acid complexes, and total citrulline. Results Sputum anti-CCP-IgA and/or anti-CCP-IgG was positive in 17/67 (25%) FDRs and 14/20 (70%) RA subjects, including a portion of FDRs who were serum anti-CCP negative. In FDRs, elevations of sputum anti-CCP-IgA and anti-CCP-IgG were associated with elevated sputum cell counts and levels of NET complexes. Anti-CCP-IgA was associated with ever-smoking and elevated sputum citrulline levels. Conclusions Anti-CCP is elevated in the sputum of FDRs, including seronegative FDRs, suggesting the lung may be one site of anti-CCP generation in this population. The association of anti-CCP with elevated cell counts and NET levels in FDRs supports a hypothesis that local airway inflammation and NET formation may drive anti-CCP production in the lung and may promote the early stages of RA development. Longitudinal studies are needed to follow the evolution of these processes relative to the development of systemic autoimmunity and articular RA. PMID:28182854

The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis thaliana heterologously expressing serine acetyl-transferase.

PubMed

Freeman, John L; Salt, David E

2007-11-28

The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni congruent with Zn, congruent with Co and slightly resistant to > Cd. We previously observed that elevated glutathione, driven by constitutive activation of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T. goesingense. Here we show that the elevated shoot concentration of glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis thaliana heterologously expressing T. goesingense mitochondrial serine acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly enhancing resistance to Cd. The level of tolerance afforded to each metal is ranked Ni congruent with Co, > Zn > Cd. The Ni congruent with Co, > Zn tolerances are positively correlated with both the accumulation of glutathione (GSH) and the ability to resist the oxidative damage induced by these different metals. Based on the relative concentrations of each metal used a relatively low level of resistance to Cd was observed in both T. goesingense and TgSATm expressing lines and Cd resistance was least correlated to GSH accumulation. Such data supports the conclusion that elevated glutathione levels, driven by constitutively enhanced SAT activity in the hyperaccumulator T. goesingense, plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi species. The hyper-activation of S assimilation through SAT is an excellent strategy for engineering enhanced metal tolerance in transgenic plants potentially used for phytoremediation.

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress.

PubMed

Jia, Xia; Zhao, YongHua; Wang, WenKe; He, Yunhua

2015-09-23

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and l-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress

PubMed Central

Jia, Xia; Zhao, YongHua; Wang, WenKe; He, Yunhua

2015-01-01

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and l-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings. PMID:26395070

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress

NASA Astrophysics Data System (ADS)

Jia, Xia; Zhao, Yonghua; Wang, Wenke; He, Yunhua

2015-09-01

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and L-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

Impact of admission blood glucose levels on prognosis of elderly patients with ST elevation myocardial infarction treated by primary percutaneous coronary intervention

PubMed Central

Ekmekci, Ahmet; Uluganyan, Mahmut; Tufan, Fatif; Uyarel, Huseyin; Karaca, Gurkan; Kul, Seref; Gungor, Barış; Ertas, Gokhan; Erer, Betul; Sayar, Nurten; Gul, Mehmet; Eren, Mehmet

2013-01-01

Objective Admission hyperglycemia in acute myocardial infarction (MI) is related with increased in-hospital and long term mortality and major cardiac adverse events. We aimed to investigate how admission hyperglycemia affects the short and long term outcomes in elderly patients (> 65 years) after primary percutaneous coronary intervention for ST elevation myocardial infarction. Methods We retrospectively analyzed 677 consecutive elderly patients (mean age 72.2 ± 5.4). Patients were divided into two groups according to admission blood glucose levels. Group 1: low glucose group (LLG), glucose < 168 mg/dL; and Group 2: high glucose group (HGG), glucose > 168 mg/dL. Results In-hospital, long term mortality and in-hospital major adverse cardiac events were higher in the high admission blood glucose group (P < 0.001). Multivariate regression analysis showed: Killip > 1, post-thrombolysis in MI < 3 and admission blood glucose levels were independent predictors of in-hospital adverse cardiac events (P < 0.001). Conclusions Admission hyperglycemia in elderly patients presented with ST elevation myocardial infarction is an independent predictor of in-hospital major adverse cardiac events and is associated with in-hospital and long term mortality. PMID:24454322

Levels of Antibodies against Human Heat Shock Protein (HSP) 60 in Patients with Glaucoma in Poland

PubMed Central

Grabska-Liberek, Iwona; Skonieczna, Katarzyna; Olesińska, Marzena; Terelak-Borys, Barbara; Kocięcki, Jarosandlstrokaw; Sikora, Mariusz; Jamrozy-Witkowska, Agnieszka; Tesla, Piotr; Czarnocka, Barbara

2015-01-01

Background Although elevated intraocular pressure is a major risk factor for the development of glaucoma, there is increasing evidence that the immune system may be involved in the development of normal-tension glaucoma (NTG). The aim of this study was to determine if NTG is associated with elevated levels of antibodies against human heat shock protein (HSP) 60. Material/Methods The study was conducted in 139 subjects (35 subjects with NTG [Group 1], 34 subjects with primary open-angle glaucoma/POAG/[Group 2], 24 subjects with autoimmune rheumatic diseases [Group 3], and 36 healthy controls [Group 4]). All subjects had complete ophthalmologic examination (visual acuity, slit-lamp examination, tonometry, gonioscopy; visual-field examination, and optical coherence tomography/OCT/of the optic nerve head and the macula). Blood samples were collected for the measurements of serum levels of antibodies against human HSP60. Results The subjects with rheumatic diseases had the highest median serum level of antibodies against HSP60 – 20.49 ng/mL. The values in the subjects with NTG, POAG, and in controls were 18.79 ng/mL, 18.61 ng/mL and 17.61 ng/mL, respectively (p=0.96). Conclusions This study does not confirm the hypothesis that normal-tension glaucoma is associated with elevated blood levels of antibodies against human heat shock protein (HSP) 60. PMID:25786333

Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

PubMed Central

2014-01-01

Background Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. Findings Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction. PMID:24576351

Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

PubMed Central

Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

2014-01-01

Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

Association of abnormal plasma bilirubin with aggressive HCC phenotype

PubMed Central

Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

2014-01-01

Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

Post-Surgical Depressive Symptoms and Pro-Inflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer

PubMed Central

Bouchard, Laura C.; Antoni, Michael H.; Blomberg, Bonnie B.; Stagl, Jamie M.; Gudenkauf, Lisa M.; Jutagir, Devika R.; Diaz, Alain; Lechner, Suzanne; Glück, Stefan; Derhagopian, Robert P.; Carver, Charles S.

2015-01-01

Objective Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and cancer patients. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early stage BCa before beginning adjuvant treatment. Method Women with stage 0–III BCa were recruited approximately 4–8 weeks post-surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression and blood samples were collected to quantify circulating levels of IL-1β, IL-6, and TNF-α by ELISA. ANCOVAs were used to test for group differences (elevated vs. low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. Results Thirty-six of 89 (40%) patients showed elevated levels of depressive symptoms, and in adjusted models had marginally higher levels of IL-1β (M=14.49, 95% CI [6.11, 32.65] vs. M=4.68, 95% CI [1.96, 9.86]) and significantly higher levels of TNF-α (M=17.07, 95% CI [8.27, 34.32] vs. M=6.94, 95% CI [3.58, 12.80]) than women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1β (β=0.06, p=0.006, R2=0.25) and TNF-α (β=0.06, p=0.003, R2=0.27). Conclusions Post-surgery and pre-adjuvant treatment for early stage BCa, depressive symptoms covary with elevated levels of multiple pro-inflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. PMID:26569533

The association between male infertility and sperm disomy: Evidence for variation in disomy levels among individuals and a correlation between particular semen parameters and disomy of specific chromosome pairs

PubMed Central

Tempest, Helen G; Homa, Sheryl T; Dalakiouridou, Maria; Christopikou, Dimitra; Wright, David; Zhai, Xiao P; Griffin, Darren K

2004-01-01

Background The association between infertility and sperm disomy is well documented. Results vary but most report that men with severely compromised semen parameters have a significantly elevated proportion of disomic sperm. The relationship between individual semen parameters and segregation of specific chromosome pairs is however less well reported as is the variation of disomy levels in individual men. Methods In order to address these questions the technique of fluorescent in-situ hybridisation (FISH) was utilised to determine the disomy levels of chromosomes X, Y and 21 in 43 sperm samples from 19 infertile males. The results generated from this study were analysed using logistic regression. Results In this study we compared levels of sperm concentration, motility and morphology with levels of sperm disomy for chromosome 21 and the sex chromosomes. Our results suggest that there is considerable variation in disomy levels for certain men. They also suggest that oligozoospermic males have significantly elevated levels of sex chromosome disomy but not disomy 21; they suggest that severe asthenozoospermic males have significantly elevated levels of disomy 21 but not sex chromosome disomy. Surprisingly, severe teratozoopsermic males appeared to have significantly lower levels of sperm disomy for both the sex chromosomes and chromosome 21. Conclusion We suggest that the association between sex chromosome disomy and oligozoospermia may be due to reduced recombination in the XY pairing region and discuss the relevance of our findings for the correlations between sperm disomy and sperm motility and morphology. PMID:15598347

Elevated oxidized glutathione in cystinotic proximal tubular epithelial cells.

PubMed

Wilmer, Martijn J G; de Graaf-Hess, Adriana; Blom, Henk J; Dijkman, Henry B P M; Monnens, Leo A; van den Heuvel, Lambertus P; Levtchenko, Elena N

2005-11-18

Cystinosis, the most frequent cause of inborn Fanconi syndrome, is characterized by the lysosomal cystine accumulation, caused by mutations in the CTNS gene. To elucidate the pathogenesis of cystinosis, we cultured proximal tubular cells from urine of cystinotic patients (n = 9) and healthy controls (n = 9), followed by immortalization with human papilloma virus (HPV E6/E7). Obtained cell lines displayed basolateral polarization, alkaline phosphatase activity, and presence of aminopeptidase N (CD-13) and megalin, confirming their proximal tubular origin. Cystinotic cell lines exhibited elevated cystine levels (0.86 +/- 0.95 nmol/mg versus 0.09 +/- 0.01 nmol/mg protein in controls, p = 0.03). Oxidized glutathione was elevated in cystinotic cells (1.16 +/- 0.83 nmol/mg versus 0.29 +/- 0.18 nmol/mg protein, p = 0.04), while total glutathione, free cysteine, and ATP contents were normal in these cells. In conclusion, elevated oxidized glutathione in cystinotic proximal tubular epithelial cell lines suggests increased oxidative stress, which may contribute to tubular dysfunction in cystinosis.

Cardiovascular Risk Factors in Severely Obese Adolescents

PubMed Central

Michalsky, Marc P.; Inge, Thomas H.; Simmons, Mark; Jenkins, Todd M.; Buncher, Ralph; Helmrath, Michael; Brandt, Mary L.; Harmon, Carroll M.; Courcoulas, Anita; Chen, Michael; Horlick, Mary; Daniels, Stephen R.; Urbina, Elaine M.

2015-01-01

IMPORTANCE Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. OBJECTIVE To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children’s Hospital in Columbus, Ohio; Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio; Texas Children’s Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children’s Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. MAIN OUTCOMES AND MEASURES This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. RESULTS The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit increase in body mass index (P < .01). Dyslipidemia (adjusted relative risk = 1.60 [95% CI, 1.26–2.03]; P < .01) and elevated blood pressure (adjusted relative risk = 1.48 [95% CI, 1.16–1.89]; P < .01) were more likely in adolescent boys compared with adolescent girls. White individuals were at greater risk of having elevated triglyceride levels (adjusted relative risk = 1.76 [95% CI, 1.14–2.72]; P = .01) but were less likely to have impaired fasting glucose levels (adjusted relative risk = 0.58 [95% CI, 0.38–0.89]; P = .01). CONCLUSIONS AND RELEVANCE Numerous CVD risk factors are apparent in adolescents undergoing weight-loss surgery. Increasing body mass index and male sex increase the relative risk of specific CVD risk factors. These data suggest that even among severely obese adolescents, recognition and treatment of CVD risk factors is important to help limit further progression of disease. PMID:25730293

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

PubMed

Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

2014-10-15

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

Elevated Serum Liver Enzymes in Patients with Obstructive Sleep Apnea-hypopnea Syndrome

PubMed Central

Li, Jie; Zhang, Yan-Lin; Chen, Rui; Wang, Yi; Xiong, Kang-Ping; Huang, Jun-Ying; Han, Fei; Liu, Chun-Feng

2015-01-01

Background: Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. Methods: All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5–14 events/h, 15–29 events/h, and ≥30 events/h. Results: A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO2), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. Conclusions: Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS. PMID:26608975

Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

PubMed

Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

1997-08-01

We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p < 0.01). Either respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

Inflammation associated anemia and ferritin as disease markers in SLE

PubMed Central

2012-01-01

Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

PubMed Central

Zabetian, Azadeh; Ferket, Bart S.; Zhou, Jing; Testani, Jeffrey M.; Garg, Amit X.; Parikh, Chirag R.

2016-01-01

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. PMID:26712525

Elevation of Plasma Cell-Free Hemoglobin in Pulmonary Arterial Hypertension

PubMed Central

Janz, David R.; Austin, Eric D.; Bastarache, Julie A.; Wheeler, Lisa A.; Ware, Lorraine B.; Hemnes, Anna R.

2014-01-01

BACKGROUND: Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and would associate with hemodynamics and clinical outcomes. METHODS: We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death. RESULTS: CFH was elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH (P ≤ .01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (ρ = 0.16, P = .03) and pulmonary vascular resistance (ρ = 0.21, P = .01) and inversely with cardiac index (ρ = −0.18, P = .02) in patients with PAH. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P = .02). CONCLUSIONS: CFH is elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH. PMID:24945582

Sedimentation and response to sea-level rise of a restored marsh with reduced tidal exchange: Comparison with a natural tidal marsh

USGS Publications Warehouse

Vandenbruwaene, W.; Maris, T.; Cahoon, D.R.; Meire, P.; Temmerman, S.

2011-01-01

Along coasts and estuaries, formerly embanked land is increasingly restored into tidal marshes in order to re-establish valuable ecosystem services, such as buffering against flooding. Along the Scheldt estuary (Belgium), tidal marshes are restored on embanked land by allowing a controlled reduced tide (CRT) into a constructed basin, through a culvert in the embankment. In this way tidal water levels are significantly lowered (ca. 3 m) so that a CRT marsh can develop on formerly embanked land with a ca. 3 m lower elevation than the natural tidal marshes. In this study we compared the long-term change in elevation (ΔE) within a CRT marsh and adjacent natural tidal marsh. Over a period of 4 years, the observed spatio-temporal variations in ΔE rate were related to variations in inundation depth, and this relationship was not significantly different for the CRT marsh and natural tidal marsh. A model was developed to simulate the ΔE over the next century. (1) Under a scenario without mean high water level (MHWL) rise in the estuary, the model shows that the marsh elevation-ΔE feedback that is typical for a natural tidal marsh (i.e. rising marsh elevation results in decreasing inundation depth and therefore a decreasing increase in elevation) is absent in the basin of the CRT marsh. This is because tidal exchange of water volumes between the estuary and CRT marsh are independent from the CRT marsh elevation but dependent on the culvert dimensions. Thus the volume of water entering the CRT remains constant regardless of the marsh elevation. Consequently the CRT MHWL follows the increase in CRT surface elevation, resulting after 75 years in a 2–2.5 times larger elevation gain in the CRT marsh, and a faster reduction of spatial elevation differences. (2) Under a scenario of constant MHWL rise (historical rate of 1.5 cm a-1), the equilibrium elevation (relative to MHWL) is 0.13 m lower in the CRT marsh and is reached almost 2 times faster. (3) Under a scenario of accelerated MHWL rise (acceleration of 0.02 cm a-1), the CRT marsh is much less able to keep up with the MHWL rise; after 75 years the CRT elevation is already 0.21 m lower than for the natural marsh. In conclusion, this study demonstrates that although short-term (4 years) ΔE rates are similar in a restored CRT marsh and natural tidal marsh, these ecosystems may evolve differently in response to sea-level rise in the longer term (10–100 years).

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

PubMed

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

The Molecular Basis of Canavan Disease: Aspartoacylase Enzyme Characteristics

DTIC Science & Technology

2006-01-01

this conclusion by observing that children with certain neurodegenerative conditions also had N-acetylaspartic aciduria , abnormally high levels of NAA...in the urine. In the late 1980’s, N-acetylaspartic aciduria and deficient ASPA activity in cultured fibroblasts were linked to cases of cerebral...symptoms of CD are found in other leukodystrophies and neurodegenerative disorders, N-acetylaspartic aciduria is exclusive to CD. Slightly elevated

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

Adenosine triphosphate bioluminescence for bacteriological surveillance and reprocessing strategies for minimizing risk of infection transmission by duodenoscopes

PubMed Central

Sethi, Saurabh; Huang, Robert J.; Barakat, Monique T.; Banaei, Niaz; Friedland, Shai; Banerjee, Subhas

2017-01-01

Background/Aims Recent outbreaks of duodenoscope-transmitted infections underscore the importance of adequate endoscope reprocessing. Adenosine triphosphate (ATP) bioluminescence testing allows rapid evaluation of endoscopes for bacteriological/biological residue. In this prospective study we evaluate the utility of ATP in bacteriological surveillance, and the effects of endoscopy staff education and dual cycles of cleaning and high-level disinfection (HLD) on endoscope reprocessing. Methods ATP bioluminescence was measured after pre-cleaning, manual cleaning and HLD on rinsates from suction-biopsy channels of all endoscopes and elevator channels of duodenoscopes/linear echoendoscopes after use. ATP bioluminescence was re-measured in duodenoscopes (1) after re-education and competency testing of endoscopy staff, and subsequently (2) after 2 cycles of pre-cleaning and manual cleaning and single cycle of HLD, or (3) after 2 cycles of pre-cleaning, manual cleaning and HLD. Results The ideal ATP bioluminescence benchmark of <200 relative light units (RLUs) after manual cleaning was achieved from suction-biopsy channel rinsates of all endoscopes, but 9 of 10 duodenoscope elevator channel rinsates failed to meet this benchmark. Re-education reduced RLUs in duodenoscope elevator channel rinsates after pre-cleaning (23218.0 vs 1340.5 RLUs, p<0.01) and HLD (177.0 vs 12.0 RLUs, p<0.01). After 2 cycles of manual cleaning/HLD, duodenoscope elevator channel RLUs achieved levels similar to sterile water, with corresponding negative cultures. Conclusions ATP testing offers a rapid, inexpensive alternative for detection of endoscope microbial residue. Re-education of endoscopy staff and 2 cycles of cleaning and HLD decrease elevator channel RLUs to levels similar to sterile water and may therefore minimize the risk of transmission of infections by duodenoscopes. PMID:27818222

Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition.

PubMed

Risberg, Anitha; Sjöquist, Mats; Wedenberg, Kaj; Larsson, Anders

2016-07-01

Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition.

Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

PubMed Central

Pun, Priti; Jones, Jesica; Wolfe, Craig; Deming, Douglas D.; Power, Gordon G.; Blood, Arlin B.

2016-01-01

Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID:26539663

Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between Depressive and Stress Symptoms and Alcohol Problems

PubMed Central

Soltis, Kathryn E.; McDevitt-Murphy, Meghan; Murphy, James G.

2017-01-01

Background Elevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. The current study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and craving. Methods Participants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problems. Results In separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problems. Conclusions Heavy drinking young adults who experience stress or depression are likely to experience alcohol problems and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value. PMID:28401985

Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle Atrophy

PubMed Central

Wang, Jing; He, Jian; Li, Wenjiong; Li, Jinglong; Chen, Shengju; Zhang, Peng; Liu, Hongju

2017-01-01

Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs) could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499) were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR). The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression. PMID:29214178

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis.

PubMed

Levin, Lynn I; Breen, Elizabeth C; Birmann, Brenda M; Batista, Julie L; Magpantay, Larry I; Li, Yuanzhang; Ambinder, Richard F; Mueller, Nancy E; Martínez-Maza, Otoniel

2017-07-01

Background: We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL). Methods: We measured serum levels of B-cell-stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository. Results: Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4-9.0; IL6 OR = 4.6; 95% CI, 2.9-7.5] and >1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6-6.7; IL6 OR = 2.9; 95% CI, 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases. Conclusion: In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis. Impact: The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community

PubMed Central

Savitz, David A.; Stein, Cheryl R.; Bartell, Scott M.; Elston, Beth; Gong, Jian; Shin, Hyeong-Moo; Wellenius, Gregory A.

2012-01-01

Background We assessed the association between perfluorooctanoic acid (PFOA) and pregnancy outcome in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases. Methods Serum PFOA was measured and reproductive and residential histories were obtained in 2005 – 2006. We estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies occurring between 1990 and 2006 based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We assessed the association between PFOA and the odds of miscarriage, stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects controlling for calendar time, age, parity, education, and smoking. PFOA exposure was evaluated as a continuous measure (with and without log-transformation) and in quintiles, combining the lowest two quintiles (<6.8 ng/mL) as the referent. Results Measures of association between PFOA and miscarriage, preterm birth, term low birthweight, and birth defects were close to the null. Odds of stillbirth were elevated in the 4th quintile only. For preeclampsia, the odds ratio was 1.13 (95% confidence interval = 1.00 – 1.28) for an interquartile shift in log-transformed PFOA, and the odds ratios were 1.1 – 1.2 across the upper three quintiles of exposure. Conclusions In this large, population-based study in a region with markedly elevated PFOA exposure, we found no associations between estimated serum PFOA levels and adverse pregnancy outcomes other than possibly preeclampsia. Conclusions are tempered by inherent limitations in exposure reconstruction and self-reported pregnancy outcome information. PMID:22370857

Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

PubMed

Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

2016-07-07

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

PubMed Central

Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

2015-01-01

Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

An Assessment of Psychological Need in Emergency Medical Staff in the Northern Health and Social Care Trust Area

PubMed Central

Aisling, Diamond; David, Curran

2016-01-01

Setting Psychological stress is increasingly recognised within emergency medicine, given the environmental and clinical stressors associated with the specialism. The current study assessed whether psychological distress is experienced by emergency medical staff and if so, what is the expressed need within this population? Participants Participants included ambulance personnel, nursing staff, doctors and ancillary support staff within two Accident and Emergency (A&E) departments and twelve ambulance bases within one Trust locality in NI (N = 107). Primary and secondary outcome measures The General Health Questionnaire (GHQ-12, Goldberg, 1972, 1978), Secondary Traumatic Stress Scale (STSS, Bride, 2004) and an assessment of need questionnaire were completed and explored using mixed method analysis. Results Results showed elevated levels of psychological distress within each profession except ambulance service clinical support officers (CSOs). Elevated levels of secondary trauma symptomatology were also found; the highest were within some nursing grades and junior doctors. Decreased enjoyment in job over time was significantly associated with higher scores. Analysis of qualitative data identified sources of stress to include low morale. A total of 65% of participants thought that work related stressors had negatively affected their mental health. Participants explored what they felt could decrease psychological distress including improved resources and psychoeducation. Conclusion There were elevated levels of distress and secondary traumatic stress within this population as well as an expressed level of need, on both systemic and support levels. PMID:27601762

Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

PubMed Central

Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

2015-01-01

Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

PubMed Central

2011-01-01

Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3) by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain. PMID:21864400

Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

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

Kou, Hao; Liu, Yansong; Liang, Gai

Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180more » mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome alterations were associated with glucocorticoid elevation. • Maternal metabonomes were altered at early stage after caffeine exposure. • Maternal glucocorticoid and associated metabolites may be involved in fetal programming.« less

High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins.

PubMed

Kim, So-Hee; Yadav, Dhananjay; Kim, Suk-Jeong; Kim, Jae-Ryong; Cho, Kyung-Hyun

2017-07-02

Elevated serum iron level is linked with an increased risk of diabetes and atherosclerosis. However, the pathological mechanism by which iron affects serum lipoprotein levels is unknown. To elucidate the mechanism, a high dose of ferrous ion was applied (final 60 µM, 120 µM) to human serum lipoproteins, macrophages, and human dermal fibroblast (HDF) cells. Iron-treated lipoproteins showed loss of antioxidant ability along with protein degradation and multimerization, especially co-treatment with fructose (final 10 mM). In the presence of fructose, HDF cells showed 3.5-fold more severe cellular senescence, as compared to the control, dependent on the dosage of fructose. In macrophages, phagocytosis of acetylated low-density lipoprotein (acLDL) was more accelerated by ferrous ion, occurring at a rate that was up to 1.8-fold higher, than acLDL alone. After 24 weeks supplementation with 0.05% and 0.1% ferrous ion in the diet (wt/wt), serum total cholesterol (TC) level was elevated 3.7- and 2.1-fold, respectively, under normal diet (ND). Serum triglyceride (TG) was elevated 1.4- and 1.7-fold, respectively, under ND upon 0.05% and 0.1% ferrous ion supplementation. Serum glucose level was elevated 2.4- and 1.2-fold under ND and high cholesterol diet (HCD), respectively. However, body weight was decreased by the Fe 2+ consumption. Iron consumption caused severe reduction of embryo laying and reproduction ability, especially in female zebrafish via impairment of follicular development. In conclusion, ferrous ion treatment caused more pro-atherogenic, and pro-senescence processes in human macrophages and dermal cells. High consumption of iron exacerbated hyperlipidemia and hyperglycemia as well as induced fatty liver changes and sterility along with reduction of female fertility.

Experiments in Wave Record Analysis.

DTIC Science & Technology

1980-09-01

manipulation of wave records in digital form to produce a power density spectrum (PDS) with great efficiency. The PDS gives a presentation of the...instantaneous surface elevation digital points (the zero level reference). The individual period, Ti, was taken as the time difference between two successive...CONCLUSIONS This thesis presents the results of experiments in the analysis of ocean wave records. For this purpose 19 digitized records obtained from a wave

Serum Analysis of Tryptophan Catabolism Pathway: Correlation with Crohn’s Disease Activity

PubMed Central

Gupta, Nitin K; Thaker, Ameet I; Kanuri, Navya; Riehl, Terrence E; Rowley, Christopher W; Stenson, William F; Ciorba, Matthew A

2011-01-01

BACKGROUND Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity. PMID:21823214

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials.

PubMed

Coca, Steven G; Zabetian, Azadeh; Ferket, Bart S; Zhou, Jing; Testani, Jeffrey M; Garg, Amit X; Parikh, Chirag R

2016-08-01

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. Copyright © 2016 by the American Society of Nephrology.

Analysis of the effects of exposure to polychlorinated biphenyls and chlorinated pesticides on serum lipid levels in residents of Anniston, Alabama

PubMed Central

2013-01-01

Background Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study. Methods Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis. Results We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196–203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components. Conclusions Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These observations show selective effects of different organochlorines on serum concentrations of different groups of lipids. This elevation in concentrations of serum lipids may be the basis for the increased incidence of cardiovascular disease found in persons with elevated exposures to PCBs and chlorinated pesticides. PMID:24325314

Single awakening salivary measurements provide reliable estimates of morning cortisol levels in pregnant women.

PubMed

Vlenterie, Richelle; Roeleveld, Nel; van Gelder, Marleen M H J

2016-12-01

Mood disorders during pregnancy have been associated with adverse effects on maternal as well as fetal health. Since mood, anxiety, and stress disorders are related with elevated cortisol levels, salivary cortisol may be a useful biomarker. Although multiple samples are generally recommended, a single measurement of awakening salivary cortisol could be a simpler and more cost-effective method to determine whether women have elevated morning cortisol levels during a specific period of pregnancy. Therefore, the aim of this validation study among 177 women in the PRIDE Study was to examine whether one awakening salivary cortisol measurement will suffice to classify pregnant women as having normal or elevated cortisol levels compared to awakening salivary cortisol measurements on three consecutive working days. We calculated intraclass correlation coefficients (ICC) and Cohen's kappa statistics (κ) overall as well as in sub-analyses within strata based on maternal age, level of education, net household income, pre-pregnancy BMI, parity, complications during pregnancy, caffeine consumption, gestational week of sampling, and awakening time. The mean cortisol concentrations were 8.98ng/ml (SD 5.32) for day one, 8.62ng/ml (SD 4.55) for day two, and 8.39ng/ml (SD 4.58) for day three. The overall ICC was 0.86 (95% CI 0.82-0.89) while the κ was 0.75 (95% CI 0.64-0.86). For the ICCs calculated within sub-analyses, a maximum difference of 0.11 was observed between the strata. For the κ statistics, most strata did not differ more than 0.12, except for pre-pregnancy BMI, severe nausea, and extreme fatigue with differences up to 0.22. In conclusion, one awakening salivary cortisol measurement is as reliable for the classification of pregnant women into normal and elevated morning cortisol levels as salivary cortisol measurements on three consecutive working days. Copyright © 2016 Elsevier Ltd. All rights reserved.

The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle.

PubMed

Carroll, Chad C; O'Connor, Devin T; Steinmeyer, Robert; Del Mundo, Jonathon D; McMullan, David R; Whitt, Jamie A; Ramos, Jahir E; Gonzales, Rayna J

2013-07-01

This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein(-1)·min(-1)). COX-2 activity was elevated at 4 and 24 h after RE (P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein(-1)·min(-1)). The protein level of COX-1 was not altered (P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.

Curcumin Attenuates Staurosporine-Mediated Death of Retinal Ganglion Cells

PubMed Central

Burugula, Balabharathi; Ganesh, Bhagyalaxmi S.

2011-01-01

Purpose. Staurosporine (SS) causes retinal ganglion cell (RGC) death in vivo, but the underlying mechanisms have been unclear. Since previous studies on RGC-5 cells indicated that SS induces cell death by elevating proteases, this study was undertaken to investigate whether SS induces RGC loss by elevating proteases in the retina, and curcumin prevents SS-mediated death of RGCs. Methods. Transformed mouse retinal ganglion-like cells (RGC-5) were treated with 2.0 μM SS and various doses of curcumin. Two optimal doses of SS (12.5 and 100 nM) and curcumin (2.5 and 10 μM) were injected into the vitreous of C57BL/6 mice. Matrix metalloproteinase (MMP)-9, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activities were assessed by zymography assays. Viability of RGC-5 cells was assessed by MTT assays. RGC and amacrine cell loss in vivo was assessed by immunostaining with Brn3a and ChAT antibodies, respectively. Frozen retinal cross sections were immunostained for nuclear factor-κB (NF-κB). Results. Staurosporine induced uPA and tPA levels in RGC-5 cells, and MMP-9, uPA, and tPA levels in the retinas and promoted the death of RGC-5 cells in vitro and RGCs and amacrine cells in vivo. In contrast, curcumin attenuated RGC and amacrine cell loss, despite elevated levels of proteases. An NF-κB inhibitory peptide reversed curcumin-mediated protective effect on RGC-5 cells, but did not inhibit protease levels. Curcumin did not inhibit protease levels in vivo, but attenuated RGC and amacrine cell loss by restoring NF-κB expression. Conclusions. The results show that curcumin attenuates RGC and amacrine cell death despite elevated levels of proteases and raises the possibility that it may be used as a plausible adjuvant therapeutic agent to prevent the loss of these cells in retinal degenerative conditions. PMID:21498608

Severe oligozoospermia in a patient with myxedema coma.

PubMed

Komiya, Akira; Watanabe, Akihiko; Kawauchi, Yoko; Takano, Atsuko; Fuse, Hideki

2012-10-01

A case of severe oligozoospermia with myxedema coma is herein presented. The patient was referred to a male infertility clinic with a 5-year history of primary infertility. Decreased serum testosterone and elevated serum prolactin without abnormal MRI findings in the hypothalamus, and decreased semen volume and sperm motility were noted. A GnRH test revealed a decreased luteinizing hormone response, whereas the HCG test showed a normal testosterone increase. Because a urinalysis after ejaculation indicated retrograde ejaculation, imipramine administration was started. However, the semen quality deteriorated, so the patient was referred to an ART clinic. Twenty-one months from the initial visit, the patient developed a loss of consciousness and edema due to myxedema coma, a life-threatening state of hypothyroidism. The patient recovered after 1 month of thyroid hormone replacement therapy (HRT) with corticosteroids. Three months after the myxedema coma, a semen analysis showed a decreased semen volume (0.2 mL) and severe oligozoospermia (two spermatozoa/ejaculate). Elevated prolactin and decreased testosterone levels were still present. These parameters gradually improved after restoration of euthyroidism by HRT. In conclusion, physicians should confirm the thyroid function in the management of male infertility, especially in patients with elevated prolactin levels.

Serum urea and uric acid concentration in pregnant women in sub-urban commercial community in Africa.

PubMed

Ahaneku, J E; Adinma, J I; Ahaneku, G I; Nwosu, B O; Nwofor, P C; Okoli, C C

2009-06-01

Serum uric acid and urea levels were determined in 27 pregnant and 17 non-pregnant black African women. Uric acid levels for the pregnant women were significantly raised, and the relationship between uric acid elevation and gestational proteinuric hypertension was discussed. In conclusion, we recommend that uric acid estimation should be included during routine antenatal clinics in normal pregnancy. That the use of uric acid levels should be encouraged for the diagnosis and management of gestational proteinuric hypertension in African pregnant women. The above recommendation will help to reduce prenatal morbidity and mortality in African pregnant women.

Evaluation of reactive oxygen metabolites in patients with non-small cell lung cancer after chemotherapy

PubMed Central

2014-01-01

Background The aim of this study was to evaluate the level of reactive oxygen metabolites (ROMs) after chemotherapy in patients with non-small cell lung cancer (NSCLC) and its association with response to treatment. Methods Fifty-eight untreated NSCLC patients and twenty-three healthy subjects were selected for the study. Patients received two courses of platinum-based chemotherapy and were evaluated for oxidative stress and treatment response. As a marker of reactive oxygen species, ROMs levels were measured using the d-ROMs test. Results ROMs level (mean ± standard deviation) before chemotherapy in NSCLC patients (416 ± 135 U.CARR) was significantly elevated (p = 0.016) compared to normal healthy subjects (320 ± 59 U.CARR). Patients who responded to chemotherapy showed significantly decreased (p = 0.014) ROMs levels after chemotherapy, whereas patients who had stable disease or progressive disease showed no change in ROMs level (p = 0.387). Conclusions NSCLC patients had significantly elevated ROMs levels before chemotherapy compared with normal healthy subjects. Chemotherapy may suppress ROMs production in responders but not in non-responders. ROMs level may be a predictor of clinical outcome in patients receiving chemotherapy for NSCLC. PMID:25180083

Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies

PubMed Central

Fischer, Michael J.; Xie, Dawei; Jordan, Neil; Kop, Willem J.; Krousel-Wood, Marie; Tamura, Manjula Kurella; Kusek, John W.; Ford, Virginia; Rosen, Leigh K.; Strauss, Louise; Teal, Valerie L.; Yaffe, Kristine; Powe, Neil R.; Lash, James P.

2012-01-01

Background Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design Cross-sectional analysis Settings and Participants Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008. Measurement Depressive symptoms measured by Beck Depression Inventory (BDI) Predictors Demographic and clinical factors Outcomes Elevated depressive symptoms (BDI >= 11) and antidepressant medication use Results Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each). Limitations Absence of clinical diagnosis of depression and use of non-pharmacologic treatments Conclusions Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. African Americans, Hispanics, and individuals with more advanced CKD had higher odds of elevated depressive symptoms and lower odds of antidepressant medication use. PMID:22497791

Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

PubMed Central

O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

2016-01-01

Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040

Thiamine and its phosphate esters in relation to cardiometabolic risk factors in Saudi Arabs

PubMed Central

2013-01-01

Background Thiamine deficiency has suggested to be linked to several insulin-resistance complications. In this study, we aim to associate circulating thiamine levels among cardiometabolic parameters in an Arab cohort using a simple, sensitive, rapid and selective high-performance liquid chromatography (HPLC) method that has recently been developed. Methods A total of 236 randomly selected, consenting Saudi adult participants (166 males and 70 females) were recruited and screened for the presence of the metabolic syndrome (MetS) using the modified National Cholesterol Education Program–Adult Treatment Panel III definition. Blood thiamine and its derivatives were quantified using HPLC. Results A total of 140 participants (53.9%) had MetS. The levels of thiamine and its derivatives of those with MetS were not significantly different from those without. However, hypertensive subjects had significantly higher urinary thiamine (P = 0.03) as well as significantly lower levels of thiamine diphosphate (TDP) (P = 0.01) and total thiamine (P = 0.02) than the normotensive subjects, even after adjusting for age and body mass index (BMI). Furthermore, age- and BMI-matched participants with elevated blood glucose levels had significantly lower levels of thiamine monophosphate (P = 0.020), TDP (P < 0.001) and total thiamine (P < 0.001) and significantly elevated levels of urinary thiamine (P = 0.005) compared to normoglycemic participants. Conclusions Low thiamine levels are associated with elevated blood glucose and hypertension in Saudi adults. Determination of thiamine status may be considered and corrected among patients with, or at high risk for, MetS, but the question whether thiamine deficiency correction translates to improved cardiometabolic status needs further longitudinal investigation. PMID:24059534

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis.

PubMed

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P

2013-11-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66b(high)) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14(+)CD33(+) cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14(+)CCL11(+) mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14(+)CD33(+) myeloid cells, CCL11, and eosinophils in adult UC.

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis

PubMed Central

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P.

2013-01-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66bhigh) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14+CD33+ cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14+CCL11+ mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14+CD33+ myeloid cells, CCL11, and eosinophils in adult UC. PMID:23904440

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome

PubMed Central

Zhang, Guangjian; Gao, Rui; Wang, Yuanbo; Liu, Yan; Li, Juan; Jia, Xi; Liang, Yiqian; Yang, Aimin

2018-01-01

Aims To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake. PMID:29423055

Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

PubMed

Koiou, Ekaterini; Tziomalos, Konstantinos; Katsikis, Ilias; Kandaraki, Eleni A; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Vosnakis, Christos; Panidis, Dimitrios

2012-01-01

Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m(2)) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

Preclinical High-Dose Acetaminophen With N-Acetylcysteine Rescue Enhances the Efficacy of Cisplatin Chemotherapy in Atypical Teratoid Rhabdoid Tumors

PubMed Central

Neuwelt, Alexander J.; Nguyen, Tam; Wu, Y. Jeffrey; Donson, Andrew M.; Vibhakar, Rajeev; Venkatamaran, Sujatha; Amani, Vladimir; Neuwelt, Edward A.; Rapkin, Louis B.; Foreman, Nicholas K.

2016-01-01

Background Atypical teratoid rhabdoid tumors (AT-RT) are pediatric tumors of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) with high dose acetaminophen (AAP), may improve therapeutic efficacy in AT-RT in vitro. Procedure BT16 (cisplatin-resistant) and BT12 (cisplatin-sensitive) AT-RT cell lines were treated with combinations of AAP, cisplatin, and the anti-oxidant N-acetylcysteine (NAC). Cell viability, GSH and peroxide concentrations, mitochondrial damage, and apoptosis were evaluated in vitro. Results AAP enhanced cisplatin cytotoxicity in cisplatin-resistant BT16 cells but not cisplatin-sensitive BT12 cells. Baseline GSH levels were elevated in BT16 cells compared to BT12 cells, and AAP decreased GSH to a greater magnitude in BT16 cells than BT12 cells. Unlike BT12 cells, BT16 cells did not have elevated peroxide levels upon treatment with cisplatin alone, but did have elevated levels when treated with AAP + cisplatin. Both cell lines had markedly increased mitochondrial injury when treated with AAP + cisplatin relative to either drug treatment alone. The enhanced toxic effects were partially reversed with concurrent administration of NAC. Conclusions Our results suggest that AAP could be used as a chemo-enhancement agent to potentiate cisplatin chemotherapeutic efficacy particularly in cisplatin-resistant AT-RT tumors with high GSH levels in clinical settings. PMID:23956023

Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum

PubMed Central

Young, Brett C.; Stanic, Aleksandar K.; Panda, Britta; Rueda, Bo R.; Panda, Alexander

2014-01-01

OBJECTIVE Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies. PMID:24291497

Type XVIII collagen degradation products in acute lung injury

PubMed Central

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

2009-01-01

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

PubMed Central

TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

2014-01-01

Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

Adult Sickle Cell Anaemia Patients in Bone Pain Crisis have Elevated Pro-Inflammatory Cytokines

PubMed Central

Alagbe, Adekunle Emmanuel; Aworanti, Oladapo Wale

2018-01-01

Background and Objectives Inflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients. Methods and Materials Sixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p<0.05. Results Plasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group. Conclusion Elevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA. PMID:29531654

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

PubMed Central

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Globalization, Binational Communities, and Imported Food Risks: Results of an Outbreak Investigation of Lead Poisoning in Monterey County, California

PubMed Central

Handley, Margaret A.; Hall, Celeste; Sanford, Eric; Diaz, Evie; Gonzalez-Mendez, Enrique; Drace, Kaitie; Wilson, Robert; Villalobos, Mario; Croughan, Mary

2007-01-01

Objectives. Although the burden of lead poisoning has decreased across developed countries, it remains the most prevalent environmental poison worldwide. Our objective was to investigate the sources of an outbreak of lead poisoning in Monterey County, California. Methods. An investigation in 3 county health department clinics in Monterey County, California, was conducted between 2001 and 2003 to identify risk factors for elevated blood lead levels (≥ 10 μg/dL) among children and pregnant women. Results. The prevalence of elevated blood lead levels was significantly higher in 1 of the 3 clinics (6% among screened children and 13% among prenatal patients). Risk factors included eating imported foods (relative risk [RR]=3.4; 95% confidence interval [CI]=1.2, 9.5) and having originated from the Zimatlan area of Oaxaca, Mexico, compared with other areas of Oaxaca (RR=4.0; 95% CI=1.7, 9.5). Home-prepared dried grasshoppers (chapulines) sent from Oaxaca were found to contain significant amounts of lead. Conclusions. Consumption of foods imported from Oaxaca was identified as a risk factor for elevated blood lead levels in Monterey County, California. Lead-contaminated imported chapulines were identified as 1 source of lead poisoning, although other sources may also contribute to the observed findings. Food transport between binational communities presents a unique risk for the importation PMID:17395841

Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

PubMed Central

Prajapati, Jayesh H.; Sahoo, Sibasis; Nikam, Tushar; Shah, Komal H.; Maheriya, Bhumika; Parmar, Meena

2014-01-01

Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) with high density lipoprotein (HDL) cholesterol levels in coronary artery disease (CAD) patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P = 0.008) and NLR (P = 0.009); however no significant relationship was obtained with HDL and isolated platelet (P = 0.488), neutrophil (P = 0.407), and lymphocyte (P = 0.952) counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P = 0.024) and NLR (P = 0.03) were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P = 0.01) and NLR (6.33 versus 5.10; P = 0.01) were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P = 0.007) and NLR (P = 0.001) were inversely associated with HDL, whereas in older population only NLR (P = 0.05) had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels. PMID:25478231

Association of high density lipoprotein with platelet to lymphocyte and neutrophil to lymphocyte ratios in coronary artery disease patients.

PubMed

Prajapati, Jayesh H; Sahoo, Sibasis; Nikam, Tushar; Shah, Komal H; Maheriya, Bhumika; Parmar, Meena

2014-01-01

Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) with high density lipoprotein (HDL) cholesterol levels in coronary artery disease (CAD) patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P = 0.008) and NLR (P = 0.009); however no significant relationship was obtained with HDL and isolated platelet (P = 0.488), neutrophil (P = 0.407), and lymphocyte (P = 0.952) counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P = 0.024) and NLR (P = 0.03) were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P = 0.01) and NLR (6.33 versus 5.10; P = 0.01) were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P = 0.007) and NLR (P = 0.001) were inversely associated with HDL, whereas in older population only NLR (P = 0.05) had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

PubMed Central

Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2014-01-01

Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

Influence of disposable, concentric needle electrodes on muscle enzyme and lactate serum levels.

PubMed

Finsterer, Josef; Mittendorfer, Bettina; Neuhuber, Werner; Löscher, Wolfgang N

2002-08-01

Several studies addressed the question whether needle-EMG causes elevation of muscle enzymes [aspartate-aminotransferase, alanine-aminotransferase, lactate-dehydrogenase, creatine-phosphokinase (CPK), isoenzyme-MB, aldolase] and lactate with conflicting results. However, these studies used sterilizable needle electrodes and different protocols and methods to record EMGs and determine muscle enzymes. This study examined if muscle enzymes are elevated immediately after or 24 h following EMGs with disposable, concentric needle-electrodes, and if they are dependent on age, sex, muscle, number of investigated sites and previous CPK-elevation. In 53 subjects, 24 woman, 29 men, aged 17-88 years, muscle enzymes were determined before, immediately after and 24 h following EMG with disposable, concentric needle-electrodes. Muscle enzymes were not different before, immediately after and 24 h following the EMG. Muscle enzymes were not different between patients 60 years of age. Apart from higher CPK in men than women, muscle enzymes were not different between the genders. Apart from CPK, muscle enzymes were not different between the brachial biceps and anterior tibial muscle. Muscle enzymes were not different if 20 sites were investigated and were independent on pre-EMG CPK-levels. In conclusion this study shows that muscle enzymes do not increase immediately or 24 h following EMG with disposable, concentric needle-electrodes, irrespective of age, gender, muscle, number of investigated sites and pre-EMG CK-levels.

Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

PubMed Central

2010-01-01

Background Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production. Methods Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis. Results Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency. Conclusion Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments. PMID:20178634

Environmental correlates underlying elevational richness, abundance, and biomass patterns of multi-feeding guilds in litter invertebrates across the treeline.

PubMed

Xu, Guorui; Zhang, Shuang; Zhang, Yuxin; Ma, Keming

2018-08-15

Elevational richness patterns and underlying environmental correlates have contributed greatly to a range of general theories of biodiversity. However, the mechanisms underlying elevational abundance and biomass patterns across several trophic levels in belowground food webs remain largely unknown. In this study, we aimed to disentangle the relationships between the elevational patterns of different trophic levels of litter invertebrates and their underlying environmental correlates for two contrasting ecosystems separated by the treeline. We sampled 119 plots from 1020 to 1770 asl in forest and 21 plots from 1790 to 2280 asl in meadow on Dongling Mountain, northwest of Beijing, China. Four functional guilds were divided based on feeding regime: omnivores, herbivores, predators, and detritivores. We used eigenvector-based spatial filters to account for spatial autocorrelation and multi-model selection to determine the best environmental correlates for the community attributes of the different feeding guilds. The results showed that the richness, abundance and biomass of omnivores declined with increasing elevation in the meadow, whereas there was a hump-shaped richness pattern for detritivores. The richness and abundance of different feeding guilds were positively correlated in the forest, while not in the meadow. In the forest, the variances of richness in omnivores, predators, and detritivores were mostly correlated with litter thickness, with omnivores being best explained by mean annual temperature in the meadow. In conclusion, hump-shaped elevational richness, abundance and biomass patterns driven by the forest gradient below the treeline existed in all feeding guilds of litter invertebrates. Climate replaced productivity as the primary factor that drove the richness patterns of omnivores above the treeline, whereas heterogeneity replaced climate for herbivores. Our results highlight that the correlated elevational richness, abundance, and biomass patterns of feeding guilds are ecosystem-dependent and that the underlying environmental correlates shifted at the treeline for most feeding guilds. Copyright © 2018 Elsevier B.V. All rights reserved.

Alanine transaminase level in a healthy population in Morocco.

PubMed

Laouina, A; Abouyoub, A; Soulaymani, A; Alami, R

2012-03-01

A little is known about the prevalence of elevated alanine transaminase in a Moroccan healthy population. Our aim was to search for the upper limit of normal alanine transaminase in the blood donors and then to apply the upper limit of normal alanine found in the population so as to assess the prevalence of subjects with abnormal transaminase level. We then, investigated for factors associated with increased level of transaminase in our population. This study was carried out on 14071 blood donors, (74.1% of men and 25.9% female) aged between 18 to 60 years, randomly chosen. Serum transaminase activity was measured using on IEMS Reader, Labsystems. Hepatitis B and C were performed by ELISA. The upper limit of normal transaminase found were 64 for men and 52 for women. Consequently, 2.08% blood donors had an abnormal level of transaminase. Follow up results revealed that drug was the first cause of elevated transaminase in our cohort followed by diet and alcohol consumption. One seroconversion for hepatitis C was identified. In conclusion, this study showed that even though there is an evident lack of efficiency in using alanine aminotransferase testing qualifying blood donors in our country, preventing viral potential transmission through transfusions was possible.

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

PubMed Central

Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

2014-01-01

Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

Rangeland -- Plant responses to elevated CO sub 2

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

Owensby, C.E.; Coyne, P.I.; Ham, J.M.

1992-01-01

Several broad conclusions which can be drawn from the work that was accomplished during the first 3-year phase of the study is described. In prairie ecosystems dominated by C{sub 4} grasses, it is likely that elevated atmospheric CO{sub 2} will increase ecosystem level productivity, with a greater increase in belowground productivity. The increased productivity will primarily result from increased water use efficiency due to the anti-transpirant action of CO{sub 2}. Fumigation chambers are directly confounded with elevated CO{sub 2} effects, in that both reduce evapotranspiration. The reduced evapotranspiration of the fumigation chamber is primarily through reduced wind speeds and reducedmore » radiation. In very dry years, fumigation chamber effects are negligible, but in years with normal precipitation, chamber effects and elevated CO{sub 2} effects are essentially equal with respect to reduced evapotranspiration effects. Increased production under elevated CO{sub 2} results in reduced nitrogen concentration in the herbage and increased fiber concentrations. Consequently, digestibility of the herbage is reduced, and microbial degradation of surface litter and soil organic matter is slowed. On the negative side, ruminant productivity will likely be reduced substantially, but increased carbon storage in the soil may buffer against future rise in atmospheric CO{sub 2}. Tallgrass prairie will not likely change greatly in botanical composition, since the C{sub 4} dominants responded to elevated CO{sub 2} more than the C{sub 3} subdominants.« less

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

PubMed Central

2013-01-01

Background A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Methods Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Results Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). Conclusion In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake. PMID:23565943

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

PubMed Central

Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

2014-01-01

Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters

PubMed Central

Anila, KR; Nayak, Nileena; Jayasree, K

2016-01-01

Introduction: Chronic lymphocytic thyroiditis [Hashimoto thyroiditis (HT)] is a common thyroid lesion diagnosed on fine-needle aspiration cytology (FNAC). Apart from FNAC, various other parameters, such as clinical features, ultrasonographic findings, antithyroid antibody levels, hormone profiles, and radionuclide thyroid scan, are also taken into consideration in making a diagnosis of HT. Aims: To grade lymphocytic thyroiditis based on the cytomorphology and to correlate the cytological grades with the levels of antithyroid peroxidase antibody (ATPO), antithyroglobulin antibody (ATG), and thyroid stimulating hormone (TSH). Materials and Methods: During a period of one and half years, 1,667 cases underwent FNAC of thyroid at our tertiary care center. Of these, 128 cases had cytological evidence of lymphocytic thyroiditis. Out of these, in 60 cases the levels of ATPO, ATG, and TSH were known. The cytological grades of lymphocytic thyroiditis in these cases were correlated with these parameters. Results: Out of the 60 cases, 55 were females. Age ranged from 5 years to 70 years, with majority of patients in third decade. Diffuse enlargement of thyroid was the commonest presentation. However, 14 cases presented with nodular disease. Majority of the patients had grade 1 thyroiditis (27 cases), followed by grade 2 thyroiditis (22 cases). Cytomorphology was diagnostic of thyroiditis in all 60 cases. ATPO was elevated in 57 cases and ATG was elevated in 40 cases. Elevated level of TSH was seen in only 18 cases. In 39 cases, TSH value was normal. There was no correlation between the cytological grades of thyroiditis and the levels of antithyroid antibodies and TSH. Conclusion: Lymphocytic infiltration of thyroid follicles is pathognomonic of lymphocytic thyroiditis. Positivity for antithyroid antibodies is strongly associated with HT but no correlation was observed between the grades of thyroiditis and the levels of ATPO, ATG, and TSH. PMID:27756987

Circulating microRNA 122 in the methionine and choline-deficient mouse model of non-alcoholic steatohepatitis.

PubMed

Clarke, John D; Sharapova, Tatiana; Lake, April D; Blomme, Eric; Maher, Jonathan; Cherrington, Nathan J

2014-06-01

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline-deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver-specific microRNA-122 (miR-122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR-122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR-122 levels were quantified in serum using RT-qPCR. Both miR-122 and ALT/AST levels were significantly elevated in serum at all timepoints. MiR-122 levels increased on average by 40-fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8- and 3.3-fold, respectively. In general, miR-122 levels remained elevated across all time points, whereas the ALT/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR-122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD-associated liver injury in mouse efficacy models. Copyright © 2013 John Wiley & Sons, Ltd.

Plasma kisspeptin levels in male cases with hypogonadism.

PubMed

Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

2014-01-01

The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

Influence of the pineal gland and melatonin on blood flow and evaporative water loss during heat stress in rats.

PubMed

Harlow, H J

1987-01-01

Plasma melatonin levels of laboratory rats were elevated both during acute heat exposure (43 degrees C for 40 min) and chronic exposure (33 degrees C for 17 days) suggesting a possible correlation between melatonin and thermoregulatory mechanisms. Pinealectomy reduced the nighttime elevation in oxygen consumption and evaporative water loss. In addition, pinealectomized animals exhibited a significantly lower cutaneous evaporative water loss both at night and during the day when exposed to an acute heat exposure of 38 degrees C for 45 min. Pinealectomy elevated the blood pressure over the control group whereas melatonin infusion depressed the blood pressure without altering the cardiac output. This relationship implies an action by melatonin on the peripheral vasculature. In support of this conclusion, melatonin pretreatment tended to dampen the vasopressive effect of infused norepinephrine. These data, therefore, suggest a role of the pineal gland and melatonin in thermoregulation through an influence on the cardiovascular system and evaporative water loss.

Elevated Plasma Soluble CD14 and Skewed CD16+ Monocyte Distribution Persist despite Normalisation of Soluble CD163 and CXCL10 by Effective HIV Therapy: A Changing Paradigm for Routine HIV Laboratory Monitoring?

PubMed Central

Castley, Alison; Berry, Cassandra; French, Martyn; Fernandez, Sonia; Krueger, Romano; Nolan, David

2014-01-01

Objective We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. Design Cross-sectional evaluation of concurrent plasma and whole blood samples. Methods A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA. Results HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001). Conclusions Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV infection. PMID:25544986

Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

PubMed

Raja, Harish; Snyder, Melissa R; Johnston, Patrick B; O'Neill, Brian P; Caraballo, Juline N; Balsanek, Joseph G; Peters, Brian E; Decker, Paul A; Pulido, Jose S

2013-01-01

Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Crucian, B. E.; Stowe, R. P.; Mehta, S.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

2010-01-01

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in 50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

PubMed Central

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, Christophe; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

2014-01-01

Background ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established. Methods and Results We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017). Conclusions In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction. PMID:18378613

Hepatopancreatic intoxication of lambda cyhalothrin insecticide on albino rats

PubMed Central

Elhalwagy, Manal EA; Abd-Alrahman, Sherif H; Nahas, AA; Ziada, Reem M; Mohamady, Aziza H

2015-01-01

Background: Despite the known adverse effects of lambda cyhalothrin insecticide, little is known about its hepatopancreatic intoxication effects. The present study was carried out to elucidate sub-chronic effect of Karat 2.5% EC formulation of lambda cyhalothrin on male albino rats. Methods: To explore the effects of exposure to lambda cyhalothrin on rats and its mechanism, low (1/40 of LD50, 5 mg/kg/day) and high dose (1/4 of LD50, 50 mg/kg/day) lambda cyhalothrin were applied to rats via drinking water for 3 months. Blood samples were collected monthly, and the animals were dissected for liver and pancreas’s examination at the end of the experiment. Lambda cyhalothrin administration was associated with the elevation in lipid peroxidation marker, malondialdehyde (MDA), reduction in SH-protein a major marker for antioxidant, as well as basel paraoxonase (PON) in both treated groups throughout the experimental periods. Results: In addition, significant elevations in liver enzymes alanin amino transferase, (ALT), and aspartate amino transferase (AST), as well as plasma acetylcholinesterase (AChE) and glucose level. While, significant reduction in insulin level through the experimental periods. Results of histopathological and histochemical studies showed that lambda cyhalothrin exposure induces liver and pancreatic tissues damage and depletion in glycogen content was pronounced in liver of both treated groups. Conclusions: In conclusion subchronic intoxication with lambda cyhalothrin formulation induced remarkable changes in the examined parameters. PMID:26221269

Elevated carbohydrate-deficient transferrin (CDT) and its normalization on dietary treatment as a useful biochemical test for hereditary fructose intolerance and galactosemia.

PubMed

Pronicka, Ewa; Adamowicz, Maciej; Kowalik, Agnieszka; Płoski, Rafał; Radomyska, Barbara; Rogaszewska, Małgorzata; Rokicki, Dariusz; Sykut-Cegielska, Jolanta

2007-07-01

Abnormalities in protein glycosylation are reported in fructosemia (HFI) and galactosemia, although, particularly in HFI, the published data are limited to single cases. The purpose was to investigate the usefulness of the carbohydrate-deficient transferrin (CDT) profile for identification and monitoring of these disorders. First we analyzed CDT values before and shortly after the diagnosis in 10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT levels were found that significantly (p < 0.0001) decreased with the therapeutic diet (27.3 +/- 11.5% versus 9.3 +/- 5.1% for HFI and 43.8 +/- 14.1% versus 11.2 +/- 4.0% for galactosemia). To evaluate the use of CDT test in monitoring compliance, the test was performed in 25 HFI patients on fructose-restricted diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 +/- 5.5%, control 1.5%-6.2%). The fructose intake was found to be 90 +/- 70 mg/kg/d, and the diet was unbalanced. A number of patients presented lower height, elevated urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal percentage of CDT (%CDT) values may allow prompt detection of HFI (or galactosemia). Persistence of some abnormalities in HFI on treatment may be caused by trace amounts of fructose ingestion and/or a deficient diet. Regular %CDT measurements are suggested for HFI treatment monitoring.

Increased Prevalence of Luminal Narrowing and Stricturing Identified by Enterography in Pediatric Crohn Disease Patients with Elevated Granulocyte-Macrophage Colony Stimulating Factor Auto-antibodies

PubMed Central

Dykes, Dana M.H.; Towbin, Alexander J.; Bonkowski, Erin; Chalk, Claudia; Bezold, Ramona; Lake, Kathleen; Kim, Mi-Ok; Heubi, James E.; Trapnell, Bruce C.; Podberesky, Daniel J.; Denson, Lee A.

2013-01-01

Background Crohn disease (CD) patients with elevated Granulocyte-Macrophage Colony-Stimulating Factor auto-antibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed Tomography or Magnetic Resonance Enterography (CTE or MRE) may detect luminal narrowing (LN) prior to stricture development. Objective To determine whether CD patients with elevated GM-CSF Ab (≥ 1.6 mcg/mL) have a higher prevalence of LN and stricturing on CTE or MRE. Methods A single center, cross-sectional study of 153 pediatric CD patients and controls undergoing CTE or MRE. A novel scoring system evaluated for disease activity, presence of LN, stricture, intra-abdominal abscess, or fistulae Ouutcomes were compared with respect to antibody status using Fisher's exact test, logistic regression, and the unpaired t-test. Results GM-CSF Ab were elevated in CD patients (n=114) with a median (IQR) GM-CSF Ab level of 2.3 mcg/mL (0.5, 6.6) compared with healthy and disease controls, p=0.001. Ileal disease location was more common in CD patients with high GM-CSF Ab, p<0.001. Luminal narrowing increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (p=0.004). High GM-CSF Ab remained significantly associated with LN in a multivariate logistic model. Stricturing increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (p=0.03). Conclusions Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients. PMID:23893081

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

PubMed Central

Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2016-01-01

OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647

Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children.

PubMed

Gabriele, Stefano; Sacco, Roberto; Altieri, Laura; Neri, Cristina; Urbani, Andrea; Bravaccio, Carmela; Riccio, Maria Pia; Iovene, Maria Rosaria; Bombace, Francesca; De Magistris, Laura; Persico, Antonio M

2016-07-01

The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus.

PubMed

Wu, Guo-Cui; Yuan, Hui; Pan, Hai-Feng; Ye, Dong-Qing

2017-06-20

Emerging evidence suggests that two heparin-binding growth factor, midkine and pleiotrophin are implicated in the pathogenesis of autoimmune diseases including SLE. To investigate the plasma midkine and pleiotrophin levels in SLE patients, as well as their correlation with major clinical parameters and interleukin-17 (IL-17) level in SLE, 83 SLE patients and 123 controls including 20 rheumatoid arthritis (RA) patients, 21 Sjögren's syndrome (SS) patients and 82 healthy controls (HCs) were recruited. Plasma midkine, pleiotrophin and IL-17 levels were detected by ELISA. Midkine and pleiotrophin levels were significantly higher in SLE, RA and SS patients compared with HCs (all P < 0.05). There were significantly lower midkine and pleiotrophin levels in SLE compared to SS (P < 0.05 and P < 0.01, respectively). No significant differences in midkine and pleiotrophin levels were found between SLE and RA (P = 0.240 and P = 0.074, respectively). Both plasma midkine and pleiotrophin levels were associated with rash and anti-SSA in SLE. In addition, both midkine and pleiotrophin levels were positively associated with IL-17 level in SLE (both P < 0.001). Area under curve (AUC) of the receiver operating characteristic (ROC) curve for midkine and pleiotrophin were 0.606 (0.527-0.681) and 0.605 (0.526-0.680) respectively. In conclusion, elevated plasma midkine and pleiotrophin levels and their associations with rash, anti-SSA and IL-17 in SLE patients suggest their involvement in this disease.

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

PubMed Central

Muehling, Bernd; Oberhuber, Alexander; Schelzig, Hubert; Bischoff, Gisela; Marx, Nikolaus; Sunder-Plassmann, Ludger; Orend, Karl H

2008-01-01

Background and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated. PMID:19337556

Serum HSP70

PubMed Central

Dutta, Sudhir K.; Girotra, Mohit; Singla, Montish; Dutta, Anand; Stephen, F. Otis; Nair, Padmanabhan P.; Merchant, Nipun B.

2014-01-01

Objectives Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. Methods Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. Results The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. Conclusions Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer. PMID:22158074

Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis

PubMed Central

Kershaw, Kiarri N.; Mezuk, Briana; Abdou, Cleopatra M.; Rafferty, Jane A.; Jackson, James S.

2010-01-01

Objective We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults. Design We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity. Main outcome measures CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L). Results Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity. Conclusion These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise. PMID:20496985

Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma

PubMed Central

Salmasi, Vafi; Schiavi, Adam; Binder, Zev A.; Ruzevick, Jacob; Orr, Brent A.; Burger, Peter C.; Ball, Douglas W.; Blitz, Ari M.; Koch, Wayne M.; Ishii, Masaru; Gallia, Gary L.

2015-01-01

Background Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. Methods We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed intraoperative hypertensive crisis. Results A patient with history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Work-up revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade prior to the second stage. Serum catecholamine levels following this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in cathecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Conclusion Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. PMID:25352487

Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

PubMed

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

2018-02-14

Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μg/L). In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients.

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

PubMed Central

Draborg, Anette H.; Lydolph, Magnus C.; Westergaard, Marie; Olesen Larsen, Severin; Nielsen, Christoffer T.; Duus, Karen; Jacobsen, Søren; Houen, Gunnar

2015-01-01

Objective In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs’ association with Epstein-Barr virus (EBV) antibodies was examined. Methods Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance. Results Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001) also after adjusting for Ig levels (p<0.0001). The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI)) score of the SLE patients (r = 0.399, p = 0.007). Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA) concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation) whereas EBV-directed antibodies reflect the extent of previous infection/reactivations. Conclusion SLE patients have elevated concentrations of serum FLCs that correlate with global disease activity scores and especially serologic markers for active disease. These findings are suggestive of circulating FLCs having potential as a new supplementary serologic biomarker in SLE. PMID:26402865

The U.S. Food and Drug Administration Risk Assessment on Lead in Women’s and Children’s Vitamins Is Based on Outdated Assumptions

PubMed Central

Miodovnik, Amir; Landrigan, Philip J.

2009-01-01

Background Following a recent report of lead in certain commercial vitamin products, the U.S. Food and Drug Administration (FDA) conducted a nationwide survey to determine the Pb content in 324 multivitamin/mineral products labeled for use by women and children. The FDA compared estimated Pb exposures from each product with safe/tolerable exposure levels, termed provisional total tolerable intake (PTTI) levels, previously developed for at-risk population groups in 1992. Objective We investigated the FDA’s conclusions that Pb concentrations in all vitamin products examined do not pose a hazard to health because they are below the PTTI levels for all groups considered. Discussion For their initial estimations of PTTI levels, the FDA used a blood lead level (BLL) of 10 μg/dL as the threshold for adverse effects in children and in pregnant or lactating women. Studies have repeatedly linked chronic exposure to BLLs < 10 μg/dL with impairments in cognitive function and behavior in young children despite the absence of overt signs of toxicity. The FDA analysis also omitted any consideration of nonfood sources of Pb exposure, which is inconsistent with our current understanding of how most children develop elevated BLLs. Conclusion We feel that based on these oversights, the FDA’s conclusions are unduly reassuring and that reconsideration of their current recommendations appears warranted. PMID:19654907

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Blood pressure interacts with APOE ε4 to predict memory performance in a midlife sample

PubMed Central

Oberlin, Lauren E.; Manuck, Stephen B.; Gianaros, Peter J.; Ferrell, Robert E.; Muldoon, Matthew F.; Jennings, J. Richard; Flory, Janine D.; Erickson, Kirk I.

2015-01-01

Objective Elevated blood pressure and the Apolipoprotein ε4 allele (APOE ε4) are independent risk factors for Alzheimer’s disease. We sought to determine whether the combined presence of the APOE ε4 allele and elevated blood pressure is associated with lower cognitive performance in cognitively healthy middle-aged adults. Methods A total of 975 participants aged 30–54 (mean age = 44.47) were genotyped for APOE. Cardiometabolic risk factors including blood pressure, lipids, and glucose were assessed and cognitive function was measured using the Trail Making Test and the Visual Reproduction and Logical Memory subtests from the Wechsler Memory Scale. Results Multivariable regression analysis showed that the association between APOE ε4 and episodic memory performance varied as a function of systolic blood pressure (SBP), such that elevated SBP was predictive of poorer episodic memory performance only in APOE ε4 carriers (β = −.092; t = −2.614; p = .009). Notably, this association was apparent at prehypertensive levels (≥ 130 mm Hg), even after adjusting for physical activity, depression, smoking, and other cardiometabolic risk factors. Conclusions The joint presence of APOE ε4 and elevated SBP, even at prehypertensive levels, is associated with lower cognitive performance in healthy, middle-aged adults. Results of this study suggest that the combination of APOE ε4 and elevated SBP may synergistically compromise memory function well before the appearance of clinically significant impairments. Interventions targeting blood pressure control in APOE ε4 carriers during midlife should be studied as a possible means to reduce the risk of cognitive decline in genetically susceptible samples. PMID:25730733

Ragweed (Ambrosia artemisiifolia) pollen allergenicity: SuperSAGE transcriptomic analysis upon elevated CO2 and drought stress

PubMed Central

2014-01-01

Background Pollen of common ragweed (Ambrosia artemisiifolia) is a main cause of allergic diseases in Northern America. The weed has recently become spreading as a neophyte in Europe, while climate change may also affect the growth of the plant and additionally may also influence pollen allergenicity. To gain better insight in the molecular mechanisms in the development of ragweed pollen and its allergenic proteins under global change scenarios, we generated SuperSAGE libraries to identify differentially expressed transcripts. Results Ragweed plants were grown in a greenhouse under 380 ppm CO2 and under elevated level of CO2 (700 ppm). In addition, drought experiments under both CO2 concentrations were performed. The pollen viability was not altered under elevated CO2, whereas drought stress decreased its viability. Increased levels of individual flavonoid metabolites were found under elevated CO2 and/or drought. Total RNA was isolated from ragweed pollen, exposed to the four mentioned scenarios and four SuperSAGE libraries were constructed. The library dataset included 236,942 unique sequences, showing overlapping as well as clear differently expressed sequence tags (ESTs). The analysis targeted ESTs known in Ambrosia, as well as in pollen of other plants. Among the identified ESTs, those encoding allergenic ragweed proteins (Amb a) increased under elevated CO2 and drought stress. In addition, ESTs encoding allergenic proteins in other plants were also identified. Conclusions The analysis of changes in the transcriptome of ragweed pollen upon CO2 and drought stress using SuperSAGE indicates that under global change scenarios the pollen transcriptome was altered, and impacts the allergenic potential of ragweed pollen. PMID:24972689

The association of the blood lead level and serum lipid concentrations may be modified by the genetic combination of the metallothionein 2A polymorphisms rs10636 GC and rs28366003 AA.

PubMed

Yang, Chen-Cheng; Chuang, Chih-Shien; Lin, Chia-I; Wang, Chao-Ling; Huang, Yung-Cheng; Chuang, Hung-Yi

Lead in blood can stimulate lipid oxidation in phosphatidylcholine and increase peroxidation in lipids. Metallothionein (MT) is a cysteine-rich protein that can influence the detoxification of heavy metals and scavenge oxidative stress for free radicals. One of the most expressive functional genes in humans is the MT2A gene. This study aims to determine if the association of the blood lead level and lipid biomarkers was influenced by MT2A polymorphisms. We recruited 677 participants after informed consent was obtained. All the samples collected were analyzed for lipid biomarkers and blood lead levels and were genotyped for MT2A polymorphisms by reverse transcription polymerase chain reaction. A short questionnaire collected the medical history and alcohol and cigarette consumption information. The data were used for descriptive analyses and linear regression models. The investigation revealed that lead elevated concentration increased low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol (HDL-C) by multiple linear models. The carriers of the rs10636 GC-rs28366003 AA genetic combination may be less susceptive to lead elevated concentration on HDL-C than other types. In conclusion, the association of the blood lead level and HDL-C may be modified by the MT2A genetic combination: the rs10636 GC-rs28366003 AA genotype could play a protective role in lead elevated concentration on HDL-C in humans. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure.

PubMed

Leonis, Mike A; Toney-Earley, Kenya; Degen, Sandra J F; Waltz, Susan E

2002-11-01

The targeted deletion of the cytoplasmic domain of the Ron receptor tyrosine kinase (TK) in mice leads to exaggerated responses to injury in several murine models of inflammation as well as increased lethality in response to endotoxin (lipopolysaccharide [LPS]). Using a well-characterized model of LPS-induced acute liver failure (ALF) in galactosamine (GalN)-sensitized mice, we show that Ron TK(-/-) mice display marked protection compared with control Ron TK(+/+) mice. Whereas control mice have profound elevation of serum aminotransferase levels (a marker of hepatocyte injury) and hemorrhagic necrosis of the liver, in dramatic contrast, Ron TK(-/-) mice have mild elevation of aminotransferase levels and relatively normal liver histology. These findings are associated with a reduction in the number of liver cells undergoing apoptosis in Ron TK(-/-) mice. Paradoxically, treatment of Ron TK(-/-) mice with LPS/GalN leads to markedly elevated (3.5-fold) serum levels of tumor necrosis factor (TNF) alpha, a key inflammatory mediator in this liver injury model, as well as reduced amounts of interleukin (IL) 10 (a suppressor of TNF-alpha production) and interferon (IFN)-gamma (a TNF-alpha sensitizer). These results show that ablation of the TK activity of the Ron receptor leads to protection from the development of hepatocellular apoptosis in response to treatment with LPS/GalN, even in the presence of excessive levels of serum TNF-alpha. In conclusion, our studies show that the Ron receptor TK plays a critical role in modulating the response of the liver to endotoxin.

Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response

PubMed Central

Halperin, John J.; Kurlan, Roger; Schwalb, Jason M.; Cusimano, Michael D.; Gronseth, Gary; Gloss, David

2015-01-01

Objective: We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. Methods: We identified and classified relevant published studies according to 2004 and 2011 American Academy of Neurology methodology. Results: Of 21 articles, we identified 3 Class I articles. Conclusions: Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI. Recommendations: Clinicians may choose to offer shunting for subjective iNPH symptoms and gait (Level C). Because of significant adverse event risk, risks and benefits should be carefully weighed (Level B). Clinicians should inform patients with iNPH with elevated Ro and their families that they have an increased chance of responding to shunting compared with those without such elevation (Level B). Clinicians may counsel patients with iNPH and their families that (1) positive response to external lumbar drainage or to repeated lumbar punctures increases the chance of response to shunting, and (2) increasing age does not decrease the chance of shunting being successful (both Level C). PMID:26644048

Effect of Hibiscus sabdariffa extract on high fat diet–induced obesity and liver damage in hamsters

PubMed Central

Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

2015-01-01

Background Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. Objective In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Method Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Results Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. Conclusions In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity. PMID:26475512

Factors determining extreme brain natriuretic peptide elevation.

PubMed

Guglin, Maya; Hourani, Rayan; Pitta, Sridevi

2007-01-01

Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects its severity. It is unknown why some patients have extremely high BNP levels. The authors retrospectively reviewed data on 179 consecutive patients whose BNP levels fell within one of several predetermined ranges: mild elevation, 500 to 1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted with the unpaired t test and Pearson's correlation coefficient. Adjustments were made for age, sex, and serum creatinine level. Patients with moderate BNP elevation were more symptomatic and had more advanced structural and hemodynamic changes than did patients with lower BNP elevation. Characteristics of the high BNP level group did not differ from those of the moderate BNP level group. Serum creatinine level correlated with BNP level, but neither age nor sex did. High BNP level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the severity of heart failure.

S100B overexpression increases behavioral and neural plasticity in response to the social environment during adolescence.

PubMed

Buschert, Jens; Hohoff, Christa; Touma, Chadi; Palme, Rupert; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

2013-11-01

Genetic variants as well as increased serum levels of the neurotrophic factor S100B are associated with different psychiatric disorders. However, elevated S100B levels are also related to a better therapeutic outcome in psychiatric patients. The functional role of elevated S100B in psychiatric disorders is still unclear. Hence, this study was designed in order to elucidate the differential effects of S100B overexpression in interaction with chronic social stress during adolescence on emotional behavior and adult neurogenesis. S100B transgenic and wild-type mice were housed either in socially stable or unstable environments during adolescence, between postnatal days 28 and 77. In adulthood, anxiety-related behavior in the open field, dark-light, and novelty-induced suppression of feeding test as well as survival of proliferating hippocampal progenitor cells were assessed. S100B transgenic mice revealed significantly reduced anxiety-related behavior in the open field compared to wild-types when reared in stable social conditions. In contrast, when transgenic mice grew up in unstable social conditions, their level of anxiety-related behavior was comparable to the levels of wild-type mice. In addition, S100B overexpressing mice from unstable housing conditions displayed higher numbers of surviving newborn cells in the adult hippocampus which developed into mature neurons. In conclusion, elevated S100B levels increase the susceptibility to environmental stimuli during adolescence resulting in more variable behavioral and neural phenotypes in adulthood. In humans, this increased plasticity might lead to both, enhanced risk for psychiatric disorders in negative environments and improved therapeutic outcome in positive environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

PubMed Central

Peluso, Michael J.; Valcour, Victor; Ananworanich, Jintanat; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L. K.; Lerdlum, Sukalya; Chomchey, Nitiya; Slike, Bonnie; Sailasuta, Napapon; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2015-01-01

Background. It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Methods. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Results. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = −0.40; P = .03), frontal white matter (r = −0.46; P = .01), and parietal gray matter (r = −0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = −0.51; P = .02) and parietal gray matter (r = −0.46; P = .04). Conclusions. CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health. PMID:25995196

Total homocysteine and cognition in a tri-ethnic cohort

PubMed Central

Wright, C.B.; Lee, H.-S.; Paik, M.C.; Stabler, S.P.; Allen, R.H.; Sacco, R.L.

2005-01-01

Objective: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. Method: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. Results: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI −3.6, −0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE −2.2 points; 95% CI −3.5, −0.9). Conclusions: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors. PMID:15277617

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I. PMID:21867536

AGEs/sRAGE, a novel risk factor in the pathogenesis of end-stage renal disease.

PubMed

Prasad, Kailash; Dhar, Indu; Zhou, Qifeng; Elmoselhi, Hamdi; Shoker, Muhammad; Shoker, Ahmed

2016-12-01

Interaction of advanced glycation end products (AGEs) with its cell-bound receptor (RAGE) results in cell dysfunction through activation of nuclear factor kappa-B, increase in expression and release of inflammatory cytokines, and generation of oxygen radicals. Circulating soluble receptors, soluble receptor (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of sRAGE and esRAGE have been proposed as biomarkers for many diseases. However sRAGE and esRAGE levels are elevated in diabetes and chronic renal diseases and still tissue injury occurs. It is possible that increases in levels of AGEs are greater than increases in the levels of soluble receptors in these two diseases. Some new parameters have to be used which could be an universal biomarkers for cell dysfunction. It is hypothesized that increases in serum levels of AGEs are greater than the increases in the soluble receptors, and that the levels of AGEs is correlated with soluble receptors and that the ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE are elevated in patients with end-stage renal disease (ESRD) and would serve as an universal risk marker for ESRD. The study subject comprised of 88 patients with ESRD and 20 healthy controls. AGEs, sRAGE and esRAGE were measured using commercially available enzyme linked immune assay kits. cRAGE was calculated by subtracting esRAGE from sRAGE. The data show that the serum levels of AGEs, sRAGE, cRAGE are elevated and that the elevation of AGEs was greater than those of soluble receptors. The ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE were elevated and the elevation was similar in AGEs/sRAGE and AGEs/cRAGE but greater than AGEs/esRAGE. The sensitivity, specificity, accuracy, and positive and negative predictive value of AGEs/sRAGE and AGEs/cRAGE were 86.36 and 84.88 %, 86.36 and 80.95 %, 0.98 and 0.905, 96.2 and 94.8 %, and 61.29 and 56.67 % respectively. There was a positive correlation of sRAGE with esRAGE and cRAGE, and AGEs with esRAGE; and negative correlation between sRAGE and AGEs/sRAGE, esRAGE and AGES/esRAGE, and cRAGE and AGES/cRAGE. In conclusion, AGEs/sRAGE, AGEs/cRAGE and AGEs/esRAGE may serve as universal risk biomarkers for ESRD and that AGEs/sRAGE and AGEs/cRAGE are better risk biomarkers than AGEs/esRAGE.

Navy Shipboard Cargo and Weapons Elevator Controller and Sensor Subsystem Problem Analysis.

DTIC Science & Technology

1981-12-24

safe operation, and standardization. The conclusion of the review was that elevator manufact - urers in general have motives in design and construction...controller. Two days are spent on the elevator theory and the rest in hands-on training and trouble-shooting bad cards. There is also a 26-week...was spent on the two computer con- trolled elevators than on all of the remaining 20 freight, food , and weapons elevators on the ship. Phoenix

Mean Cancer Mortality Rates in Low Versus High Elevation Counties in Texas

PubMed Central

Hart, John

2010-01-01

There is controversy as to whether low levels of radiation (i.e., < 5 rem) pose a health risk. This brief inquiry compares archived cancer mortality data in counties having relatively low (0–250 feet above sea level), medium (500–1000 feet above sea level), and high (3000+ feet above sea level) elevations also having corresponding greater natural background levels of radiation respectively. Cancer mortality was found to be lowest in the high elevation counties (mean = 58.2) followed by low elevation counties (67.5) and then medium elevation counties (70.4). Statistically significant differences were found between low –high elevations (p = 0.003), and medium – high elevations (p = 0.010), but not between low and medium elevations (p = 0.5). More rigorous research, with an accounting of confounding variables, is indicated. PMID:21191484

Cardiac ACE2/angiotensin 1–7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy

PubMed Central

Diniz, Gabriela P.; Senger, Nathalia; Carneiro-Ramos, Marcela S.; Santos, Robson A. S.; Barreto-Chaves, Maria Luiza M.

2015-01-01

Objectives: Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin–angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1–7 (Ang 1–7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1–7, ACE2 and Mas receptor levels. Methods: Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Results: Although plasma Ang 1–7 levels were unchanged by hyperthyroidism, cardiac Ang 1–7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1–7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1–7 levels were accompanied by increased Mas receptor protein levels. Conclusion: The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. PMID:26715125

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

PubMed Central

Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu; Bonkowski, Erin; Rowehl, Leahana; Krumsiek, Julia; Nix, Billy; Chalk, Claudia; Trapnell, Bruce; Zhu, Wei; Newberry, Rodney; Denson, Lee; Li, Ellen

2018-01-01

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. PMID:29434451

Chronic Restraint Stress after Injury and Shock is Associated with Persistent Anemia despite Prolonged Elevation in Erythropoietin Levels

PubMed Central

Bible, Letitia E.; Pasupuleti, Latha V.; Gore, Amy V.; Sifri, Ziad C.; Kannan, Kolenkode B.; Mohr, Alicia M.

2015-01-01

Background Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (CS) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia, and prolong the initial anemia, despite elevated erythropoietin levels. Methods Male Sprague-Dawley Rats (N=6–8/group) underwent lung contusion (LC) or combined lung contusion/hemorrhagic shock (LCHS) followed by six days of chronic stress (CS). CS consisted of a two hour restraint period interrupted with repositioning and alarms every 30 minutes. At seven days, urine was assessed for norepinephrine (NE) levels, blood for erythropoietin (EPO) and hemoglobin (Hgb), and BM for erythroid progenitor growth. Results Animals undergoing LC or combined LCHS predictably recovered by day seven; urine NE, EPO and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on day six. The addition of CS to LC led to a persistent 20–25% decrease in the growth of BM HPCs. These findings were further exaggerated when CS was added following LCHS, resulting in a 20–40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared to LCHS alone. Conclusions Exposing injured animals to CS results in prolonged elevation of norepinephrine and erythropoietin which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating chronic stress after severe injury is a potential therapeutic target to improve BM dysfunction and anemia. PMID:26091320

Role of CYP2E1 immunoglobulin G4 subclass antibodies and complement in pathogenesis of idiosyncratic drug-induced hepatitis.

PubMed

Njoku, Dolores B; Mellerson, Jenelle L; Talor, Monica V; Kerr, Douglas R; Faraday, Nauder R; Outschoorn, Ingrid; Rose, Noel R

2006-02-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.

Proteins altered by elevated levels of palmitate or glucose implicated in impaired glucose-stimulated insulin secretion

PubMed Central

Sol, E-ri M; Hovsepyan, Meri; Bergsten, Peter

2009-01-01

Background Development of type 2 diabetes mellitus (T2DM) is characterized by aberrant insulin secretory patterns, where elevated insulin levels at non-stimulatory basal conditions and reduced hormonal levels at stimulatory conditions are major components. To delineate mechanisms responsible for these alterations we cultured INS-1E cells for 48 hours at 20 mM glucose in absence or presence of 0.5 mM palmitate, when stimulatory secretion of insulin was reduced or basal secretion was elevated, respectively. Results After culture, cells were protein profiled by SELDI-TOF-MS and 2D-PAGE. Differentially expressed proteins were discovered and identified by peptide mass fingerprinting. Complimentary protein profiles were obtained by the two approaches with SELDI-TOF-MS being more efficient in separating proteins in the low molecular range and 2D-PAGE in the high molecular range. Identified proteins included alpha glucosidase, calmodulin, gars, glucose-6-phosphate dehydrogenase, heterogenous nuclear ribonucleoprotein A3, lon peptidase, nicotineamide adenine dinucleotide hydrogen (NADH) dehydrogenase, phosphoglycerate kinase, proteasome p45, rab2, pyruvate kinase and t-complex protein. The observed glucose-induced differential protein expression pattern indicates enhanced glucose metabolism, defense against reactive oxygen species, enhanced protein translation, folding and degradation and decreased insulin granular formation and trafficking. Palmitate-induced changes could be related to altered exocytosis. Conclusion The identified altered proteins indicate mechanism important for altered β-cell function in T2DM. PMID:19607692

Allergological and Toxicological Aspects in a Multiple Chemical Sensitivity Cohort

PubMed Central

Pigatto, Paolo D.; Minoia, Claudio; Ronchi, Anna; Brambilla, Lucia; Ferrucci, Silvia M.; Spadari, Francesco; Passoni, Manuela; Somalvico, Francesco; Bombeccari, Gian Paolo

2013-01-01

Background. Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. Methods. We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. Results. The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 μg/L; mean in urine was 1.9 ± 2.5 μg/L; mean in scalp hair was 2.2 ± 2.5 μg/g; mean in saliva was 38.1 ± 52.1 μg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). Conclusions. Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS. PMID:24367721

Psychiatric symptoms, risky behavior, and HIV infection.

PubMed

Woody, G E; Metzger, D; Navaline, H; McLellan, T; O'Brien, C P

1997-01-01

These data are internally consistent and lead to several conclusions, as follows: Elevated levels of psychiatric symptoms were found among IDUs in methadone treatment as compared to their counterparts who were out of treatment. IVDUs who entered treatment had higher symptom levels than those who did not enter treatment. Higher symptom levels were found among injectors than noninjectors, and needle sharers had especially high psychiatric symptom levels. Higher symptom levels were found among those who seroconverted in the 6 months following notification, but not thereafter. Symptom levels did not distinguish between HIV-positive and HIV-negative individuals 24 months following notification of seropositivity. Taken together, these findings indicate that elevated psychiatric symptoms are risk factors for continued high risk behavior, as well as for seroconversion. The data add to those of Brooner and colleagues (1993), who demonstrated that ASPD serves as a risk factor for HIV infection. The fact that antisocial personality disorder and psychiatric severity are associated with risky behavior and with actual HIV infection further expands earlier findings showing that these two factors are associated with poorer treatment outcome. Other axis II disorders (e.g., borderline or narcissistic), as well as other axis I disorders with high symptom levels that were not well represented in these studies (schizophrenia, manic depressive illness), may also show similar elevated rates of risky behavior and seroconversion, although there is a scarcity of data currently available to assess the risk behavior of these patients. The evidence from treatment studies that psychiatrically focused therapies, when combined with substance abuse treatment, can improve overall outcome for patients with clinically significant levels of psychiatric symptoms may be relevant in the design of future risk reduction efforts. That is, these treatment outcome studies may serve as a starting point for exploring the feasibility and efficacy of using psychiatrically focused treatment to reduce risky behavior and HIV infection among psychiatrically symptomatic IDUs.

Atmospheric Characterization During Super-Resolution Vision System Developmental Testing

DTIC Science & Technology

2013-05-01

local time each day of the test. RM Young 81000 sonic anemometers were located at 0-, 800-, and 1800-m target points at 1.5-m elevation to provide point...estimates of C2n. Sonic anemometer data were also collected at a 0-km tower at several levels, providing a vertical turbulence profile. Turbulence...Atmospheric Instrumentation and Analysis 8 4. Estimation of C2n from Sonic Anemometer Data 11 5. Data Plots 14 6. Derived Results 32 7. Conclusions 36 8

Homocystein as a Risk Factor for Developing Complications in Chronic Renal Failure

PubMed Central

Jakovljevic, Biljana; Gasic, Branislav; Kovacevic, Pedja; Rajkovaca, Zvezdana; Kovacevic, Tijana

2015-01-01

Aim: Cardiovascular diseases are leading cause of death in patients with chronic renal failure. The aim of our study was to establish connection between levels of homocysteine and traditional and nontraditional risk factors for developing cardiovascular diseases in dialysis and pre dialysis patients. Methods: We included 33 pre dialysis (23 in stage three and 10 in stage four of chronic kidney disease) and 43 patients receiving hemodialysis longer than six months. Besides standard laboratory parameters, levels of homocysteine and blood pressure were measured in all patients. Glomerular filtration rate was measured in pre dialysis patients and dialysis quality parameters in dialysis patients. Results: Homocysteine levels were elevated in all patients (19±5.42mmol/l). The connection between homocysteine levels and other cardiovascular diseases risk factors was not established in pre dialysis patients. In patients treated with hemodialysis we found negative correlation between homocysteine levels and patients’ age (p<0.05) and positive correlation between homocysteine levels and length of dialysis (p<0.01) as well as between homocysteine and anemia parameters (erythrocytes, hemoglobin), (p<0.01). Homocysteine and LDL (and total cholesterol) were in negative correlation (p<0.01). Conclusion: Homocysteine, as one of nontraditional cardiovascular diseases risk factors, is elevated in all patients with chronic renal failure and it’s positive correlation with some other risk factors was found. PMID:26005384

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid, and Strontium Levels in Adult Men According to the US 2011–2012 National Health and Nutrition Examination Survey

PubMed Central

Liu, Hui; Héroux, Paul; Zhang, Qunwei; Jiang, Zhao-Yan; Gu, Aihua

2015-01-01

Background Little is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012). Methods Urinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio. Results Adjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone. Conclusions The National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men. PMID:25996772

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction

PubMed Central

Kim, Dong Hun; Kim, Hyun-Wook; Choi, Seo-Won; Kim, Bo-Bae; Chung, Joong-Wha; Koh, Young-Youp; Chang, Kyong-Sig; Hong, Soon-Pyo

2014-01-01

Background/Aims The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). Methods We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. Results The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). Conclusions The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity. PMID:25045293

Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease

PubMed Central

Liang, Jianbo; Yue, Caifeng; Wang, Fen; Song, Junli; Wang, Jianfeng; Liu, Min; Luo, Jinmei; Li, Laisheng

2016-01-01

Background Human epididymis protein 4 (HE4), has recently been reported as a mediator of renal fibrosis. However, serum HE4 levels appear in a large number of patient samples with chronic kidney disease (CKD), and the relationship of these levels to disease severity and renal fibrosis is unknown. Methods In 427 patients at different stages of CKD excluding gynecologic cancer and 173 healthy subjects, serum HE4 concentrations were tested by chemiluminescent microparticle immunoassay. Renal biopsy was performed on 259 of 427 subjects. Histological findings were evaluated using standard immunohistochemistry. Results The levels of serum HE4 were higher in CKD patients than in healthy subjects, and higher levels were associated with more severe CKD stages. Patients with more severe renal fibrosis tended to have higher HE4 levels, and correlation analysis showed a significant correlation between HE4 and degree of renal fibrosis (r = 0.938, P < 0.0001). HE4 can be a predictor of renal fibrosis in CKD patients; the area under the receiver-operating characteristic curve (AUC-ROC) was 0.99, higher than the AUC-ROC of serum creatinine (0.89). Conclusion Elevated levels of serum HE4 are associated with decreased kidney function, and also with an advanced stage of renal fibrosis, suggesting that HE4 may serve as a valuable clinical biomarker for renal fibrosis of CKD. PMID:27589683

Elevated Blood Pressure and Obesity in Childhood: A Cross-Sectional Evaluation of 4,609 Schoolchildren

PubMed Central

Rosaneli, Caroline Filla; Baena, Cristina Pellegrio; Auler, Flavia; Nakashima, Alika Terumi Arasaki; Netto-Oliveira, Edna Regina; Oliveira, Amauri Bássoli; Guarita-Souza, Luiz César; Olandoski, Marcia; Faria-Neto, José Rocha

2014-01-01

Background: The incidence of obesity in children is increasing worldwide, primarily in urbanized, high-income countries, and hypertension development is a detrimental effect of this phenomenon. Objective: In this cross-sectional study, we evaluated the prevalence of excess weight and its association with high blood pressure (BP) in schoolchildren. Methods: Here 4,609 male and female children, aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were evaluated. Nutritional status was assessed by body mass index (BMI) according to cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th percentile for gender, age and height percentile were considered elevated. Results: The prevalence of excess weight among the schoolchildren was 24.5%; 16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics were not associated with elevated BP. In all age groups, systolic and diastolic BP correlated with BMI and waist and hip measurements, but not with waist-hip ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61-2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89). Conclusion: Obese and overweight children had a higher prevalence of elevated BP than normal-weight children. Our data confirm that the growing worldwide epidemic of excess weight and elevated BP in schoolchildren may also be ongoing in Brazil. PMID:25076178

Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic β-Cell Dysfunction.

PubMed

Batchuluun, Battsetseg; Al Rijjal, Dana; Prentice, Kacey J; Eversley, Judith A; Burdett, Elena; Mohan, Haneesha; Bhattacharjee, Alpana; Gunderson, Erica P; Liu, Ying; Wheeler, Michael B

2018-05-01

Specific circulating metabolites have emerged as important risk factors for the development of diabetes. The acylcarnitines (acylCs) are a family of metabolites known to be elevated in type 2 diabetes (T2D) and linked to peripheral insulin resistance. However, the effect of acylCs on pancreatic β-cell function is not well understood. Here, we profiled circulating acylCs in two diabetes cohorts: 1 ) women with gestational diabetes mellitus (GDM) and 2 ) women with recent GDM who later developed impaired glucose tolerance (IGT), new-onset T2D, or returned to normoglycemia within a 2-year follow-up period. We observed a specific elevation in serum medium-chain (M)-acylCs, particularly hexanoyl- and octanoylcarnitine, among women with GDM and individuals with T2D without alteration in long-chain acylCs. Mice treated with M-acylCs exhibited glucose intolerance, attributed to impaired insulin secretion. Murine and human islets exposed to elevated levels of M-acylCs developed defects in glucose-stimulated insulin secretion and this was directly linked to reduced mitochondrial respiratory capacity and subsequent ability to couple glucose metabolism to insulin secretion. In conclusion, our study reveals that an elevation in circulating M-acylCs is associated with GDM and early stages of T2D onset and that this elevation directly impairs β-cell function. © 2018 by the American Diabetes Association.

Rangeland -- Plant responses to elevated CO{sub 2}. Progress report

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

Owensby, C.E.; Coyne, P.I.; Ham, J.M.

1992-10-01

Several broad conclusions which can be drawn from the work that was accomplished during the first 3-year phase of the study is described. In prairie ecosystems dominated by C{sub 4} grasses, it is likely that elevated atmospheric CO{sub 2} will increase ecosystem level productivity, with a greater increase in belowground productivity. The increased productivity will primarily result from increased water use efficiency due to the anti-transpirant action of CO{sub 2}. Fumigation chambers are directly confounded with elevated CO{sub 2} effects, in that both reduce evapotranspiration. The reduced evapotranspiration of the fumigation chamber is primarily through reduced wind speeds and reducedmore » radiation. In very dry years, fumigation chamber effects are negligible, but in years with normal precipitation, chamber effects and elevated CO{sub 2} effects are essentially equal with respect to reduced evapotranspiration effects. Increased production under elevated CO{sub 2} results in reduced nitrogen concentration in the herbage and increased fiber concentrations. Consequently, digestibility of the herbage is reduced, and microbial degradation of surface litter and soil organic matter is slowed. On the negative side, ruminant productivity will likely be reduced substantially, but increased carbon storage in the soil may buffer against future rise in atmospheric CO{sub 2}. Tallgrass prairie will not likely change greatly in botanical composition, since the C{sub 4} dominants responded to elevated CO{sub 2} more than the C{sub 3} subdominants.« less

Whole-body vibration exposure of haul truck drivers at a surface coal mine.

PubMed

Wolfgang, Rebecca; Burgess-Limerick, Robin

2014-11-01

Haul truck drivers at surface mines are exposed to whole-body vibration for extended periods. Thirty-two whole-body vibration measurements were gathered from haul trucks under a range of normal operating conditions. Measurements taken from 30 of the 32 trucks fell within the health guidance caution zone defined by ISO2631-1 for an 8 h daily exposure suggesting, according to ISO2631-1, that "caution with respect to potential health risks is indicated". Maintained roadways were associated with substantially lower vibration amplitudes. Larger trucks were associated with lower vibration levels than small trucks. The descriptive nature of the research, and small sample size, prevents any strong conclusion regarding causal links. Further investigation of the variables associated with elevated vibration levels is justified. The operators of mining equipment such as haul trucks are exposed to whole-body vibration amplitudes which have potential to lead to long term health effects. Systematic whole-body vibration measurements taken at frequent intervals are required to provide an understanding of the causes of elevated vibration levels and hence determine appropriate control measures. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Cardiovascular risk factors in pre-pubertal schoolchildren in Angola

PubMed Central

Silva, Amílcar BT; Rodrigues, Sérgio L; Baldo, Marcelo P; Mill, José Geraldo; Silva, Amílcar BT; Capingana, Daniel P; Magalhães, Pedro; Gonçalves, Mauer AA; Mateus, Miguel SB; Molina, Maria del Carmen B

2016-01-01

Summary Methods The incidence of obesity is increasing worldwide, especially in countries with accelerated economic growth. We determined the prevalence of and associations between overweight/ obesity and cardiovascular risk factors in pre-pubertal (seven- to 11-year-old) schoolchildren (both genders, n = 198) in Luanda, Angola. Biochemical (fasting blood) and clinical examinations were obtained in a single visit. Data are reported as prevalence (95% confidence intervals) and association (r, Pearson). Results Prevalence of overweight/obesity was 17.7% (12.4–23.0%), high blood pressure (BP < 90% percentile) was 14.6% (9.7–19.5%), elevated glucose level was 16.7% (11.5–21.9%) and total cholesterol level < 170 mg/dl (4.4 mmol/l) was 69.2% (62.8–75.6%). Significant associations between body mass index (BMI) and systolic and diastolic BP (r = 0.46 and 0.40, respectively; p < 0.05) were found. No association between BMI and elevated glucose or cholesterol levels was found. Conclusion The prevalence of cardiovascular risk factors was high in pre-pubertal schoolchildren in Angola and fat accumulation was directly associated with blood pressure increase but not with other cardiovascular risk factors. PMID:27805243

Stigmatization and Mental Health in a Diverse Sample of Transgender Women

PubMed Central

Yang, Mei-Fen; Manning, David; van den Berg, Jacob J.

2015-01-01

Abstract Purpose: Previous research indicates elevated risk for psychological distress in sexual and gender minority populations, and some research suggests that stigma contributes to elevated psychological distress among members of these groups. This study examined the hypothesis that exposure to transgender-related stigma (TRS) is associated with both higher levels of depression and anxiety among transgender women. Methods: We analyzed data from a diverse sample of 191 adult transgender women living or working in the San Francisco Bay area who were recruited using purposive sampling methods to participate in a cross-sectional survey, which included measures of stigmatization, depression, and anxiety. Results: Higher levels of exposure to TRS were independently associated with higher levels of depression (β=0.31, P<.001) and anxiety (β=39, P<.001), adjusting for self-reported health and sociodemographic co-variates. Associations between stigmatization, depression, and anxiety were not moderated by participants' age or race/ethnicity. Conclusion: Findings suggest a need for counseling interventions to address the role of stigmatization as a factor potentially contributing to psychological distress among transgender women. This research further highlights the need to develop a stronger evidence base on effective counseling approaches to improve the mental health of transgender women. PMID:26788771

Relationships among Blood Pressure, Triglycerides and Verbal Learning in African Americans

PubMed Central

Sims, Regina C.; Madhere, Serge; Gordon, Shalanda; Clark, Elijah; Abayomi, Kobi A.; Callender, Clive O.; Campbell, Alfonso L.

2013-01-01

Background Individuals at greater risk for cardiovascular disease (CVD) display poorer cognitive functioning across various cognitive domains. This finding is particularly prevalent among older adults; however, few studies examine these relationships among younger adults or among African Americans. Purpose The objective was to examine the relationships among 2 cardiovascular risk factors, elevated blood pressure and elevated triglycerides, and verbal learning in a community-based sample of African Americans. Methods Measurements of blood pressure and triglycerides were obtained in 121 African-American adults and compared to performance on 3 domains of the California Verbal Learning Test-II (CVLT-II). Results Blood pressure was not related to CVLT-II performance. Triglyceride levels were inversely related to CVLT-II performance. Higher triglyceride levels were associated with poorer immediate, short delay and long delay recall. Conclusions Consistent with studies involving older participants, the current investigation shows that in a nonelderly sample of African Americans, triglyceride levels may be related to cognitive functioning. Because early detection and intervention of vascular-related cognitive impairment may have a salutary effect, future studies should include younger adults to highlight the impact of cardiovascular risk on cognition. PMID:18942281

Environmental Lead Pollution and Elevated Blood Lead Levels Among Children in a Rural Area of China

PubMed Central

Lin, Sihao; Yu, Ignatius Tak Sun; Tang, Wenjuan; Miao, Jianying; Li, Jin; Wu, Siying; Lin, Xing

2011-01-01

Objectives. We investigated environmental lead pollution and its impact on children's blood lead levels (BLLs) in a rural area of China. Methods. In 2007, we studied 379 children younger than 15 years living in 7 villages near lead mines and processing plants, along with a control group of 61 children from another village. We determined their BLLs and collected environmental samples, personal data, and information on other potential exposures. We followed approximately 86% of the children who had high BLLs (> 15 μg/dL) for 1 year. We determined factors influencing BLLs by multivariate linear regression. Results. Lead concentrations in soil and household dust were much higher in polluted villages than in the control village, and more children in the polluted area than in the control village had elevated BLLs (87%, 16.4 μg/dL vs 20%, 7.1 μg/dL). Increased BLL was independently associated with environmental lead levels. We found a significant reduction of 5 micrograms per deciliter when we retested children after 1 year. Conclusions. Our data show that the lead industry caused serious environmental pollution that led to high BLLs in children living nearby. PMID:21421950

Women With Breast Cancer: Self-Reported Distress in Early Survivorship

PubMed Central

Lester, Joanne; Crosthwaite, Kara; Stout, Robin; Jones, Rachel N.; Holloman, Christopher; Shapiro, Charles; Andersen, Barbara L.

2015-01-01

Purpose/Objectives To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. Design Descriptive, cross-sectional. Setting A National Cancer Institute–designated comprehensive cancer center. Sample 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. Methods Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. Main Research Variables Distress scores, problem reports, and time groups. Findings Participants scored in range of the cutoff of more than 4 (range = 4.1–5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). Conclusions Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. Implications for Nursing Interventions to reduce or prevent distress may improve outcomes in early survivorship. PMID:25542330

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

PubMed Central

Richardson, Jason R.; Roy, Ananya; Shalat, Stuart L.; von Stein, Richard T.; Hossain, Muhammad M.; Buckley, Brian; Gearing, Marla; Levey, Allan I.; German, Dwight C.

2014-01-01

IMPORTANCE The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). OBJECTIVE To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. DESIGN, SETTING, AND PARTICIPANTS A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. MAIN OUTCOMES AND MEASURES Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. RESULTS Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54–5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. CONCLUSIONS AND RELEVANCE Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD. PMID:24473795

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

PubMed Central

Shin, So Youn; Jeong, Sook-Hyang; Sung, Pil Soo; Lee, Jino; Kim, Hyung Joon; Lee, Hyun Woong

2016-01-01

Purpose Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. Materials and Methods Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. Results Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. Conclusion We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis. PMID:26996565

Comparison of cardiovascular disease risk in two main forms of periodontitis

PubMed Central

Chopra, Rahul; Patil, Sudhir R.; Mathur, Shivani

2012-01-01

Background: C-reactive protein (CRP) is an acute phase reactant and has been proved to be a significant predictor of future cardiovascular events. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. However, comparison between the levels of CRP in two main forms of periodontitis is ambiguous. This study aims at determining and comparing the relative levels of serum CRP in aggressive and chronic periodontitis patients. Materials and Methods: A total of 240 systemically healthy subjects were divided into three groups of 80 based on having generalized aggressive periodontitis, chronic generalized periodontitis and non-periodontitis (NP; controls). Venous blood samples were collected for quantitative CRP analysis using turbidimetric immunoassay. Results: Mean CRP levels were significantly greater in both generalized aggressive periodontitis (7.49±2.31 mg/l) and chronic generalized periodontitis (4.88±1.80 mg/l) groups as compared to NP (0.68±0.23 mg/l) controls. Moreover, CRP levels were significantly higher in aggressive periodontitis as compared to chronic periodontitis patients. Also, CRP levels positively correlated with the amount of periodontal destruction as measured by probing depth and clinical attachment loss for both chronic generalized periodontitis and generalized aggressive periodontitis. Conclusion: Findings of the present study indicated that periodontitis should be of particular concern in younger individuals, where elevated levels of CRP may contribute to early or more rapid cardiovascular disease in susceptible patients. Thus, further research should be carried out at a community level to ascertain these findings. PMID:22363367

Elevation Withdrawal Letter - signed January 19, 1994

EPA Pesticide Factsheets

A letter to inform of the conclusion not to pursue elevation of permit decision regarding the Delta Environmental Land Trust Association for the development of mitigation banks in Louisiana, Mississippi, and Arkansas.

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

PubMed

Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

2018-04-17

Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable (P interaction =0.002). Conclusions -In the EXCEL trial, elevated baseline BNP levels in patients with LMCAD undergoing revascularization were independently associated with long-term mortality but not non-fatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI vs. CABG for revascularization of LMCAD may be conditioned by the baseline BNP level. Clinical Trial Registration -URL: http://www.clinicaltrials.gov. Unique identifier: NCT01205776.

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners

PubMed Central

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-01-01

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT (p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW (p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW (p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron. PMID:28335426

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners.

PubMed

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-03-14

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT ( p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW ( p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW ( p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron.

Polymorphism in beta fibrinogen -455 g/a gene was associated with diabetic in severe ischemic stroke patients

NASA Astrophysics Data System (ADS)

Ritarwan, Kiking; Kadri, Alfansuri; Juwita Sembiring, Rosita

2018-03-01

There is a association of polymorphism in the promoter region of the beta fibrinogen gene -455 G/A with enhancement plasma fibrinogen level. Diabetes mellitus is a risk factor for early neurologic deterioration in acute ischemic stroke. The prothrombotic fibrinogen protein is frequently elevated in patients with diabetes and may be association with poorer prognosis. This study evaluated the association of beta fibrinogen gene -455 G/A promoter polymorphism on modified Ranking Scale of Ischemic Stroke patients treated with diabetic and nondiabetic group. In a Cohort study design comprises 200 consecutive patients diabetic and a nondiabetic who, three months using completed a detailed outcome stroke. Of 200 samples genotype distribution were 27.1% for GG+GA and 0% for AA with diabetic and than 4.4% for GG+GA and 0.05% diabetic patients. Fibrinogen levels were higher in diabetic than nondiabetic group patients (307.7 + 106.3 vs 278 + 84 gr/dl, p=0.002). Fibrinogen level was found to be an independent predictor for diabetic patients. On Genotype GG+GA were associated wth diabetic and nondiabetic group patients. Modified Rankin Scale on day 90 were found associated with diabetic and nondiabetic patients. Conclusion: Elevated fibrinogen level is dose-dependently associated with 90 days outcome severity stroke with diabetic following ischemic stroke

Both hypothyroidism and hyperthyroidism increase plasma irisin levels in rats.

PubMed

Atici, Emine; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim; Menevse, Esma

2017-11-28

Background A recently discovered hormone, irisin is accepted to be significantly involved in the regulation of body weight. Thyroid functions may be, directly or indirectly, associated with irisin. Aim The aim of the present study is to determine the effect of experimental thyroid dysfunction on irisin levels in rats. Methods The study registered 40 adult male Sprague-Dawley rats, which were allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3. Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4. Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5. Hyperthyroidism + PTU. At the end of the study, blood samples were collected to quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin levels. Results FT3 and FT4 levels were reduced in hypothyroidism and were significantly elevated in hyperthyroidism (p < 0.001). Irisin values, on the other hand, were found to be elevated in both hypothyroidism and hyperthyroidism groups (p < 0.001). Conclusion The results of the study suggest that irisin values increase in thyroid dysfunction, hypo- and hyperthyroidism, and that when hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU injection, plasma irisin values go back to normal.

Neutrophil Collagenase, Gelatinase and Myeloperoxidase in Tears of Stevens-Johnson Syndrome and Ocular Cicatricial Pemphigoid Patients

PubMed Central

Arafat, Samer N.; Suelves, Ana M.; Spurr-Michaud, Sandra; Chodosh, James; Foster, C. Stephen; Dohlman, Claes H.; Gipson, Ilene K.

2013-01-01

Objective To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design Prospective non-interventional cohort study. Participants Four SJS patients (7 eyes), 19 OCP patients (37 eyes) and 20 post-phacoemulsification healthy controls (40 eyes). Methods Tear washes were collected from all patients and were analyzed for levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 using multi-analyte bead-based enzyme-linked immunosorbent assays (ELISA). Total MMP activity was determined using a fluorimetric assay. Correlation studies were performed between the various analytes within study groups. Main Outcome Measures Levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 (in ng/µg protein), total MMP activity (in relative fluorescent units/min/µg protein) in tears, MMP-8/TIMP-1, MMP-9/TIMP-1 ratios and the correlations between MMP-8 and MMP-9 and each MMP and MPO. Results MMP-8, MMP-9 and MPO levels were significantly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. MMP activity was highest in SJS while OCP and controls showed lower and similar activities. TIMP-1 levels were decreased in SJS and OCP when compared to controls with OCP levels reaching significance. MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels and MMP-8 correlated with MPO but did not reach significance in SJS. There was no relationship between MMP-7 and MPO. Conclusions Since MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes including MMP-9 in SJS and OCP tears. Elevated MMP/TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to develop corneal melting and chronic complications associated with persistent inflammation. MPO in tears may be a sensitive and specific marker for the quantification of ocular inflammation. PMID:23962653

Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide

PubMed Central

Wang, Zeneng; Tang, W. H. Wilson; Buffa, Jennifer A.; Fu, Xiaoming; Britt, Earl B.; Koeth, Robert A.; Levison, Bruce S.; Fan, Yiying; Wu, Yuping; Hazen, Stanley L.

2014-01-01

Aims Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and results We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P < 0.05], and betaine levels [1.33 (1.03–1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO. PMID:24497336

Effects of elevated CO2 levels on root morphological traits and Cd uptakes of two Lolium species under Cd stress*

PubMed Central

Jia, Yan; Tang, Shi-rong; Ju, Xue-hai; Shu, Li-na; Tu, Shu-xing; Feng, Ren-wei; Giusti, Lorenzino

2011-01-01

This study was conducted to investigate the combined effects of elevated CO2 levels and cadmium (Cd) on the root morphological traits and Cd accumulation in Lolium multiflorum Lam. and Lolium perenne L. exposed to two CO2 levels (360 and 1000 μl/L) and three Cd levels (0, 4, and 16 mg/L) under hydroponic conditions. The results show that elevated levels of CO2 increased shoot biomass more, compared to root biomass, but decreased Cd concentrations in all plant tissues. Cd exposure caused toxicity to both Lolium species, as shown by the restrictions of the root morphological parameters including root length, surface area, volume, and tip numbers. These parameters were significantly higher under elevated levels of CO2 than under ambient CO2, especially for the number of fine roots. The increases in magnitudes of those parameters triggered by elevated levels of CO2 under Cd stress were more than those under non-Cd stress, suggesting an ameliorated Cd stress under elevated levels of CO2. The total Cd uptake per pot, calculated on the basis of biomass, was significantly greater under elevated levels of CO2 than under ambient CO2. Ameliorated Cd toxicity, decreased Cd concentration, and altered root morphological traits in both Lolium species under elevated levels of CO2 may have implications in food safety and phytoremediation. PMID:21462388

Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure

PubMed Central

Wilson Tang, Wai Hong; Tong, Wilson; Shrestha, Kevin; Wang, Zeneng; Levison, Bruce S.; Delfraino, Brian; Hu, Bo; Troughton, Richard W.; Klein, Allan L.; Hazen, Stanley L.

2008-01-01

Aims To investigate the association of arginine methylation with myocardial function and prognosis in chronic systolic heart failure patients. Methods and results Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as N-mono-methylarginine (MMA) and methyl-lysine, were simultaneously measured by tandem mass spectrometry in 132 patients with chronic systolic heart failure with echocardiographic evaluation and follow-up. Increasing ADMA and SDMA levels were associated with elevated natriuretic peptide levels (both P < 0.001), and increasing SDMA levels were associated with worsening renal function (P < 0.001). Higher plasma levels of methylated arginine metabolites (but not methyl-lysine) were associated with the presence of left ventricular (LV) diastolic dysfunction (E/septal E′, Spearman's r = 0.31–0.36, P < 0.001). Patients taking beta-blockers had lower ADMA levels than those not taking beta-blockers [0.42 (0.33, 0.50) vs. 0.51 (0.40, 0.58), P < 0.001]. Only increasing ADMA levels were associated with advanced right ventricular (RV) systolic dysfunction. Elevated ADMA levels remained a consistent independent predictor of adverse clinical events (hazard ratio = 1.64, 95% CI: 1.20–2.22, P = 0.002). Conclusion In chronic systolic heart failure, accumulation of methylated arginine metabolites is associated with the presence of LV diastolic dysfunction. Among the methylated derivatives of arginine, ADMA provides the strongest independent prediction of disease progression and adverse long-term outcomes. PMID:18687662

Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core

PubMed Central

Corban, Michel T; Hung, Olivia Y; Mekonnen, Girum; Eshtehardi, Parham; Eapen, Danny J; Rasoul-Arzrumly, Emad; Kassem, Hatem Al; Manocha, Pankaj; Ko, Yi-An; Sperling, Laurence S; Quyyumi, Arshed A; Samady, Habib

2016-01-01

Background Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. Methods and Results Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47–63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. Conclusions In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC. PMID:26911453

Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium

PubMed Central

Wu, Yu-Chieh; Buckner, Benjamin R.; Zhu, Meifang; Cavanagh, H. Dwight; Robertson, Danielle M.

2012-01-01

Purpose To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Methods Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. Results There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (P<0.001) following culture of hTCEpi cells under elevated glucose conditions in vitro. Treatment with glucose and the mannitol control reduced IGFBP3 mRNA (P<0.001). Total IGF-1R levels were unchanged. The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. Conclusions Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes. PMID:22482470

Transplantation of Porcine Hepatocytes Cultured with Polylactic Acid-O-Carboxymethylated Chitosan Nanoparticles Promotes Liver Regeneration in Acute Liver Failure Rats

PubMed Central

Chen, Zhong; Chang, Renan; Guan, Weijun; Cai, Hongyu; Tang, Fei; Zhu, Wencai; Chen, Jiahui

2011-01-01

In this study, free porcine hepatocytes suspension (Group A), porcine hepatocytes embedded in collagen gel (Group B), porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C), and PLA-O-CMC nanoparticles alone (Group D) were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI) at day 1 post-HTx (P < .05). Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats. PMID:21603218

Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

PubMed

Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

2015-01-01

Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Perception and reality of particulate matter exposure in New York City taxi drivers

PubMed Central

Gany, Francesca; Bari, Sehrish; Prasad, Lakshmi; Leng, Jennifer; Lee, Trevor; Thurston, George D; Gordon, Terry; Acharya, Sudha; Zelikoff, Judith T

2017-01-01

Background Exposure to fine particulate matter (PM2.5) and black carbon (BC) have been linked to negative health risks, but exposure among professional taxi drivers is unknown. This study measured drivers' knowledge, attitudes, and beliefs (KAB) about air pollution compared to direct measures of exposures. Methods Roadside and in-vehicle levels of PM2.5 and BC were continuously measured over a single shift and compared to central site monitoring. Participants completed an air pollution KAB questionnaire. Results Taxicab PM2.5 and BC concentrations were elevated compared to central monitoring. Average PM2.5 concentrations per 15-minute interval were 4 - 49 μg/m3; 1-minute peaks measured up to 452 μg/m3. BC levels were also elevated; reaching > 10 μg/m3. 56 of 100 drivers surveyed believed they were more exposed than non-drivers; 81 believed air pollution causes health problems. Conclusions Air pollution exposure among drivers likely exceeds EPA recommendations. Future studies should focus on reducing exposures and increasing awareness among taxi drivers. PMID:27168392

COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH

PubMed Central

LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.

2008-01-01

Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972

Mesalamine Intolerance in Three Children with Crohn's Disease

PubMed Central

Tuna Kirsaclioglu, Ceyda; Kuloglu, Zarife; Ustundag, Gonca; Kansu, Aydan; İnce, Erdal; Ensari, Arzu; Girgin, Nurten

2016-01-01

Objective To present the mesalamine-induced acute exacerbation of symptoms and inflammatory markers in children with Crohn's disease (CD). Clinical Presentation and Intervention Three children who presented with CD had acute exacerbation of colitis symptoms or elevated inflammatory markers when mesalamine was added to treatment while tapering/ceasing steroid treatment. While on steroid treatment, the patients maintained clinical and laboratory remission, but with the initiation of mesalamine treatment, they had abdominal pain and bloody mucoid diarrhoea and/or elevation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Bacterial pathogens were excluded from the urine, throat and blood cultures, parasites with stool examination, viral pathogens with serology. Within 3–7 days after the mesalamine treatment had been stopped, the patients showed improvement of colitis symptoms and normalisation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Conclusion In this study mesalamine mimicked CD relapse in children with CD while tapering or after stopping steroid treatment. Awareness of this side effect of mesalamine could prevent a misdiagnosis of steroid dependency. PMID:26630041

Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

PubMed Central

Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel

2013-01-01

Purpose Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. Materials and Methods We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. Results In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Conclusion Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients. PMID:24142649

Effects of elevated pCO2 on physiological performance of marine microalgae Dunaliella salina (Chlorophyta, Chlorophyceae

NASA Astrophysics Data System (ADS)

Hu, Shunxin; Wang, You; Wang, Ying; Zhao, Yan; Zhang, Xinxin; Zhang, Yongsheng; Jiang, Ming; Tang, Xuexi

2018-03-01

The present study was conducted to determine the effects of elevated pCO2 on growth, photosynthesis, dark respiration and inorganic carbon acquisition in the marine microalga Dunaliella salina. To accomplish this, D. salina was incubated in semi-continuous cultures under present-day CO2 levels (390 μatm, pHNBS: 8.10), predicted year 2100 CO2 levels (1 000 μatm, pHNBS: 7.78) and predicted year 2300 CO2 levels (2 000 μatm, pHNBS: 7.49). Elevated pCO2 significantly enhanced photosynthesis (in terms of gross photosynthetic O2 evolution, effective quantum yield (Δ F/ F' m ), photosynthetic efficiency ( α), maximum relative electron transport rate (rETRmax) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity) and dark respiration of D. salina, but had insignificant effects on growth. The photosynthetic O2 evolution of D. salina was significantly inhibited by the inhibitors acetazolamide (AZ), ethoxyzolamide (EZ) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), indicating that D. salina is capable of acquiring HCOˉ 3 via extracellular carbonic anhydrase and anion-exchange proteins. Furthermore, the lower inhibition of the photosynthetic O2 evolution at high pCO2 levels by AZ, EZ and DIDS and the decreased carbonic anhydrase showed that carbon concentrating mechanisms were down-regulated at high pCO2. In conclusion, our results show that photosynthesis, dark respiration and CCMs will be affected by the increased pCO2/low pH conditions predicted for the future, but that the responses of D. salina to high pCO2/low pH might be modulated by other environmental factors such as light, nutrients and temperature. Therefore, further studies are needed to determine the interactive effects of pCO2, temperature, light and nutrients on marine microalgae.

Effects of elevated pCO2 on physiological performance of marine microalgae Dunaliella salina (Chlorophyta, Chlorophyceae)

NASA Astrophysics Data System (ADS)

Hu, Shunxin; Wang, You; Wang, Ying; Zhao, Yan; Zhang, Xinxin; Zhang, Yongsheng; Jiang, Ming; Tang, Xuexi

2017-06-01

The present study was conducted to determine the effects of elevated pCO2 on growth, photosynthesis, dark respiration and inorganic carbon acquisition in the marine microalga Dunaliella salina. To accomplish this, D. salina was incubated in semi-continuous cultures under present-day CO2 levels (390 μatm, pHNBS: 8.10), predicted year 2100 CO2 levels (1 000 μatm, pHNBS: 7.78) and predicted year 2300 CO2 levels (2 000 μatm, pHNBS: 7.49). Elevated pCO2 significantly enhanced photosynthesis (in terms of gross photosynthetic O2 evolution, effective quantum yield (ΔF/F' m ), photosynthetic efficiency (α), maximum relative electron transport rate (rETRmax) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity) and dark respiration of D. salina, but had insignificant effects on growth. The photosynthetic O2 evolution of D. salina was significantly inhibited by the inhibitors acetazolamide (AZ), ethoxyzolamide (EZ) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), indicating that D. salina is capable of acquiring HCO3 - via extracellular carbonic anhydrase and anion-exchange proteins. Furthermore, the lower inhibition of the photosynthetic O2 evolution at high pCO2 levels by AZ, EZ and DIDS and the decreased carbonic anhydrase showed that carbon concentrating mechanisms were down-regulated at high pCO2. In conclusion, our results show that photosynthesis, dark respiration and CCMs will be affected by the increased pCO2/low pH conditions predicted for the future, but that the responses of D. salina to high pCO2/low pH might be modulated by other environmental factors such as light, nutrients and temperature. Therefore, further studies are needed to determine the interactive effects of pCO2, temperature, light and nutrients on marine microalgae.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

PubMed Central

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes

PubMed Central

Sims, Emily K.; Chaudhry, Zunaira; Watkins, Renecia; Syed, Farooq; Blum, Janice; Ouyang, Fangqian; Perkins, Susan M.; Mirmira, Raghavendra G.; Sosenko, Jay; DiMeglio, Linda A.

2016-01-01

OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. PMID:27385327

Allergen exposure modifies the relation of sensitization to FENO levels in children at risk for allergy and asthma

PubMed Central

Sordillo, Joanne E; Webb, Tara; Kwan, Doris; Kamel, Jimmy; Hoffman, Elaine; Milton, Donald K; Gold, Diane R

2011-01-01

Background Studies on airway inflammation, measured as fraction exhaled nitric oxide (FENO), have focused on its relation to control of asthma, but the contribution of allergen exposure to elevation of FENO is unknown. Objective We evaluated (1) whether FENO was elevated in children with allergic sensitization or asthma; (2) whether specific allergen exposure increased FENO levels in sensitized, but not in unsensitized children; and (3) whether sedentary behavior increased FENO, independent of allergen exposures. Methods At age 12, in a birth cohort of children with parental history of allergy or asthma, we measured bed dust allergen (dust mite, cat, cockroach) by ELISA; specific allergic sensitization primarily by specific IgE ; and respiratory disease (current asthma, rhinitis, and wheeze) and hours of TV viewing/video game playing by questionnaire. Children performed spirometry maneuvers before and after bronchodilator responses, and had FENO measured using electrochemical detection methods (NIOX MINO). Results FENO was elevated in children with current asthma (32.2 ppb), wheeze (27.0 ppb), or rhinitis (23.2ppb) as compared to individuals without these respective symptoms/diagnoses (16.4 ppb to 16.6 ppb, p< 0.005 for all comparisons). Allergic sensitization to indoor allergens (cat, dog, dust mite) predicted higher levels of FENO, and explained one third of the variability of FENO. FENO levels were highest in children both sensitized and exposed to dust mite. Greater than 10 hours of weekday TV viewing was associated with a 0.64 log increase in FENO, after controlling indoor allergen exposure, BMI and allergic sensitization. Conclusion Allergen exposures and sedentary behavior (TV viewing/ video game playing), may increase airway inflammation, measured as FENO. PMID:21463890

Inhibition of phosphodiesterase 4 amplifies cytokine-dependent induction of arginase in macrophages.

PubMed

Erdely, Aaron; Kepka-Lenhart, Diane; Clark, Melissa; Zeidler-Erdely, Patti; Poljakovic, Mirjana; Calhoun, William J; Morris, Sidney M

2006-03-01

Arginase is greatly elevated in asthma and is thought to play a role in the pathophysiology of this disease. As inhibitors of phosphodiesterase 4 (PDE4), the predominant PDE in macrophages, elevate cAMP levels and reduce inflammation, they have been proposed for use in treatment of asthma and chronic obstructive pulmonary disease. As cAMP is an inducer of arginase, we tested the hypothesis that a PDE4 inhibitor would enhance macrophage arginase induction by key cytokines implicated in asthma and other pulmonary diseases. RAW 264.7 cells were stimulated with IL-4 or transforming growth factor (TGF)-beta, with and without the PDE4 inhibitor rolipram. IL-4 and TGF-beta increased arginase activity 16- and 5-fold, respectively. Rolipram alone had no effect but when combined with IL-4 and TGF-beta synergistically enhanced arginase activity by an additional 15- and 5-fold, respectively. The increases in arginase I protein and mRNA levels mirrored increases in arginase activity. Induction of arginase II mRNA was also enhanced by rolipram but to a much lesser extent than arginase I. Unlike its effect in RAW 264.7 cells, IL-4 alone did not increase arginase activity in human alveolar macrophages (AM) from healthy volunteers. However, combining IL-4 with agents to induce cAMP levels induced arginase activity in human AM significantly above the level obtained with cAMP-inducing agents alone. In conclusion, agents that elevate cAMP significantly enhance induction of arginase by cytokines. Therefore, consequences of increased arginase expression should be evaluated whenever PDE inhibitors are proposed for treatment of inflammatory disorders in which IL-4 and/or TGF-beta predominate.

An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor ADMA

PubMed Central

Ghebremariam, Yohannes T.; LePendu, Paea; Lee, Jerry C.; Erlanson, Daniel A.; Slaviero, Anna; Shah, Nigam H.; Leiper, James; Cooke, John P.

2013-01-01

Background Proton pump inhibitors (PPIs) are gastric acid suppressing agents widely prescribed for the treatment of gastro-esophageal reflux disease (GERD). Recently, several studies in patients with acute coronary syndrome (ACS) have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events (MACE). The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed. Methods and Results Plasma ADMA is an endogenous inhibitor of nitric oxide synthase (NOS). Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely due to its attenuation of the vasoprotective effects of endothelial NOS. We find that PPIs elevate plasma asymmetric dimethylarginine (ADMA) level and reduce nitric oxide (NO) levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to, and inhibit dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA. Conclusions We present a plausible biological mechanism to explain the association of PPIs with increased MACE in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with use of the PPIs in the general population. PMID:23825361

Serum Amylase in Bulimia Nervosa and Purging Disorder: Differentiating the Association with Binge Eating versus Purging Behavior

PubMed Central

Wolfe, Barbara E.; Jimerson, David C.; Smith, Adrian; Keel, Pamela K.

2011-01-01

Objective Elevated serum amylase levels in bulimia nervosa (BN), associated with increased salivary gland size and self-induced vomiting in some patients, provide a possible marker of symptom severity. The goal of this study was to assess whether serum hyperamylasemia in BN is more closely associated with binge eating episodes involving consumption of large amounts of food or with purging behavior. Method Participants included women with BN (n=26); women with “purging disorder” (PD), a subtype of EDNOS characterized by recurrent purging in the absence of objectively large binge eating episodes (n=14); and healthy non-eating disorder female controls (n=32). There were no significant differences in age or body mass index (BMI) across groups. The clinical groups reported similar frequency of self-induced vomiting behavior and were free of psychotropic medications. Serum samples were obtained after overnight fast and were assayed for alpha-amylase by enzymatic method. Results Serum amylase levels were significantly elevated in BN (60.7 ± 25.4 international units [IU]/liter, mean ± sd) in comparison to PD (44.7 ± 17.1 IU/L, p < 02) and to Controls (49.3 ± 15.8, p < .05). Conclusion These findings provide evidence to suggest that it is recurrent binge eating involving large amounts of food, rather than self-induced vomiting, which contributes to elevated serum amylase values in BN. PMID:21781981

The Predictive Prognostic Values of Serum TNF-α in Comparison to SOFA Score Monitoring in Critically Ill Patients

PubMed Central

Yousef, Ayman Abd Al-Maksoud; Suliman, Ghada Abdulmomen

2013-01-01

Background. The use of inflammatory markers to follow up critically ill patients is controversial. The short time frame, the need for frequent and serial measurement of biomarkers, the presence of soluble receptor and their relatively high cost are the major drawbacks. Our study's objective is to compare the prognostic values of serum TNF-α and SOFA score monitoring in critically ill patients. Patients and Methods. A total of ninety patients were included in the study. Forty-five patients developed septic complication (sepsis group). Forty-five patients were critically ill without evidence of infectious organism (SIRS group). Patients' data include clinical status, central venous pressure, and laboratory analysis were measured. A serum level of TNF-α and SOFA score were monitored. Results. Monitoring of TNF-α revealed significant elevation of TNF-α at 3rd and 5th days of ICU admission in both groups. Monitoring of SOFA score revealed significant elevation of SOFA scores in both groups throughout their ICU stay, particularly in nonsurvivors. Positive predictive ability of SOFA score was demonstrated in critically ill patients. Conclusion. Transient significant increase in serum levels of TNF-α were detected in septic patients. Persistent elevation of SOFA score was detected in nonsurvivor septic patients. SOFA score is an independent prognostic value in critically ill patients. PMID:24175285

Fiber type- and fatty acid composition-dependent effects of high-fat diets on rat muscle triacylglyceride and fatty acid transporter protein-1 content.

PubMed

Marotta, Mario; Ferrer-Martnez, Andreu; Parnau, Josep; Turini, Marco; Macé, Katherine; Gómez Foix, Anna M

2004-08-01

Intramuscular triacylglyceride (TAG) is considered an independent marker of insulin resistance in humans. Here, we examined the effect of high-fat diets, based on distinct fatty acid compositions (saturated, monounsaturated or n-6 polyunsaturated), on TAG levels and fatty acid transporter protein (FATP-1) expression in 2 rat muscles that differ in their fiber type, soleus, and gastrocnemius; the relationship to whole body glucose intolerance was also studied. Compared with carbohydrate-fed rats, the groups subjected to any one of the high-fat diets consistently exhibited enhanced body weight gain and adiposity, elevated plasma free fatty acids and TAG in the fed condition, hyperinsulinemia, and glucose intolerance. TAG content was consistently higher in soleus than in gastrocnemius, but was only significantly elevated by the n-6 polyunsaturated-based diet. FATP-1 levels in soleus were double those in gastrocnemius muscle in carbohydrate-fed animals. High-fat diets caused an elevation in FATP-1 protein content in soleus, but a reduction in gastrocnemius. In conclusion, the hyperinsulinemic hyperlipidemic condition upregulates FATP-1 expression in soleus and downregulates that of gastrocnemius. Hypercaloric saturated, monounsaturated, or n-6 polyunsaturated lipid diets cause equivalent whole body insulin resistance in rats, but only an n-6 polyunsaturated acid-based diet triggers intramuscular TAG accumulation. Copyright 2004 Elsevier Inc.

Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation

PubMed Central

Abd-Ellatef, Gamal-Eldein F; Ahmed, Osama M; Abdel-Reheim, Eman S; Abdel-Hamid, Abdel-Hamid Z

2017-01-01

Background Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. Methods Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. Results Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. Conclusion In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system. PMID:28280387

Lead poisoning in United States-bound refugee children: Thailand-Burma border, 2009.

PubMed

Mitchell, Tarissa; Jentes, Emily; Ortega, Luis; Scalia Sucosky, Marissa; Jefferies, Taran; Bajcevic, Predrag; Parr, Valentina; Jones, Warren; Brown, Mary Jean; Painter, John

2012-02-01

Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described. Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary <3.3 µg/dL) blood lead levels participated in a case-control study. Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged <2 years had the highest prevalence (14.5%). Among children aged <2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin <10 g/dL, exposure to car batteries, and taking traditional medicines. The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children <2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.

Aqueous levels of erythropoietin in acute retinal vein occlusion with macular edema

PubMed Central

Shin, Hyun Jin; Kim, Hyung Chan; Moon, Jun Woong

2014-01-01

AIM To investigate the aqueous erythropoietin (EPO) levels and associated factors in patients with acute retinal vein occlusion (RVO). METHODS The aqueous EPO level was measured in patients with macular edema (ME) secondary to acute branched retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Aqueous fluid from cataract patients served as the control. We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level, non-perfusion area, central macular thickness (CMT), and arterio-venous (AV) transit time RESULTS Twenty-seven RVO patients (16 BRVO, 11 CRVO) and 9 control subjects were enrolled in the study. The aqueous EPO level (mU/mL) was higher in RVO (68.2±54.3) than that in the control subjects (12.9±5.9). More specifically, the aqueous EPO level was higher in CRVO (118.9±52.1) than that in BRVO (33.3±10.8). However, no differences were found in serum EPO levels among three groups. CMT in RVO patients had a positive correlation with the aqueous EPO level (r=0.66). Also, in terms of non-perfusion area, the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO. CONCLUSION Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO. Patients with CRVO have higher EPO levels than those with BRVO. The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area. These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO. PMID:24967199

Effect of Intravitreal Methotrexate and Rituximab on Interleukin-10 Levels in Aqueous Humor of Treated Eyes with Vitreoretinal Lymphoma

PubMed Central

Raja, Harish; Snyder, Melissa R.; Johnston, Patrick B.; O’Neill, Brian P.; Caraballo, Juline N.; Balsanek, Joseph G.; Peters, Brian E.; Decker, Paul A.; Pulido, Jose S.

2013-01-01

Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response. PMID:23750271

Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

NASA Technical Reports Server (NTRS)

Shearer, W. T.; Reuben, J. M.; Mullington, J. M.; Price, N. J.; Lee, B. N.; Smith, E. O.; Szuba, M. P.; Van Dongen, H. P.; Dinges, D. F.

2001-01-01

BACKGROUND: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. OBJECTIVE: We sought to measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-alpha receptor (sTNF-alpha R) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. METHODS: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-alpha RI, sTNF-alpha RII, IL-6, soluble IL-2 receptor, IL-10, and TNF-alpha. RESULTS: Interactions between the effects of time and sleep deprivation level were detected for sTNF-alpha RI and IL-6 but not for sTNF-alpha RII, soluble IL-2 receptor, IL-10, and TNF-alpha. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-alpha RI on day 2 (P =.04), day 3 (P =.01), and across days 2 to 4 of sleep loss (P =.01) and elevated levels of IL-6 on day 4 (P =.04). CONCLUSIONS: Total sleep loss produced significant increases in plasma levels of sTNF-alpha RI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight.

Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats

PubMed Central

Pattanashetti, Laxmi Adiveppa; Taranalli, Ashok D.; Parvatrao, Vinay; Malabade, Rohit H.; Kumar, Dushyant

2017-01-01

Objective: The objective of this study was to evaluate the neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. Materials and Methods: Five groups of adult male Wistar rats (12 months old) weighing 180–200 g (n = 6) were used. The normal control group received normal saline and test group animals were pretreated orally with quercetin (25 mg/kg), donepezil (3 mg/kg), and a combination of quercetin (25 mg/kg) with donepezil (3 mg/kg), respectively, dosed at every 24 h interval for 14 consecutive days, afterward amnesia was induced by scopolamine (3 mg/kg) on the 14th day through intraperitoneal route. Cognitive performance was assessed by the Morris water maze, elevated plus maze, and passive avoidance paradigm. Acetylcholinesterase enzyme (AchE) level, biochemical markers such as lipid peroxidase (LPO), glutathione (GSH), β amyloid1-42level, and histopathological study of rat brain were estimated. Statistical analysis was done by one-way analysis of variance, followed by Dunnett's post hoc test. P ≥ 0.05 was considered statistically significant. Results: Pretreatment with quercetin, donepezil, and their combination showed a significant increase in escape latency, step-through latency, and decreased transfer latency in respective cognitive models of the Morris water maze, passive avoidance test, and elevated plus maze. Further coadministration significantly decreased AchE level, β amyloid1-42level as compared to individual therapy. Biochemical markers such as elevated GSH, decreased LPO were observed, and histopathological studies revealed the reversal of neuronal damage in the treatment group (P < 0.05) as compared to scopolamine-treated control group. Conclusion: Pretreatment with quercetin potentiates the action of donepezil in scopolamine-induced amnesia in rats. The improved cognitive memory could be due to the synergistic effect of the drugs by decreasing AchE level, β amyloid1-42level, and antioxidant action in rat brain. PMID:28458424

Suckling induced insulin-like growth factor-1 (IGF-1) release in mother rats.

PubMed

Lékó, András H; Cservenák, Melinda; Dobolyi, Árpád

2017-12-01

Lactation involves significant neuroendocrine changes. The elevated prolactin (PRL) release from the pituitary, induced markedly by suckling, is the most relevant example. Suckling also causes a significant and rapid elevation in growth hormone (GH) levels. GH is necessary for milk synthesis as milk yield is stopped completely in the absence of PRL and GH, while the absence of PRL alone causes only a 50% reduction. Insulin-like growth factor-1 (IGF-1) plays an important role in the GH axis. GH exerts its effects through IGF-1 in the periphery, for example in the mammary gland. In addition, IGF-1 is responsible for the long-loop feedback control of GH secretion. IGF-1 secretion has not been established yet in mothers. Therefore, in the present study, we investigated the effect of suckling on serum IGF-1 level in rat mothers and correlated it with serum PRL levels. We examined a potential mechanism of the regulation of IGF-1 level during suckling by administering IGF-1 into the lateral ventricle of rat mothers continuously for 12days, or acutely, right before the start of suckling. We described that suckling affected IGF-1 release based on one-way repeated measures ANOVA (F=10.8 and p<0.001) and caused a marked increase of IGF-1 level 30min after the start of suckling (p<0.001). We demonstrated a significant (p<0.05; the correlation coefficient was 0.29) correlation to PRL level during suckling which supports that PRL could induce IGF-1 release. The prolonged central IGF-1 administration diminished the suckling-induced IGF-1 surge (F=9.19 and p<0.001) while the acute treatment did not have any effect compared to artificial cerebrospinal fluid injection, analysed with two-way repeated measures ANOVA. In conclusion, suckling induces IGF-1 release either by elevating PRL or GH. Long-loop feedback via IGF-1 in the GH axis can diminish this action. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nitrogen use efficiencies of spring barley grown under varying nitrogen conditions in the field and growth chamber

PubMed Central

Beatty, Perrin H.; Anbessa, Yadeta; Juskiw, Patricia; Carroll, Rebecka T.; Wang, Juan; Good, Allen G.

2010-01-01

Background and Aims Nitrogen-use efficiency (NUE) of cereals needs to be improved by nitrogen (N) management, traditional plant breeding methods and/or biotechnology, while maintaining or, optimally, increasing crop yields. The aims of this study were to compare spring-barley genotypes grown on different nitrogen levels in field and growth-chamber conditions to determine the effects on N uptake (NUpE) and N utilization efficiency (NUtE) and ultimately, NUE. Methods Morphological characteristics, seed yield and metabolite levels of 12 spring barley (Hordeum vulgare) genotypes were compared when grown at high and low nitrogen levels in field conditions during the 2007 and 2008 Canadian growing seasons, and in potted and hydroponic growth-chamber conditions. Genotypic NUpE, NUtE and NUE were calculated and compared between field and growth-chamber environments. Key Results Growth chamber and field tests generally showed consistent NUE characteristics. In the field, Vivar, Excel and Ponoka, showed high NUE phenotypes across years and N levels. Vivar also had high NUE in growth-chamber trials, showing NUE across complex to simplistic growth environments. With the high NUE genotypes grown at low N in the field, NUtE predominates over NUpE. N metabolism-associated amino acid levels were different between roots (elevated glutamine) and shoots (elevated glutamate and alanine) of hydroponically grown genotypes. In field trials, metabolite levels were different between Kasota grown at high N (elevated glutamine) and Kasota at low N plus Vivar at either N condition. Conclusions Determining which trait(s) or gene(s) to target to improve barley NUE is important and can be facilitated using simplified growth approaches to help determine the NUE phenotype of various genotypes. The genotypes studied showed similar growth and NUE characteristics across field and growth-chamber tests demonstrating that simplified, low-variable growth environments can help pinpoint genetic targets for improving spring barley NUE. PMID:20308048

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

PubMed Central

2013-01-01

Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. Conclusion The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. Trial registration ClinicalTrials.gov: http://NCT01634256 PMID:23497020

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.

Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave

PubMed Central

2010-01-01

Introduction The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented. Methods In a post hoc analysis, we evaluated 514 patients admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature >38.5°C and who had analysis of cTnI levels. cTnI was considered as normal, moderately elevated (abnormality threshold to 1.5 ng.mL-1), or severely elevated (>1.5 ng.mL-1). Patients were classified according to our previously described risk score (high, intermediate, and low-risk of death). Results Mean age was 84 ± 12 years, mean body temperature 40.3 ± 1.2°C. cTnI was moderately elevated in 165 (32%) and severely elevated in 97 (19%) patients. One-year survival was significantly decreased in patients with moderate or severe increase in cTnI (24 and 46% vs 58%, all P < 0.05). Using logistic regression, four independent variables were associated with an elevated cTnI: previous coronary artery disease, Glasgow coma scale <12, serum creatinine >120 μmol.L-1, and heart rate >110 bpm. Using Cox regression, only severely elevated cTnI was an independent prognostic factor (hazard ratio 1.93, 95% confidence interval 1.35 to 2.77) when risk score was taken into account. One-year survival was decreased in patients with elevated cTnI only in high risk patients (17 vs 31%, P = 0.04). Conclusions cTnI is frequently elevated in patients with non-exertional heat-related illnesses during a heat wave and is an independent risk factor only in high risk patients where severe increase (>1.5 ng.mL-1) indicates severe myocardial damage. PMID:20507603

Mixed dyslipidemias in primary care patients in France

PubMed Central

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

Objective To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. Methods This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Main outcome measures Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. Results At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. Conclusions At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients. PMID:22566746

Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil

PubMed Central

2010-01-01

Background Poor control of blood pressure leads to hypertension which is a major risk factor for development of cardiovascular disease. The present study aimed to explore possible mechanisms of elevation in blood pressure following consumption of heated vegetable oil. Methods Forty-two male Sprague-Dawley rats were equally divided into six groups: Group I (control) - normal rat chow, Group II - fresh soy oil, Group III - soy oil heated once, Group IV - soy oil heated twice, Group V - soy oil heated five times, Group VI - soy oil heated ten times. Blood pressure was measured at the baseline level and at a monthly interval for six months. Plasma nitric oxide, heme oxygenase and angiotensin-converting enzyme levels were measured prior to treatment, at month-three and month-six later. At the end of treatment, the rats were sacrificed and thoracic aortas were taken for measurement of vascular reactivity. Results Blood pressure increased significantly (p < 0.01) in the repeatedly heated oil groups compared to the control and fresh soy oil groups. Consumption of diet containing repeatedly heated oil resulted higher plasma angiotensin-converting enzyme level and lower nitric oxide content and heme oxygenase concentration. Reheated soy oil groups exhibited attenuated relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Conclusion As a result of consumption of repeatedly heated soy oil, an elevation in blood pressure was observed which may be due to the quantitative changes in endothelium dependent and independent factors including enzymes directly involved in the regulation of blood pressure. PMID:20573259

Low-calcium diets increase both production and clearance of 1,25-dihydroxyvitamin D3 in rats

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

Fox, J.; Bunker, J.E.; Kamimura, M.

1990-02-01

Administration of large doses of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to animals induces 1,25(OH)2D3 side-chain oxidative pathways. This study determined if the elevated plasma 1,25(OH)2D3 seen in rats fed low-Ca diets is associated not only with an increased production rate (PR) but also with an increased metabolic clearance rate (MCR) of the hormone. In vitamin D-replete rats fed a Ca-deficient diet for 3-4 wk, the PR increased 21-fold, plasma levels 15-fold, and the MCR by 37%. The increased MCR in Ca-deficient rats was associated with a 48% increase in hepatic microsomal UDP glucuronyl transferase enzyme activity, whereas 1,25(OH)2D3 catabolism by homogenates ofmore » liver and small intestinal mucosa was unchanged. In contrast to the effects of low-Ca diets, acute (7 h) pharmacological elevation of plasma 1,25(OH)2D3 to 1.5 ng/ml in normal rats did not influence the MCR. Thus chronically elevated 1,25(OH)2D3 levels are necessary to stimulate clearance. In conclusion, 1,25(OH)2D3 clearance in rats can be stimulated not only by chronic pharmacological doses of 1,25(OH)2D3 but also by the physiological stimulus of a low-Ca diet. Hence, plasma 1,25(OH)2D3 levels can be regulated by changes in both PR and MCR.« less

Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.

PubMed

Kátai, Emese; Pál, József; Poór, Viktor Soma; Purewal, Rupeena; Miseta, Attila; Nagy, Tamás

2016-12-01

O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H 2 O 2 for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H 2 O 2 -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The influence of phosphate, calcium and magnesium on matrix Gla-protein and vascular calcification: a systematic review.

PubMed

Houben, E; Neradova, A; Schurgers, L J; Vervloet, Marc

2016-01-01

Vitamin K-dependent matrix Gla protein (MGP) is a key inhibitor of vascular calcification (VC). MGP is synthesized by chondrocytes and vascular smooth muscle cells (VSMC) and the absence or inactivity of MGP results in excessive calcification of both growth plate and vasculature. Apart from its vitamin K dependency little is known about other factors that influence MGP metabolism. Phosphate, calcium and magnesium are involved in bone mineralization and play an important role in VC. In this review we provide a summary of the effect of phosphate, calcium, and magnesium on MGP metabolism. Elevated phosphate and calcium levels promote VC, in part by increasing the release of matrix vesicles (MV) that under the influence of calcium and phosphate become calcification competent. Phosphate and calcium simultaneously induce an upregulation of MGP protein and gene expression, which possibly inhibits calcification. Elevated phosphate levels did not change MGP protein levels in MV. On the contrary, elevated calcium concentrations caused a decrease of MGPloading in MV, which might in part explainthe calcifying effects of MV. Magnesium is a known inhibitor of VC. However, magnesium has been shown to have an inhibitory effect on MGP synthesis induced through downregulation of the calcium-sensing receptor and hereby causing a decrease in calcium induced MGP upregulation. There might also be stimulatory effect of magnesium on MGP in which the TRPM7 channel is involved. In conclusion there is a clear interaction between MGP and phosphate, calcium and magnesium. The upregulation of MGP by phosphate and calcium might be a cellular response that possibly results in the mitigation of VC.

Brain natriuretic peptide predicts functional outcome in ischemic stroke

PubMed Central

Rost, Natalia S; Biffi, Alessandro; Cloonan, Lisa; Chorba, John; Kelly, Peter; Greer, David; Ellinor, Patrick; Furie, Karen L

2011-01-01

Background Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic (CE) stroke and increased post-stroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke. Methods We measured BNP in consecutive patients aged ≥18 years admitted to our Stroke Unit between 2002–2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using TOAST criteria. Outcomes were measured as 6-month modified Rankin Scale score (“good outcome” = 0–2 vs. “poor”) as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared to clinical model alone was assessed by comparing ROC curves. Results Of 569 ischemic stroke patients, 46% were female; mean age was 67.9 ± 15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (p<0.0001) and left atrial dilatation (p<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR 0.64, 95%CI 0.41–0.98) and increased the odds of death (OR 1.75, 95%CI 1.36–2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (p=0.013) and mortality (p<0.03) after CE stroke. Conclusions Serum BNP levels are strongly associated with CE stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with CE stroke. PMID:22116811

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

PubMed Central

Njoku, Dolores B.; Mellerson, Jenelle L.; Talor, Monica V.; Kerr, Douglas R.; Faraday, Nauder R.; Outschoorn, Ingrid; Rose, Noel R.

2006-01-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation. PMID:16467335

Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.

PubMed

Chen, Pei; Jou, Yuh-Shan; Fann, Cathy S J; Chen, Jaw-Wen; Chung, Chia-Min; Lin, Chin-Yu; Wu, Sheng-Yeu; Kang, Mei-Jyh; Chen, Ying-Chuang; Jong, Yuh-Shiun; Lo, Huey-Ming; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Huang, Nai-Kuei; Wu, Yi-Lin; Pan, Wen-Harn

2009-01-01

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Copyright 2008 Wiley-Liss, Inc.

Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication.

PubMed

Furuhashi, Masato; Omori, Akina; Matsumoto, Megumi; Kataoka, Yu; Tanaka, Marenao; Moniwa, Norihito; Ohnishi, Hirofumi; Yoshida, Hideaki; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

2016-07-15

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender-different correlation between PCSK9 level and age: negatively in men (r = -0.250, p = 0.013) and positively in women (r = 0.183, p = 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

Determination of the origin of elevated uranium at a Former Air Force Landfill using non-parametric statistics analysis and uranium isotope ratio analysis

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

Weismann, J.; Young, C.; Masciulli, S.

2007-07-01

Lowry Air Force Base (Lowry) was closed in September 1994 as part of the Base Realignment and Closure (BRAC) program and the base was transferred to the Lowry Redevelopment Authority in 1995. As part of the due diligence activities conducted by the Air Force, a series of remedial investigations were conducted across the base. A closed waste landfill, designated Operable Unit 2 (OU 2), was initially assessed in a 1990 Remedial Investigation (RI; [1]). A Supplemental Remedial Investigation was conducted in 1995 [2] and additional studies were conducted in a 1998 Focused Feasibility Study. [3] The three studies indicated thatmore » gross alpha, gross beta, and uranium concentrations were consistently above regulatory standards and that there were detections of low concentrations other radionuclides. Results from previous investigations at OU 2 have shown elevated gross alpha, gross beta, and uranium concentrations in groundwater, surface water, and sediments. The US Air Force has sought to understand the provenance of these radionuclides in order to determine if they could be due to leachates from buried radioactive materials within the landfill or whether they are naturally-occurring. The Air Force and regulators agreed to use a one-year monitoring and sampling program to seek to explain the origins of the radionuclides. Over the course of the one-year program, dissolved uranium levels greater than the 30 {mu}g/L Maximum Contaminant Level (MCL) were consistently found in both up-gradient and down-gradient wells at OU 2. Elevated Gross Alpha and Gross Beta measurements that were observed during prior investigations and confirmed during the LTM were found to correlate with high dissolved uranium content in groundwater. If Gross Alpha values are corrected to exclude uranium and radon contributions in accordance with US EPA guidance, then the 15 pCi/L gross alpha level is not exceeded. The large dataset also allowed development of gross alpha to total uranium correlation factors so that gross alpha action levels can be applied to future long-term landfill monitoring to track radiological conditions at lower cost. Ratios of isotopic uranium results were calculated to test whether the elevated uranium displayed signatures indicative of military use. Results of all ratio testing strongly supports the conclusion that the uranium found in groundwater, surface water, and sediment at OU 2 is naturally-occurring and has not undergone anthropogenic enrichment or processing. U-234:U-238 ratios also show that a disequilibrium state, i.e., ratio greater than 1, exists throughout OU 2 which is indicative of long-term aqueous transport in aged aquifers. These results all support the conclusion that the elevated uranium observed at OU 2 is due to the high concentrations in the regional watershed. Based on the results of this monitoring program, we concluded that the elevated uranium concentrations measured in OU 2 groundwater, surface water, and sediment are due to the naturally-occurring uranium content of the regional watershed and are not the result of waste burials in the former landfill. Several lines of evidence indicate that natural uranium has been naturally concentrated beneath OU 2 in the geologic past and the higher of uranium concentrations in down-gradient wells is the result of geochemical processes and not the result of a uranium ore disposal. These results therefore provide the data necessary to support radiological closure of OU 2. (authors)« less

Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

PubMed Central

Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

2014-01-01

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

Protection of LLC-PK1 cells against hydrogen peroxide-induced cell death by modulation of ceramide level.

PubMed

Yoo, Jae-Myung; Lee, Youn-Sun; Choi, Heon-Kyo; Lee, Yong-Moon; Hong, Jin-Tae; Yun, Yeo-Pyo; Oh, Seikwan; Yoo, Hwan-Soo

2005-03-01

Oxidative stress has been reported to elevate ceramide level during cell death. The purpose of the present study was to modulate cell death in relation to cellular glutathione (GSH) level and GST (glutathione S-transferase) expression by regulating the sphingolipid metabolism. LLC-PK1 cells were treated with H2O2 in the absence of serum to induce cell death. Subsequent to exposure to H2O2, LLC-PK1 cells were treated with desipramine, sphingomyelinase inhibitor, and N-acetylcysteine (NAC), GSH substrate. Based on comparative visual observation with H2O2-treated control cells, it was observed that 0.5 microM of desipramine and 25 mM of NAC exhibited about 90 and 95% of cytoprotection, respectively, against H2O2-induced cell death. Desipramine and NAC lowered the release of LDH activity by 36 and 3%, respectively, when compared to 71% in H2O2-exposed cells. Cellular glutathione level in 500 microM H2O2-treated cells was reduced to 890 pmol as compared to control level of 1198 pmol per mg protein. GST P1-1 expression was decreased in H2O2-treated cells compared to healthy normal cells. In conclusion, it has been inferred that H2O2-induced cell death is closely related to cellular GSH level and GST P1-1 expression in LLC-PK1 cells and occurs via ceramide elevation by sphingomyelinase activation.

Is elevated Red cell distribution width a prognostic predictor in adult patients with community acquired Pneumonia?

PubMed Central

2014-01-01

Background Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. We recently demonstrated that among young patients (<60 years old) with CAP, elevated red blood cell distribution width (RDW) level on admission was associated with significant higher rates of mortality and severe morbidity. We aimed to investigate the prognostic predictive value of RDW among CAP patients in general population of internal wards. Methods The cohort included patients of 18 years old or older who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between January 1, 2005 and December 31, 2010. Patients were retrospectively analyzed for risk factors for a primary endpoint of 90-day mortality. Secondary endpoint was defined as complicated hospitalization (defined as at least one of the following: In- hospital mortality, length of stay of at least 10 days or ICU admission). Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in univariate and multivariate analysis to identify association between patient characteristic, 90-day mortality and complicated hospitalization. Results The cohort included 3815 patients. In univariate analysis, patients with co-morbid conditions tended to have a complicated course of CAP. In multivariate regression analysis, variables associated with an increased risk of 90-day mortality included age > 70 years, high Charlson comorbidity index (>2), Hb < 10 mg/dl, Na <130 meq/l, blood urea nitrogen (BUN) >30 mg/dl, systolic blood pressure < 90 mmHg and elevated RDW >15%. Variables associated with complicated hospitalization included high Charlson comorbidity index, BUN > 30 mg/dl, hemoglobin < 10 g/dl, heart rate >124 bpm, systolic blood pressure < 90 mmHg and elevated RDW. Mortality rate and complicated hospitalization were significantly higher among patients with increased RDW regardless of the white blood cell count or hemoglobin levels. Conclusions Elevated RDW levels on admission are associated with significant higher rates of mortality and severe morbidity in adult patients with CAP. RDW as a prognostic marker was unrelated with hemoglobin levels, WBC count, age or Charlson score. PMID:24597687

Surgical and healing changes to ocular aberrations following refractive surgery

NASA Astrophysics Data System (ADS)

Straub, Jochen; Schwiegerling, Jim

2003-07-01

Purpose: To measure ocular aberrations before and at several time periods after LASIK surgery to determine the change to the aberration structure of the eye. Methods: A Shack-Hartmann wavefront sensor was used to measure 88 LASIK patients pre-operatively and at 1 week and 12 months following surgery. Reconstructed wavefront errors are compared to look at induced differences. Manifest refraction was measured at 1 week, 1 month, 3 months, 6 months and 12 months following surgery. Sphere, cylinder, spherical aberration, and pupil diameter are analyzed. Results: A dramatic elevation in spherical aberration is seen following surgery. This elevation appears almost immediately and remains for the duration of the study. A temporary increase in pupil size is seen following surgery. Conclusions: LASIK surgery dramatically reduces defocus and astigmatism in the eye, but simultaneously increases spherical aberration levels. This increase occurs at the time of surgery and is not an effect of the healing response.

The Association between Tobacco Smoke and Serum Immunoglobulin E Levels in Korean Adults.

PubMed

Kim, Young Soo; Kim, Hee Yeon; Ahn, Hyo-Suk; Sohn, Tae Seo; Song, Jae Yen; Lee, Young Bok; Lee, Dong-Hee; Lee, Jae-Im; Jeong, Seong Cheol; Chae, Hiun Suk; Han, Kyungdo; Yeo, Chang Dong

2017-10-01

Objective Smoking is common in patients with allergic diseases. The aim of this study was to evaluate the cross-sectional association between the current smoking status and total and specific Immunoglobulin E (IgE) levels in Korean adults. Methods Data were obtained from the 2010 Korean National Health and Nutrition Examination Survey, a national cross-sectional study. We analyzed the data of subjects whose smoking status and serum IgE levels were of acceptable quality. Results A total of 1,963 subjects (1,118 never smokers, 340 ex-smokers, and 505 current smokers) were included. The total IgE levels and specific IgE levels to house dust mite Dermatophagoides farinae (Df), cockroach, and dog allergens in never smokers were significantly (p<0.0001) lower than in ex-smokers or current smokers. After adjusting for other variables, current smokers independently had significantly higher levels of total IgE and cockroach-specific IgE than ex-smokers or never smokers. The proportions of subjects with total IgE ≥150 kU/L and specific IgE ≥0.35 kU/L to Df-specific IgE were significantly (p value for trend <0.05) increased in ex-smokers and current smokers. The total IgE levels and IgE levels specific to Df, cockroaches, and dogs significantly (p value for trend <0.05) and proportionally increased with increasing numbers of cigarettes smoked daily. Conclusion Smoking was associated with elevated total IgE levels and IgE levels specific to Df, cockroach, and dog allergens in a cumulative, dose-dependent manner. Furthermore, current smoking status was an independent risk factor for elevated total IgE levels and IgE levels specific to cockroach allergen.

Flowering responses of insect-pollinated plants to elevated CO{sub 2} levels

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

Cushman, J.H.; Koch, G.W.; Chiariello, N.R.

1995-06-01

Elevated atmospheric CO{sub 2} concentrations have been predicted or shown to substantially influence plants, communities and ecosystems in a variety of ways. Here, we examined the effects of elevated CO{sub 2} levels on the timing and magnitude of flowering for two insect-pollinated annual plant species in a serpentine grassland. We focused on Lasthenia californica and Linanthus parviflorus and addressed three questions: (1) Do elevated CO{sub 2} levels influence flowering phenologies and is this species specific? (2) Do elevated CO{sub 2} levels affect flower production and is this due to altered numbers of individuals, flowers per plant, or both? and (3)more » Are effects on flowering due to elevated CO{sub 2} levels per se or changes in environmental conditions associated with methods used to manipulate CO{sub 2} levels? To address these questions, we used the ecosystem experiment at Stanford University`s Jasper Ridge Biological Preserve (San Mateo Co., CA). This system consists of 20 open-topped chambers - half receiving ambient CO{sub 2} (360 ppm) and half receiving elevated CO{sub 2} (720 ppm) - and 10 untreated plots serving as chamber controls. Results from the 1994 season demonstrated that there were species-specific responses to elevated CO{sub 2} levels and the field chambers. For Lasthenia californica, elevated CO{sub 2} per se did not affect relative abundance, inflorescence production, or phenology, but chambers did significantly increase inflorescence production and extend the duration of flowering. For Linanthus parviflorus, elevated CO{sub 2} levels significantly increased relative abundance and flower production, and extended the flowering period slightly, while the chambers significantly decreased flower production early in the season and increased it later in the season.« less

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

PubMed

Robertson, M C; Owens, R E; McCoshen, J A; Friesen, H G

1984-01-01

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

Comparison of plasma B-type natriuretic peptide levels in single ventricle patients with systemic ventricle heart failure versus isolated cavopulmonary failure.

PubMed

Law, Yuk Ming; Ettedgui, Jose; Beerman, Lee; Maisel, Alan; Tofovic, Stevan

2006-08-15

The measurement of plasma B-type natriuretic peptide (BNP) has emerged as a useful biomarker of heart failure in patients with cardiomyopathy. The pathophysiology of heart failure in single ventricle (SV) circulation may be distinct from that of cardiomyopathies. A distinct pattern of BNP elevation in heart failure in the SV population was hypothesized: it is elevated in heart failure secondary to ventricular dysfunction but not in isolated cavopulmonary failure. BNP was measured prospectively in SV patients at catheterization (n = 22) and when assessing for heart failure (n = 11) (7 normal controls). Of 33 SV subjects (median age 62 months), 13 had aortopulmonary connections and 20 had cavopulmonary connections. Median and mean +/- SD BNP levels by shunt type were 184 and 754 +/- 1,086 pg/ml in the patients with aortopulmonary connections, 38 and 169 +/- 251 pg/ml in the patients with cavopulmonary connections, and 10 and 11 +/- 5 pg/ml in normal controls, respectively (p = 0.004). Median systemic ventricular end-diastolic pressure (8mm Hg, R = 0.45), mean pulmonary artery pressure (14.5 mm Hg, R = 0.62), and mean right atrial pressure (6.5 mm Hg, R = 0.54) were correlated with plasma BNP. SV subjects with symptomatic heart failure from dysfunctional systemic ventricles had median and mean +/- SD BNP levels of 378 and 714 +/- 912 pg/ml (n = 18) compared with patients with isolated failed Glenn or Fontan connections (19 and 23 +/- 16 pg/ml [n = 7, p = 0.001]) and those with no heart failure (22 and 22 +/- 12 pg/ml [n = 8, p = 0.001]). Excluding the group with cavopulmonary failure, the severity of heart failure from systemic ventricular dysfunction was associated with plasma BNP. In conclusion, plasma BNP is elevated in SV patients with systemic ventricular or left-sided cardiac failure. BNP is not elevated in patients missing a pulmonary ventricle with isolated cavopulmonary failure.

Elevated Circulating Osteoprotegerin and Renal Dysfunction Predict 15-Year Cardiovascular and All-Cause Mortality: A Prospective Study of Elderly Women

PubMed Central

Zhu, Kun; Lim, Ee M.; Bollerslev, Jens; Prince, Richard L.

2015-01-01

Background Data on the predictive role of estimated glomerular filtration rate (eGFR) and osteoprotegerin (OPG) for cardiovascular (CVD) and all-cause mortality risk have been presented by our group and others. We now present data on the interactions between OPG with stage I to III chronic kidney disease (CKD) for all-cause and CVD mortality. Methods and Results The setting was a 15-year study of 1,292 women over 70 years of age initially randomized to a 5-year controlled trial of 1.2 g of calcium daily. Serum OPG and creatinine levels with complete mortality records obtained from the Western Australian Data Linkage System were available. Interactions were detected between OPG levels and eGFR for both CVD and all-cause mortality (P < 0.05). Compared to participants with eGFR ≥60ml/min/1.73m2 and low OPG, participants with eGFR of <60ml/min/1.73m2 and elevated OPG had a 61% and 75% increased risk of all-cause and CVD mortality respectively (multivariate-adjusted HR, 1.61; 95% CI, 1.27-2.05; P < 0.001 and HR, 1.75; 95% CI, 1.22-2.55; P = 0.003). This relationship with mortality was independent of decline in renal function (P<0.05). Specific causes of death in individuals with elevated OPG and stage III CKD highlighted an excess of coronary heart disease, renal failure and chronic obstructive pulmonary disease deaths (P < 0.05). Conclusion The association between elevated OPG levels with CVD and all-cause mortality was more evident in elderly women with poorer renal function. Assessment of OPG in the context of renal function may be important in studies investigating its relationship with all-cause and CVD mortality. PMID:26222774

Glomerular Hyperfiltration as Predictor of Cardiometabolic Risk Factors among Children and Adolescents: The Childhood and Adolescence Surveillance and Prevention of Adult-V Study

PubMed Central

Kelishadi, Roya; Qorbani, Mostafa; Assadi, Farahnak; Motlagh, Mohammad Esmaeil; Djalalinia, Shirin; Shahsavari, Ali; Ziaodini, Hasan; Taheri, Majzoubeh; Shafiee, Gita; Aminianfar, Azadeh; Esmaeili, Sajjad; Aminaei, Tahereh; Mansourian, Morteza; Heshmat, Ramin

2018-01-01

Background: The prevalence of glomerular hyperfiltration and chronic kidney disease is increasing worldwide in parallel with obesity hypertension epidemic. The effect of increases in glomerular filtrations (GFR) in children with metabolic syndrome has not been studied. The purpose of the present study is to investigate the relationship between GFR and cardiometabolic risk factors in a large sample of pediatric population. Methods: In this nationwide survey, 3800 participants were selected by cluster random sampling from 30 provinces in Iran. Anthropometric measures, biochemical, and clinical parameters were measured. We also measured estimated GFR (eGFR) using the recently modified Schwartz equations and other known cardiometabolic risk factors such as elevated total cholesterol, high low-density lipoprotein cholesterol (LDL-C), and obesity. Results: The response rate was 91.5% (n = 3843). The mean and standard deviation (SD) (Mean ± SD) of eGFR for girls, boys, and total population were 96.71 ± 19.46, 96.49 ± 21.69, and 96.59 ± 20 ml/min/1.73 m2, respectively. Overall, 38.7% of the participants did not have any cardiometabolic risk factor. In multivariate models, the risk of elevated systolic blood pressure (BP) (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.08–2.02), elevated diastolic BP (OR: 1.48; 95% CI: 1.08–2.02), elevated LDL-C (OR: 1.35; 95% CI: 1.07–1.70), and obesity (OR: 1.70; 95%CI: 1.24–2.33) were significantly higher in participants with higher eGFR level than those with the lower level but not with low level of high-density lipoprotein cholesterol (OR: 0.72; 95% CI: 0.60–0.88). Conclusions: This study demonstrates an association between glomerular hyperfiltration and obesity-related hypertension in a large sample of the Iranian pediatric population, independently of other classical risk factors. PMID:29619157

Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

PubMed Central

2010-01-01

Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304

Wetland Accretion Rate Model of Ecosystem Resilience (WARMER) and its application to habitat sustainability for endangered species in the San Francisco Estuary

USGS Publications Warehouse

Swanson, Kathleen M.; Drexler, Judith Z.; Schoellhamer, David H.; Thorne, Karen M.; Casazza, Michael L.; Overton, Cory T.; Callaway, John C.; Takekawa, John Y.

2014-01-01

Salt marsh faunas are constrained by specific habitat requirements for marsh elevation relative to sea level and tidal range. As sea level rises, changes in relative elevation of the marsh plain will have differing impacts on the availability of habitat for marsh obligate species. The Wetland Accretion Rate Model for Ecosystem Resilience (WARMER) is a 1-D model of elevation that incorporates both biological and physical processes of vertical marsh accretion. Here, we use WARMER to evaluate changes in marsh surface elevation and the impact of these elevation changes on marsh habitat for specific species of concern. Model results were compared to elevation-based habitat criteria developed for marsh vegetation, the endangered California clapper rail (Rallus longirostris obsoletus), and the endangered salt marsh harvest mouse (Reithrodontomys raviventris) to determine the response of marsh habitat for each species to predicted >1-m sea-level rise by 2100. Feedback between vertical accretion mechanisms and elevation reduced the effect of initial elevation in the modeled scenarios. Elevation decreased nonlinearly with larger changes in elevation during the latter half of the century when the rate of sea-level rise increased. Model scenarios indicated that changes in elevation will degrade habitat quality within salt marshes in the San Francisco Estuary, and degradation will accelerate in the latter half of the century as the rate of sea-level rise accelerates. A sensitivity analysis of the model results showed that inorganic sediment accumulation and the rate of sea-level rise had the greatest influence over salt marsh sustainability.

Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response.

PubMed

Hanna-Attisha, Mona; LaChance, Jenny; Sadler, Richard Casey; Champney Schnepp, Allison

2016-02-01

We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure.

Long-term response of a Mojave Desert winter annual plant community to a whole-ecosystem atmospheric CO2 manipulation (FACE).

PubMed

Smith, Stanley D; Charlet, Therese N; Zitzer, Stephen F; Abella, Scott R; Vanier, Cheryl H; Huxman, Travis E

2014-03-01

Desert annuals are a critically important component of desert communities and may be particularly responsive to increasing atmospheric (CO2 ) because of their high potential growth rates and flexible phenology. During the 10-year life of the Nevada Desert FACE (free-air CO2 enrichment) Facility, we evaluated the productivity, reproductive allocation, and community structure of annuals in response to long-term elevated (CO2 ) exposure. The dominant forb and grass species exhibited accelerated phenology, increased size, and higher reproduction at elevated (CO2 ) in a wet El Niño year near the beginning of the experiment. However, a multiyear dry cycle resulted in no increases in productivity or reproductive allocation for the remainder of the experiment. At the community level, early indications of increased dominance of the invasive Bromus rubens at elevated (CO2 ) gave way to an absence of Bromus in the community during a drought cycle, with a resurgence late in the experiment in response to higher rainfall and a corresponding high density of Bromus in a final soil seed bank analysis, particularly at elevated (CO2 ). This long-term experiment resulted in two primary conclusions: (i) elevated (CO2 ) does not increase productivity of annuals in most years; and (ii) relative stimulation of invasive grasses will likely depend on future precipitation, with a wetter climate favoring invasive grasses but currently predicted greater aridity favoring native dicots. © 2013 John Wiley & Sons Ltd.

Small-scale topography modulates elevational α-, β- and γ-diversity of Andean leaf beetles.

PubMed

Thormann, Birthe; Ahrens, Dirk; Espinosa, Carlos Iván; Armijos, Diego Marín; Wagner, Thomas; Wägele, Johann W; Peters, Marcell K

2018-05-01

Elevational diversity gradients are typically studied without considering the complex small-scale topography of large mountains, which generates habitats of strongly different environmental conditions within the same elevational zones. Here we analyzed the importance of small-scale topography for elevational diversity patterns of hyperdiverse tropical leaf beetles (Coleoptera: Chrysomelidae). We compared patterns of elevational diversity and species composition of beetles in two types of forests (on mountain ridges and in valleys) and analyzed whether differences in the rate of species turnover among forest habitats lead to shifts in patterns of elevational diversity when scaling up from the local study site to the elevational belt level. We sampled beetle assemblages at 36 sites in the Podocarpus National Park, Ecuador, which were equally distributed over two forest habitats and three elevational levels. DNA barcoding and Poisson tree processes modelling were used to delimitate putative species. On average, local leaf beetle diversity showed a clear hump-shaped pattern. However, only diversity in forests on mountain ridges peaked at mid-elevation, while beetle diversity in valleys was similarly high at low- and mid-elevation and only declined at highest elevations. A higher turnover of species assemblages at lower than at mid-elevations caused a shift from a hump-shaped diversity pattern found at the local level to a low-elevation plateau pattern (with similar species numbers at low and mid-elevation) at the elevational belt level. Our study reveals an important role of small-scale topography and spatial scale for the inference on gradients of elevational species diversity.

Evaluating Tidal Marsh Sustainability in the Face of Sea-Level Rise: A Hybrid Modeling Approach Applied to San Francisco Bay

PubMed Central

Stralberg, Diana; Brennan, Matthew; Callaway, John C.; Wood, Julian K.; Schile, Lisa M.; Jongsomjit, Dennis; Kelly, Maggi; Parker, V. Thomas; Crooks, Stephen

2011-01-01

Background Tidal marshes will be threatened by increasing rates of sea-level rise (SLR) over the next century. Managers seek guidance on whether existing and restored marshes will be resilient under a range of potential future conditions, and on prioritizing marsh restoration and conservation activities. Methodology Building upon established models, we developed a hybrid approach that involves a mechanistic treatment of marsh accretion dynamics and incorporates spatial variation at a scale relevant for conservation and restoration decision-making. We applied this model to San Francisco Bay, using best-available elevation data and estimates of sediment supply and organic matter accumulation developed for 15 Bay subregions. Accretion models were run over 100 years for 70 combinations of starting elevation, mineral sediment, organic matter, and SLR assumptions. Results were applied spatially to evaluate eight Bay-wide climate change scenarios. Principal Findings Model results indicated that under a high rate of SLR (1.65 m/century), short-term restoration of diked subtidal baylands to mid marsh elevations (−0.2 m MHHW) could be achieved over the next century with sediment concentrations greater than 200 mg/L. However, suspended sediment concentrations greater than 300 mg/L would be required for 100-year mid marsh sustainability (i.e., no elevation loss). Organic matter accumulation had minimal impacts on this threshold. Bay-wide projections of marsh habitat area varied substantially, depending primarily on SLR and sediment assumptions. Across all scenarios, however, the model projected a shift in the mix of intertidal habitats, with a loss of high marsh and gains in low marsh and mudflats. Conclusions/Significance Results suggest a bleak prognosis for long-term natural tidal marsh sustainability under a high-SLR scenario. To minimize marsh loss, we recommend conserving adjacent uplands for marsh migration, redistributing dredged sediment to raise elevations, and concentrating restoration efforts in sediment-rich areas. To assist land managers, we developed a web-based decision support tool (www.prbo.org/sfbayslr). PMID:22110638

The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse

PubMed Central

Jacobsen, Jacob P.R.; Plenge, Per; Sachs, Benjamin D.; Pehrson, Alan L.; Cajina, Manuel; Du, Yunzhi; Roberts, Wendy; Rudder, Meghan L.; Dalvi, Prachiti; Robinson, Taylor J.; O’Neill, Sharon P.; Khoo, King S.; Morillo, Connie Sanchez; Zhang, Xiaodong; Caron, Marc G.

2015-01-01

Rationale Escitalopram is a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and antidepressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram’s inhibition hereof. Objectives Primary: Investigate at the human (h)SERT, at clinical relevant doses, whether R-citalopram antagonizes escitalopram-induced 5-HTExt elevation. Secondary: Investigate whether abolishing the putative allosteric site affects escitalopram-induced 5-HTExt elevation and/or modulates the effect of R-citalopram. Methods Recombinant technology; in vivo microdialysis; receptor binding; pharmacokinetics; 5-HT sensitive behaviors (tail suspension, marble burying). Results We generated mice expressing either the wild-type human SERT (hSERTWT) or hSERT carrying amino acid substitutions (A505V, L506F, I507L, S574T and I575T) collectively abolishing the putative allosteric site (hSERTALI/VFL+SI/TT). One mg/kg escitalopram yielded clinical relevant plasma levels and brain levels consistent with therapeutic SERT occupancy. Importantly, escitalopram-induced 5-HTExt elevation was not decreased by R-citalopram co-treatment. Further, escitalopram-induced 5-HTExt elevation was not affected by loss of the allosteric site. The behavioral effects of the clinically relevant escitalopram dose were small, tending to be enhanced by R-citalopram co-administration. Conclusions We find no evidence that R-citalopram directly antagonizes escitalopram or that the putative allosteric site is important for hSERT inhibition by escitalopram. Our findings points to mechanisms for R-citalopram antagonism of escitalopram’s antidepressant action other than direct antagonistic binding interactions at the hSERT. PMID:24810106

Sirtuin 1 Enzymatic Activity Is Required for Cartilage Homeostasis In Vivo in a Mouse Model

PubMed Central

Gabay, Odile; Sanchez, Christelle; Dvir-Ginzberg, Mona; Gagarina, Viktoria; Zaal, Kristien J.; Song, Yingjie; He, Xiao Hong; McBurney, Michael W.

2014-01-01

Objective We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. Methods Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1tm2.1Mcby (SIRT-1y/y), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 6–7 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. Results We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. Conclusion Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein. PMID:23124828

Indirect Effects of Elevated Body Mass Index on Memory Performance Through Altered Cerebral Metabolite Concentrations

PubMed Central

Gonzales, Mitzi M.; Takashi, Tarumi; Eagan, Danielle E.; Tanaka, Hirofumi; Vaghasia, Miral; Haley, Andreana P.

2012-01-01

Objective Elevated body mass index (BMI) at midlife is associated with increased risk of cognitive decline in later life. The goal of the current study was to assess mechanisms of early brain vulnerability by examining if higher BMI at midlife has an effect on current cognitive performance through alterations in cerebral neurochemistry. Methods Fifty-five participants, aged 40–60 years, underwent neuropsychological testing, health screen, and proton magnetic resonance spectroscopy (1H MRS) examining N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in occipitoparietal grey matter. Concentrations of NAA, Cho, mI, and Glu were calculated as a ratio over Cr and examined in relation to BMI using multivariate regression analyses. Structural equation modeling was used to determine if BMI had an indirect effect on cognition through cerebral metabolite levels. Results Higher BMI was associated with elevations in mI/Cr (F(5,45)= 3.843, p=0.006, β=0.444, p=0.002), independent of age, sex, fasting glucose levels, and systolic blood pressure. Moreover, a chi-square difference test of the direct and indirect structural equation models revealed that BMI had an indirect effect on global cognitive performance (ΔX2(df=2) =19.939, p<0.001). Subsequent follow-up analyses revealed that this effect was specific to memory (ΔX2(df=2) = 22.027, p<0.001). Conclusions Higher BMI was associated with elevations in mI/Cr concentrations in the occipitoparietal grey matter and indirectly related to poorer memory performance through mI/Cr, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain vulnerability. PMID:22822230

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

PubMed Central

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

2015-01-01

Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207

Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: involvement of the peripheral nicotinic acetylcholine receptors.

PubMed

Ilcol, Yesim Ozarda; Yilmaz, Zeki; Cansev, Mehmet; Ulus, Ismail H

2009-09-01

We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.

Changes in Peripheral Serum Creatine Phosphokinase (CPK) and Lactic Dehydrogenase (LDH) in Acute Experimental Colonic Infarction

PubMed Central

Graeber, Geoffrey M.; Wukich, Dane K.; Cafferty, Patrick J.; O'Neill, John F.; Wolf, Robert E.; Ackerman, Norman B.; Harmon, John W.

1981-01-01

No satisfactory laboratory test for the early diagnosis of bowel infarction exists at this time. We have delineated changes in serum CPK levels after acute superior mesenteric artery infarction; whether or not comparable changes occur with inferior mesenteric artery infarction has not yet been determined. Furthermore, the changes in LDH associated with acute bowel infarction have not been documented. To determine the changes in serum CPK and LDH in acute colonic infarction, laparotomies were performed on dogs after peripheral baseline blood samples were drawn and each subject was randomly placed in one of three groups: laparotomy alone, acute colonic obstruction, and acute colonic infarction by ligation of the inferior mesenteric artery. The marginal artery of the colon was ligated at the peritoneal reflection and at the cecum to interrupt arterial collaterals. Blood samples were taken from each subject at intervals of three hours for 48 hours after injury. Serum from each sample was analyzed for total CPK and LDH by automated spectrophotometry. Isoenzymes were determined by agarose gel electrophoresis. Necropsies were conducted on all the dogs to confirm that the intended condition had been produced and that no intercurrent disease was present. The data support the conclusion that total CPK, total LDH and their isoenzymes become elevated in the peripheral serum after colonic infarction. The maximal elevations were all seen within the first 12 hours after acute colonic infarction. Total LDH and LDH3, the most prevalent isoenzyme of LDH in bowel, do not become elevated in the serum to as high a level as CPK, but the combination of serum elevations in both enzyme systems may prove to be of diagnostic significance. PMID:7305484

Leaves of the Arabidopsis maltose exporter1 Mutant Exhibit a Metabolic Profile with Features of Cold Acclimation in the Warm

PubMed Central

Purdy, Sarah J.; Bussell, John D.; Nunn, Christopher P.; Smith, Steven M.

2013-01-01

Background Arabidopsis plants accumulate maltose from starch breakdown during cold acclimation. The Arabidopsis mutant, maltose excess1-1, accumulates large amounts of maltose in the plastid even in the warm, due to a deficient plastid envelope maltose transporter. We therefore investigated whether the elevated maltose level in mex1-1 in the warm could result in changes in metabolism and physiology typical of WT plants grown in the cold. Principal Findings Grown at 21 °C, mex1-1 plants were much smaller, with fewer leaves, and elevated carbohydrates and amino acids compared to WT. However, after transfer to 4 °C the total soluble sugar pool and amino acid concentration was in equal abundance in both genotypes, although the most abundant sugar in mex1-1 was still maltose whereas sucrose was in greatest abundance in WT. The chlorophyll a/b ratio in WT was much lower in the cold than in the warm, but in mex1-1 it was low in both warm and cold. After prolonged growth at 4 °C, the shoot biomass, rosette diameter and number of leaves at bolting were similar in mex1-1 and WT. Conclusions The mex1-1 mutation in warm-grown plants confers aspects of cold acclimation, including elevated levels of sugars and amino acids and low chlorophyll a/b ratio. This may in turn compromise growth of mex1-1 in the warm relative to WT. We suggest that elevated maltose in the plastid could be responsible for key aspects of cold acclimation. PMID:24223944

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection

PubMed Central

Sasmono, R. Tedjo; Sinto, Robert; Ibrahim, Eppy; Suryamin, Maulana

2017-01-01

Abstract Background. The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods. A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results. A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001–1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025–1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000–1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004–1.074) had an adjusted association with severe plasma leakage. Conclusions. In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage. PMID:28453844

Impact of lipid disorders on mortality among Saudi patients with heart failure

PubMed Central

Al Qahtani, M.; Al Backer, T.; Al Anazi, T.; Al Johani, N.; Binsalih, S.; AlGobain, M.; Alshammari, H.

2014-01-01

Background Dyslipidemia, a known cardiovascular risk factor, is extremely common among Saudis, both adults and children. The impact, however, of dyslipidemia and several other lipid disorders in patients with congestive heart failure in this particular population has not been documented. This study aims to fill the gap. Methods This retrospective, single center study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Of the 500 cases seen during the period between 2002 and 2008, 392 were included in the study. Charts were reviewed and information on medical history, medications, and lipid status were documented. Results Low HDL-cholesterol level was the most common lipid disorder with 82.9%, followed by hypertriglyceridemia (35.2%), atherogenic dyslipidemia (27.8%), and hypercholesterolemia (9.2%). Diabetes mellitus was the single most significant predictor of mortality (p = 0.001). Among the lipid disorders, only low levels of HDL-cholesterol contributed to significant mortality risk [OR 1.29 (Confidence Interval 1.04–1.59) (p-value < 0.01)] adjusted for age, gender and statin use. Conclusion The results of this study suggest that emphasis should be on the elevation of HDL-cholesterol levels among subjects with congestive heart failure, without compromising any ongoing management of LDL-lowering drugs. Management should not be limited to conventional statin use and should promote other treatments to elevate HDL-cholesterol levels. PMID:25870502

Ameliorative effect of pumpkin seed oil against emamectin induced toxicity in mice.

PubMed

Abou-Zeid, Shimaa M; AbuBakr, Huda O; Mohamed, Mostafa A; El-Bahrawy, Amanallah

2018-02-01

The current study was conducted to evaluate the toxic effects of emamectin insecticide in mice and the possible protective effect of pumpkin seed oil. Treated mice received emamectin benzoate in the diet at 75-ppm for 8 weeks, while another group of animals received emamectin in addition to pumpkin seed oil at a dose of 4 ml/kg. Biochemical analysis of MDA, DNA fragmentation, GSH, CAT and SOD was performed in liver, kidney and brain as oxidant/antioxidant biomarkers. In addition, gene expression of CYP2E1 and Mgst1 and histopathological alterations in these organs were evaluated. Emamectin administration induced oxidative stress in liver and kidney evidenced by elevated levels of MDA and percentage of DNA fragmentation with suppression of GSH level and CAT and SOD activities. Brain showed increase of MDA level with inhibition of SOD activity. Relative expressions of CYP2E1 and Mgst1 genes were significantly elevated in both liver and kidney. Emamectin produced several histopathological changes in liver, kidney and brain. Co-administration of pumpkin seed oil produced considerable protection of liver and kidney and complete protection of brain. In conclusion, pumpkin seed oil has valuable value in ameliorating the toxic insult produced by emamectin in mice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prevalence and Predictors of Abnormal Liver Enzymes in Young Women with Anorexia Nervosa

PubMed Central

Fong, Hiu-fai; DiVasta, Amy D.; DiFabio, Diane; Ringelheim, Julie; Jonas, Maureen M.; Gordon, Catherine M.

2008-01-01

Objective To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN). Study design In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables. Results Elevated alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = −0.27 to −0.30, p ≤ 0.049) and percentage body fat (r = −0.36 to −0.47, p ≤ 0.007), but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs. 18.0 U/L, p = 0.01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, p = 0.04). Conclusions Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine if these liver enzyme elevation signify unrecognized, clinically relevant liver disease. PMID:18534220

Mortality associated with bilirubin levels in insurance applicants.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2009-01-01

Determine the relationship between bilirubin levels with and without other liver function test (LFT) elevations and relative mortality in life insurance applicants. By use of the Social Security Death Master File mortality was determined in 1,905,664 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 50,174 deaths observed in this study population. Results were stratified by 3 age/sex groups: females, age <60; males, age <60; and all, age 60+. The median follow-up was 12 years. Relative mortality increased as bilirubin decreased below bilirubin levels seen for the middle 50% of the population. The known association of smoking with lower bilirubin values explained only part of the additional elevated risk at low bilirubin levels. In the absence of other LFT elevations, relative mortality remained unchanged as bilirubin increased beyond levels seen for the middle 50% of the population. When a bilirubin elevation was combined with other LFT elevations, mortality further increased only at the highest elevations of other LFTs, seen only in <2.5% of applicants. Isolated elevations of bilirubin in this healthy screening population were not associated with excess mortality but values below the midpoint were. Other investigations have suggested a cardiovascular cause may underlie the excess mortality associated with low bilirubin. In association with other LFT elevations, bilirubin elevation further increases the mortality risk only at the highest elevations of other LFTs.

Ca2+ influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery

PubMed Central

Ihara, Eikichi; Derkach, Dmitry N; Hirano, Katsuya; Nishimura, Junji; Nawata, Hajime; Kanaide, Hideo

2001-01-01

To determine the mechanism of bradykinin-induced production of endothelium-derived contracting factors, we monitored the changes in cytosolic Ca2+ concentration ([Ca2+]i) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca2+]i of smooth muscle cells and force in porcine interlobar renal arterial strips using front-surface fluorometry of fura-2. In the presence of Nω-nitro-l-arginine methyl ester, bradykinin caused an endothelium-dependent transient elevation of [Ca2+]i and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H2/thromboxane A2 receptor antagonist. In the absence of extracellular Ca2+, bradykinin failed to induce contraction. However, replenishing extracellular Ca2+ to 0.75 mm and higher induced an instantaneous contraction. However, replenishing Ca2+per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10−5m 1-(β-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365) or 0.2 mm Ni2+ abolished the contraction induced by bradykinin in the presence of extracellular Ca2+. Treatment with 10−5m indomethacin completely inhibited the contractile response induced by Ca2+ replenishment, regardless of the timing of its application, before or after the application of bradykinin. In endothelial cells in the valvular strips, bradykinin caused a transient [Ca2+]i elevation in the presence of 1.25 mm extracellular Ca2+, but [Ca2+]i returned to the resting level within 10 min. Neither 10−5m SKF96365 nor 0.2 mm Ni2+ had any effect on the peak [Ca2+]i elevation, but decreased [Ca2+]i in the declining phase. In the absence of extracellular Ca2+, bradykinin induced a transient [Ca2+]i elevation to a level similar to that seen in the presence of 1.25 mm extracellular Ca2+. However, [Ca2+]i then rapidly returned to the prestimulation level within 5 min. Subsequent Ca2+ replenishment to 0.75 mm and higher in the presence of bradykinin elevated [Ca2+]i to significantly higher levels than the resting level seen in the media containing 1.25 mm Ca2+. In conclusion, Ca2+ influx in the endothelial cells is essential for bradykinin to induce endothelium-dependent contraction in the porcine interlobar renal artery. PMID:11483701

Cardiac output in idiopathic normal pressure hydrocephalus: association with arterial blood pressure and intracranial pressure wave amplitudes and outcome of shunt surgery

PubMed Central

2011-01-01

Background In patients with idiopathic normal pressure hydrocephalus (iNPH) responding to shunt surgery, we have consistently found elevated intracranial pressure (ICP) wave amplitudes during diagnostic ICP monitoring prior to surgery. It remains unknown why ICP wave amplitudes are increased in these patients. Since iNPH is accompanied by a high incidence of vascular co-morbidity, a possible explanation is that there is reduced vascular compliance accompanied by elevated arterial blood pressure (ABP) wave amplitudes and even altered cardiac output (CO). To investigate this possibility, the present study was undertaken to continuously monitor CO to determine if it is correlated to ABP and ICP wave amplitudes and the outcome of shunting in iNPH patients. It was specifically addressed whether the increased ICP wave amplitudes seen in iNPH shunt responders were accompanied by elevated CO and/or ABP wave amplitude levels. Methods Prospective iNPH patients (29) were clinically graded using an NPH grading scale. Continuous overnight minimally-invasive monitoring of CO and ABP was done simultaneously with ICP monitoring; the CO, ABP, and ICP parameters were parsed into 6-second time windows. Patients were assessed for shunt surgery on clinical grade, Evan's index, and ICP wave amplitude. Follow-up clinical grading was performed 12 months after surgery. Results ICP wave amplitudes but not CO or ABP wave amplitude, showed good correlation with the response to shunt treatment. The patients with high ICP wave amplitude did not have accompanying high levels of CO or ABP wave amplitude. Correlation analysis between CO and ICP wave amplitudes in individual patients showed different profiles [significantly positive in 10 (35%) and significantly negative in 16 (55%) of 29 recordings]. This depended on whether there was also a correlation between ABP and ICP wave amplitudes and on the average level of ICP wave amplitude. Conclusions These results gave no evidence that the increased levels of ICP wave amplitudes seen in iNPH shunt responders prior to surgery were accompanied by elevated levels of ABP wave amplitudes or elevated CO. In the individual patients the correlation between CO and ICP wave amplitude was partly related to an association between ABP and ICP wave amplitudes which can be indicative of the state of cerebrovascular pressure regulation, and partly related to the ICP wave amplitude which can be indicative of the intracranial compliance. PMID:21349148

Modeling tidal marsh distribution with sea-level rise: evaluating the role of vegetation, sediment, and upland habitat in marsh resiliency.

PubMed

Schile, Lisa M; Callaway, John C; Morris, James T; Stralberg, Diana; Parker, V Thomas; Kelly, Maggi

2014-01-01

Tidal marshes maintain elevation relative to sea level through accumulation of mineral and organic matter, yet this dynamic accumulation feedback mechanism has not been modeled widely in the context of accelerated sea-level rise. Uncertainties exist about tidal marsh resiliency to accelerated sea-level rise, reduced sediment supply, reduced plant productivity under increased inundation, and limited upland habitat for marsh migration. We examined marsh resiliency under these uncertainties using the Marsh Equilibrium Model, a mechanistic, elevation-based soil cohort model, using a rich data set of plant productivity and physical properties from sites across the estuarine salinity gradient. Four tidal marshes were chosen along this gradient: two islands and two with adjacent uplands. Varying century sea-level rise (52, 100, 165, 180 cm) and suspended sediment concentrations (100%, 50%, and 25% of current concentrations), we simulated marsh accretion across vegetated elevations for 100 years, applying the results to high spatial resolution digital elevation models to quantify potential changes in marsh distributions. At low rates of sea-level rise and mid-high sediment concentrations, all marshes maintained vegetated elevations indicative of mid/high marsh habitat. With century sea-level rise at 100 and 165 cm, marshes shifted to low marsh elevations; mid/high marsh elevations were found only in former uplands. At the highest century sea-level rise and lowest sediment concentrations, the island marshes became dominated by mudflat elevations. Under the same sediment concentrations, low salinity brackish marshes containing highly productive vegetation had slower elevation loss compared to more saline sites with lower productivity. A similar trend was documented when comparing against a marsh accretion model that did not model vegetation feedbacks. Elevation predictions using the Marsh Equilibrium Model highlight the importance of including vegetation responses to sea-level rise. These results also emphasize the importance of adjacent uplands for long-term marsh survival and incorporating such areas in conservation planning efforts.

Application of Geographic Information System Methods to Identify Areas Yielding Water that will be Replaced by Water from the Colorado River in the Vidal and Chemehuevi Areas, California, and the Mohave Mesa Area, Arizona

USGS Publications Warehouse

Spangler, Lawrence E.; Angeroth, Cory E.; Walton, Sarah J.

2008-01-01

Relations between the elevation of the static water level in wells and the elevation of the accounting surface within the Colorado River aquifer in the vicinity of Vidal, California, the Chemehuevi Indian Reservation, California, and on Mohave Mesa, Arizona, were used to determine which wells outside the flood plain of the Colorado River are presumed to yield water that will be replaced by water from the Colorado River. Wells that have a static water-level elevation equal to or below the elevation of the accounting surface are presumed to yield water that will be replaced by water from the Colorado River. Geographic Information System (GIS) interpolation tools were used to produce maps of areas where water levels are above, below, and near (within ? 0.84 foot) the accounting surface. Calculated water-level elevations and interpolated accounting-surface elevations were determined for 33 wells in the vicinity of Vidal, 16 wells in the Chemehuevi area, and 35 wells on Mohave Mesa. Water-level measurements generally were taken in the last 10 years with steel and electrical tapes accurate to within hundredths of a foot. A Differential Global Positioning System (DGPS) was used to determine land-surface elevations to within an operational accuracy of ? 0.43 foot, resulting in calculated water-level elevations having a 95-percent confidence interval of ? 0.84 foot. In the Vidal area, differences in elevation between the accounting surface and measured water levels range from -2.7 feet below to as much as 17.6 feet above the accounting surface. Relative differences between the elevation of the water level and the elevation of the accounting surface decrease from west to east and from north to south. In the Chemehuevi area, differences in elevation range from -3.7 feet below to as much as 8.7 feet above the accounting surface, which is established at 449.6 feet in the vicinity of Lake Havasu. In all of the Mohave Mesa area, the water-level elevation is near or below the elevation of the accounting surface. Differences in elevation between water levels and the accounting surface range from -0.2 to -11.3 feet, with most values exceeding -7.0 feet. In general, the ArcGIS Triangulated Irregular Network (TIN) Contour and Natural Neighbor tools reasonably represent areas where the elevation of water levels in wells is above, below, and near (within ? 0.84 foot) the elevation of the accounting surface in the Vidal and Chemehuevi study areas and accurately delineate areas around outlying wells and where anomalies exist. The TIN Contour tool provides a strict linear interpolation while the Natural Neighbor tool provides a smoothed interpolation. Using the default options in ArcGIS, the Inverse Distance Weighted (IDW) and Spline tools also reasonably represent areas above, below, and near the accounting surface in the Vidal and Chemehuevi areas. However, spatial extent of and boundaries between areas above, below, and near the accounting surface vary among the GIS methods, which results largely from the fundamentally different mathematical approaches used by these tools. The limited number and spatial distribution of wells in comparison to the size of the areas, and the locations and relative differences in elevation between water levels and the accounting surface of wells with anomalous water levels also influence the contouring by each of these methods. Qualitatively, the Natural Neighbor tool appears to provide the best representation of the difference between water-level and accounting-surface elevations in the study areas, on the basis of available well data.

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

PubMed Central

2014-01-01

Introduction We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Methods Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables. Results In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Conclusion Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production. PMID:24766912

Antibodies to CBir1 are Associated with Glycogen Storage Disease Type Ib

PubMed Central

Davis, Michael K.; Valentine, John F.; Weinstein, David A.; Polyak, Steven

2009-01-01

Objectives Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil and monocyte dysfunction, and an inflammatory bowel disease (IBD) that mimics a Crohn's disease phenotype. The enteric microflora is implicated in the pathogenesis of IBD; however, its role in the development of GSD-associated IBD is unknown. Antibody reactivity to Saccharomyces cerevisiae antibodies (ASCA), Escherichia coli outer membrane porin C (anti-OmpC) and bacterial flagellin (anti-CBir1) have been associated with Crohn's disease in the general population, but they have an undetermined association in children and adults with GSD-Ib. Our goal was to examine the association of ASCA, anti-OmpC and anti-CBir1 with the clinical features of GSD-Ib enterocolitis. Methods A retrospective review identified 19 GSD-Ib patients with or without a known diagnosis of enterocolitis. Radiographic, endoscopic and serologic data were collected and assays for ASCA, anti-OmpC, and anti-CBir1 obtained. Results Seven patients had combined radiographic, endoscopic, and histological evidence of intestinal inflammation; the majority had ileocolonic involvement. Seventeen of 19 (89%) patients had elevated anti-CBir1 levels (6/7 in the IBD group and 11/12 in the no clinical evidence of IBD group). Thirteen of 19 (68%) had elevated anti-OmpC levels (5/7 in the IBD group and 8/12 in the no clinical evidence of IBD group). Eleven of 19 (58%) patients had elevated ASCA IgA levels (4/7 in the IBD group and 7/12 in the no clinical evidence of IBD group). Conclusion Nearly all of the GSD type Ib patients had elevated anti-CBir1 levels. The antibody did not differentiate those with and without a diagnosis of GSD-Ib-associated IBD. Seroreactivity to flagellin may represent immune dysfunction rather than active enterocolitis in this patient population. Long-term follow-up of the group without known IBD is required to determine if these antibodies can predict intestinal inflammation. PMID:20410847

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

PubMed Central

2014-01-01

Introduction High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. Methods and results We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. Conclusion The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up. PMID:24661773

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

PubMed Central

Zahrieh, David; Young, Sean G.; Oleson, Jacob; Ryckman, Kelli K.; Wels, Brian; Simmons, Donald L.; Saftlas, Audrey

2017-01-01

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact. PMID:28520816

Serum Aminotransferase Levels are Associated with Markers of Hypoxia in Patients with Obstructive Sleep Apnea

PubMed Central

Norman, Daniel; Bardwell, Wayne A.; Arosemena, Farah; Nelesen, Richard; Mills, Paul J.; Loredo, Jose S.; Lavine, Joel E.; Dimsdale, Joel E.

2008-01-01

Study Objectives: Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). Design: Retrospective case series. Patients and Setting: 109 adult patients with OSA at a university hospital general clinical research center. Measurements and Results: Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = −0.31 to −0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. Conclusions: In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome. Citation: Norman D; Bardwell WA; Arosemena F; Nelesen R; Mills PJ; Loredo JS; Lavine JE; Dimsdale JE. Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea. SLEEP 2008;31(1):-121-126. PMID:18220085

Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

PubMed Central

Chan, Te-Fu; Lin, Wei-Ting; Chen, Yi-Ling; Huang, Hsiao-Ling; Yang, Wei-Zeng; Lee, Chun-Ying; Chen, Meng-Hsueh; Wang, Tsu-Nai; Huang, Meng-Chuan; Chiu, Yu-Wen; Huang, Chun-Chi; Tsai, Sharon; Lin, Chih-Lung; Lee, Chien-Hung

2014-01-01

Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4. PMID:24475021

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens.

PubMed

Adermark, Louise; Clarke, Rhona B C; Olsson, Torsten; Hansson, Elisabeth; Söderpalm, Bo; Ericson, Mia

2011-01-01

Elevated dopamine levels are believed to contribute to the rewarding sensation of ethanol (EtOH), and previous research has shown that strychnine-sensitive glycine receptors in the nucleus accumbens (nAc) are involved in regulating dopamine release and in mediating the reinforcing effects of EtOH. Furthermore, the osmoregulator taurine, which is released from astrocytes treated with EtOH, can act as an endogenous ligand for the glycine receptor, and increase extracellular dopamine levels. The aim of this study was to address if EtOH-induced swelling of astrocytes could contribute to elevated dopamine levels by increasing the extracellular concentration of taurine. Cell swelling was estimated by optical sectioning of fluorescently labeled astrocytes in primary cultures from rat, and showed that EtOH (25-150 mM) increased astrocyte cell volumes in a concentration- and ion-dependent manner. The EtOH-induced cell swelling was inhibited in cultures treated with the Na(+) /K(+) /2Cl⁻ cotransporter blocker furosemide (1 mM), Na(+) /K(+) -ATPase inhibitor ouabain (0.1 mM), potassium channel inhibitor BaCl₂ (50 µM) and in cultures containing low extracellular sodium concentration (3 mM). In vivo microdialysis performed in the nAc of awake and freely moving rats showed that local treatment with EtOH enhanced the concentrations of dopamine and taurine in the microdialysate, while glycine and β-alanine levels were not significantly modulated. EtOH-induced dopamine release was antagonized by local treatment with the glycine receptor antagonist strychnine (20 µM) or furosemide (100 µM or 1 mM). Furosemide also prevented EtOH-induced taurine release in the nAc. In conclusion, our data suggest that extracellular concentrations of dopamine and taurine are interconnected and that swelling of astrocytes contributes to the acute rewarding sensation of EtOH. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

Diabetes in Relation to Serum Levels of Polychlorinated Biphenyls and Chlorinated Pesticides in Adult Native Americans

PubMed Central

Codru, Neculai; Schymura, Maria J.; Negoita, Serban; Rej, Robert; Carpenter, David O.

2007-01-01

Background Recent research suggests that diabetes, a condition whose incidence is increasing, is associated with exposure to polychlorinated biphenyls (PCBs) and chlorinated pesticides. Objectives We investigated the potential association between diabetes and serum levels of PCBs, dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and mirex in a cross-sectional study of an adult Native-American (Mohawk) population. Methods Through a standardized questionnaire we collected demographic, medical, and lifestyle information from 352 adults, ≥30 years of age. We collected fasting serum samples that were analyzed for 101 PCB congeners, DDE, HCB, and mirex along with fasting glucose, triglycerides, and cholesterol. Participants who had fasting-glucose values > 125 mg/dL and/or who were taking antidiabetic medication were defined as persons with diabetes. We conducted logistic regression to assess the potential association between organochlorine serum levels and diabetes, while controlling for the potential confounding variables of age, body mass index (BMI), smoking, sex, and serum lipid levels. Organochlorine serum levels were categorized in tertiles, and the lowest tertile was used as the reference category. Results The prevalence of diabetes was 20.2%. The odds ratio (OR) of having diabetes for participants in the highest tertile of total PCB concentration compared with the lowest tertile was 3.9 (95% confidence interval, 1.5–10.6). The corresponding ORs for DDE and HCB were even higher. Elevated serum mirex was not associated with diabetes. After adjustment for other analytes, the OR for HCB remained significant, whereas ORs for PCBs and DDE remained elevated but not statistically significant. In contrast, after adjustment for other analytes, the OR for mirex became statistically significant and indicated an inverse association. Conclusions In this study of adult Native Americans, elevated serum PCBs, DDE, and HCB were positively associated with diabetes after controlling for potential confounders, whereas a negative association was observed for mirex. PMID:17938733

Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver.

PubMed

Aissa, Alexandre Ferro; Amaral, Catia Lira do; Venancio, Vinicius Paula; Machado, Carla da Silva; Hernandes, Lívia Cristina; Santos, Patrick Wellington da Silva; Curi, Rui; Bianchi, Maria de Lourdes Pires; Antunes, Lusânia Maria Greggi

2017-01-01

Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.

Elevated polyamines in urothelial cells from OAB subjects mediate oxotremorine-evoked rapid intracellular calcium rise and delayed acetylcholine release.

PubMed

Li, Mingkai; Sun, Yan; Tomiya, Noboru; Hsu, Yuchao; Chai, Toby C

2013-08-15

Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca(2+)]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca(2+)]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca(2+)]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca(2+)]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 μM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca(2+)]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC.

Elevated polyamines in urothelial cells from OAB subjects mediate oxotremorine-evoked rapid intracellular calcium rise and delayed acetylcholine release

PubMed Central

Li, Mingkai; Sun, Yan; Tomiya, Noboru; Hsu, Yuchao

2013-01-01

Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca2+]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca2+]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca2+]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca2+]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 μM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca2+]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC. PMID:23698115

Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function

PubMed Central

Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.

2015-01-01

Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%–60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015

Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases

PubMed Central

Schultz, Olaf; Oberhauser, Frank; Saech, Jasemine; Rubbert-Roth, Andrea; Hahn, Moritz; Krone, Wilhelm; Laudes, Matthias

2010-01-01

Background Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab. Methodology/Principal Findings 11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased. Conclusions/Significance Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects. PMID:21179199

Neuroprotective Effects of Transcription Factor Brn3b in an Ocular Hypertension Rat Model of Glaucoma

PubMed Central

Stankowska, Dorota L.; Minton, Alena Z.; Rutledge, Margaret A.; Mueller, Brett H.; Phatak, Nitasha R.; He, Shaoqing; Ma, Hai-Ying; Forster, Michael J.; Yorio, Thomas; Krishnamoorthy, Raghu R.

2015-01-01

Purpose. Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration. Methods. Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests. Results. Adeno-associated virus–mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b–injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP– injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes. Conclusions. Adeno-associated virus–mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma. PMID:25587060

Different Effects of Oral Contraceptive and Dydrogesterone Treatment on Oxidative Stress Levels in Premenopausal Women

PubMed Central

Chen, Jui-Tung; Kotani, Kazuhiko

2018-01-01

Background The aim of the study was to observe the changes in blood oxidative stress levels by oral contraceptive (OC) and/or dydrogesterone (DG) treatment. Methods A retrospective cohort of 27 premenopausal women with primary dysmenorrhea consisted of the OC treatment group (N = 17) and the DG treatment group (N = 10) by choice of the initial treatment. The OC group included two subgroups: patients with continuous OC treatment (treated for at least 15 months, N = 10) and patients with discontinuous OC treatment (switched to DG treatment after approximately 6 months of initial OC treatment: N = 7). The DG group had 15 months of continuous DG treatment. Blood parameters, including diacron-reactive oxygen metabolites (d-ROMs: an oxidative stress marker), were measured. Results The d-ROMs level was elevated in the OC group 3 months after initial treatment (mean: from 321 (at baseline) to 512 Carratelli Units (Carr U); P < 0.01), while such changes were not observed in the DG group. The d-ROMs level was reduced in the discontinuous OC subgroup 15 months after initial treatment (from 508 (3 months after initial treatment) to 372 Carr U; P < 0.01), while such changes were not observed in the continuous OC subgroup. The DG group displayed unchanged the d-ROMs level. Conclusion Replacing OC with DG can attenuate oxidative stress as elevated by OC, thereby alleviating the possible vascular risks with OC treatment. PMID:29317960

Acid Sphingomyelinase Mediates Oxidized-LDL Induced Apoptosis in Macrophage via Endoplasmic Reticulum Stress

PubMed Central

Zhao, Min; Pan, Wei; Shi, Rui-zheng; Bai, Yong-ping; You, Bo-yang; Zhang, Kai; Fu, Qiong-mei; Schuchman, Edward H.

2016-01-01

Aim: Macrophage apoptosis is a vital event in advanced atherosclerosis, and oxidized low-density lipoprotein (ox-LDL) is a major contributor to this process. Acid sphingomyelinase (ASM) and ceramide are also involved in the induction of apoptosis, particularly in macrophages. Our current study focuses on ASM and investigates its role in ox-LDL-induced macrophage apoptosis. Methods: Human THP-1 and mouse peritoneal macrophages were cultured in vitro and treated with ox-LDL. ASM activity and ceramide levels were quantified using ultra performance liquid chromatography. Protein and mRNA levels were analyzed using Western blot analysis and quantitative realtime PCR, respectively. Cell apoptosis was determined using Hoechst staining and flow cytometry. Results: Ox-LDL-induced macrophage apoptosis was triggered by profound endoplasmic reticulum (ER) stress, leading to an upregulation of ASM activity and ceramide levels at an early stage. ASM was inhibited by siRNA or desipramine (DES), and/or ceramide was degraded by recombinant acid ceramidase (AC). These events attenuated the effect of ox-LDL on ER stress. In contrast, recombinant ASM upregulated ceramide and ER stress. ASM siRNA, DES, recombinant AC, and ER stress inhibitor 4-phenylbutyric acid were blocked by elevated levels of C/EBP homologous protein (CHOP); ox-LDL induced elevated levels of CHOP. These events attenuated macrophage apoptosis. Conclusion: These results indicate that ASM/ceramide signaling pathway is involved in ox-LDL-induced macrophage apoptosis via ER stress pathway. PMID:26923251

Evidence for a Cystic Fibrosis Enteropathy

PubMed Central

Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

2015-01-01

Background Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. Methods Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. Results Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. Conclusion This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance. PMID:26484665

Elevated CO2 levels affects the concentrations of copper and cadmium in crops grown in soil contaminated with heavy metals under fully open-air field conditions.

PubMed

Guo, Hongyan; Zhu, Jianguo; Zhou, Hui; Sun, Yuanyuan; Yin, Ying; Pei, Daping; Ji, Rong; Wu, Jichun; Wang, Xiaorong

2011-08-15

Elevated CO(2) levels and the increase in heavy metals in soils through pollution are serious problems worldwide. Whether elevated CO(2) levels will affect plants grown in heavy-metal-polluted soil and thereby influence food quality and safety is not clear. Using a free-air CO(2) enrichment (FACE) system, we investigated the impacts of elevated atmospheric CO(2) on the concentrations of copper (Cu) or cadmium (Cd) in rice and wheat grown in soil with different concentrations of the metals in the soil. In the two-year study, elevated CO(2) levels led to lower Cu concentrations and higher Cd concentrations in shoots and grain of both rice and wheat grown in the respective contaminated soil. Elevated CO(2) levels slightly but significantly lowered the pH of the soil and led to changes in Cu and Cd fractionation in the soil. Our study indicates that elevated CO(2) alters the distribution of contaminant elements in soil and plants, thereby probably affecting food quality and safety.

The Impact of Clean Indoor Air Exemptions and Preemption Policies on the Prevalence of a Tobacco-Specific Lung Carcinogen Among Nonsmoking Bar and Restaurant Workers

PubMed Central

Stark, Michael J.; Rohde, Kristen; Maher, Julie E.; Pizacani, Barbara A.; Dent, Clyde W.; Bard, Ronda; Carmella, Steven G.; Benoit, Adam R.; Thomson, Nicole M.; Hecht, Stephen S.

2007-01-01

Objectives. We studied the impact of clean indoor air law exemptions and preemption policies on the prevalence of a tobacco-specific lung carcinogen—4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)—among nonsmoking bar and restaurant workers. Methods.secondhand smoke were compared with results from participants who were exposed to it. Results. Participants exposed to workplace secondhand smoke were more likely to have any detectable level of NNAL (P=.005) and higher mean levels of NNAL (P < .001) compared with nonexposed participants. Increased levels of NNAL were also associated with hours of a single workplace exposure (P=.005). Conclusions. Nonsmoking employees left unprotected from workplace secondhand smoke exposure had elevated levels of a tobacco-specific carcinogen in their bodies. All workers—including bar and restaurant workers—should be protected from indoor workplace exposure to cancer-causing secondhand smoke. PMID:17600262

Elevation trends and shrink-swell response of wetland soils to flooding and drying

USGS Publications Warehouse

Cahoon, Donald R.; Perez, Brian C.; Segura, Bradley D.; Lynch, James C.

2011-01-01

Given the potential for a projected acceleration in sea-level rise to impact wetland sustainability over the next century, a better understanding is needed of climate-related drivers that influence the processes controlling wetland elevation. Changes in local hydrology and groundwater conditions can cause short-term perturbations to marsh elevation trends through shrink—swell of marsh soils. To better understand the magnitude of these perturbations and their impacts on marsh elevation trends, we measured vertical accretion and elevation dynamics in microtidal marshes in Texas and Louisiana during and after the extreme drought conditions that existed there from 1998 to 2000. In a Louisiana marsh, elevation was controlled by subsurface hydrologic fluxes occurring below the root zone but above the 4 m depth (i.e., the base of the surface elevation table benchmark) that were related to regional drought and local meteorological conditions, with marsh elevation tracking water level variations closely. In Texas, a rapid decline in marsh elevation was related to severe drought conditions, which lowered local groundwater levels. Unfragmented marshes experienced smaller water level drawdowns and more rapid marsh elevation recovery than fragmented marshes. It appears that extended drawdowns lead to increased substrate consolidation making it less resilient to respond to future favorable conditions. Overall, changes in water storage lead to rapid and large short-term impacts on marsh elevation that are as much as five times greater than the long-term elevation trend, indicating the importance of long-term, high-resolution elevation data sets to understand the prolonged effects of water deficits on marsh elevation change.

Associations between Fibroblast Growth Factor 23 and Cardiac Characteristics in Pediatric Heart Failure

PubMed Central

Isakova, Tamara; Houston, Jessica; Santacruz, Laura; Schiavenato, Eva; Somarriba, Gabriel; Harmon, William G.; Lipshultz, Steven E.; Miller, Tracie L.; Rusconi, Paolo G.

2013-01-01

Background In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking. Patients and Methods We conducted a cross-sectional study of 17 healthy children (mean age, 13 years) and 20 pediatric patients with heart failure (mean age, 12 years) who underwent echocardiography and the following measurements: plasma FGF23 and parathyroid hormone (PTH); serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association (NYHA) and the Ross classification systems. Results Of 20 patients, 11 had dilated cardiomyopathy; 4, congenital heart disease; 3, hypertrophic cardiomyopathy; 1, a failing heart transplant; and 1, pulmonary hypertension. Mean phosphate levels in patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients vs. controls (110.9 vs. 66.4 RU/ml, P=0.03) and higher in patients on diuretics vs. other patients (222.4 vs. 82.1 RU/ml, P=0.01). Levels of FGF23 and NT-proBNP were directly correlated (r=0.47, P=0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P=0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r=0.63, P=0.04). Conclusion FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation. PMID:23740037

Cardiac Biomarkers in HIV-Exposed Uninfected Children: The Pediatric HIV/AIDS Cohort Study (PHACS)

PubMed Central

WILKINSON, James D.; WILLIAMS, Paige L.; LEISTER, Erin; ZELDOW, Bret; SHEARER, William T.; COLAN, Steven D.; SIBERRY, George K.; DOOLEY, Laurie B.; SCOTT, Gwendolyn B.; RICH, Kenneth C.; LIPSHULTZ, Steven E.

2014-01-01

Objectives To evaluate associations of cardiac biomarkers with in utero antiretroviral (ARV) drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. Design and methods We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal ARV exposures, maternal-child characteristics, and echocardiographic parameters. Results Among 338 HEU children (mean age=4.3 years), 51% had at least 1 elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP (adjusted odds ratio [aOR]=2.28, P=0.02). Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR=3.56, P=0.01 and aOR=2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left ventricular (LV) thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean LV end-diastolic (ED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean LV contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). Conclusion Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation. PMID:23211773

Soybean leaf hydraulic conductance does not acclimate to growth at elevated [CO2] or temperature in growth chambers or in the field

PubMed Central

Locke, Anna M.; Sack, Lawren; Bernacchi, Carl J.; Ort, Donald R.

2013-01-01

Background and Aims Leaf hydraulic properties are strongly linked with transpiration and photosynthesis in many species. However, it is not known if gas exchange and hydraulics will have co-ordinated responses to climate change. The objective of this study was to investigate the responses of leaf hydraulic conductance (Kleaf) in Glycine max (soybean) to growth at elevated [CO2] and increased temperature compared with the responses of leaf gas exchange and leaf water status. Methods Two controlled-environment growth chamber experiments were conducted with soybean to measure Kleaf, stomatal conductance (gs) and photosynthesis (A) during growth at elevated [CO2] and temperature relative to ambient levels. These results were validated with field experiments on soybean grown under free-air elevated [CO2] (FACE) and canopy warming. Key results In chamber studies, Kleaf did not acclimate to growth at elevated [CO2], even though stomatal conductance decreased and photosynthesis increased. Growth at elevated temperature also did not affect Kleaf, although gs and A showed significant but inconsistent decreases. The lack of response of Kleaf to growth at increased [CO2] and temperature in chamber-grown plants was confirmed with field-grown soybean at a FACE facility. Conclusions Leaf hydraulic and leaf gas exchange responses to these two climate change factors were not strongly linked in soybean, although gs responded to [CO2] and increased temperature as previously reported. This differential behaviour could lead to an imbalance between hydraulic supply and transpiration demand under extreme environmental conditions likely to become more common as global climate continues to change. PMID:23864003

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma

PubMed Central

Vongsuvanh, Roslyn; van der Poorten, David; Iseli, Tristan; Strasser, Simone I.; McCaughan, Geoffrey W.; George, Jacob

2016-01-01

Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. Conclusion: AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC. PMID:27219517

Usefulness of C-Reactive Protein as a Disease Activity Marker in Crohn’s Disease according to the Location of Disease

PubMed Central

Yang, Dong-Hoon; Yang, Suk-Kyun; Park, Sang Hyoung; Lee, Ho-Su; Boo, Sun-Jin; Park, Jae-Ho; Na, Soo Young; Jung, Kee Wook; Kim, Kyung-Jo; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Kim, Jin-Ho

2015-01-01

Background/Aims C-reactive protein (CRP) is a serologic activity marker in Crohn’s disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. Methods Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician’s prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. Results Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (γ=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. Conclusions CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD. PMID:25170056

Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats.

PubMed

Rehakova, R; Klimentova, J; Cebova, M; Barta, A; Matuskova, Z; Labas, P; Pechanova, O

2016-10-24

Deuterium-depleted water (DDW) has a lower concentration of deuterium than occurs naturally (less than 145 ppm). While effects of DDW on cancer started to be intensively studied, the effects on cardiovascular system are completely unknown. Thus, we aimed to analyze the effects of DDW (55+/-5 ppm) administration to 12-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) treated with 15 % fructose for 6 weeks. Blood pressure (BP) and selected biochemical parameters were measured together with determination of nitric oxide synthase (NOS) activity and iNOS and eNOS protein expressions in the left ventricle (LV) and aorta. Neither DDW nor fructose had any significant effect on BP in both strains. DDW treatment decreased total cholesterol and triglyceride levels in WKY, but it was not able to prevent increase in the same parameters elevated due to fructose treatment in SHR. Both fructose and DDW increased insulin level in WKY. Fructose did not affect NOS activity either in WKY or SHR. DDW increased NOS activity in LV of both WKY and SHR, while it decreased NOS activity and iNOS expression in the aorta of SHR with or without fructose treatment. In conclusion, DDW treatment significantly modified biochemical parameters in WKY together with NOS activity elevation in the heart. On the other hand, it did not affect biochemical parameters in SHR, but decreased NOS activity elevated due to iNOS upregulation in the aorta.

Scrub typhus associated hepatic dysfunction and abdominal CT findings

PubMed Central

Park, Man Je; Lee, Hyoun Soo; Shim, Sang Goon; Kim, So Hee

2015-01-01

Objective: This retrospective study investigated abnormal hepatic dysfunction and abdominal computed tomography (CT) findings in scrub typhus. Methods: Three hundred forty nine adult patients were diagnosed with scrub typhus. Ninety four underwent abdominal CT. The CT images were reviewed by the attending radiologist. Patient data of history, symptoms, signs, and results of laboratory tests were collected from the electronic medical records. Results: In 349 patients with scrub typhus, elevation of aspartate aminotransferase (78.5%) and alanine aminotransferase (63.0%) were dominant compared to alkaline phosphatase (27.2%) and total bilirubin (16.1%). Abdominal CT findings of 94 patients were, in descending order of frequency, enlarged lymph node (53.2%), inhomogeneous enhancement of liver (47.9%), splenomegaly (46.8%), ascites (28.7%), low attenuation of periportal areas (27.7%), gallbladder wall thickening (17.0%), and splenic infarct (6.4%). Also, the level of aspartate aminotransferase tended to be elevated according to the number of CT findings (P= 0.028) Conclusions: We found that abdominal CT manifestations of scrub typhus with elevated aminotransferases were varied and not specific. However, knowledge of these findings may evoke the recognition of scrub typhus by clinicians in endemic areas. PMID:26101478

Osthole Enhances Osteogenesis in Osteoblasts by Elevating Transcription Factor Osterix via cAMP/CREB Signaling In Vitro and In Vivo.

PubMed

Zhang, Zhong-Rong; Leung, Wing Nang; Li, Gang; Kong, Siu Kai; Lu, Xiong; Wong, Yin Mei; Chan, Chun Wai

2017-06-08

Anabolic anti-osteoporotic agents are desirable for treatment and prevention of osteoporosis and fragility fractures. Osthole is a coumarin derivative extracted from the medicinal herbs Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim.f. Osthole has been reported with osteogenic and anti-osteoporotic properties, whereas the underlying mechanism of its benefit still remains unclear. The objective of the present study was to investigate the osteopromotive action of osthole on mouse osteoblastic MC3T3-E1 cells and on mouse femoral fracture repair, and to explore the interaction between osthole-induced osteopromotive effect and cyclic adenosine monophosphate (cAMP) elevating effect. Osthole treatment promoted osteogenesis in osteoblasts by enhancing alkaline phosphatase (ALP) activity and mineralization. Oral gavage of osthole enhanced fracture repair and increased bone strength. Mechanistic study showed osthole triggered the cAMP/CREB pathway through the elevation of the intracellular cAMP level and activation of the phosphorylation of the cAMP response element-binding protein (CREB). Blockage of cAMP/CREB downstream signals with protein kinase A (PKA) inhibitor KT5720 partially suppressed osthole-mediated osteogenesis by inhibiting the elevation of transcription factor, osterix. In conclusion, osthole shows osteopromotive effect on osteoblasts in vitro and in vivo. Osthole-mediated osteogenesis is related to activation of the cAMP/CREB signaling pathway and downstream osterix expression.

Osthole Enhances Osteogenesis in Osteoblasts by Elevating Transcription Factor Osterix via cAMP/CREB Signaling In Vitro and In Vivo

PubMed Central

Zhang, Zhong-Rong; Leung, Wing Nang; Li, Gang; Kong, Siu Kai; Lu, Xiong; Wong, Yin Mei; Chan, Chun Wai

2017-01-01

Anabolic anti-osteoporotic agents are desirable for treatment and prevention of osteoporosis and fragility fractures. Osthole is a coumarin derivative extracted from the medicinal herbs Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim.f. Osthole has been reported with osteogenic and anti-osteoporotic properties, whereas the underlying mechanism of its benefit still remains unclear. The objective of the present study was to investigate the osteopromotive action of osthole on mouse osteoblastic MC3T3-E1 cells and on mouse femoral fracture repair, and to explore the interaction between osthole-induced osteopromotive effect and cyclic adenosine monophosphate (cAMP) elevating effect. Osthole treatment promoted osteogenesis in osteoblasts by enhancing alkaline phosphatase (ALP) activity and mineralization. Oral gavage of osthole enhanced fracture repair and increased bone strength. Mechanistic study showed osthole triggered the cAMP/CREB pathway through the elevation of the intracellular cAMP level and activation of the phosphorylation of the cAMP response element-binding protein (CREB). Blockage of cAMP/CREB downstream signals with protein kinase A (PKA) inhibitor KT5720 partially suppressed osthole-mediated osteogenesis by inhibiting the elevation of transcription factor, osterix. In conclusion, osthole shows osteopromotive effect on osteoblasts in vitro and in vivo. Osthole-mediated osteogenesis is related to activation of the cAMP/CREB signaling pathway and downstream osterix expression. PMID:28629115

Phospholipases D1 and D2 Suppress Appetite and Protect against Overweight.

PubMed

Trujillo Viera, Jonathan; El-Merahbi, Rabih; Nieswandt, Bernhard; Stegner, David; Sumara, Grzegorz

2016-01-01

Obesity is a major risk factor predisposing to the development of peripheral insulin resistance and type 2 diabetes (T2D). Elevated food intake and/or decreased energy expenditure promotes body weight gain and acquisition of adipose tissue. Number of studies implicated phospholipase D (PLD) enzymes and their product, phosphatidic acid (PA), in regulation of signaling cascades controlling energy intake, energy dissipation and metabolic homeostasis. However, the impact of PLD enzymes on regulation of metabolism has not been directly determined so far. In this study we utilized mice deficient for two major PLD isoforms, PLD1 and PLD2, to assess the impact of these enzymes on regulation of metabolic homeostasis. We showed that mice lacking PLD1 or PLD2 consume more food than corresponding control animals. Moreover, mice deficient for PLD2, but not PLD1, present reduced energy expenditure. In addition, deletion of either of the PLD enzymes resulted in development of elevated body weight and increased adipose tissue content in aged animals. Consistent with the fact that elevated content of adipose tissue predisposes to the development of hyperlipidemia and insulin resistance, characteristic for the pre-diabetic state, we observed that Pld1-/- and Pld2-/- mice present elevated free fatty acids (FFA) levels and are insulin as well as glucose intolerant. In conclusion, our data suggest that deficiency of PLD1 or PLD2 activity promotes development of overweight and diabetes.

Potential antianxiety activity of Fumaria indica: A preclinical study

PubMed Central

Singh, Gireesh K.; Chauhan, Sudhir K.; Rai, Geeta; Chatterjee, Shyam S.; Kumar, Vikas

2013-01-01

Background: In the view of diverse CNS modulating properties of Fumaria indica, present study was planned to evaluate its putative anxiolytic activity in behavioural models of rats, followed by elucidation of mechanism of observed activity through biochemical estimations. Materials and Methods: Effects of seven daily 100, 200 and 400 mg/kg oral doses of a Fumaria indica extract (FI) was compared with those of an acute oral dose (5 mg/kg) of lorazepam in a battery of rat models consisting of open-field, elevated plus and zero maze, social interaction, and novelty induced feeding tests. Results: Dose dependant antianxiety effects of FI observed in all tests were qualitatively similar to those of the reference anxiolytic drug. Although FI treatments did not alter the concentrations of noradrenaline and serotonin in hippocampus and hypothalamus, concentrations of both these monoamines were dose dependently elevated in prefrontal cortex of FI treated animals. Flunitrazepam binding in brain frontal cortex was also elevated by the extract. Moreover, higher levels of brain expressions of the cytokines TNF-α, IL-1β, and IL-10 observed in animals with prior experience on elevated plus maze were almost completely reversed by the lowest dose of FI tested in the behavioral models. Conclusion: Taken together, these observations strongly suggest that FI is a functionally novel type of antianxiety agent, and that inhibition of cytokine expressions in the brain could be involved in its mode of action. PMID:23661988

[Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion].

PubMed

Kuhli-Hattenbach, C; Hellstern, P; Miesbach, W; Kohnen, T; Hattenbach, L-O

2018-01-01

The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). Georg Thieme Verlag KG Stuttgart · New York.

Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus aureus.

PubMed

Samuelsen, Orjan; Haukland, Hanne H; Jenssen, Håvard; Krämer, Manuela; Sandvik, Kjersti; Ulvatne, Hilde; Vorland, Lars H

2005-06-20

This study was designed to investigate inducible intrinsic resistance against lactoferricin B in Staphylococcus aureus. Serial passage of seven S. aureus strains in medium with increasing concentrations of peptide resulted in an induced resistance at various levels in all strains. The induced resistance was unstable and decreased relatively rapidly during passages in peptide free medium but the minimum inhibitory concentration remained elevated after thirty passages. Cross-resistance to penicillin G and low-level cross-resistance to the antimicrobial peptides indolicidin and Ala(8,13,18)-magainin-II amide [corrected] was observed. No cross-resistance was observed to the human cathelicidin LL-37. In conclusion, this study shows that S. aureus has intrinsic resistance mechanisms against antimicrobial peptides that can be induced upon exposure, and that this may confer low-level cross-resistance to other antimicrobial peptides.

Selenium and mercury have a synergistic negative effect on fish reproduction.

PubMed

Penglase, S; Hamre, K; Ellingsen, S

2014-04-01

Selenium (Se) can reduce the negative impacts of mercury (Hg) toxicity on growth and survival, but little is known about how these two elements interact in reproduction. In the following study we explored the effects of organic Hg and Se on the growth, survival and reproduction of female zebrafish (Danio rerio). Fish were fed one of four diets from 73 until 226 dpf in a 2 × 2 factorial design, using selenomethionine (SeMet) and methylmercury (MeHg) as the Se and Hg sources, respectively. Each diet contained Se at either requirement (0.7 mg Se/kg DM) or elevated levels (10 mg Se/kgDM), and Hg at either low (0.05 mg Hg/kg DM) or elevated (12 mg Hg/kg DM) levels. Between 151 and 206 dpf the female fish were pairwise crossed against untreated male fish and the mating success, fecundity, embryo survival, and subsequent overall reproductive success were measured. Elevated dietary Se reduced Hg levels in both the adult fish and their eggs. Elevated dietary Hg and Se increased egg Se levels to a greater extent than when dietary Se was elevated alone. At elevated maternal intake levels, egg concentrations of Se and Hg reflected the maternal dietary levels and not the body burdens of the adult fish. Elevated dietary Hg reduced the growth and survival of female fish, but these effects were largely prevented with elevated dietary Se. Elevated dietary Se alone did not affect fish growth or survival. Compared to other treatments, elevated dietary Hg alone increased both mating and overall reproductive success with <100 days of exposure, but decreased these parameters with >100 days exposure. Elevated dietary Se decreased fecundity, embryo survival, and overall reproductive success. The combination of elevated Se and Hg had a synergistic negative effect on all aspects of fish reproduction compared to those groups fed elevated levels of either Se or Hg. Overall the data demonstrate that while increased dietary Se may reduce adverse effects of Hg on the growth and survival in adult fish, it can negatively affect fish reproductive potential, and the effect on reproduction is enhanced in the presence of elevated Hg. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased SHP-1 Protein Expression by High Glucose Levels Reduces Nephrin Phosphorylation in Podocytes*

PubMed Central

Denhez, Benoit; Lizotte, Farah; Guimond, Marie-Odile; Jones, Nina; Takano, Tomoko; Geraldes, Pedro

2015-01-01

Nephrin, a critical podocyte membrane component that is reduced in diabetic nephropathy, has been shown to activate phosphotyrosine signaling pathways in human podocytes. Nephrin signaling is important to reduce cell death induced by apoptotic stimuli. We have shown previously that high glucose level exposure and diabetes increased the expression of SHP-1, causing podocyte apoptosis. SHP-1 possesses two Src homology 2 domains that serve as docking elements to dephosphorylate tyrosine residues of target proteins. However, it remains unknown whether SHP-1 interacts with nephrin and whether its elevated expression affects the nephrin phosphorylation state in diabetes. Here we show that human podocytes exposed to high glucose levels exhibited elevated expression of SHP-1, which was associated with nephrin. Coexpression of nephrin-CD16 and SHP-1 reduced nephrin tyrosine phosphorylation in transfected human embryonic kidney 293 cells. A single tyrosine-to-phenylalanine mutation revealed that rat nephrin Tyr1127 and Tyr1152 are required to allow SHP-1 interaction with nephrin. Overexpression of dominant negative SHP-1 in human podocytes prevented high glucose-induced reduction of nephrin phosphorylation. In vivo, immunoblot analysis demonstrated that nephrin expression and phosphorylation were decreased in glomeruli of type 1 diabetic Akita mice (Ins2+/C96Y) compared with control littermate mice (Ins2+/+), and this was associated with elevated SHP-1 and cleaved caspase-3 expression. Furthermore, immunofluorescence analysis indicated increased colocalization of SHP-1 with nephrin in diabetic mice compared with control littermates. In conclusion, our results demonstrate that high glucose exposure increases SHP-1 interaction with nephrin, causing decreased nephrin phosphorylation, which may, in turn, contribute to diabetic nephropathy. PMID:25404734

Effects of Antiproteinuric Intervention on Elevated Connective Tissue Growth Factor (CTGF/CCN-2) Plasma and Urine Levels in Nondiabetic Nephropathy

PubMed Central

Slagman, Maartje C.J.; Nguyen, Tri Q.; Waanders, Femke; Vogt, Liffert; Hemmelder, Marc H.; Goldschmeding, Roel; Navis, Gerjan

2011-01-01

Summary Background and objectives Connective Tissue Growth Factor (CTGF/CCN-2) is a key player in fibrosis. Plasma CTGF levels predict end-stage renal disease and mortality in diabetic chronic kidney disease (CKD), supporting roles in intra- and extrarenal fibrosis. Few data are available on CTGF in nondiabetic CKD. We investigated CTGF levels and effects of antiproteinuric interventions in nondiabetic proteinuric CKD. Design, setting, participants, & measurements In a crossover randomized controlled trial, 33 nondiabetic CKD patients (3.2 [2.5 to 4.0] g/24 h proteinuria) were treated during 6-week periods with placebo, ARB (100 mg/d losartan), and ARB plus diuretics (100 mg/d losartan plus 25 mg/d hydrochlorothiazide) combined with consecutively regular and low sodium diets (193 ± 62 versus 93 ± 52 mmol Na+/d). Results CTGF was elevated in plasma (464 [387 to 556] pmol/L) and urine (205 [135 to 311] pmol/24 h) of patients compared with healthy controls (n = 21; 96 [86 to 108] pmol/L and 73 [55 to 98] pmol/24 h). Urinary CTGF was lowered by antiproteinuric intervention, in proportion to the reduction of proteinuria, with normalization during triple therapy (CTGF 99 [67 to 146] in CKD versus 73 [55 to 98] pmol/24 h in controls). In contrast, plasma CTGF was not affected. Conclusions Urinary and plasma CTGF are elevated in nondiabetic CKD. Only urinary CTGF is normalized by antiproteinuric intervention, consistent with amelioration of tubular dysfunction. The lack of effect on plasma CTGF suggests that its driving force might be independent of proteinuria and that short-term antiproteinuric interventions are not sufficient to correct the systemic profibrotic state in CKD. PMID:21784839

Blood Lead Levels and Associated Factors among Children in Guiyu of China: A Population-Based Study

PubMed Central

Guo, Pi; Xu, Xijin; Huang, Binliang; Sun, Di; Zhang, Jian; Chen, Xiaojuan; Zhang, Qin

2014-01-01

Objectives Children's health problems caused by the electronic waste (e-waste) lead exposure in China remains. To assess children's blood lead levels (BLLs) in Guiyu of China and investigate risk factors of children's elevated BLLs in Guiyu. Material and Methods 842 children under 11 years of age from Guiyu and Haojiang were enrolled in this population-based study during 2011–2013. Participants completed a lifestyle and residential environment questionnaire and their physical growth indices were measured, and blood samples taken. Blood samples were tested to assess BLLs. Children's BLLs between the two groups were compared and factors associated with elevated BLLs among Guiyu children were analyzed by group Lasso logistic regression model. Results Children living in Guiyu had significant higher BLLs (7.06 µg/dL) than the quantity (5.89 µg/dL) of Haojiang children (P<0.05). Subgroup analyses of BLLs exceeding 10 µg/dL showed the proportion (24.80%) of high-level BLLs for Guiyu children was greater than that (12.84%) in Haojiang (P<0.05). Boys had greater BLLs than girls, irrespectively of areas (P<0.05). The number of e-waste piles or recycling workshops around the house (odds ratio, 2.28; 95% confidence interval [CI], 1.37 to 3.87) significantly contributed to the elevated BLLs of children in Guiyu, and girls had less risk (odds ratio, 0.51; 95% CI, 0.31 to 0.83) of e-waste lead exposure than boys. Conclusions This analysis reinforces the importance of shifting e-waste recycling piles or workshops to non-populated areas as part of a comprehensive response to e-waste lead exposure control in Guiyu. To correct the problem of lead poisoning in children in Guiyu should be a long-term mission. PMID:25136795

Metabolomic analysis reveals metabolic changes caused by bisphenol A in rats.

PubMed

Chen, Minjian; Zhou, Kun; Chen, Xiaojiao; Qiao, Shanlei; Hu, Yanhui; Xu, Bo; Xu, Bin; Han, Xiumei; Tang, Rong; Mao, Zhilei; Dong, Congcong; Wu, Di; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2014-04-01

Bisphenol A (BPA) is a widely used material known to cause adverse effects in humans and other mammals. To date, little is known about the global metabolomic alterations caused by BPA using urinalysis. Sprague-Dawley rats were orally administrated BPA at the levels of 0, 0.5 μg/kg/day and 50 mg/kg/day covering a low dose and a reference dose for 8 weeks. We conducted a capillary electrophoresis in tandem with electrospray ionization time-of-flight mass spectrometry based nontargeted metabolomic analysis using rat urine. To verify the metabolic alteration at both low and high doses, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were further conducted to analyze hepatic expression of methionine adenosyltransferase Iα (Mat1a) and methionine adenosyltransferase IIα (Mat2a). Hepatic S-adenosylmethionine (SAMe) was also analyzed. A total of 199 metabolites were profiled. Statistical analysis and pathway mapping indicated that the most significant metabolic perturbations induced by BPA were the increased biotin and riboflavin excretion, increased synthesis of methylated products, elevated purine nucleotide catabolism, and increased flux through the choline metabolism pathway. We found significantly higher mRNA and protein levels of Mat1a and Mat2a, and significantly higher SAMe levels in rat liver at both low and high doses. These two genes encode critical isoenzymes that catalyze the formation of SAMe, the principal biological methyl donor involved in the choline metabolism. In conclusion, an elevated choline metabolism is underlying the mechanism of highly methylated environment and related metabolic alterations caused by BPA. The data of BPA-elevated accepted biomarkers of injury indicate that BPA induces DNA methylation damage and broad protein degradation, and the increased deleterious metabolites in choline pathway may also be involved in the toxicity of BPA.

Antacids and dietary supplements with an influence on the gastric pH increase the risk for food sensitization

PubMed Central

Pali-Schöll, I.; Herzog, R.; Wallmann, J.; Szalai, K.; Brunner, R.; Lukschal, A.; Karagiannis, P.; Diesner, S. C.; Jensen-Jarolim, E.

2010-01-01

Summary Background Elevation of the gastric pH increases the risk for sensitization against food allergens by hindering protein breakdown. This can be caused by acid-suppressing medication like sucralphate, H2-receptor blockers and proton pump inhibitors, as shown in recent murine experimental and human observational studies. Objective The aim of the present study was to assess the sensitization capacity of the dietary supplement base powder and of over-the-counter antacids. Methods Changes of the pH as well as of protein digestion due to base powder or antacids were measured in vitro. To examine the in vivo influence, BALB/c mice were fed codfish extract with one of the acid-suppressing substances. Read-out of antibody levels in the sera, of cytokine levels of stimulated splenocytes and of intradermal skin tests was performed. Results The pH of hydrochloric acid was substantially increased in vitro by base powder as well as antacids in a time- and dose-dependent manner. This elevation hindered the digestion of codfish proteins in vitro. A significant increase in codfish-specific IgE antibodies was found in the groups fed codfish combined with Rennie® Antacidum or with base powder; the latter also showed significantly elevated IgG1 and IgG2a levels. The induction of an anaphylactic immune response was proven by positive results in intradermal skin tests. Conclusions Antacids and dietary supplements influencing the gastric pH increase the risk for sensitization against allergenic food proteins. As these substances are commonly used in the general population without consulting a physician, our data may have a major practical and clinical impact. PMID:20214670

Galectin-3 in Ambulatory Patients with Heart Failure: Results from the HF-ACTION Study

PubMed Central

Felker, G. Michael; Fiuzat, Mona; Shaw, Linda K.; Clare, Robert; Whellan, David J.; Bettari, Luca; Shirolkar, Shailesh C.; Donahue, Mark; Kitzman, Dalane W.; Zannad, Faiez; Piña, Ileana L.; O’Connor, Christopher M.

2011-01-01

Background Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results HF-ACTION was a randomized controlled trial of exercise training in patients with chronic heart failure due to left ventricular (LV) systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher NYHA class, lower systolic blood pressure, higher creatinine, higher NTproBNP, and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio = 1.14 per 3 ng/mL increase in galectin-3, P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. PMID:22016505

A molecular survey of S. mutans and P. gingivalis oral microbial burden in human saliva using Relative Endpoint Polymerase Chain Reaction (RE-PCR) within the population of a Nevada dental school revealed disparities among minorities

PubMed Central

2012-01-01

Background The University of Nevada, Las Vegas School of Dental Medicine recently opened an orthodontic treatment clinic to address the needs of the racially and ethnically diverse population of Southern Nevada, primarily focusing on the treatment and care of low-income and minority patients. Although orthodontic treatment and therapy has been shown to induce changes in the oral cavity, much of this evidence was collected from traditional White, teenage orthodontic clinic populations. The primary goal of this study was to describe the microbial burden of the cariogenic and periodontal pathogens, Streptococcus mutans and Porphyromonas gingivalis within the UNLV-SDM patient population. Methods Representative saliva samples were collected from healthy adult patients for DNA isolation. Relative endpoint polymerase chain reaction (RE-PCR) was performed to ascertain the presence and relative microbial burden of these oral pathogens. Results Nearly one quarter (13/56) or 23.3% of these patients had elevated levels of S. mutans, while (10/56) and 17.8% of these samples were found to have elevated levels of P. gingivalis, - with (90%) of P. gingivalis-positive samples from minority patients (X2 = 17.921, d.f. = 1; p < 0.0001). Conclusions These findings of elevated P. gingivalis levels, primarily among minority patients, may suggest underlying oral health practices contributing to adverse oral health conditions within this population. Oral health knowledge and practices among minority patients may be strongly influenced by other factors, including education and socioeconomic status, suggesting additional research may be needed to accurately determine the most appropriate standards for care and oral health education within this patient population. PMID:22925755

Biphasic activation of nuclear factor-κB and expression of p65 and c-Rel following traumatic neuronal injury.

PubMed

Zhang, Huasheng; Zhang, Dingding; Li, Hua; Yan, Huiying; Zhang, Zihuan; Zhou, Chenhui; Chen, Qiang; Ye, Zhennan; Hang, Chunhua

2018-06-01

The transcription factor nuclear factor-κB (NF-κB) has been shown to function as a key regulator of cell death or survival in neuronal cells. Previous studies indicate that the biphasic activation of NF-κB occurs following experimental neonatal hypoxia-ischemia and subarachnoid hemorrhage. However, the comprehensive understanding of NF-κB activity following traumatic brain injury (TBI) is incomplete. In the current study, an in vitro model of TBI was designed to investigate the NF-κB activity and expression of p65 and c-Rel subunits following traumatic neuronal injury. Primary cultured neurons were assigned to control and transected groups. NF-κB activity was detected by electrophoretic mobility shift assay. Western blotting and immunofluorescence were used to investigate the expression and distribution of p65 and c-Rel. Reverse transcription-quantitative polymerase chain reaction was performed to assess the downstream genes of NF-κB. Lactate dehydrogenase (LDH) quantification and trypan blue staining were used to estimate the neuronal injury. Double peaks of elevated NF-κB activity were observed at 1 and 24 h following transection. The expression levels of downstream genes exhibited similar changes. The protein levels of p65 also presented double peaks while c-Rel was elevated significantly in the late stage. The results of the trypan blue staining and LDH leakage assays indicated there was no sustained neuronal injury during the late peak of NF-κB activity. In conclusion, biphasic activation of NF-κB is induced following experimental traumatic neuronal injury. The elevation of p65 and c-Rel levels at different time periods suggests that within a single neuron, NF-κB may participate in different pathophysiological processes.

Cytokine responses in acute and persistent human parvovirus B19 infection

PubMed Central

Isa, A; Lundqvist, A; Lindblom, A; Tolfvenstam, T; Broliden, K

2007-01-01

The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-γ response. During follow-up (20–130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response correlated with the previously identified sustained CD8+ T cell response and viraemia. A cross-sectional study on patients with persistent B19 infection showed no apparent imbalance of their cytokine pattern, except for an elevated level of IFN-γ response. No general immunodeficiency was diagnosed as an explanation for the viral persistence in this later group. Neither the acutely infected nor the persistently infected patients demonstrated a Th2 cytokine response. In conclusion, the acutely infected patients demonstrated a sustained Th1 cytokine response whereas the persistently infected patients did not exhibit an apparent imbalance of their cytokine pattern except for an elevated IFN-γ response. PMID:17302890

Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension.

PubMed

Chen, Ning-Yuan; D Collum, Scott; Luo, Fayong; Weng, Tingting; Le, Thuy-Trahn; M Hernandez, Adriana; Philip, Kemly; Molina, Jose G; Garcia-Morales, Luis J; Cao, Yanna; Ko, Tien C; Amione-Guerra, Javier; Al-Jabbari, Odeaa; Bunge, Raquel R; Youker, Keith; Bruckner, Brian A; Hamid, Rizwan; Davies, Jonathan; Sinha, Neeraj; Karmouty-Quintana, Harry

2016-08-01

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. The development of pulmonary hypertension (PH) is considered the single most significant predictor of mortality in patients with chronic lung diseases. The processes that govern the progression and development of fibroproliferative and vascular lesions in IPF are not fully understood. Using human lung explant samples from patients with IPF with or without a diagnosis of PH as well as normal control tissue, we report reduced BMPR2 expression in patients with IPF or IPF+PH. These changes were consistent with dampened P-SMAD 1/5/8 and elevated P-SMAD 2/3, demonstrating reduced BMPR2 signaling and elevated TGF-β activity in IPF. In the bleomycin (BLM) model of lung fibrosis and PH, we also report decreased BMPR2 expression compared with control animals that correlated with vascular remodeling and PH. We show that genetic abrogation or pharmacological inhibition of interleukin-6 leads to diminished markers of fibrosis and PH consistent with elevated levels of BMPR2 and reduced levels of a collection of microRNAs (miRs) that are able to degrade BMPR2. We also demonstrate that isolated bone marrow-derived macrophages from BLM-exposed mice show reduced BMPR2 levels upon exposure with IL6 or the IL6+IL6R complex that are consistent with immunohistochemistry showing reduced BMPR2 in CD206 expressing macrophages from lung sections from IPF and IPF+PH patients. In conclusion, our data suggest that depletion of BMPR2 mediated by a collection of miRs induced by IL6 and subsequent STAT3 phosphorylation as a novel mechanism participating to fibroproliferative and vascular injuries in IPF. Copyright © 2016 the American Physiological Society.

Antihypertensive and cardioprotective effects of pumpkin seed oil.

PubMed

El-Mosallamy, Aliaa E M K; Sleem, Amany A; Abdel-Salam, Omar M E; Shaffie, Nermeen; Kenawy, Sanaa A

2012-02-01

Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L-NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO.

Elevated Hemostasis Markers after Pneumonia Increases One-Year Risk of All-Cause and Cardiovascular Deaths

PubMed Central

Yende, Sachin; D'Angelo, Gina; Mayr, Florian; Kellum, John A.; Weissfeld, Lisa; Kaynar, A. Murat; Young, Tammy; Irani, Kaikobad; Angus, Derek C.

2011-01-01

Background Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. PMID:21853050

Elevated Blood Lead Levels of Children in Guiyu, an Electronic Waste Recycling Town in China

PubMed Central

Huo, Xia; Peng, Lin; Xu, Xijin; Zheng, Liangkai; Qiu, Bo; Qi, Zongli; Zhang, Bao; Han, Dai; Piao, Zhongxian

2007-01-01

Background Electronic waste (e-waste) recycling has remained primitive in Guiyu, China, and thus may contribute to the elevation of blood lead levels (BLLs) in children living in the local environment. Objectives We compared the BLLs in children living in the e-waste recycling town of Guiyu with those living in the neighboring town of Chendian. Methods We observed the processing of e-waste recycling in Guiyu and studied BLLs in a cluster sample of 226 children < 6 years of age who lived in Guiyu and Chendian. BLLs were determined with atomic absorption spectrophotometry. Hemoglobin (Hgb) and physical indexes (height and weight, head and chest circumferences) were also measured. Results BLLs in 165 children of Guiyu ranged from 4.40 to 32.67 μg/dL with a mean of 15.3 μg/dL, whereas BLLs in 61 children of Chendian were from 4.09 to 23.10 μg/dL with a mean of 9.94 μg/dL. Statistical analyses showed that children living in Guiyu had significantly higher BLLs compared with those living in Chendian (p < 0.01). Of children in Guiyu, 81.8% (135 of 165) had BLLs > 10 μg/dL, compared with 37.7% of children (23 of 61) in Chendian (p < 0.01). In addition, we observed a significant increasing trend in BLLs with increasing age in Guiyu (p < 0.01). It appeared that there was correlation between the BLLs in children and numbers of e-waste workshops. However, no significant difference in Hgb level or physical indexes was found between the two towns. Conclusions The primitive e-waste recycling activities may contribute to the elevated BLLs in children living in Guiyu. PMID:17637931

Total Composite Flap Facelift and the Deep-Plane Transition Zone: A Critical Consideration in SMAS-Release Midface Lifting

PubMed Central

Mani, Marc

2016-01-01

Background Recent anatomic studies suggest the superficial musculoaponeurotic system (SMAS) layer attenuates in the midface. This led the author to switch from a bilamellar high SMAS dissection to a “total composite flap” technique, preserving skin and SMAS/platysma as one layer in a critical “deep-plane transition zone” (DTZ) lateral to the zygomaticus major muscle. This allows traction on the SMAS to translate to the malar fat pad via a “cantilever bridge” effect, which is lost when skin is undermined in the DTZ. Objectives This paper attempts to answer the question of whether the composite flap or bilamellar technique better lifts the midface, comparing groups where the DTZ was undermined: (1) only at a sub-SMAS level; or (2) at both subcutaneous and sub-SMAS levels. Methods Thirty-five patients underwent bilamellar facelifts with skin and SMAS separated in the DTZ. Midfacial elevation was measured using size-matched preoperative and 18-month (average) postoperative photographs for the 70 hemi-midfaces. The same analysis was done for 35 patients undergoing total composite flap facelift, maintaining skin and SMAS as one layer in the DTZ. The two groups were compared. Results In the bilamellar group, the mean percentage of midfacial elevation at 18 months postoperative was 5.5% (range, 0.0%-17.8%). In the composite flap group, the percentage was 11.7% (range, 0.1%-32.3%). The difference was statistically significant. Conclusions Maintaining skin-SMAS attachments in the DTZ improves midface elevation during SMAS facelifting, exploiting a “cantilever bridge” effect of the skin transferring traction on the SMAS to the malar fat pad. Level of Evidence: 4 Therapeutic PMID:26931306

Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

PubMed Central

2011-01-01

Background Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD. PMID:22145886

Serum biochemical markers in lung cancer.

PubMed Central

Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

1978-01-01

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

Falsely Elevated Serum Vitamin B12 Levels Were Associated with the Severity and Prognosis of Chronic Viral Liver Disease

PubMed Central

Sugihara, Takaaki; Koda, Masahiko; Okamoto, Toshiaki; Miyoshi, Kenichi; Matono, Tomomitsu; Oyama, Kenji; Hosho, Keiko; Okano, Jun-ichi; Isomoto, Hajime; Murawaki, Yoshikazu

2017-01-01

Background Vitamin B12 is stored primarily in the liver, and highly elevated serum vitamin B12 levels occur in acute hepatitis and severe alcoholic liver disease. We evaluated the relationship between vitamin B12 levels and liver disease severity and long term prognosis in patients with chronic viral hepatitis and cirrhosis. Methods We enrolled 90 patients (57 men, 33 women) with chronic viral hepatitis and cirrhosis who admitted to our hospital as a prospective cohort study. Overall, 37 patients had chronic hepatitis and 53 had cirrhosis (Child-Pugh A 33, B 13, and C 7); 57 patients had primary liver cancer. Serum vitamin B12 concentration and holotranscobalamin (holoTC) II (active form of vitamin B12) were determined and followed prospectively for at least 5 years. Results Mean total serum vitamin B12 concentration was significantly higher in Child-Pugh C (1308 ± 599 pg/mL) compared to those with chronic hepatitis (655 ± 551 pg/mL), Child-Pugh A (784 ± 559 pg/mL), and Child-Pugh B (660 ± 464 pg/mL) (P = 0.036) Presence of primary liver cancer also influenced serum vitamin B12 levels [657 (167–2956) vs. 432 (189–2956); P = 0.015]. Patients were divided into quartiles by vitamin B12 level. Patients without primary liver cancer in quartile 4 (≥ 880 pg/mL) demonstrated significantly poorer prognosis than those in quartiles 1–3 (< 880 pg/mL) (P = 0.023). The percentage of holohaptocorrin (holoHC) [(total vitamin B12 – holoTC II) × 100] was significantly higher in Child-Pugh B and C 86 (80–87)% than chronic hepatitis and Child-Pugh A 77 (31–89)% (P = 0.006) Multivariate analysis indicated serum vitamin B12 levels (HR = 1.001, P = 0.029) as a prognostic factor. Conclusion Falsely elevated serum vitamin B12 levels mainly composed of increased holoHC were associated with severity (Child-Pugh C and primary liver cancer) and prognosis in chronic viral liver disease. PMID:28331419

Effects of hypergravity on gene levels in anti-gravity muscle and bone through the vestibular system in mice.

PubMed

Kawao, Naoyuki; Morita, Hironobu; Nishida, Kazuaki; Obata, Koji; Tatsumi, Kohei; Kaji, Hiroshi

2017-09-07

We recently reported that hypergravity with 3 g for 4 weeks affects muscle and bone through the vestibular system in mice. The purpose of this study was to investigate the effects of hypergravity with 2 g, which had no influence on circulating glucocorticoid level, on the gene levels in muscle and bone, as well as the roles of the vestibular system in those changes using vestibular lesioned (VL) mice. Hypergravity for 2 and 8 weeks or VL exerted little effects on the mRNA levels of muscle differentiation factors and myokines in the soleus muscle. Although hypergravity for 2 weeks significantly elevated alkaline phosphatase (ALP) and type I collagen mRNA levels in the tibia, VL significantly attenuated the levels of ALP mRNA enhanced by hypergravity. In conclusion, the present study suggests that a 2-g load for 2 weeks enhances osteoblast differentiation partly through the vestibular system in mice.

Hfe Deficiency Impairs Pulmonary Neutrophil Recruitment in Response to Inflammation

PubMed Central

Benesova, Karolina; Vujić Spasić, Maja; Schaefer, Sebastian M.; Stolte, Jens; Baehr-Ivacevic, Tomi; Waldow, Katharina; Zhou, Zhe; Klingmueller, Ursula; Benes, Vladimir; Mall, Marcus A.; Muckenthaler, Martina U.

2012-01-01

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis. PMID:22745741

Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

PubMed Central

Schäfer, Michaela; Oeing, Christian U.; Rohm, Maria; Baysal-Temel, Ezgi; Lehmann, Lorenz H.; Bauer, Ralf; Volz, H. Christian; Boutros, Michael; Sohn, Daniela; Sticht, Carsten; Gretz, Norbert; Eichelbaum, Katrin; Werner, Tessa; Hirt, Marc N.; Eschenhagen, Thomas; Müller-Decker, Karin; Strobel, Oliver; Hackert, Thilo; Krijgsveld, Jeroen; Katus, Hugo A.; Berriel Diaz, Mauricio; Backs, Johannes; Herzig, Stephan

2015-01-01

Objectives Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven “cachexokines”, including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia. PMID:26909315

Naringenin exhibits the protective effect on cardiac hypertrophy via EETs-PPARs activation in streptozocin-induced diabetic mice.

PubMed

Zhang, Jie; Qiu, Hongmei; Huang, Jiajun; Ding, Shumei; Huang, Bo; Wu, Qin; Jiang, Qingsong

2018-07-07

Cardiac hypertrophy is one of the key structural changes in diabetic cardiomyopathy. Naringenin, a dihydroflavonoid extracted from citrus plants with multiple pharmacological activities, yet the underlying effects on diabetic cardiac hypertrophy remain unclear. This study aimed to evaluate the potential effects of naringenin on cardiac hypertrophy in diabetic mice. Long-term high-fat feeding combined with streptozotocin resulted in cardiac hypertrophy after a diabetic model has been established for 4 weeks in mice, which were improved by naringenin supplementation (25 or 75 mg/kg/day, i. g.) for another 4 weeks. The protein and mRNA expressions of PPARs were down-regulated, the protein express of CYP2J3 and level of 14, 15-EET were decreased following diabetic cardiac hypertrophy. Naringenin administration up-regulated PPARs expression, elevated CYP2J3 protein and 14,15-EET content. In conclusion, naringenin can improve cardiac hypertrophy in diabetic mice, which may be related to up-regulate the expression of CYP2J3, elevate the level of EETs, and activate the expression of PPARs. Copyright © 2018 Elsevier Inc. All rights reserved.

Puerarin protects against lead-induced cytotoxicity in cultured primary rat proximal tubular cells.

PubMed

Liu, Gang; Li, Zifa; Wang, Jinqiu; Wang, Hong; Wang, Zhenyong; Wang, Lin

2014-10-01

Puerarin, a potent free radicals scavenger, has been demonstrated to have protective efficacy in oxidative damage induced by nephrotoxins. In the present study, the attenuating effect of puerarin (PU) on lead (Pb)-induced apoptosis and oxidative stress was investigated in cultured primary rat proximal tubular (rPT) cells. Results showed that exposure to 0.5 µM Pb induced a decrease in cell viability accompanied with obvious cellular morphological alterations and caused an increase in apoptotic rate and apoptotic morphological changes. Simultaneously, depletion of mitochondrial membrane potential (ΔΨ) and intracellular glutathione (GSH); elevation of caspase-3 activity, intracellular reactive oxygen species, and malondialdehyde levels; and inhibition of GSH peroxidase (GSH-Px) activity were revealed in the cells exposed to Pb alone. However, simultaneous supplementation with PU (50 and 100 µM) protected rPT cells from Pb-induced cytotoxicity through inhibiting apoptosis, attenuating lipid peroxidation, renewing mitochondrial function, and elevating the intracellular antioxidants (nonenzymatic and enzymic) levels. In conclusion, these findings suggested that PU, as a widely distributed dietary antioxidant, contributes potentially to inhibition of Pb-induced cytotoxicity in rPT cells. © The Author(s) 2014.

Negative Life Events, Social Support, and Self-Efficacy in Anxious Adolescents.

PubMed

Raknes, Solfrid; Pallesen, Ståle; Bjaastad, Jon Fauskanger; Wergeland, Gro Janne; Hoffart, Asle; Dyregrov, Kari; Håland, Åshild Tellefsen; Haugland, Bente Storm Mowatt

2017-01-01

Purpose To examine the prevalence and correlates of anxiety in a community sample of adolescents. Knowing the prevalence and characteristics of anxious adolescents is valuable to improve anxiety prevention strategies and interventions. Design Cross-sectional data about anxiety were collected via a school survey from a community sample of Norwegian adolescents aged 12-17 ( N = 1719). Methods Based on scores from the Spence Children's Anxiety Scale, the adolescents were categorized as not anxious or anxious. Logistic regression analysis was performed to access the impact of each factor on the likelihood that participants would report an elevated level of anxiety. Results A total of 22% of the adolescents were categorized as anxious. Female gender, experienced negative life events, low social support, and low self-efficacy were associated with elevated level of anxiety. Conclusions The high prevalence of anxiety in adolescents demonstrates the importance of improved prevention interventions targeting anxious adolescents. We argue that addressing is the responsibility of not only the individual adolescents and their families but also schools, school health services, and policy makers. School-based interventions that increase social support and self-efficacy would probably be particularly beneficial for anxious adolescents.

Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles.

PubMed

Xu, Peng-Tao; Li, Quan; Sheng, Juan-Juan; Chang, Hui; Song, Zhen; Yu, Zhi-Bin

2012-08-01

Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

PubMed Central

Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

2008-01-01

Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

Effects of lanthanum(III) on nitrogen metabolism of soybean seedlings under elevated UV-B radiation.

PubMed

Cao, Rui; Huang, Xiao-hua; Zhou, Qing; Cheng, Xiao-ying

2007-01-01

The hydroponic culture experiments of soybean bean seedlings were conducted to investigate the effect of lanthanum (La) on nitrogen metabolism under two different levels of elevated UV-B radiation (UV-B, 280-320 nm). The whole process of nitrogen metabolism involves uptake and transport of nitrate, nitrate assimilation, ammonium assimilation, amino acid biosynthesis, and protein synthesis. Compared with the control, UV-B radiation with the intensity of low level 0.15 W/m2 and high level 0.45 W/m2 significantly affected the whole nitrogen metabolism in soybean seedlings (p < 0.05). It restricted uptake and transport of NO3(-), inhibited activity of some key nitrogen-metabolism-related enzymes, such as: nitrate reductase (NR) to the nitrate reduction, glutamine systhetase (GS) and glutamine synthase (GOGAT) to the ammonia assimilation, while it increased the content of free amino acids and decreased that of soluble protein as well. The damage effect of high level of UV-B radiation on nitrogen metabolism was greater than that of low level. And UV-B radiation promoted the activity of the anti-adversity enzyme glutamate dehydrogenase (GDH), which reduced the toxicity of excess ammonia in plant. After pretreatment with the optimum concentration of La (20 mg/L), La could increase the activity of NR, GS, GOGAT, and GDH, and ammonia assimilation, but decrease nitrate and ammonia accumulation. In conclusion, La could relieve the damage effect of UV-B radiation on plant by regulating nitrogen metabolism process, and its alleviating effect under low level was better than that under the high one.

Association between Periodontopathogens and CRP Levels in Patients with Periodontitis in Serbia

PubMed Central

Pejcic, Ana; Kesic, Ljiljana; Milasin, Jelena

2011-01-01

Background and aims Recent epidemiological studies have shown that individuals with periodontitis have a significantly higher risk of developing coronary heart disease, which might be attributed to the complex microbiota in the dental plaque. Periodontopathogens have been reported as risk factors for cardiovascular disease. This study evaluated association of chronic periodontitis and periodontopathogens with CRP in systemically healthy Serbian adults. Materials and methods Serum C-reactive protein levels were measured in 24 patients with moderate periodontitis, 26 patients with severe periodontitis, and 25 periodontally healthy subjects. Periodontal health indicators included gingival bleeding on probing and periodontal disease status. Patients with moderate periodontitis had low attachment loss and pocket depths of <4 mm. Patients with severe periodontitis had high AL and pocket depth of >5 mm. The control group with healthy gingiva had gingival sulcus of <2 mm and no attachment loss. Presence of periodontopathogens in subgingival plaque samples was analyzed by polymerase chain reaction. Results The periodontal parameters and CRP levels were significantly higher in the patients with periodontitis. Patients who had both severe and moderate periodontitis had higher mean CRP levels. The percentage of subjects with elevated CRP leves of >5 mol/L was greater in the higher clinical AL group compared to the group with less attachment loss. Presence of periodontopathogens was also associated with elevated CRP levels and poor periodontal status. Conclusion PD and subgingival periodontopathogens are associated with increased CRP levels. These findings suggest that periodontal infection may contribute to systemic inflammatory burden in otherwise healthy individuals. PMID:23019501

Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

PubMed Central

Waschki, Benjamin; Watz, Henrik; Holz, Olaf; Magnussen, Helgo; Olejnicka, Beata; Welte, Tobias; Rabe, Klaus F; Janciauskiene, Sabina

2017-01-01

Introduction Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. Conclusion The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. PMID:28356730

Resistance training inhibits the elevation of skeletal muscle derived-BDNF level concomitant with improvement of muscle strength in zucker diabetic rat

PubMed Central

Kim, Hee-Jae; So, Byunghun; Son, Jun Seok; Song, Han Sol; Oh, Seung Lyul; Seong, Je Kyung; Lee, Hoyoung; Song, Wook

2015-01-01

[Purpose] In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats. [Methods] Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week). [Results] After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle. [Conclusion] Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes. PMID:27274460

Diagnostic value of drain amylase for detecting intrathoracic leakage after esophagectomy

PubMed Central

Berkelmans, Gijs HK; Kouwenhoven, Ewout A; Smeets, Boudewijn JJ; Weijs, Teus J; Silva Corten, Luis C; van Det, Marc J; Nieuwenhuijzen, Grard AP; Luyer, Misha DP

2015-01-01

AIM: To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage (AL) after minimally invasive Ivor-Lewis esophagectomy (MI-ILE). METHODS: This was a retrospective analysis of prospectively collected data in two hospitals in the Netherlands. Consecutive patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the dorsal side of the anastomosis and bilateral chest drains were placed at the end of the thoracoscopic procedure. Amylase levels in drain fluid were determined in all patients during at least the first four postoperative days. Contrast computed tomography scans and/or endoscopic imaging were performed in cases of a clinically suspected AL. Anastomotic leakage was defined as any sign of leakage of the esophago-gastric anastomosis on endoscopy, re-operation, radiographic investigations, post mortal examination or when gastro-intestinal contents were found in drain fluid. Receiver operator characteristic curves were used to determine the cut-off values. Sensitivity, specificity, positive predictive value, negative predictive value, risk ratio and overall test accuracy were calculated for elevated drain amylase concentrations. RESULTS: A total of 89 patients were included between March 2013 and August 2014. No differences in group characteristics were observed between patients with and without AL, except for age. Patients with AL were older than were patients without AL (P = 0.01). One patient (1.1%) without AL died within 30 d after surgery due to pneumonia and acute respiratory distress syndrome. Anastomotic leakage that required any intervention occurred in 15 patients (16.9%). Patients with proven anastomotic leakage had higher drain amylase levels than patients without anastomotic leakage [median 384 IU/L (IQR 34-6263) vs median 37 IU/L (IQR 26-66), P = 0.003]. Optimal cut-off values on postoperative days 1, 2, and 3 were 350 IU/L, 200 IU/L and 160 IU/L, respectively. An elevated amylase level was found in 9 of the 15 patients with AL. Five of these 9 patients had early elevations of their amylase levels, with a median of 2 d (IQR 2-5) before signs and symptoms occurred. CONCLUSION: Measurement of drain amylase levels is an inexpensive and easy tool that may be used to screen for anastomotic leakage soon after MI-ILE. However, clinical validation of this marker is necessary. PMID:26290638

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

PubMed Central

Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-01-01

Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn’t predict vascular involvement and liver metastasis. PMID:27134925

Follistatin-like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling

PubMed Central

El-Armouche, Ali; Ouchi, Noriyuki; Tanaka, Komei; Doros, Gheorghe; Wittköpper, Katrin; Schulze, Thomas; Eschenhagen, Thomas; Walsh, Kenneth; Sam, Flora

2011-01-01

Background Follistatin-like 1 (FSTL1) is an extracellular glycoprotein that is found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results Here, we examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The distribution of the sample, from these chronic heart failure patients, was separated into three tertiles of low, medium and high FSTL1 levels. Serum FSTL1 levels were increased 56% above age- and gender-matched, healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death [hazard ratio (95% confidence limits) 1.028, (0.98 and 1.78)]; (P=0.26). To determine whether elevated FSTL1 may be derived from the myocardium, FSTL1 protein expression was measured in samples from explanted, failing (n=18) and non-failing human hearts (n=7). LV failing hearts showed 2.5-fold higher FSTL1 protein levels than non-failing control hearts (P<0.05). Conclusions Elevated serum FSTL1 in human heart failure patients was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. PMID:21622850

25-hydroxyvitamin D levels and risk of stroke: A prospective study and meta-analysis

PubMed Central

Sun, Qi; Pan, An; Hu, Frank B.; Manson, JoAnn E.; Rexrode, Kathryn M.

2012-01-01

Background and Purpose Despite evidence suggesting that vitamin D deficiency may lead to elevated cardiovascular disease risk, results regarding the association of 25(OH)D levels with stroke risk are inconclusive. We aimed to examine this association in a prospective study in women and to summarize all existing data in a meta-analysis. Methods We measured 25(OH)D levels among 464 women who developed ischemic stroke and an equal number of controls who were free of stroke through 2006 in the Nurses’ Health Study (NHS). We searched MEDLINE and EMBASE for articles published through March 2011 that prospectively evaluated 25(OH)D levels in relation to stroke. Results After multivariable adjustment for lifestyle and dietary covariates, lower 25(OH)D levels were associated with an elevated risk of ischemic stroke in the NHS: the odds ratio (95% CI) comparing women in the lowest vs. highest tertiles was 1.49 (1.01, 2.18; Ptrend=0.04). We found 6 other prospective studies that examined 25(OH)D in relation to stroke outcomes. After pooling our results with these prospective studies that included 1,214 stroke cases in total, low 25(OH)D levels were associated with increased risk of developing stroke outcomes in comparison to high levels: the pooled relative risk (95% CI) was 1.52 (1.20, 1.85; I2 = 0.0%, Pheterogeneity=0.63). In two studies that explicitly examined ischemic stroke, this association was 1.59 (1.07, 2.12; I2 = 0.0%, Pheterogeneity=0.80). Conclusions These data provide evidence that low vitamin D levels are modestly associated with risk of stroke. Maintaining adequate vitamin D status may lower risk of stroke in women. PMID:22442173

High serum IGF-1 levels are associated with pregnancy loss following frozen-thawed euploid embryo transfer cycles.

PubMed

Irani, Mohamad; Nasioudis, Dimitrios; Witkin, Steven S; Gunnala, Vinay; Spandorfer, Steven D

2018-06-01

An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. To account for aneuploidy and the effect of hormonal supplementation on serum IGF levels, we only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera collected in the follicular phase (cycle day 10) were tested for levels of IGF-1, IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of 156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a first trimester pregnancy loss. Women with a pregnancy loss had significantly higher serum IGF-1 levels compared to those who achieved a live birth (18.0 ± 1.1 vs. 14.6 ± 0.7 ng/mL, respectively). The two groups had comparable serum IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age, body mass index, gravidity, parity, number of prior miscarriages, peak endometrial thickness, or infertility diagnosis between the two groups. In conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF-1 concentrations may be at increased risk of pregnancy loss. This may constitute a novel molecular explanation of pregnancy loss of euploid conceptus. Copyright © 2018. Published by Elsevier B.V.

Genetic drivers of von Willebrand Factor levels in an ischemic stroke population and association with risk for recurrent stroke

PubMed Central

Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L; Chen, Wei-Min; Dzhivhuho, Godfrey; Rowles, Joe L; Southerland, Andrew M; Furie, Karen L; Rich, Stephen S; Worrall, Bradford B; Sale, Michèle M

2017-01-01

Background and Purpose von Willebrand Factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. Methods We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the Vitamin Intervention for Stroke Prevention (VISP) trial as well as the utility of vWF in reclassification over traditional factors. We conducted a genome-wide association study (GWAS) with imputation, based upon 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus (eQTL) analysis for vWF across different tissues. Results Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified SNPs significantly associated with circulating vWF at the ABO locus (p < 5×10-8) and replicated findings from previous genetic associations of vWF levels in humans. eQTL analyses demonstrate that most associated ABO SNPs were also associated with vWF gene expression. Conclusions Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk, and may have implications for clinical care decision-making. PMID:28495826

Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study

PubMed Central

Islam, Md Reazul; Ahmed, Imtiaz; Moktadir, Abdullah Al; Nahar, Zabun; Islam, Mohammad Safiqul; Shahid, Shelina Fatema Binte; Islam, Sheikh Nazrul; Islam, Md Saiful; Hasnat, Abul

2018-01-01

Objectives: Major depressive disorder is diagnosed on the basis of patient’s self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. Methods: We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. Results: We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients (r =−0.170, p = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. Conclusion: The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder. PMID:29770218

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

PubMed Central

Miyake, Teruki; Kumagi, Teru; Furukawa, Shinya; Hirooka, Masashi; Kawasaki, Keitarou; Koizumi, Mitsuhito; Todo, Yasuhiko; Yamamoto, Shin; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

2014-01-01

Background It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. Methods We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period. Results In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041). Conclusions Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose. PMID:25237894

Effects of Elevated CO2 on Levels of Primary Metabolites and Transcripts of Genes Encoding Respiratory Enzymes and Their Diurnal Patterns in Arabidopsis thaliana: Possible Relationships with Respiratory Rates

PubMed Central

Watanabe, Chihiro K.; Sato, Shigeru; Yanagisawa, Shuichi; Uesono, Yukifumi; Terashima, Ichiro; Noguchi, Ko

2014-01-01

Elevated CO2 affects plant growth and photosynthesis, which results in changes in plant respiration. However, the mechanisms underlying the responses of plant respiration to elevated CO2 are poorly understood. In this study, we measured diurnal changes in the transcript levels of genes encoding respiratory enzymes, the maximal activities of the enzymes and primary metabolite levels in shoots of Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780 parts per million by volume CO2, respectively). We examined the relationships between these changes and respiratory rates. Under elevated CO2, the transcript levels of several genes encoding respiratory enzymes increased at the end of the light period, but these increases did not result in changes in the maximal activities of the corresponding enzymes. The levels of some primary metabolites such as starch and sugar phosphates increased under elevated CO2, particularly at the end of the light period. The O2 uptake rate at the end of the dark period was higher under elevated CO2 than under moderate CO2, but higher under moderate CO2 than under elevated CO2 at the end of the light period. These results indicate that the changes in O2 uptake rates are not directly related to changes in maximal enzyme activities and primary metabolite levels. Instead, elevated CO2 may affect anabolic processes that consume respiratory ATP, thereby affecting O2 uptake rates. PMID:24319073

A comparison of bat activity at low and high elevations in the Black Hills of western Washington

USGS Publications Warehouse

Erickson, J.; Adams, Michael J.

2003-01-01

We examined the differences in activity patterns and community structure of bats between low (<150 m) and high ( ! 575 m) elevation sites in two habitats of the Capitol State Forest, Washington. Total bat activity averaged four times higher at low elevation sites than at high elevation sites. Feeding activity was almost 20 times higher at low elevation sites. However, the non-myotis group had similar activity levels at high and low elevation, whereas myotis group activity decreased at higher elevations. Different levels of activity between elevations could be the result of differences in insect availability, climatic conditions, and morphology of the bat species.

Serial 1H-MRS in GM2 gangliosidoses.

PubMed

Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola

2008-03-01

GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations.

Comparing trapezius muscle activity in the different planes of shoulder elevation

PubMed Central

Ishigaki, Tomonobu; Ishida, Tomoya; Samukawa, Mina; Saito, Hiroshi; Hirokawa, Motoki; Ezawa, Yuya; Sugawara, Makoto; Tohyama, Harukazu; Yamanaka, Masanori

2015-01-01

[Purpose] The purpose of this study was to compare the upper, middle, and lower trapezius muscles’ activity in the different planes of shoulder elevation. [Subjects] Twenty male subjects volunteered for this study. [Methods] Surface electromyographic (EMG) activity for each of the three regions of the trapezius muscles in the three different planes of elevation were collected while the participants maintained 30, 60, and 90 degrees of elevation in each plane. The EMG data were normalized with maximum voluntary isometric contraction (%MVIC), and compared among the planes at each angle of elevation. [Results] There were significantly different muscle activities among the elevation planes at each angle. [Conclusion] This study found that the three regions of the trapezius muscles changed their activity depending on the planes of shoulder elevation. These changes in the trapezius muscles could induce appropriate scapular motion to face the glenoid cavity in the correct directions in different planes of shoulder elevation. PMID:26157248

Comparing trapezius muscle activity in the different planes of shoulder elevation.

PubMed

Ishigaki, Tomonobu; Ishida, Tomoya; Samukawa, Mina; Saito, Hiroshi; Hirokawa, Motoki; Ezawa, Yuya; Sugawara, Makoto; Tohyama, Harukazu; Yamanaka, Masanori

2015-05-01

[Purpose] The purpose of this study was to compare the upper, middle, and lower trapezius muscles' activity in the different planes of shoulder elevation. [Subjects] Twenty male subjects volunteered for this study. [Methods] Surface electromyographic (EMG) activity for each of the three regions of the trapezius muscles in the three different planes of elevation were collected while the participants maintained 30, 60, and 90 degrees of elevation in each plane. The EMG data were normalized with maximum voluntary isometric contraction (%MVIC), and compared among the planes at each angle of elevation. [Results] There were significantly different muscle activities among the elevation planes at each angle. [Conclusion] This study found that the three regions of the trapezius muscles changed their activity depending on the planes of shoulder elevation. These changes in the trapezius muscles could induce appropriate scapular motion to face the glenoid cavity in the correct directions in different planes of shoulder elevation.

Elevated CO2 enhances biological contributions to elevation change in coastal wetlands by offsetting stressors associated with sea-level rise

USGS Publications Warehouse

Cherry, J.A.; McKee, K.L.; Grace, J.B.

2009-01-01

1. Sea-level rise, one indirect consequence of increasing atmospheric CO2, poses a major challenge to long-term stability of coastal wetlands. An important question is whether direct effects of elevated CO 2 on the capacity of marsh plants to accrete organic material and to maintain surface elevations outweigh indirect negative effects of stressors associated with sea-level rise (salinity and flooding). 2. In this study, we used a mesocosm approach to examine potential direct and indirect effects of atmospheric CO2 concentration, salinity and flooding on elevation change in a brackish marsh community dominated by a C3 species, Schoenoplectus americanus, and a C4 grass, Spartina patens. This experimental design permitted identification of mechanisms and their role in controlling elevation change, and the development of models that can be tested in the field. 3. To test hypotheses related to CO2 and sea-level rise, we used conventional anova procedures in conjunction with structural equation modelling (SEM). SEM explained 78% of the variability in elevation change and showed the direct, positive effect of S. americanus production on elevation. The SEM indicated that C3 plant response was influenced by interactive effects between CO2 and salinity on plant growth, not a direct CO2 fertilization effect. Elevated CO2 ameliorated negative effects of salinity on S. americanus and enhanced biomass contribution to elevation. 4. The positive relationship between S. americanus production and elevation change can be explained by shoot-base expansion under elevated CO 2 conditions, which led to vertical soil displacement. While the response of this species may differ under other environmental conditions, shoot-base expansion and the general contribution of C3 plant production to elevation change may be an important mechanism contributing to soil expansion and elevation gain in other coastal wetlands. 5. Synthesis. Our results revealed previously unrecognized interactions and mechanisms contributing to marsh elevation change, including amelioration of salt stress by elevated CO2 and the importance of plant production and shoot-base expansion for elevation gain. Identification of biological processes contributing to elevation change is an important first step in developing comprehensive models that permit more accurate predictions of whether coastal marshes will persist with continued sea-level rise or become submerged. ?? 2008 The Authors.

Is elevated creatinine a reliable marker for methanol toxicity in nitromethane-containing model fuel ingestions in children?

PubMed

Padmanabhan, Pradeep; Spiller, Henry A; Ross, Mitchell P; Bosse, George M

2011-01-01

In the absence of a rapid serum methanol level estimation, it is difficult to assess the risk from unintentional childhood ingestion of model fuels containing methanol and nitromethane (MFNM). Previous reports have documented false elevations of serum creatinine from the nitromethane in these fuels, suggesting its utility as a readily available marker of significant methanol ingestion. We performed a 2-year retrospective chart review of cases of ingestion of MFNM in children, with both a methanol level and measured creatinine level. Seven children, ages 19 months to 3 years, ingested MFNM. All seven children were seen in a hospital and had measured methanol and creatinine levels. All blood samples for methanol and creatinine were drawn within 3 hours of ingestion with methanol estimation delayed up to 24 hours. Creatinine ranged from 0.39 (0.034 mmol/l) to 10.7 mg/dl (0.95 mmol/l). All methanol levels were <10 mg/dl (0.31 mmol/l) or reported as negative. Fomepizole was initiated empirically in two patients due to delay in obtaining methanol analysis results. Transient elevations of creatinine occurred in five of the seven children. Blood urea nitrogen was within normal limits, and there was no history of renal impairment in these children, suggesting the elevated creatinine was mostly related to nitromethane ingestion. No child had a significantly elevated methanol level. Elevated creatinine level, as measured by Jaffe colorimetric method, is not a reliable marker for elevated methanol levels after unintentional ingestion of MFNM.

Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

PubMed

Gaillard, Romy; Eilers, Paul H C; Yassine, Siham; Hofman, Albert; Steegers, Eric A P; Jaddoe, Vincent W V

2014-05-01

To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications. © 2014 John Wiley & Sons Ltd.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

PubMed

Rozen, Todd; Swidan, Sahar Z

2007-01-01

To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system.

PubMed

Chen, Luohai; Zhang, Yu; Lin, Yuan; Deng, Langhui; Feng, Shiting; Chen, Minhu; Chen, Jie

2017-12-01

Elevated serum procalcitonin (PCT) was reported in patients with certain type of neuroendocrine neoplasms (NENs). The aim of this study was to assess the role of elevated serum PCT in NENs from digestive system. Serum PCT and serum CgA level were measured in 155 patients with NENs from digestive system. Elevated serum PCT was found in 63 patients (40.6%). Grade 3 disease was a significant factor associated with elevated serum PCT (OR, 9.24; 95%CI, 3.04-28.08; P<0.001). Serum PCT level was significantly decreased after treatment both in patients with stable disease (P=0.003) and patients with partial remission (P=0.001). In these patients, serum PCT level significantly increased again at the time of progression disease (P=0.001). Elevated serum PCT was a significant factor of worse survival (HR, 2.86; 95%CI, 1.36-6.03; P=0.006). Compared with patients with normal serum PCT and CgA level, patients with either PCT or CgA elevated and patients with both PCT and CgA elevated had progressively worse survival. Additionally, PCT expression in tumor cells was found in 24.0% of patients but did not correlate with other clinicopathological factors, including serum PCT. Serum PCT is elevated in part of patients with NENs of digestive system, especially in patients with grade 3 disease. Serum PCT level can help evaluate treatment response and its elevation indicates poor prognosis. Combination of serum PCT and CgA can improve outcome prediction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Association Between Concussion and Lower Extremity Injuries in Collegiate Athletes.

PubMed

Gilbert, Frances C; Burdette, G Trey; Joyner, A Barry; Llewellyn, Tracy A; Buckley, Thomas A

Concussions have been associated with elevated musculoskeletal injury risk; however, the influence of unreported and unrecognized concussions has not been investigated. The purpose of this study was to examine the association between concussion and lower extremity musculoskeletal injury rates across a diverse array of sports among collegiate student-athletes at the conclusion of their athletic career. The hypothesis was that there will be a positive association between athletes who reported a history of concussions and higher rates of lower extremity injuries. Cross-sectional study. Level 3. Student-athletes (N = 335; 62.1% women; mean age, 21.2 ± 1.4 years) from 13 sports completed a reliable injury history questionnaire. Respondents indicated the total number of reported, unreported, and potentially unrecognized concussions as well as lower extremity injuries including ankle sprains, knee injuries, and muscle strains. Chi-square analyses were performed to identify the association between concussion and lower extremity injuries. There were significant associations between concussion and lateral ankle sprain ( P = 0.012), knee injury ( P = 0.002), and lower extremity muscle strain ( P = 0.031). There were also significant associations between reported concussions and knee injury ( P = 0.003), unreported concussions and knee injury ( P = 0.002), and unrecognized concussions and lateral ankle sprain ( P = 0.001) and lower extremity muscle strains ( P = 0.006), with odds ratios ranging from 1.6 to 2.9. There was a positive association between concussion history and lower extremity injuries (odds ratios, 1.6-2.9 elevated risk) among student-athletes at the conclusion of their intercollegiate athletic careers. Clinicians should be aware of these elevated risks when making return-to-participation decisions and should incorporate injury prevention protocols.

Surface elevation dynamics in a regenerating mangrove forest at Homebush Bay, Australia

USGS Publications Warehouse

Rogers, K.; Saintilan, N.; Cahoon, D.

2005-01-01

Following the dieback of an interior portion of a mangrove forest at Homebush Bay, Australia, surface elevation tables and feldspar marker horizons were installed in the impacted, intermediate and control forest to measure vertical accretion, elevation change, and shallow subsidence. The objectives of the study were to determine current vertical accretion and elevation change rates as a guide to understanding mangrove dieback, ascertain the factors controlling surface elevation change, and investigate the sustainability of the mangrove forest under estimated sea-level rise conditions. The study demonstrates that the influences on surface dynamics are more complex than soil accretion and soil autocompaction alone. During strong vegetative regrowth in the impacted forest, surface elevation increase exceeded vertical accretion apparently as a result of belowground biomass production. In addition, surface elevation in all forest zones was correlated with total monthly rainfall during a severe El Ni?o event, highlighting the importance of rainfall to groundwater recharge and surface elevation. Surface elevation increase for all zones exceeded the 85-year sea level trend for Sydney Harbour. Since mean sea-level also decreased during the El Ni?o event, the decrease in surface elevation did not translate to an increase in inundation frequency or influence the sustainability of the mangrove forest. These findings indicate that subsurface soil processes such as organic matter accumulation and groundwater flux can significantly influence mangrove surface elevation, and contribute to the long-term sustainability of mangrove systems under a scenario of rising sea levels.

Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study

PubMed Central

Staerk, Laila; Wang, Biqi; Preis, Sarah R; Larson, Martin G; Lubitz, Steven A; Ellinor, Patrick T; McManus, David D; Ko, Darae; Weng, Lu-Chen; Lunetta, Kathryn L; Frost, Lars; Benjamin, Emelia J

2018-01-01

Abstract Objective To examine the association between risk factor burdens—categorized as optimal, borderline, or elevated—and the lifetime risk of atrial fibrillation. Design Community based cohort study. Setting Longitudinal data from the Framingham Heart Study. Participants Individuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age. Main outcome measure Lifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death. Results At index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years. Conclusions Regardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three in individuals with at least one elevated risk factor. PMID:29699974

Leveling

USGS Publications Warehouse

1966-01-01

Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

Yeast Infection and Diabetes Mellitus among Pregnant Mother in Malaysia

PubMed Central

Sopian, Iylia Liyana; Shahabudin, Sa’adiah; Ahmed, Mowaffaq Adam; Lung, Leslie Than Thian; Sandai, Doblin

2016-01-01

Background Vaginal yeast infection refers to irritation of the vagina due to the presence of opportunistic yeast of the genus Candida (mostly Candida albicans). About 75% of women will have at least one episode of vaginal yeast infection during their lifetime. Several studies have shown that pregnancy and uncontrolled diabetes increase the infection risk. Reproductive hormone fluctuations during pregnancy and elevated glucose levels characteristic of diabetes provide the carbon needed for Candida overgrowth and infection. The goal of this study was to determine the prevalence of vaginal yeast infection among pregnant women with and without diabetes. Methods This was a case-control study using cases reports from Kepala Batas Health Clinic, Penang State, Malaysia from 2006 to 2012. In total, 740 pregnant ladies were chosen as sample of which 370 were diabetic and 370 were non-diabetic cases. Results No relationship between diabetes and the occurrence of vaginal yeast infection in pregnant women was detected, and there was no significant association between infection and age group, race or education level. Conclusion In conclusion, within radius of this study, vaginal yeast infection can occur randomly in pregnant women. PMID:27540323

Nonlinear Distribution Pattern of Hibernating Bats in Caves along an Elevational Gradient in Mountain (Carpathians, Southern Poland)

PubMed Central

Piksa, Krzysztof; Nowak, Jakub; Żmihorski, Michał; Bogdanowicz, Wiesław

2013-01-01

Background Thermal gradients along changes in elevation in mountainous environments are reflected by different biotas. Although there have been studies of elevation variation in bat assemblages in summer, winter changes in the same gradients remain unknown. Methodology/Principal Findings The objective of this study was to document changes in the species composition of bats hibernating in caves along a temperate elevational gradient. We studied 70 caves between from 300 m to 1,930 m altitude along a slope of the Carpathian Mountains in southern Poland. We recorded changes in bats, including species richness, abundance, altitudinal distribution and dominance during consecutive winters between 2003 and 2009. Similarity of dominance of faunal structure was assessed by using the Bray-Curtis similarity index. We used the generalised additive model and rarefaction to study the variation in species richness, and generalized additive mixed models to examine the effect of abiotic factors on the qualitative and quantitative structure of bat assemblages. During 351 surveys we recorded 13,856 hibernating bats from 15 species. Species richness peaked around mid-elevation (1,100–1,400 m a.s.l.) with richness declining at both higher and lower elevations. Based on the results of a cluster analysis, we could distinguish among four altitudinal zones that differed in species richness and dominance structure. Conclusions/Significance This is the first study documenting changes in species richness and variation of structure of bats hibernating in caves along an elevational gradient. The most surprising and key finding is the fact that changes in the structure of assemblages of hibernating bats along the altitudinal gradient occurred in jumps, forming zones similar to those observed in the vegetation zones. Moreover, species richness and dominance structure of assemblages of hibernating bats in the mountains depended not only on location above sea level, but also on local geomorphologic conditions which strongly affected the microclimate of the caves. PMID:23861850

Association of Fibroblast Growth Factor 23 With Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study

PubMed Central

Mehta, Rupal; Cai, Xuan; Lee, Jungwha; Scialla, Julia J.; Bansal, Nisha; Sondheimer, James H.; Chen, Jing; Hamm, L. Lee; Ricardo, Ana C.; Navaneethan, Sankar D.; Deo, Rajat; Rahman, Mahboob; Feldman, Harold I.; Go, Alan S.; Isakova, Tamara; Wolf, Myles

2016-01-01

Importance Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. Objective To investigate the association of FGF23 with atrial fibrillation in CKD. Design, Setting, and Participants Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Exposures Baseline plasma FGF23 levels. Main Outcomes and Measures Prevalent and incident atrial fibrillation. Results The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8% (1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95% CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95% CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Conclusions and Relevance Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effect may be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events. PMID:27434583

Th22 cells are associated with hepatocellular carcinoma development and progression

PubMed Central

Qin, Shanyu; Ma, Shijia; Huang, Xiaoli; Lu, Donghong

2014-01-01

Objective IL-22-producing CD4+ T helper cells (Th22 cells) have been identified as major inducers of tissue inflammation and immune responses. Currently, no previous study explored the role of Th22 cells in the pathogenesis of hepatocellular carcinoma (HCC). The study aimed to determine the biological function of Th22 cells and its effector IL-22 in HCC patients. Methods Forty-five HCC patients and 19 healthy controls were recruited and their peripheral blood was collected. The fresh HCC tissues, adjacent HCC tissues and ten normal liver tissues were also collected. Flow cytometry analysis was used to determine the frequencies of circulating Th22 cells and Th17 cells. Serum IL-22 levels were tested by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to detect IL-22 protein and mRNA in tissues specimens, respectively. Results Circulating Th22 cells, Th17 cells and serum IL-22 levels were significantly elevated in HCC patients compared with those of healthy controls (P<0.001). Th22 cells were showed to be positively correlated with IL-22 in HCC patients (P<0.05), but not in healthy controls. No significant differences were found in HCC patients with HBeAg positivity or negativity in term of Th22 cells and serum IL-22 levels. The expression of IL-22 protein and mRNA was highest in HCC tissues, followed by adjacent HCC tissues and normal liver tissues. Furthermore, Th22 cells, serum IL-22 levels and IL-22 mRNA were elevated at stage III-IV compared with stage I-II of HCC (P<0.05). Conclusions Elevation of circulating Th22 cells and IL-22 may be implicated in the pathogenesis of HCC, and potentially be cellular targets for therapeutic intervention. PMID:24826053

Factors Associated With Elevated Blood Lead Levels in Children.

PubMed

Chaudhary, Sakshi; Firdaus, Uzma; Ali, Syed Manazir; Mahdi, Abbas Ali

2018-01-15

To determine the prevalence and correlates of elevated blood lead level in children (6-144 months) of Aligarh. A hospital-based cross-sectional study was conducted. Venous blood was obtained for lead estimation and a structured questionnaire was filled. A total of 260 children were enrolled. The prevalence of elevated blood lead level was 44.2%, seen mostly in children below 5 years of age. Old and deteriorating wall paints at home was found to be significantly associated with elevated levels. Lead-based house paints are potential source of lead exposure. Meticulous renovation and painting of the walls with safe paints is desirable.

Elevated ground-level O(3) changes the diversity of anoxygenic purple phototrophic bacteria in paddy field.

PubMed

Feng, Youzhi; Lin, Xiangui; Yu, Yongchang; Zhu, Jianguo

2011-11-01

The knowledge of the impact of elevated ground-level O(3) below ground the agro-ecosystem is limited. A field experiment in China Ozone Free-Air Concentration Enrichment (FACE-O(3)) facility on a rice-wheat rotation system was carried out to investigate responses of anoxygenic phototrophic purple bacteria (AnPPB) to elevated ground-level O(3). AnPPB community structures and sizes in paddy soil were monitored by molecular approaches including PCR-DGGE and real-time quantitative PCR based upon the pufM gene on three typical rice growth stages. Repetitive sequence-based PCR (rep-PCR) in combination with culture-reliant method was conducted to reveal changes in genotypic diversity. Elevated ground-level O(3) statistically reduce AnPPB abundance and percentage in total bacterial community in flooded rice soil via decreasing their genotypic diversity and metabolic versatility. Concomitantly, their community composition changed after rice anthesis stage under elevated ground-level O(3). Our results from AnPPB potential responses imply that continuously elevated ground-level O(3) in the future would eventually harm the health of paddy ecosystem through negative effect on soil microorganisms.

Inside the covered hopper car loading dock at railroad level, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Inside the covered hopper car loading dock at railroad level, looking east from the 1945 elevator into the 1913 elevator, control for the railroad car puller in background - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

Association of Serum Ferritin and the Development of Metabolic Syndrome in Middle-Aged Korean Men

PubMed Central

Park, Sung Keun; Ryoo, Jae-Hong; Kim, Min-Gi; Shin, Ju-Young

2012-01-01

OBJECTIVE Elevated serum ferritin has been known to be associated with the prevalence of metabolic syndrome (MetS). However, there was no research to examine whether serum ferritin levels have been actually associated with the prospective development of MetS. Accordingly, we carried out a prospective study to evaluate the longitudinal effects of baseline serum ferritin levels on the development of MetS. RESEARCH DESIGN AND METHODS A MetS-free cohort of 18,022 healthy Korean men, who had participated in a medical health checkup program in 2005, was followed until 2010. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Cox proportional hazards models were performed. RESULTS During 45,919.3 person-years of follow-up, 2,127 incident cases of MetS developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% CI) for incident MetS comparing the second quintile to the fifth quintile of serum ferritin levels versus the first quintile were 1.19 (0.98–1.45), 1.17 (0.96–1.43), 1.36 (1.12–1.65), and 1.66 (1.38–2.01), respectively (P for trend <0.001). These associations were apparent in the clinically relevant subgroup analyses. CONCLUSIONS Elevated serum ferritin levels were independently associated with future development of MetS during the 5-year follow-up period. PMID:22933431

Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

PubMed

Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

2016-05-01

Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of Estrogen and Estrus Cycle on Pharmacokinetics, Absorption and Disposition of Genistein in Female Sprague-Dawley Rats

PubMed Central

Kulkarni, Kaustubh H.; Yang, Zhen; Tao, Niu; Hu, Ming

2014-01-01

Genistein is an active soy isoflavone with anticancer activities but it is unknown why it has a higher oral bioavailability in female than in male rats. Our study determined the effects of estrus cycle on genistein’s oral bioavailability. Female rats with various levels of estrogen were orally administered with genistein or used in a four-site rat intestinal perfusion experiment. Rats in “proestrus” group (with elevated estrogen) had significantly reduced (57% decrease, p<0.05) oral bioavailability of total genistein (aglycone+conjugates) than those in “metoestrus” group (with basal level of estrogen). Female ovariectomized rats, due to lack of estrogen, showed oral bioavailability of total genistein similar to the “metoestrus” group but higher (155% increase, p<0.05) than the “proestrus” group. Based on intestinal perfusion studies, the increased bioavailability was partially attributed to the higher (>100% increase, p<0.05) hepatic disposition via glucuronidation and possibly more efficient enterohepatic recycling of genistein in the “metoestrus” group. Furthermore, chronic exogenous supplementation of estradiol in ovariectomized rats significantly reduced (77%, p<0.05) the oral bioavailability of total genistein, mostly via increased sulfation (>10 folds) in liver, to a level comparable to those in the “proestrus” group. In conclusion, the oral bioavailability of total genistein was inversely proportional to elevated estrogen levels in female rats, which is partially mediated through the regulation of hepatic enzymes responsible disposition of genistein. PMID:22757747

Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

NASA Technical Reports Server (NTRS)

Kohl, R. L.; Chelen, W. E.

1992-01-01

Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

Assessment of selected psychological factors in patients with inflammatory bowel disease

PubMed Central

Kaczówka, Anna; Jeżewska, Maria

2015-01-01

Introduction In the majority of patients with inflammatory bowel diseases (IBD) mental health problems are demonstrated in the form of excessive anxiety and unstable emotional reactions. Emotional instability affects the wellbeing of these patients, and also their attitude towards the disease and the course of treatment. Aim The objective of the study is to evaluate psychological factors in patients with IBD, and to compare patients with ulcerative colitis (UC) and patients suffering from Crohn's disease (CD) with respect to intensity of these factors. Material and methods The study included 108 patients with IBD. NEO-FFI and type-D Scale were used to evaluate personality traits. Anxiety level was measured with STAI. CECS was used to measure the patients’ tendency to suppress negative emotions. Results In the patients with CD 45% of subjects presented type D personality. In the group of patients with UC, type D personality was found in 38%. The higher levels of neuroticism and extraversion were observed in patients with UC, whereas the patients with CD exhibited a higher level of openness to experience and agreeableness. In patients with CD the levels of state anxiety were elevated, whereas in patients with UC higher scores were both for state and trait anxiety. Conclusions There were no statistically significant differences in terms of personality factors in a group of patients with CD and UC. It was found that the majority of patients with IBD suffer elevated or high sense of anxiety. PMID:27110311

Risk Factors for Mortality in Patients with Serratia marcescens Bacteremia

PubMed Central

Kim, Sun Bean; Jeon, Yong Duk; Kim, Jung Ho; Kim, Jae Kyoung; Ann, Hea Won; Choi, Heun; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

2015-01-01

Purpose Over the last 30 years, Serratia marcescens (S. marcescens) has emerged as an important pathogen, and a common cause of nosocomial infections. The aim of this study was to identify risk factors associated with mortality in patients with S. marcescens bacteremia. Materials and Methods We performed a retrospective cohort study of 98 patients who had one or more blood cultures positive for S. marcescens between January 2006 and December 2012 in a tertiary care hospital in Seoul, South Korea. Multiple risk factors were compared with association with 28-day all-cause mortality. Results The 28-day mortality was 22.4% (22/98 episodes). In a univariate analysis, the onset of bacteremia during the intensive care unit stay (p=0.020), serum albumin level (p=0.011), serum C-reactive protein level (p=0.041), presence of indwelling urinary catheter (p=0.023), and Sequential Oran Failure Assessment (SOFA) score at the onset of bacteremia (p<0.001) were significantly different between patients in the fatal and non-fatal groups. In a multivariate analysis, lower serum albumin level and an elevated SOFA score were independently associated with 28-day mortality [adjusted odds ratio (OR) 0.206, 95% confidential interval (CI) 0.044-0.960, p=0.040, and adjusted OR 1.474, 95% CI 1.200-1.810, p<0.001, respectively]. Conclusion Lower serum albumin level and an elevated SOFA score were significantly associated with adverse outcomes in patients with S. marcescens bacteremia. PMID:25683980

Efficacy of a Calcium Sucrose Phosphate Based Toothpaste in Elevating the Level of Calcium, Phosphate Ions in Saliva and Reducing Plaque: A Clinical Trial

PubMed Central

Menon, Leena Unnikrishnan; Varma, R. Balagopal; Kumaran, Parvathy; Xavier, Arun Mamachan; Govinda, Bhat Sangeetha; Kumar, J. Suresh

2018-01-01

Aim: To evaluate and compare the efficacy of “calcium sucrose phosphate” (CaSP) toothpaste (Enafix 5%) with ordinarily used calcium, phosphate-containing toothpaste in elevating the level of calcium, phosphate ions in saliva. Secondary aims were to evaluate substantivity and plaque-reducing ability of CaSP toothpaste. Materials and Methods: Thirty study participants of age group 6–13 years were divided into two groups: Group X (Control group) was made to continue brushing with their regularly used calcium, phosphate-containing toothpaste and Group Y (Test group) was allotted CaSP toothpaste. 1 ml of unstimulated saliva was periodically collected from both groups to determine any alteration in the salivary calcium, phosphate level. Parameters such as substantivity and plaque-reducing ability of CaSP toothpaste were also evaluated. Salivary mineral's intergroup comparison was evaluated by Student's t-test while its intragroup comparison along with the plaque amount variation in Group Y was evaluated by ANOVA and Tukey's post hoc test. Results: Group Y showed an increase in the salivary calcium level though not statistically significant. The increase was pronounced in samples collected on day 1. Group Y showed a consistent level of calcium, phosphate in samples collected immediately and 6 h postbrushing, indicating its substantivity. In addition, Group Y had an impact in reducing the plaque level when the 1st-month plaque score was compared with the 12th-month score. Conclusion: CaSP leads to an increase in the salivary calcium level though it was not statistically significant. Supervised brushing and dietary habits showed a positive effect on both the groups. CaSP toothpaste also showed substantivity and plaque-reducing ability.

Workplace Secondhand Smoke Exposure in the U.S. Trucking Industry

PubMed Central

Chiu, Yueh-Hsiu; Hart, Jaime E.; Spiegelman, Donna; Garshick, Eric; Smith, Thomas J.; Dockery, Douglas W.; Hammond, S. Katharine; Laden, Francine

2010-01-01

Background Although the smoking rate in the United States is declining because of an increase of smoke-free laws, among blue-collar workers it remains higher than that among many other occupational groups. Objectives We evaluated the factors influencing workplace secondhand smoke (SHS) exposures in the U.S. unionized trucking industry. Methods From 2003 through 2005, we measured workplace SHS exposure among 203 nonsmoking and 61 smoking workers in 25 trucking terminals. Workers in several job groups wore personal vapor-phase nicotine samplers on their lapels for two consecutive work shifts and completed a workplace SHS exposure questionnaire at the end of the personal sampling. Results Median nicotine level was 0.87 μg/m3 for nonsmokers and 5.96 μg/m3 for smokers. As expected, smokers experienced higher SHS exposure duration and intensity than did nonsmokers. For nonsmokers, multiple regression analyses indicated that self-reported exposure duration combined with intensity, lack of a smoking policy as reported by workers, having a nondriver job, and lower educational level were independently associated with elevated personal nicotine levels (model R2 = 0.52). Nondriver job and amount of active smoking were associated with elevated personal nicotine level in smokers, but self-reported exposure, lack of a smoking policy, and lower educational level were not. Conclusions Despite movements toward smoke-free laws, this population of blue-collar workers was still exposed to workplace SHS as recently as 2005. The perceived (reported by the workers), rather than the official (reported by the terminal managers), smoking policy was associated with measured SHS exposure levels among the nonsmokers. Job duties and educational level might also be important predictors of workplace SHS exposure. PMID:20123606

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

PubMed Central

Eapen, Danny J.; Manocha, Pankaj; Ghasemzedah, Nima; Patel, Riyaz S.; Al Kassem, Hatem; Hammadah, Muhammad; Veledar, Emir; Le, Ngoc‐Anh; Pielak, Tomasz; Thorball, Christian W.; Velegraki, Aristea; Kremastinos, Dimitrios T.; Lerakis, Stamatios; Sperling, Laurence; Quyyumi, Arshed A.

2014-01-01

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD. PMID:25341887

Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices

PubMed Central

Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K.; Parker, Anita; Bergeron, Angela L.; Pradhan, Subhashree; Vijayan, K. Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R.; Delgado, Reynolds M.; Dong, Jing Fei; Frazier, O.H.

2014-01-01

BACKGROUND Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. METHODS We enrolled 20 patients undergoing implantation of the HeartMate II LVAD and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. RESULTS During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm (n=1), non–ST-elevation myocardial infarction (n=2), arterial thrombosis (n=2), gastrointestinal bleeding (n=2), and stroke (n=3). Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11%±1.26 vs 0.69±0.46, P=0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39%±1.22 at discharge and then leveled to 1.97%±1.25 at 3-month follow-up. Importantly, patients who developed an adverse event had significantly higher levels of PS+ microparticles than did patients with no events (3.82%±1.17 vs 1.57%±0.59, P<0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters. CONCLUSIONS Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. PMID:24656391

Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea

PubMed Central

Matsumura, Takuma; Kinoshita, Taku; Sakurai, Yoriko; Yahaba, Misuzu; Tsushima, Kenji; Sakao, Seiichiro; Nagashima, Kengo; Ozaki, Toshinori; Kobayashi, Yoshio; Hiwasa, Takaki; Tatsumi, Koichiro

2018-01-01

Objective Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. Methods Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. Results NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. Conclusions Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further. PMID:29596467

Light Levels, Refractive Development, and Myopia – a Speculative Review

PubMed Central

Norton, Thomas T.; Siegwart, John T.

2013-01-01

Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways. PMID:23680160

Airborne asbestos in public buildings

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

Chesson, J.; Hatfield, J.; Schultz, B.

The U.S. Environmental Protection Agency sampled air in 49 government-owned buildings (six buildings with no asbestos-containing material, six buildings with asbestos-containing material in generally good condition, and 37 buildings with damaged asbestos-containing material). This is the most comprehensive study to date of airborne asbestos levels in U.S. public buildings during normal building activities. The air outside each building was also sampled. Air samples were analyzed by transmission electron microscopy using a direct transfer preparation technique. The results show an increasing trend in average airborne asbestos levels; outdoor levels are lowest and levels in buildings with damaged asbestos-containing material are highest.more » However, the measured levels and the differences between indoors and outdoors and between building categories are small in absolute magnitude. Comparable studies from Canada and the UK, although differing in their estimated concentrations, also conclude that while airborne asbestos levels may be elevated in buildings that contain asbestos, levels are generally low. This conclusion does not eliminate the possibility of higher airborne asbestos levels during maintenance or renovation that disturbs the asbestos-containing material.« less

Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer

PubMed Central

Xu, Xiaowen; Zhu, Yan; Guo, Aizhen; Shen, Xian; Cao, Fuao; Chang, Wenjun

2017-01-01

The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An in vivo animal model further confirmed that UBR5 knockdown reduced the growth of CRC tumors. In conclusion, our study is the first to systematically investigate the clinical and biological significance of UBR5 and to conclude that an elevated UBR5 level plays an oncogenic role and may be a potential prognostic marker in CRC. PMID:29296225

Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing.

PubMed

Krishnaswamy, Venkat Raghavan; Manikandan, Mayakannan; Munirajan, Arasambattu Kannan; Vijayaraghavan, Doraiswamy; Korrapati, Purna Sai

2014-12-01

Chronic cutaneous wound (CCW) is a major health care burden wherein the healing process is slow or rather static resulting in anatomical and functional restriction of the damaged tissue. Dysregulated expression and degradation of matrix proteins, growth factors and cytokines contribute to the disrupted and uncoordinated healing process of CCW. Therefore, therapeutic approaches for effective management of CCW should be focused towards identifying and manipulating the molecular defects, such as reduced bioavailability of the pro-healing molecules and elevated activity of proteases. This study essentially deals with assessing the expression and integrity of an extracellular matrix protein, Dermatopontin (DPT), in CCW using real-time quantitative reverse transcriptase PCR and immunological techniques. The results indicate that, despite DPT's high mRNA expression, the protein levels are markedly reduced in both CCW tissue and its exudate. To elucidate the cause for this contradiction in mRNA and protein levels, the stability of DPT is analyzed in the presence of wound exudates and various proteases that are naturally elevated in CCW. DPT was observed to be degraded at higher rates when incubated with certain recombinant proteases or chronic wound exudate. In conclusion, the susceptibility of DPT protein to specific proteases present at high levels in the wound milieu resulted in the degradation of DPT, thus leading to impaired healing response in CCW.

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr-/- Mice.

PubMed

Pollock, Abigail H; Tedla, Nicodemus; Hancock, Sarah E; Cornely, Rhea; Mitchell, Todd W; Yang, Zhengmin; Kockx, Maaike; Parton, Robert G; Rossy, Jérémie; Gaus, Katharina

2016-05-15

Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4(+) and CD8(+) T cell proliferation and resulted in an increased proportion of CD4(+) central-memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment. Copyright © 2016 by The American Association of Immunologists, Inc.

TNF Inhibits Notch-1 in Skeletal Muscle Cells by Ezh2 and DNA Methylation Mediated Repression: Implications in Duchenne Muscular Dystrophy

PubMed Central

Acharyya, Swarnali; Sharma, Sudarshana M.; Cheng, Alfred S.; Ladner, Katherine J.; He, Wei; Kline, William; Wang, Huating; Ostrowski, Michael C.; Huang, Tim H.; Guttridge, Denis C.

2010-01-01

Background Classical NF-κB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFα on skeletal muscle differentiation are mediated in part through sustained NF-κB activity. In dystrophic muscles, NF-κB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFα that is also under IKKβ and NF-κB control. Methodology/Principal Findings Based on these findings we speculated that in DMD, TNFα secreted from myotubes inhibits regeneration by directly acting on satellite cells. Analysis of several satellite cell regulators revealed that TNFα is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts, which was also found to be dependent on NF-κB. Notch-1 inhibition occurred at the mRNA level suggesting a transcriptional repression mechanism. Unlike its classical mode of action, TNFα stimulated the recruitment of Ezh2 and Dnmt-3b to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was dependent on Ezh2. Conclusions/Significance We propose that in dystrophic muscles, elevated levels of TNFα and NF-κB inhibit the regenerative potential of satellite cells via epigenetic silencing of the Notch-1 gene. PMID:20814569

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

Mathee, Angela

Introduction: Lead exposure in shooting ranges has been under scrutiny for decades, but no information in this regard is available in respect of African settings, and in South Africa specifically. The aim of this study was to determine the blood lead levels in the users of randomly selected private shooting ranges in South Africa's Gauteng province. Methods: An analytical cross sectional study was conducted, with participants recruited from four randomly selected shooting ranges and three archery ranges as a comparator group. Results: A total of 118 (87 shooters and 31 archers) were included in the analysis. Shooters had significantly highermore » blood lead levels (BLL) compared to archers with 36/85 (42.4%) of shooters versus 2/34 (5.9%) of archers found to have a BLL ≥10 μg/dl (p<0.001). Conclusion: Shooting ranges may constitute an import site of elevated exposure to lead. Improved ventilation, low levels of awareness of lead hazards, poor housekeeping, and inadequate personal hygiene facilities and practices at South African shooting ranges need urgent attention. - Highlights: • This is the first study, to our knowledge, of lead exposure in shooting ranges in an African setting. • This study indicates highly elevated lead exposure amongst the users of certain private shooting ranges in South Africa. • Lead exposure may be a serious, yet under-studied, source of adult lead exposure in South Africa, and possibly elsewhere on the African continent.« less

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

PubMed Central

Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

2015-01-01

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

National Prevalence and Exposure Risk for Cockroach Allergen in U.S. Households

PubMed Central

Cohn, Richard D.; Arbes, Samuel J.; Jaramillo, Renee; Reid, Laura H.; Zeldin, Darryl C.

2006-01-01

We characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations. Design We used data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey. Participants Participants were residents of 831 U.S. homes in the survey. Evaluations/Measurements We analyzed allergen, questionnaire, and observational data of 831 U.S. homes. Results Cockroach allergen (Bla g 1) concentrations exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S. living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a level associated with asthma morbidity, in 3% of living room floors and 10% of kitchen floors. Elevated concentrations were observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. Odds of having concentrations > 8.0 U/g were greatest when roach problems were reported or observed and increased with the number of cockroaches observed and with indications of recent cockroach activity. Conclusions Household cockroach allergen exposure is characterized in a nationally representative context. The allergen is prevalent in many settings, at levels that may contribute to allergic sensitization and asthma morbidity. Relevance to Clinical or Professional Practice Likelihood of exposure can be assessed by consideration of demographic and household determinants. PMID:16581539

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease

PubMed Central

Kotze, Paulo Gustavo; Martinez, Carlos Augusto Real; Camargo, Michel Gardere; Guadagnini, Dioze; Calixto, Antonio Ramos; Vasques, Ana Carolina Junqueira; Ayrizono, Maria de Lourdes Setsuko; Geloneze, Bruno; Pareja, José Carlos; Saad, Mario José; Coy, Claudio Saddy Rodrigues

2017-01-01

Background/Aims Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). Methods Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. Results Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. Conclusions Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers. PMID:28670232

4th level of 1913 elevator indicating sacking scale, part of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW SHOWS VERTICAL LADDER AND CAGE ALONG ELEVATOR SHAFT. - U.S. Naval Base, Pearl Harbor, Signal Tower, Corner of Seventh Street & Avenue D east of Drydock No. 1, Pearl City, Honolulu County, HI

Hypolipidemic and antioxidant activity of mountain celery (Cryptotaenia japonica Hassk) seed essential oils.

PubMed

Cheng, Ming-Ching; Lin, Li-Yun; Yu, Tung-Hsi; Peng, Robert Y

2008-06-11

Mountain celery seed essential oils (MC-E) contained 109 compounds, including mainly nine kinds of monoterpenoids, 31 kinds of of sesquiterpenoids, and 22 kinds of alcohols. A successive gel column adsorption with solvent fractionation yielded four fractionates. The pentane fractionate revealed potent hypolipidemic but poor antioxidant activities. The ether fractionate exhibited strong hypolipidemic activity in addition to excellent 1,1-diphenyl-2-picrylhydrazyl free radical- and superoxide anion-scavenging capabilities. The third acetone fractionate only showed moderate superoxide anion-scavenging activity. Finally, the fourth methanol fractionate having a rather high content of gamma-selinene, 2-methylpropanal, and Z-9-octadecenamide uniquely revealed very strong superoxide anion-scavenging capability. All MC diets except the MC-E-added diet simultaneously exhibited both significant hypolipidemic and high-density lipoprotein-cholesterol (HDL-C)-elevating capabilities. However, all diets totally failed to affect the hepatic phospholipid levels. Conclusively, the MC-E can be fractionated by such a separation technology to produce products uniquely possessing hypolipidemic and HDL-C-elevating activities.

Preliminary study of injury from heating systemically delivered, nontargeted dextran–superparamagnetic iron oxide nanoparticles in mice

PubMed Central

Kut, Carmen; Zhang, Yonggang; Hedayati, Mohammad; Zhou, Haoming; Cornejo, Christine; Bordelon, David; Mihalic, Jana; Wabler, Michele; Burghardt, Elizabeth; Gruettner, Cordula; Geyh, Alison; Brayton, Cory; Deweese, Theodore L; Ivkov, Robert

2013-01-01

Aim To assess the potential for injury to normal tissues in mice due to heating systemically delivered magnetic nanoparticles in an alternating magnetic field (AMF). Materials & methods Twenty three male nude mice received intravenous injections of dextran–superparamagnetic iron oxide nanoparticles on days 1–3. On day 6, they were exposed to AMF. On day 7, blood, liver and spleen were harvested and analyzed. Results Iron deposits were detected in the liver and spleen. Mice that had received a high-particle dose and a high AMF experienced increased mortality, elevated liver enzymes and significant liver and spleen necrosis. Mice treated with low-dose superparamagnetic iron oxide nanoparticles and a low AMF survived, but had elevated enzyme levels and local necrosis in the spleen. Conclusion Magnetic nanoparticles producing only modest heat output can cause damage, and even death, when sequestered in sufficient concentrations. Dextran–superparamagnetic iron oxide nanoparticles are deposited in the liver and spleen, making these the sites of potential toxicity. PMID:22830502

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study.

PubMed

Chen, Yimin; Zhao, Ying; Feng, Linmin; Zhang, Jie; Zhang, Juanwen; Feng, Guofang

2016-04-27

Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population. A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome. Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides. These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation.

PubMed

Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

2017-11-01

We evaluated the effect of the antioxidant N-acetyl-L-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after 131 I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post- 131 I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

PubMed

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-11-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Iron dysregulation combined with aging prevents sepsis-induced apoptosis

PubMed Central

Javadi, Pardis; Buchman, Timothy G.; Stromberg, Paul E.; Turnbull, Isaiah R.; Vyas, Dinesh; Hotchkiss, Richard S.; Karl, Irene E.; Coopersmith, Craig M.

2005-01-01

Background Sepsis, iron loading and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Methods Hfe−/− mice (a murine homolog of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24–26 months) or mature (16–18 months) Hfe−/− mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 hours later and assessed for apoptosis and cytokine levels. Results Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe−/− mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe−/− mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe−/− mice than septic mature Hfe−/− animals. Interleukin-6 was elevated in septic aged Hfe−/− mice compared to sham mice. Conclusions Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe−/− mice are able to mount an inflammatory response following CLP and mature Hfe−/− mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation. PMID:15921699

Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

PubMed

Gong, Gordon; Mattevada, Sravan; O'Bryant, Sid E

2014-04-01

Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular. Published by Elsevier Inc.

Serum interleukin-17 in Egyptian children with systemic lupus erythematosus: is it related to pulmonary affection?

PubMed

Hammad, A; Osman, E; Mosaad, Y; Wahba, M

2017-04-01

Objective Pulmonary involvement in paediatric systemic lupus erythematosus (pSLE) is not an uncommon finding; however, subclinical affection occurs more frequently. Many studies have reported that cytokine dysregulation as interleukin-17 (IL-17) over-expression plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). We aim to assess serum levels of IL-17 A and their association with pulmonary involvement in children with SLE. Methods Serum IL-17A levels - determined by solid phase sandwich ELISA - were assessed in forty-two pSLE patients and compared to 45 age-matched healthy controls. All patients were subjected to pulmonary function tests to detect subclinical pulmonary affection. High-resolution CT (HRCT) chest scan was carried out in patients with abnormal pulmonary function tests (PFTs) and those with chronic respiratory symptoms. Results Abnormal PFTs were found in 73% of patients; of them, only 25% had abnormal findings in HRCT chest. Serum levels of IL-17 A were significantly elevated in pSLE patients as compared to healthy controls ( p < 0.001). The serum levels of IL-17 A had a highly significant positive correlation with SLEDAI ( r = 0.811 and p < 0.001) Strong negative correlation was found between serum levels of IL-17A with both FEV1 and FVC ( p < 0.05). Conclusions Serum IL-17A is elevated in pSLE patients, which correlates with disease activity. IL-17 seems to have a possible role in the pathogenesis of subclinical lung affection. Abnormal PFTS may be found in pSLE patients even with normal radiology.

Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis.

PubMed

Luo, Qing; Deng, Zhen; Xu, Chuxin; Zeng, Lulu; Ye, Jianqing; Li, Xue; Guo, Yang; Huang, Zikun; Li, Junming

2017-03-10

BACKGROUND It is well known that lymphocytes play an important role in rheumatoid arthritis (RA). T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (TIGIT) have immunosuppressive co-stimulatory molecules that mediate inhibitory effects, but their roles in RA are poorly understood. MATERIAL AND METHODS Were recruited 76 patients with RA and 33 healthy controls (HC). Clinical manifestations, laboratory measurements, physical examination, and medical history of RA patients were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes, and CD3+CD8+ T lymphocytes was determined using flow cytometry. The expression of TIGIT on T lymphocytes in patients with RA was further analyzed to investigate its correlations with markers of autoimmune response, inflammation, and disease activity in RA. RESULTS Compared with HC, the expression levels of TIGIT on CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were significantly increased in patients with RA (P < 0.01). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was positively correlated with RF, increased ACPA, ESR, and CRP levels. The frequency of TIGIT-expressing CD3+CD8+ T lymphocytes was positively correlated with RF and ESR levels. Furthermore, the expression level of TIGIT on CD3+CD4+ T lymphocytes was positively correlated with the DAS28 score in RA. CONCLUSIONS The expression levels of TIGIT on T lymphocytes were elevated and correlated with disease activity in RA.

Estimating relative sea-level rise and submergence potential at a coastal wetland

USGS Publications Warehouse

Cahoon, Donald R.

2015-01-01

A tide gauge records a combined signal of the vertical change (positive or negative) in the level of both the sea and the land to which the gauge is affixed; or relative sea-level change, which is typically referred to as relative sea-level rise (RSLR). Complicating this situation, coastal wetlands exhibit dynamic surface elevation change (both positive and negative), as revealed by surface elevation table (SET) measurements, that is not recorded at tide gauges. Because the usefulness of RSLR is in the ability to tie the change in sea level to the local topography, it is important that RSLR be calculated at a wetland that reflects these local dynamic surface elevation changes in order to better estimate wetland submergence potential. A rationale is described for calculating wetland RSLR (RSLRwet) by subtracting the SET wetland elevation change from the tide gauge RSLR. The calculation is possible because the SET and tide gauge independently measure vertical land motion in different portions of the substrate. For 89 wetlands where RSLRwet was evaluated, wetland elevation change differed significantly from zero for 80 % of them, indicating that RSLRwet at these wetlands differed from the local tide gauge RSLR. When compared to tide gauge RSLR, about 39 % of wetlands experienced an elevation rate surplus and 58 % an elevation rate deficit (i.e., sea level becoming lower and higher, respectively, relative to the wetland surface). These proportions were consistent across saltmarsh, mangrove, and freshwater wetland types. Comparison of wetland elevation change and RSLR is confounded by high levels of temporal and spatial variability, and would be improved by co-locating tide gauge and SET stations near each other and obtaining long-term records for both.

The transcriptomic fingerprint of glucoamylase over-expression in Aspergillus niger

PubMed Central

2012-01-01

Background Filamentous fungi such as Aspergillus niger are well known for their exceptionally high capacity for secretion of proteins, organic acids, and secondary metabolites and they are therefore used in biotechnology as versatile microbial production platforms. However, system-wide insights into their metabolic and secretory capacities are sparse and rational strain improvement approaches are therefore limited. In order to gain a genome-wide view on the transcriptional regulation of the protein secretory pathway of A. niger, we investigated the transcriptome of A. niger when it was forced to overexpression the glaA gene (encoding glucoamylase, GlaA) and secrete GlaA to high level. Results An A. niger wild-type strain and a GlaA over-expressing strain, containing multiple copies of the glaA gene, were cultivated under maltose-limited chemostat conditions (specific growth rate 0.1 h-1). Elevated glaA mRNA and extracellular GlaA levels in the over-expressing strain were accompanied by elevated transcript levels from 772 genes and lowered transcript levels from 815 genes when compared to the wild-type strain. Using GO term enrichment analysis, four higher-order categories were identified in the up-regulated gene set: i) endoplasmic reticulum (ER) membrane translocation, ii) protein glycosylation, iii) vesicle transport, and iv) ion homeostasis. Among these, about 130 genes had predicted functions for the passage of proteins through the ER and those genes included target genes of the HacA transcription factor that mediates the unfolded protein response (UPR), e.g. bipA, clxA, prpA, tigA and pdiA. In order to identify those genes that are important for high-level secretion of proteins by A. niger, we compared the transcriptome of the GlaA overexpression strain of A. niger with six other relevant transcriptomes of A. niger. Overall, 40 genes were found to have either elevated (from 36 genes) or lowered (from 4 genes) transcript levels under all conditions that were examined, thus defining the core set of genes important for ensuring high protein traffic through the secretory pathway. Conclusion We have defined the A. niger genes that respond to elevated secretion of GlaA and, furthermore, we have defined a core set of genes that appear to be involved more generally in the intensified traffic of proteins through the secretory pathway of A. niger. The consistent up-regulation of a gene encoding the acetyl-coenzyme A transporter suggests a possible role for transient acetylation to ensure correct folding of secreted proteins. PMID:23237452

Complementary and alternative medicine for lowering blood lipid levels: A systematic review of systematic reviews.

PubMed

Posadzki, Paul; AlBedah, Abdullah M N; Khalil, Mohamed M K; AlQaed, Meshari S

2016-12-01

The aim of this article is to summarize and critically evaluate the evidence from systematic reviews (SRs) of complementary and alternative medicine (CAM) for lowering blood lipid levels (BLL). Eight electronic databases were searched until March 2016. Additionally, all the retrieved references were inspected manually for further relevant papers. Systematic reviews were considered eligible, if they included patients of any age and/or gender with elevated blood lipid levels using any type of CAM. We used the Oxman and AMSTAR criteria to critically appraise the methodological quality of the included SRs. Twenty-seven SRs were included in the analyses. The majority of the SRs were of high methodological quality (mean Oxman score=4.81, SD=4.88; and the mean AMSTAR score=7.22, SD=3.38). The majority of SRs (56%) arrived at equivocal conclusions (of these 8 were of high quality); 7 SRs (37%) arrived at positive conclusions (of these 6 were of high quality), and 2 (7%) arrived at negative conclusions (both were of high quality). There was conflicting evidence regarding the effectiveness of garlic; and promising evidence for yoga. To conclude, the evidence from SRs evaluating the effectiveness of CAM in lowering BLL is predominantly equivocal and confusing. Several limitations exist, such as variety of doses and preparations, confounding effects of diets and lifestyle factors, or heterogeneity of the primary trials among others. Copyright © 2016. Published by Elsevier Ltd.

Comment on the Nanoparticle Conclusions in Crüts et al. (2008), "Exposure to diesel exhaust induces changes in EEG in human volunteers"

PubMed Central

Valberg, Peter A; Long, Christopher M; Hesterberg, Thomas W

2008-01-01

A recent publication in this journal reported interesting changes in electroencephalographic (EEG) waves that occurred in 10 young, male volunteers following inhalation for one hour of elevated levels of diesel-engine exhaust fumes [1]. The authors then proposed a chain of causal events that they hypothesized underlay their observed EEG changes. Their reasoning linked the observed results to nanoparticles in diesel-engine exhaust (DEE), and went on to suggest that associations between changes in ambient particulate matter (PM) levels and changes in health statistics might be due to the effects of diesel-engine exhaust (DEE) nanoparticles on EEG. We suggest that the extrapolations of the Crüts et al. EEG findings to casual mechanisms about how ambient levels of DEE particulate might affect electrical signals in the brain, and subsequently to how DEE particulate might alter disease risk, are premature. PMID:18652692

Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

PubMed

Uher, Tomas; Bob, Petr

2013-03-01

There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

Silibinin ameliorates Aβ25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress.

PubMed

Song, Xiaoyu; Zhou, Biao; Cui, Lingyu; Lei, Di; Zhang, Pingping; Yao, Guodong; Xia, Mingyu; Hayashi, Toshihiko; Hattori, Shunji; Ushiki-Kaku, Yuko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2017-04-01

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ 25-35 -injected rats. Results demonstrated that silibinin significantly attenuated Aβ 25-35 -induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ 25-35 -injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ 25-35 -injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.

75 FR 31342 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... referenced ground [caret] Communities affected elevation Elevation in meters (MSL) Effective Modified... Level, rounded to the nearest 0.1 meter. ** BFEs to be changed include the listed downstream and... ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ** BFEs to be changed include the...

Will fluctuations in salt marsh–mangrove dominance alter vulnerability of a subtropical wetland to sea‐level rise?

USGS Publications Warehouse

Mckee, Karen L.; Vervaeke, William

2018-01-01

To avoid submergence during sea-level rise, coastal wetlands build soil surfaces vertically through accumulation of inorganic sediment and organic matter. At climatic boundaries where mangroves are expanding and replacing salt marsh, wetland capacity to respond to sea-level rise may change. To compare how well mangroves and salt marshes accommodate sea-level rise, we conducted a manipulative field experiment in a subtropical plant community in the subsiding Mississippi River Delta. Experimental plots were established in spatially equivalent positions along creek banks in monospecific stands of Spartina alterniflora (smooth cordgrass) or Avicennia germinans (black mangrove) and in mixed stands containing both species. To examine the effect of disturbance on elevation dynamics, vegetation in half of the plots was subjected to freezing (mangrove) or wrack burial (salt marsh), which caused shoot mortality. Vertical soil development was monitored for 6 years with the surface elevation table-marker horizon system. Comparison of land movement with relative sea-level rise showed that this plant community was experiencing an elevation deficit (i.e., sea level was rising faster than the wetland was building vertically) and was relying on elevation capital (i.e., relative position in the tidal frame) to survive. Although Avicennia plots had more elevation capital, suggesting longer survival, than Spartina or mixed plots, vegetation type had no effect on rates of accretion, vertical movement in root and sub-root zones, or net elevation change. Thus, these salt marsh and mangrove assemblages were accreting sediment and building vertically at equivalent rates. Small-scale disturbance of the plant canopy also had no effect on elevation trajectories—contrary to work in peat-forming wetlands showing elevation responses to changes in plant productivity. The findings indicate that in this deltaic setting with strong physical influences controlling elevation (sediment accretion, subsidence), mangrove replacement of salt marsh, with or without disturbance, will not necessarily alter vulnerability to sea-level rise.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

PubMed Central

Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

2017-01-01

Background: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. Objective: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. Materials and Methods: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). Results: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. Conclusions: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase. PMID:28808392

Contrasting Decadal-Scale Changes in Elevation and ...

EPA Pesticide Factsheets

Northeastern US salt marshes face multiple co-stressors, including accelerating rates of relative sea level rise (RSLR), elevated nutrient inputs, and low sediment supplies. In order to evaluate how marsh surface elevations respond to such factors, we used surface elevation tables (SETs) and surface elevation pins to measure changes in marsh surface elevation in two eastern Long Island Sound salt marshes, Barn Island and Mamacoke marshes. We compare marsh elevation change at these two systems with recent rates of RSLR and find evidence of differences between the two sites; Barn Island is maintaining its historic rate of elevation gain (2.3 ± 0.24 mm year−1 from 2003 to 2013) and is no longer keeping pace with RSLR, while Mamacoke shows evidence of a recent increase in rates (4.2 ± 0.52 mm year−1 from 1994 to 2014) to maintain its elevation relative to sea level. In addition to data on short-term elevation responses at these marshes, both sites have unusually long and detailed data on historic vegetation species composition extending back more than half a century. Over this study period, vegetation patterns track elevation change relative to sea levels, with the Barn Island plant community shifting towards those plants that are found at lower elevations and the Mamacoke vegetation patterns showing little change in plant composition. We hypothesize that the apparent contrasting trend in marsh elevation at the sites is due to differences in sediment a

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

Elevated expression of the proto-oncogene c-kit in patients with mastocytosis.

PubMed

Nagata, H; Worobec, A S; Semere, T; Metcalfe, D D

1998-02-01

The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the development and survival of mast cells. Several studies have also associated c-kit receptor mutations with the human diseases, mastocytosis and piebaldism. Overexpression of c-kit has been reported to be associated with myeloproliferative disorders and myelodysplastic syndromes. Using peripheral blood mononuclear cells (PBMCs) from 11 patients with indolent mastocytosis (category I), mastocytosis with an associated hematologic disorder (category II), or aggressive mastocytosis (category III); a patient with CMML unassociated with mastocytosis, and PBMCs from 13 normal subjects, we examined the level of expression of c-kit mRNA along with other c-kit isoforms to determine if overexpression of the c-kit receptor was associated with mastocytosis. Using quantitative competitive PCR, c-kit mRNA levels on average were found to be statistically elevated in the five patients with mastocytosis with an associated hematologic disorder and in the patient with aggressive mastocytosis as compared with controls, but not elevated in patients with indolent mastocytosis. The relative mRNA expression for the two c-kit isoforms was not significantly different in the mastocytosis patients compared with controls. This demonstration of the overexpression of c-kit mRNA in mastocytosis, and particularly those patients with clinical evidence of myelodysplastic syndrome, adds evidence to support the conclusion that mastocytosis, at least in some patients, is a feature of myelodysplasia; and suggests that determination of c-kit mRNA expression in PBMCs may provide an additional approach to assessing prognosis.

Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

PubMed Central

Xu, Ping; Xu, Cheng-Fu; Wan, Xing-Yong; Yu, Chao-Hui; Shen, Chao; Chen, Peng; Xu, Gen-Yun; Li, You-Ming

2014-01-01

AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population. METHODS: A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. FLD was diagnosed based on an ultrasonography examination. Serum AFP levels were measured with a chemiluminescence immunoassay. RESULTS: Of the 9800 subjects enrolled, 2601 were diagnosed with FLD. Subjects with FLD had higher serum AFP levels than those without the disease. Subjects with high serum AFP levels had a higher prevalence of FLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AFP levels were associated with an increased risk of FLD (OR = 1.057, 95%CI: 1.031-1.084). However, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for FLD. CONCLUSION: Our results suggest that serum AFP levels are significantly associated with FLD and that AFP acts as a cofactor, but not as an independent factor, for FLD. PMID:25206293

Properties of hail storms over China and the United States from the Tropical Rainfall Measuring Mission

PubMed Central

Ni, Xiang; Liu, Chuntao; Zhang, Qinghong; Cecil, Daniel J.

2018-01-01

A 16-yr record of hail reports over the south U.S. and from weather stations in China are collocated with Precipitation Features (PF) derived from the Tropical Rainfall Measuring Mission (TRMM) radar and passive microwave observations. Differences in the way hail is reported in the two nations make it difficult to draw meaningful conclusions about storm frequency. But taking the two together yields a wide spectrum of hail sizes, suitable for comparing with remote sensing measurements. While U.S. hail reports are dominated by cases with hail size greater than 19 mm, hail reports in China mostly include diameters of 1–10 mm and mostly occur over the Tibetan Plateau. The fraction of PFs collocated with hail reports (hail PFs) reaches 3% in the plains of the U.S. In China, the fraction is higher in high elevation regions than low elevation regions. Hail PFs (as reported in the U.S.) show lower brightness temperatures, higher lightning flash rates, stronger maximum reflectivity, and higher echo tops than those with smaller hail, as reported in China. The average near surface maximum reflectivity of hail PFs at high elevations (≥ 2000 m) in China is about 5 dB smaller than those at low elevations. Larger hail is reported with PFs having stronger maximum reflectivity above 6 km, though the median of maximum reflectivity values at levels below 5 km is similar among the storms with large and small hail sizes. PMID:29377045

Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression

PubMed Central

Wei, Y B; Liu, J J; Villaescusa, J C; Åberg, E; Brené, S; Wegener, G; Mathé, A A; Lavebratt, C

2016-01-01

Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms. PMID:27529677

Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression.

PubMed

Wei, Y B; Liu, J J; Villaescusa, J C; Åberg, E; Brené, S; Wegener, G; Mathé, A A; Lavebratt, C

2016-08-16

Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms.

Pain Coping Skills Training for Patients with Elevated Pain Catastrophizing who are Scheduled for Knee Arthroplasty: A Quasi-Experimental Study

PubMed Central

Riddle, Daniel L.; Keefe, Francis J.; Nay, William T.; McKee, Daphne; Attarian, David E.; Jensen, Mark P.

2011-01-01

Objectives To (1) describe a behavioral intervention designed for patients with elevated pain catastrophizing who are scheduled for knee arthroplasty, and (2) use a quasi-experimental design to evaluate the potential efficacy of the intervention on pain severity, catastrophizing cognitions, and disability. Design Quasi-experimental non-equivalent control group design with a 2 month follow-up. Setting Two university-based Orthopedic Surgery departments. Participants Adults scheduled for knee replacement surgery who reported elevated levels of pain catastrophizing. Patients were recruited from two clinics and were assessed prior to surgery and 2 months following surgery. Intervention A group of 18 patients received a psychologist directed pain coping skills training intervention comprising 8 sessions and the other group, a historical cohort of 45 patients, received usual care. Main Outcome Measures WOMAC Pain and Disability scores as well as scores on the Pain Catastrophizing Scale. Results Two months following surgery, the patients who received pain coping skills training reported significantly greater reductions in pain severity and catastrophizing, and greater improvements in function as compared to the usual care cohort. Conclusion Pain catastrophizing is known to increase risk of poor outcome following knee arthroplasty. The findings provide preliminary evidence that the treatment may be highly efficacious for reducing pain, catastrophizing, and disability, in patients reporting elevated catastrophizing prior to knee arthroplasty. A randomized clinical trial is warranted to confirm these effects. PMID:21530943

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

75 FR 31368 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... referenced ground [caret] Communities affected elevation Elevation in meters (MSL) Effective Modified Santa.... Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ** BFEs to be... Vertical Datum. Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter...

77 FR 21476 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Randolph County... Vertical Datum. Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter.... [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Beebe Maps are available for...

77 FR 7540 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Sebastian County... Level, rounded to the nearest 0.1 meter. ADDRESSES City of Fort Smith Maps are available for inspection.... [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Rolling Fork Maps are...

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

PubMed

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Bee (Hymenoptera: Apoidea) Diversity and Sampling Methodology in a Midwestern USA Deciduous Forest.

PubMed

McCravy, Kenneth W; Ruholl, Jared D

2017-08-04

Forests provide potentially important bee habitat, but little research has been done on forest bee diversity and the relative effectiveness of bee sampling methods in this environment. Bee diversity and sampling methodology were studied in an Illinois, USA upland oak-hickory forest using elevated and ground-level pan traps, malaise traps, and vane traps. 854 bees and 55 bee species were collected. Elevated pan traps collected the greatest number of bees (473), but ground-level pan traps collected greater species diversity (based on Simpson's diversity index) than did elevated pan traps. Elevated and ground-level pan traps collected the greatest bee species richness, with 43 and 39 species, respectively. An estimated sample size increase of over 18-fold would be required to approach minimum asymptotic richness using ground-level pan traps. Among pan trap colors/elevations, elevated yellow pan traps collected the greatest number of bees (266) but the lowest diversity. Malaise traps were relatively ineffective, collecting only 17 bees. Vane traps collected relatively low species richness (14 species), and Chao1 and abundance coverage estimators suggested that minimum asymptotic species richness was approached for that method. Bee species composition differed significantly between elevated pan traps, ground-level pan traps, and vane traps. Indicator species were significantly associated with each of these trap types, as well as with particular pan trap colors/elevations. These results indicate that Midwestern deciduous forests provide important bee habitat, and that the performance of common bee sampling methods varies substantially in this environment.

Elevator ride comfort monitoring and evaluation using smartphones

NASA Astrophysics Data System (ADS)

Zhang, Yang; Sun, Xiaowei; Zhao, Xuefeng; Su, Wensheng

2018-05-01

With rapid urbanization, the demand for elevators is increasing, and their level of safety and ride comfort under vibrating conditions has also aroused interest. It is therefore essential to monitor the ride comfort level of elevators. The traditional method for such monitoring depends significantly on regular professional inspections, and requires expensive equipment and professional skill. With this regard, a new method for elevator ride comfort monitoring using a smartphone is demonstrated herein in detail. A variety of high-precision sensors are installed in a smartphone with strong data processing and telecommunication capabilities. A series of validation tests were designed and completed, and the international organization for standardization ISO2631-1997 was applied to evaluate the level of elevator ride comfort. Experimental results indicate that the proposed method is stable and reliable, its precision meets the engineering requirements, and the elevator ride comfort level can be accurately monitored under various situations. The method is very economical and convenient, and provides the possibility for the public to participate in elevator ride comfort monitoring. In addition, the method can both provide a wide range of data support and eliminate data errors to a certain extent.

Blood lead levels in children aged 24 to 36 months in Vancouver.

PubMed Central

Jin, A; Hertzman, C; Peck, S H; Lockitch, G

1995-01-01

OBJECTIVES: To determine the blood lead levels in children and to identify risk factors for elevated levels. DESIGN: Cross-sectional study. SETTING: Vancouver. PARTICIPANTS: Random sample of children aged 24 to 36 months, born and still resident in Vancouver. The sample was stratified proportionally by the median annual family income in the census tract where each family resided. OUTCOME MEASURES: Blood lead levels and risk factors for elevated blood lead levels, determined from a questionnaire administered to parents. RESULTS: Of the children in the sample, 42% (178/422) were ineligible or could not be located. Of the remaining children, 73% (177/244) participated and adequate blood specimens were obtained from 172. The mean blood lead level was 0.29 mumol/L (standard deviation 0.13 mumol/L). (A blood lead level of 1 mumol/L is equivalent to 20.7 micrograms/dL.) The lowest level was 0.06 mumol/L, and the highest was 0.85 mumol/L. Of children with adequate samples, 8.1% (14/172) had blood lead levels of 0.48 mumol/L or higher, and 0.6% (1/172) had a level higher than 0.72 mumol/L. The logarithms of the levels were normally distributed, with a geometric mean (GM) of 0.26 mumol/L (geometric standard deviation 1.56). Of approximately 70 possible predictors of blood lead levels analysed, those that showed a statistically significant association (p < 0.05) with increased blood lead levels were soldering performed in the home as part of an electronics hobby (GM blood lead level 0.34 mumol/L, 95% confidence interval [CI] 0.27 to 0.39 mumol/L), aboriginal heritage (GM blood lead level 0.33 mumol/L, 95% CI 0.28 to 0.39 mumol/L), dwelling built before 1921 (GM blood lead level 0.32 mumol/L, 95% CI 0.28 to 0.37 mumol/L), age of water service connection to dwelling (predicted blood lead level 0.00087 mumol/L [95% CI 0.00005 to 0.00169 mumol/L] higher per year since service connection) and decreased stature (predicted blood lead level 0.018 mumol/L [95% CI 0.0353 to 0.0015 mumol/L] higher for every standard deviation below the age-specific mean height). CONCLUSIONS: This study found much lower blood lead levels in children than those found in previous Canadian studies. The authors believe that this result is not an artefact due to differences in population sampling or methods of collection of blood specimens. The study showed no clear risk factors for elevated blood lead levels: although a few factors had a statistically significant association with increased blood lead levels, the differences in levels were small and unimportant. PMID:7712420

Neighborhood Screening in Communities Throughout the Nation for Children with Elevated Blood Lead Levels

PubMed Central

Anderson, Dudley G.; Clark, John L.

1974-01-01

From the spring of 1971 to September 1973, neighborhood surveys were conducted in 58 communities throughout the nation to determine whether children with confirmed elevated blood lead levels could be identified. Another purpose of these screenings was to assist communities in identifying children with elevated blood lead levels and thereby demonstrate to community officials that such children do exist in communities screened. The children screened were not a random sample. In those communities where the initial elevated blood levels were confirmed all but seven had one or more children requiring followup and/or treatment. Of those children screened, black children had an elevated rate about three times as great as nonblack children. With few exceptions, the homes in the neighborhoods had at least one interior surface with sufficient quantities of lead paint to be dangerous if the paint were ingested. PMID:4831146

Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice

PubMed Central

Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

2012-01-01

Background and Design: Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. Methods and Results: The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Conclusion: Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity. PMID:23446660

Iron, Oxidative Stress, and Δ9 Stearoyl-CoenzymeA Desaturase Index (C16:1/C16:0): An Analysis Applying the National Health and Nutrition Examination Survey 2003–04

PubMed Central

Wu, Yue; Baylin, Ana; Colacino, Justin A

2018-01-01

Abstract Background Stearoyl-coenzyme A desaturase (SCD) is a key enzyme in fatty acid metabolism, and elevated SCD activity is associated with multiple adverse health outcomes. Diet, hormone levels, and environmental exposures are potential factors affecting SCD activity. Less is known about the relationship between micronutrients, including iron, and SCD activity. Objective The aim of this study was to investigate the association between serum ferritin level, a biomarker of circulating iron levels, and the Δ9 desaturase index (C16:1/C16:0), a biomarker of estimated SCD activity, among women in the United States. Methods The association between serum ferritin and the Δ9 desaturase index was assessed in a cross-sectional study of 447 female participants, aged 20–49 y, from NHANES 2003–2004. The multivariate analyses were performed utilizing generalized linear modeling, adjusting for potential confounders. Mediation of the relationship between serum ferritin and Δ9 desaturase index by γ-glutamyltranspeptidase (GGT), a biomarker of oxidative stress, was also assessed. Results Increased ferritin was significantly associated with a higher Δ9 desaturase index. Adjusting for waist circumference, age, race, and cotinine levels, an interquartile range increase in serum ferritin corresponded to 3.92% (95% CI: 0.88%, 7.05%) higher Δ9 desaturase index. GGT, the biomarker used to measure oxidative stress level, did not appear to mediate the association between ferritin and Δ9 desaturase index. After stratifying by pregnancy status, these associations were limited to nonpregnant individuals. Conclusions Elevated SCD activity may be associated with increased iron storage inside the human body; the association did not appear to be mediated via oxidative stress, as estimated by GGT levels.

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.

PubMed

Freiberg, Matthew S; Bebu, Ionut; Tracy, Russell; So-Armah, Kaku; Okulicz, Jason; Ganesan, Anuradha; Armstrong, Adam; O'Bryan, Thomas; Rimland, David; Justice, Amy C; Agan, Brian K

2016-01-01

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

Association study of methylenetetrahydrofolate reductase C677T mutation with cerebral venous thrombosis in an Iranian population.

PubMed

Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad S

2015-12-01

There are limited data on the role of methylenetetrahydrofolate reductase C677T polymorphism and hyperhomocysteinemia as risk factors for cerebral venous thrombosis in Iranian population. We examined a possible association between fasting plasma homocysteine levels, methylenetetrahydrofolate reductase C677T polymorphism, and cerebral venous thrombosis in 50 patients with a diagnosis of cerebral venous thrombosis (20-63 years old) and 75 healthy controls (18-65 years old). Genotyping of the methylenetetrahydrofolate reductase C677T gene polymorphism was performed by PCR-restriction fragment length polymorphism analysis, and homocysteine levels were measured by enzyme immunoassay. Fasting plasma homocysteine levels were significantly higher in cerebral venous thrombosis patients than in controls (P = 0.015). Moreover, plasma homocysteine levels were significantly higher in methylenetetrahydrofolate reductase 677TT genotype compared to 677CT and 677CC genotypes in both cerebral venous thrombosis patients (P = 0.01) and controls (P = 0.03). Neither 677CT heterozygote genotype [odds ratio (OR) 1.35, 95% confidence interval (CI) 0.64-2.84, P = 0.556] nor 677TT homozygote genotype (OR 1.73, 95% CI 0.32-9.21, P = 0.833) was significantly associated with cerebral venous thrombosis. Additionally, no significant differences in the frequency of 677T allele between cerebral venous thrombosis patients and controls were identified (OR 1.31, 95% CI 0.69-2.50, P = 0.512). In conclusion, our study demonstrated that elevated plasma homocysteine levels are significant risk factors for cerebral venous thrombosis. Also, methylenetetrahydrofolate reductase 677TT genotype is not linked with cerebral venous thrombosis, but is a determinant of elevated plasma homocysteine levels.

[Relationship between inflammatory markers and the risk of colorectal cancer in Kailuan male cohort].

PubMed

Wang, G; Xu, W G; Li, F; Su, K; Li, N; Lü, Z Y; Feng, X S; Wei, L P; Chen, H D; Chen, Y H; Guo, L W; Cui, H; Yang, W J; Li, Z F; Ren, J S; Wu, S L; Shi, J F; Dai, M; He, J

2017-10-31

Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios ( HR ) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P =0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer ( HR =1.38, 95% CI: 1.05-1.81, P =0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.

Deoxysphingoid bases as plasma markers in Diabetes mellitus

PubMed Central

2010-01-01

Background Sphingoid bases are formed from the precursors L-serine and palmitoyl-CoA-a reaction which is catalyzed by the serine-palmitoyltransferase (SPT). SPT metabolizes, besides palmitoyl-CoA also other acyl-CoAs but shows also variability towards the use of other amino acid substrates. The enzyme is also able to metabolize alanine, which results in the formation of an atypical deoxy-sphingoid base (DSB). This promiscuous activity is greatly increased in the case of the sensory neuropathy HSAN1, and pathologically elevated DSB levels have been identified as the cause of this disease. Clinically, HSAN1 shows a pronounced similarity to the diabetic sensory neuropathy (DSN), which is the most common chronic complication of diabetes mellitus. Since serine and alanine metabolism is functionally linked to carbohydrate metabolism by their precursors 3-phosphoglycerate and pyruvate, we were interested to see whether the levels of certain sphingoid base metabolites are altered in patients with diabetes. Results In a case-control study we compared plasma sphingoid base levels between healthy and diabetic individuals. DSB levels were higher in the diabetic group whereas C16 and C18 sphingoid bases were not significantly different. Plasma serine, but not alanine levels were lower in the diabetic group. A subsequent lipoprotein fractionation showed that the DSBs are primarily present in the LDL and VLDL fraction. Conclusion Our results suggest that DSBs are a novel category of plasma biomarkers in diabetes which reflect functional impairments of carbohydrate metabolism. Furthermore, elevated DSB levels as we see them in diabetic patients might also contribute to the progression of the diabetic sensory neuropathy, the most frequent complication of diabetes. PMID:20712864

Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement.

PubMed

Thi Hong Nguyen, Chuyen; Kambe, Naotomo; Kishimoto, Izumi; Ueda-Hayakawa, Ikuko; Okamoto, Hiroyuki

2017-07-01

Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin-2 receptor (sIL-2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL-2R compared with two other common markers, angiotensin-converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL-2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL-2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL-2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression-specific signs by imaging analysis. Receiver-operator curve analysis showed that sIL-2R was a better marker at the threshold cut-off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL-2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow-up period. In conclusion, sIL-2R may be considered a good marker for diagnosis and a potential indicator of disease activity. © 2017 Japanese Dermatological Association.

Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

PubMed Central

2010-01-01

Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB). Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects. Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes. PMID:20426869

Roles of Autophagy in MPP+-Induced Neurotoxicity In Vivo: The Involvement of Mitochondria and α-Synuclein Aggregation

PubMed Central

Lin, Ming-Wei; Lei, Yen-Ping; Lin, Anya Maan-yuh

2014-01-01

Macroautophagy (also known as autophagy) is an intracellular self-eating mechanism and has been proposed as both neuroprotective and neurodestructive in the central nervous system (CNS) neurodegenerative diseases. In the present study, the role of autophagy involving mitochondria and α-synuclein was investigated in MPP+ (1-methyl-4-phenylpyridinium)-induced oxidative injury in chloral hydrate-anesthetized rats in vivo. The oxidative mechanism underlying MPP+-induced neurotoxicity was identified by elevated lipid peroxidation and heme oxygenase-1 levels, a redox-regulated protein in MPP+-infused substantia nigra (SN). At the same time, MPP+ significantly increased LC3-II levels, a hallmark protein of autophagy. To block MPP+-induced autophagy in rat brain, Atg7siRNA was intranigrally infused 4 d prior to MPP+ infusion. Western blot assay showed that in vivo Atg7siRNA transfection not only reduced Atg7 levels in the MPP+-infused SN but attenuated MPP+-induced elevation in LC3-II levels, activation of caspase 9 and reduction in tyrosine hydroxylase levels, indicating that autophagy is pro-death. The immunostaining study demonstrated co-localization of LC3 and succinate dehydrogenase (a mitochondrial complex II) as well as LC3 and α-synuclein, suggesting that autophagy may engulf mitochondria and α-synuclein. Indeed, in vivo Atg7siRNA transfection mitigated MPP+-induced reduction in cytochrome c oxidase. In addition, MPP+-induced autophagy differentially altered the α-synuclein aggregates in the infused SN. In conclusion, autophagy plays a prodeath role in the MPP+-induced oxidative injury by sequestering mitochondria in the rat brain. Moreover, our data suggest that the benefits of autophagy depend on the levels of α-synuclein aggregates in the nigrostriatal dopaminergic system of the rat brain. PMID:24646838

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

PubMed Central

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

The Effects of Niacin on Inflammation in Patients with Non-ST Elevated Acute Coronary Syndrome

PubMed Central

Karacaglar, Emir; Atar, Ilyas; Altin, Cihan; Yetis, Begum; Cakmak, Abdulkadir; Bayraktar, Nilufer; Coner, Ali; Ozin, Bulent; Muderrisoglu, Haldun

2015-01-01

Background In this study, we aimed to evaluate the effects of niacin on high sensitivity C reactive protein (hs-CRP) and cholesterol levels in non-ST elevated acute coronary syndrome (NSTE-ACS) patients. Methods In this prospective, open label study, 48 NSTE-ACS were randomized to niacin or control group. Patients continued their optimal medical therapy in the control group. In the niacin group patients were assigned to receive extended-release niacin 500 mg/day. Patients were contacted 1 month later to assess compliance and side effects. Blood samples for hs-CRP were obtained upon admittance to the coronary care unit, in the third day and in the first month of the treatment. Fasting blood samples for cholesterol levels were obtained before and 30 days after the treatment. The primary end point of the study was to evaluate changes in hs-CRP, cholesterol levels, short-term cardiovascular events, and the safety of niacin in NSTE-ACS. Results Baseline demographic, clinical and laboratory characteristics were similar between the two groups. Logarithmic transformation of baseline and 3rd day hs-CRP levels were similar between the groups; but 1 month later, logarithmic transformation of hs-CRP level was significantly lower in the niacin group (0.43 ± 0.39 to 0.83 ± 0.91, p = 0.04). HDL-C level was significantly increased in the niacin group during follow-up. Drug related side effects were seen in 7 patients in the niacin group but no patients discontinued niacin. Conclusions Our findings demonstrate that lower dose extended release niacin can be used safely and decreases hs-CRP and lipid parameters successfully in NSTE-ACS patients. PMID:27122858

Sound-localization experiments with barn owls in virtual space: influence of broadband interaural level different on head-turning behavior.

PubMed

Poganiatz, I; Wagner, H

2001-04-01

Interaural level differences play an important role for elevational sound localization in barn owls. The changes of this cue with sound location are complex and frequency dependent. We exploited the opportunities offered by the virtual space technique to investigate the behavioral relevance of the overall interaural level difference by fixing this parameter in virtual stimuli to a constant value or introducing additional broadband level differences to normal virtual stimuli. Frequency-specific monaural cues in the stimuli were not manipulated. We observed an influence of the broadband interaural level differences on elevational, but not on azimuthal sound localization. Since results obtained with our manipulations explained only part of the variance in elevational turning angle, we conclude that frequency-specific cues are also important. The behavioral consequences of changes of the overall interaural level difference in a virtual sound depended on the combined interaural time difference contained in the stimulus, indicating an indirect influence of temporal cues on elevational sound localization as well. Thus, elevational sound localization is influenced by a combination of many spatial cues including frequency-dependent and temporal features.

Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as indicator for methanol antidote use.

PubMed

Leonard, Charlene P; Akhtar, Javed

2007-07-01

To report a case of co-ingestion of methanol and nitromethane in a child in order to heighten the awareness of false elevation of serum creatinine from nitromethane ingestion. Case report. Pediatric intensive care unit. A 4-yr-old previously healthy girl ingested an unknown quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and nitromethane. The patient was treated with fomepizole for methanol ingestion using elevated creatinine level as a reason for treatment. The patient was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4 mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained within normal limits. When the serum creatinine level was measured with enzymatic method instead of Jaffe's method, a normal creatinine level was obtained. The falsely elevated creatinine level was due to nitromethane. The falsely elevated serum creatinine levels due to nitromethane ingestion can lead to unnecessary therapeutic interventions. We intend to heighten awareness of this potential misstep by reporting this case.

Elevated blood pressure, race/ethnicity, and C-reactive protein levels in children and adolescents.

PubMed

Lande, Marc B; Pearson, Thomas A; Vermilion, Roger P; Auinger, Peggy; Fernandez, Isabel D

2008-12-01

Adult hypertension is independently associated with elevated C-reactive protein levels, after controlling for obesity and other cardiovascular risk factors. The objective of this study was to determine, with a nationally representative sample of children, whether the relationship between elevated blood pressure and C-reactive protein levels may be evident before adulthood. Cross-sectional data for children 8 to 17 years of age who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 were analyzed. Bivariate analyses compared children with C-reactive protein levels of >3 mg/L versus or=95th percentile and 1.3% had diastolic blood pressure of >or=95th percentile. Children with C-reactive protein levels of >3 mg/L had higher systolic blood pressure, compared with children with C-reactive protein levels of or=95th percentile was independently associated with C-reactive protein levels in boys but not girls. Subset analyses according to race/ethnicity demonstrated that the independent association of elevated systolic blood pressure with C-reactive protein levels was largely limited to black boys. These data indicate that there is interplay between race/ethnicity, elevated systolic blood pressure, obesity, and inflammation in children, a finding that has potential implications for disparities in cardiovascular disease later in life.

Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study

PubMed Central

Esparham, Anna E.; Smith, Teri; Belmont, John M.; Haden, Michael; Wagner, Leigh E.; Evans, Randall G.; Drisko, Jeanne A.

2015-01-01

Context Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. Objective The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. Design This study was a retrospective, descriptive chart review. Setting The study took place at the University of Kansas Medical Center (KUMC). Participants Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. Results A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)— C13:3W3, and (2) linoleic acid (LA)—C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2). Conclusions The findings from this small group of children with ASD points to the existence of nutritional, metabolic, and genetic correlates of ASD. These factors appear to be important potential abnormalities that warrant a case control study to evaluate their reliability and validity as markers of ASD. PMID:26770138

Metabolic shifts in the Antarctic fish Notothenia rossii in response to rising temperature and PCO2

PubMed Central

2012-01-01

Introduction Ongoing ocean warming and acidification increasingly affect marine ecosystems, in particular around the Antarctic Peninsula. Yet little is known about the capability of Antarctic notothenioid fish to cope with rising temperature in acidifying seawater. While the whole animal level is expected to be more sensitive towards hypercapnia and temperature, the basis of thermal tolerance is set at the cellular level, with a putative key role for mitochondria. This study therefore investigates the physiological responses of the Antarctic Notothenia rossii after long-term acclimation to increased temperatures (7°C) and elevated PCO2 (0.2 kPa CO2) at different levels of physiological organisation. Results For an integrated picture, we analysed the acclimation capacities of N. rossii by measuring routine metabolic rate (RMR), mitochondrial capacities (state III respiration) as well as intra- and extracellular acid–base status during acute thermal challenges and after long-term acclimation to changing temperature and hypercapnia. RMR was partially compensated during warm- acclimation (decreased below the rate observed after acute warming), while elevated PCO2 had no effect on cold or warm acclimated RMR. Mitochondrial state III respiration was unaffected by temperature acclimation but depressed in cold and warm hypercapnia-acclimated fish. In both cold- and warm-exposed N. rossii, hypercapnia acclimation resulted in a shift of extracellular pH (pHe) towards more alkaline values. A similar overcompensation was visible in muscle intracellular pH (pHi). pHi in liver displayed a slight acidosis after warm normo- or hypercapnia acclimation, nevertheless, long-term exposure to higher PCO2 was compensated for by intracellular bicarbonate accumulation. Conclusion The partial warm compensation in whole animal metabolic rate indicates beginning limitations in tissue oxygen supply after warm-acclimation of N. rossii. Compensatory mechanisms of the reduced mitochondrial capacities under chronic hypercapnia may include a new metabolic equilibrium to meet the elevated energy demand for acid–base regulation. New set points of acid–base regulation under hypercapnia, visible at the systemic and intracellular level, indicate that N. rossii can at least in part acclimate to ocean warming and acidification. It remains open whether the reduced capacities of mitochondrial energy metabolism are adaptive or would impair population fitness over longer timescales under chronically elevated temperature and PCO2. PMID:23075125

The Prevalence of Obesity and Elevated Blood Pressure in Adolescent Student Athletes From the State of Mississippi

PubMed Central

Stiefel, Eric C.; Field, Larry; Replogle, William; McIntyre, Louis; Igboechi, Oduche; Savoie, Felix H.

2016-01-01

Background: Over the past 30 years, there has been a dramatic increase in the prevalence of childhood obesity and hypertension in the United States. The prevalence of these diagnoses among individuals participating in school-sanctioned sports has not been clearly defined. Purpose: To identify the prevalence of obesity and elevated blood pressure (BP) among student athletes and investigate associations between race, sex, type and number of sports played, and the prevalence of these diseases. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Pre–sports participation medical examinations (N = 7705) performed between 2009 and 2013 were reviewed to identify the prevalence of obesity and elevated BP and examine relationships between the type of sports played, participation in multiple sports versus a single sport, and the athlete’s body weight and body mass index (BMI). Results: The prevalence of obesity was 23.5%. There was a significant association (P < .001) between the number of sports played by the student and BMI. The risk of obesity among single-sport athletes was more than 2-fold the risk (relative risk [RR], 2.13) compared with ≥3-sport athletes and 1.42 times greater compared with 2-sport athletes (RR, 1.42). The prevalence of elevated BP was 21.2%. There was a significant association (P < .001) between the number of sports played by the student and elevated BP. The risk of elevated BP among single-sport athletes was 1.59 times greater (RR, 1.59) than ≥3-sport athletes and 1.30 times greater compared with 2-sport athletes (RR, 1.30). Finally, obese students were 2.40 times more likely to have elevated BP compared with nonobese students (P < .001). Conclusion: The result of this study confirms the progressive nature of the obesity epidemic and identifies the contribution of obesity to the worsening cardiometabolic profiles in student athletes. The study also identifies that participation in multiple sports and running sports decreases the individual’s risk for obesity and hypertension. Clinical Relevance: The present study emphasizes the importance of screening for obesity and elevated blood pressure during the athlete’s preparticipation physical examination. PMID:26962540

Effects of post-hatch brooding temperature on broiler behavior, welfare, and growth.

PubMed

Henriksen, S; Bilde, T; Riber, A B

2016-10-01

An elevated brooding temperature during the first wk post hatch of broilers may potentially increase activity levels and reduce welfare problems in terms of non- and slow-starters, lameness, and contact dermatitis. The effects of an elevated brooding temperature the first 7 d post hatch on behavior, welfare, and growth of Ross 308 broilers were investigated. Groups of 28 broilers (14 males and 14 females) were distributed in a balanced way according to their hatching weight (below or above mean), the age of parent breeders (28 or 50 wk of age), and initial brooding temperature (normal 33°C; warm: 37°C) resulting in 8 different treatment groups. Behavioral data were collected on d zero to 6 of age, data on body weight on d zero, 7, 21, and 34 of age, and data on gait and contact dermatitis on d 21 and 34 of age. An elevated brooding temperature resulted in increased body temperature of broilers 5 h after placement (39.9 ± 0.04°C vs. 39.1 ± 0.04°C; P < 0.0001) whereas no difference was found 24 h after placement (P = 0.35). Broilers reared with elevated brooding temperature initiated feeding and drinking earlier, apart from broilers with low hatching weight from old parent breeders (P < 0.0001). They also showed higher activity levels from d one to 6 of age (P < 0.0001) and a higher inter-individual distance at d zero and one of age (P < 0.0001). Broilers with a high hatching weight reared at normal brooding temperature had a higher prevalence of hock burns at d 34 of age (P = 0.001). Broilers reared at elevated brooding temperature had lower body weight at d 7 of age (P < 0.0001); however, no difference appeared from d 21 of age (P = 0.58). No effect of brooding temperature was found on body weight uniformity (P = 0.81). In conclusion, the welfare of broilers may be improved from an elevated brooding temperature the first 7 d post hatch without affecting body weight uniformity and final body weight. © 2016 Poultry Science Association Inc.

Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

PubMed

Vásquez-Elizondo, Román Manuel; Enríquez, Susana

2016-01-07

In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification.

Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

NASA Astrophysics Data System (ADS)

Vásquez-Elizondo, Román Manuel; Enríquez, Susana

2016-01-01

In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification.

Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm newborns

PubMed Central

Yanni, Diana; Korzeniewski, Steven J.; Allred, Elizabeth N.; Fichorova, Raina N.; O'Shea, T. Michael; Kuban, Karl; Dammann, Olaf; Leviton, Alan

2017-01-01

Background Preterm newborns exposed to intrauterine inflammation are at increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone. Methods We defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders. Results The risk of white matter damage was increased when placental inflammation was followed by sustained elevation of CRP or ICAM-1. We found the same for spastic cerebral palsy when placental inflammation was followed by elevation of TNF-α or IL-8. The presence of both placental inflammation and elevated levels of IL-6, TNF-α, or ICAM-1 was associated with an increased risk for microcephaly. Conclusion Compared to a single hit, two inflammatory hits are associated with stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years. PMID:28549057

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG).

PubMed

Shimada, Akiko; Cairns, Brian E; Vad, Nynne; Ulriksen, Kathrine; Pedersen, Anne Marie Lynge; Svensson, Peter; Baad-Hansen, Lene

2013-01-24

A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

IL-6 signalling in patients with acute ST-elevation myocardial infarction

PubMed Central

Ritschel, Vibeke N.; Seljeflot, Ingebjørg; Arnesen, Harald; Halvorsen, Sigrun; Weiss, Thomas; Eritsland, Jan; Andersen, Geir Ø

2013-01-01

Cytokines of the IL-6 family have been related to infarct size and prognosis in patients with myocardial infarction. The aims of the present study were to elucidate possible associations between myocardial necrosis and left ventricular impairment and members of the IL-6 transsignalling system including soluble (s) IL-6R and (s) glycoprotein 130 (sgp130) in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. In blood samples from 1028 STEMI patients, collected in-hosptial, we found significant correlations between peak TnT and IL-6 and CRP (p < 0.001, all) and between IL-6 and CRP and LV ejection fraction and NT-proBNP (p < 0.001, all). On the contrary, no significant associations were found between peak TnT and sgp130 or sIL-6R. Furthermore sgp130 was significantly elevated in diabetic patients and also associated with the glucometabolic state. In conclusion, circulating levels of IL-6 and CRP, but not the soluble forms of the receptor (sIL-6R) or the receptor signalling subunit (sgp130) were associated with the extent of myocardial necrosis. The biological importance of the IL-6/gp130-mediated signalling pathways in patients with acute myocardial infarction and dysglycemia should be further elucidated. PMID:24707455

Persistent Exposure to Arsenic via Drinking Water in Rural Bangladesh Despite Major Mitigation Efforts

PubMed Central

Gardner, Renee; Hamadani, Jena; Grandér, Margaretha; Tofail, Fahmida; Nermell, Barbro; Palm, Brita; Kippler, Maria

2011-01-01

Objectives. Elevated arsenic levels in tube-well water in Bangladesh have prompted extensive mitigation projects. We evaluated the effectiveness of long-term mitigation efforts by longitudinally measuring arsenic exposure in pregnant women and their children, the most susceptible population groups. Methods. The study was nested in a population-based nutrition intervention in Matlab, Bangladesh. Mother–child pairs (n = 1951) were followed from 2001 to 2003, beginning in early gestation and continuing to 5 years postpartum. We measured arsenic concentrations in urine (U-As) of the 5-year-old children by using high-performance liquid chromatography online with hydride generation and inductively coupled plasma mass spectrometry and compared them with earlier childhood U-As and maternal U-As during pregnancy. Results. Children had elevated U-As at 5 years old (median = 51 μg/L, 5th–95th percentiles = 16–355 μg/L), and U-As distribution was similar to that observed in the mothers during gestation. Children's U-As at 5 years old significantly correlated with their U-As at 1.5 years old and to maternal U-As during early and late gestation. Conclusions. Despite major mitigation efforts, arsenic exposure remains highly elevated in rural Bangladesh. Further mitigation strategies are required and must be rigorously evaluated for long-term efficacy. PMID:21778503

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

PubMed

Larrieta-Carrasco, Elena; Flores, Yvonne N; Macías-Kauffer, Luis R; Ramírez-Palacios, Paula; Quiterio, Manuel; Ramírez-Salazar, Eric G; León-Mimila, Paola; Rivera-Paredez, Berenice; Cabrera-Álvarez, Guillermo; Canizales-Quinteros, Samuel; Zhang, Zuo-Feng; López-Pérez, Tania V; Salmerón, Jorge; Velázquez-Cruz, Rafael

2018-02-01

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9-12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1-4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypsographic demography: The distribution of human population by altitude

PubMed Central

Cohen, Joel E.; Small, Christopher

1998-01-01

The global distribution of the human population by elevation is quantified here. As of 1994, an estimated 1.88 × 109 people, or 33.5% of the world’s population, lived within 100 vertical meters of sea level, but only 15.6% of all inhabited land lies below 100 m elevation. The median person lived at an elevation of 194 m above sea level. Numbers of people decreased faster than exponentially with increasing elevation. The integrated population density (IPD, the number of people divided by the land area) within 100 vertical meters of sea level was significantly larger than that of any other range of elevations and represented far more people. A significant percentage of the low-elevation population lived at moderate population densities rather than at the highest densities of central large cities. Assessments of coastal hazards that focus only on large cities may substantially underestimate the number of people who could be affected. PMID:9826643

Familial aggregation of circulating C-reactive protein in polycystic ovary syndrome.

PubMed

Sasidevi, Arunachalam; Vellanki, Priyathama; Kunselman, Allen R; Raja-Khan, Nazia; Dunaif, Andrea; Legro, Richard S

2013-03-01

What is the heritability of C-reactive protein (CRP) levels in women with polycystic ovary syndrome (PCOS) and their first-degree relatives? Women with PCOS and their siblings are more likely to have elevated CRP levels when both of their parents have elevated CRP. This PCOS family-based study indicates that CRP levels are likely a heritable trait. Previous studies have established that an elevated blood level of CRP is variably present in women with PCOS, and may be present independent of metabolic status. A familial based phenotyping study consisting of 81 families comprised of PCOS patients and their first-degree relatives for 305 subjects. Study conducted at an academic health center. An elevated CRP level was defined as >28.6 nmol/l. To account for familial clustering, generalized estimating equations with a logit link were used to model the association between elevated CRP levels in patients with PCOS and their siblings with their parental group (A = neither parent with elevated CRP; B = one parent with elevated CRP; C= both parents with elevated CRP), adjusting for gender, age and BMI of the offspring. We did additional heritability analyses by using a variance component estimation method for CRP levels, adjusting for sex, age and BMI. We observed elevated CRP levels in 94% of the offspring in group C, 45% in group B and 10% in group A after adjusting for age, gender and BMI of the offspring. The median BMI of the offspring in group A, B and C were 30.0, 28.7 and 31.2 kg/m², respectively. Heritability estimates of CRP levels ranged from 0.75 to 0.83 and remained significant after excluding for type 2 diabetes mellitus. Our small sample size increases the possibility of a type 1 error. This is a single report in an adequately powered but limited sample size study identifying the strong heritability of CRP levels. Replication in other large family cohorts is necessary. These findings support the concept that there is an increased cardiovascular disease risk profile in families of women with PCOS. This research was supported by National Institutes of Health grants U54HD-034449 and P50 HD044405 (A.D.). Priyathama Vellanki is supported in part by NIH/NIDDK Training Grant T32 DK007169.

Over-expressing the C3 photosynthesis cycle enzyme Sedoheptulose-1-7 Bisphosphatase improves photosynthetic carbon gain and yield under fully open air CO2 fumigation (FACE)

PubMed Central

2011-01-01

Background Biochemical models predict that photosynthesis in C3 plants is most frequently limited by the slower of two processes, the maximum capacity of the enzyme Rubisco to carboxylate RuBP (Vc,max), or the regeneration of RuBP via electron transport (J). At current atmospheric [CO2] levels Rubisco is not saturated; consequently, elevating [CO2] increases the velocity of carboxylation and inhibits the competing oxygenation reaction which is also catalyzed by Rubisco. In the future, leaf photosynthesis (A) should be increasingly limited by RuBP regeneration, as [CO2] is predicted to exceed 550 ppm by 2050. The C3 cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC 3.1.3.17) has been shown to exert strong metabolic control over RuBP regeneration at light saturation. Results We tested the hypothesis that tobacco transformed to overexpressing SBPase will exhibit greater stimulation of A than wild type (WT) tobacco when grown under field conditions at elevated [CO2] (585 ppm) under fully open air fumigation. Growth under elevated [CO2] stimulated instantaneous A and the diurnal photosynthetic integral (A') more in transformants than WT. There was evidence of photosynthetic acclimation to elevated [CO2] via downregulation of Vc,max in both WT and transformants. Nevertheless, greater carbon assimilation and electron transport rates (J and Jmax) for transformants led to greater yield increases than WT at elevated [CO2] compared to ambient grown plants. Conclusion These results provide proof of concept that increasing content and activity of a single photosynthesis enzyme can enhance carbon assimilation and yield of C3 crops grown at [CO2] expected by the middle of the 21st century. PMID:21884586

Pulse oximetry in the evaluation of peripheral vascular disease.

PubMed

Jawahar, D; Rachamalla, H R; Rafalowski, A; Ilkhani, R; Bharathan, T; Anandarao, N

1997-08-01

The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD) was investigated. In addition, the value of elevating the limb to improve the sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse oximetry reading in the toes were obtained in 40 young, healthy volunteers and in 40 randomly selected patients referred to the vascular investigation laboratory over a period of two months. All 40 healthy volunteers had normal pulse oximetry readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry readings were either normal or not detected at all. Since there was no gradation in decrease in the pulse oximetry reading with severity of disease or with elevation of the patient's lower extremity, an absent or no reading was considered as an abnormal result from the test. The frequency of abnormal pulse oximetry readings increased significantly in groups with abnormal ankle-brachial pressure index (ABPI) and also varied significantly with elevation of the patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9), pulse oximetry readings were normal in all. However, in patients with moderate PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry readings and 16% had an abnormal reading at baseline level (flat). An additional 12% of the lower limbs in this group had an abnormal reading on elevation of the limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients' lower limbs had an abnormal reading at baseline and an additional 23% had an abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse oximetry was not a sensitive test for detecting early PVD.

Diagnosis of neurosyphilis: appraisal of clinical caseload.

PubMed Central

Rodgers, C A; Murphy, S

1997-01-01

OBJECTIVES: To review the management of a cohort of patients with positive treponemal serology and psychiatric and/or neurological disorders. METHODS: A retrospective case note review of 172 patients with positive treponemal serology attending the Patrick Clement's Clinic, Central Middlesex Hospital between December 1990 and November 1995 was performed. RESULTS: 101 men and 71 women were new attenders diagnosed with positive treponemal serology. A neurological problem was identified in 27 patients (12 women and 15 men) with psychiatric and/or neurological disorders, of whom 20 (six women and 14 men) underwent investigation of the cerebrospinal fluid (CSF). With the medical history and results of CSF-RPR and FTA tests, white cell count (WCC), and total protein level in the CSF, 10 patients (eight men and two women) were diagnosed with likely neurosyphilis and 17 with neurological disorders not thought to be caused by syphilis. The clinical features in those having neurosyphilis were sensorineural hearing loss (n = 5) and tabes dorsalis (n = 5). In the seven patients diagnosed with neurosyphilis who underwent CSF examination one patient had a reactive CSF-FTA, elevated protein, and elevated WCC; one patient had a reactive CSF-FTA and RPR with elevated protein; the total protein only was elevated in three cases and the WCC elevated in one case. Nine of the 10 patients with neurosyphilis received adequate neurosyphilitic treatment; one patient was lost to follow up. CONCLUSIONS: The management of patients with positive treponemal serology and psychiatric and/or neurological disorders was consistent. Patients with suspected neurosyphilis or patients with neurological signs compatible with neurosyphilis (who did not undergo CSF examination) were treated with adequate neurosyphilitic therapy. PMID:9582475

Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests

Treesearch

Alan F. Talhelm; Kurt S. Pregitzer; Mark E. Kubiske; Donald R. Zak; Courtney E. Campany; Andrew J. Burton; Richard E. Dickson; George R. Hendrey; J. G. Isebrands; Keith F. Lewin; John Nagy; David F. Karnosky

2014-01-01

Three young northern temperate forest communities in the north-central United States were exposed to factorial combinations of elevated carbon dioxide (CO2) and tropospheric ozone (O3) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment...

USING 30-METER RESOLUTION DIGITAL ELEVATION DATA FOR BASIN ANALYSIS-A PRACTICAL UTILIZATION OF USGS 24K DIGITAL ELEVATION DATA-COMPLICATIONS AND SOLUTIONS. (R826595)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Consideration of vertical uncertainty in elevation-based sea-level rise assessments: Mobile Bay, Alabama case study

USGS Publications Warehouse

Gesch, Dean B.

2013-01-01

The accuracy with which coastal topography has been mapped directly affects the reliability and usefulness of elevationbased sea-level rise vulnerability assessments. Recent research has shown that the qualities of the elevation data must be well understood to properly model potential impacts. The cumulative vertical uncertainty has contributions from elevation data error, water level data uncertainties, and vertical datum and transformation uncertainties. The concepts of minimum sealevel rise increment and minimum planning timeline, important parameters for an elevation-based sea-level rise assessment, are used in recognition of the inherent vertical uncertainty of the underlying data. These concepts were applied to conduct a sea-level rise vulnerability assessment of the Mobile Bay, Alabama, region based on high-quality lidar-derived elevation data. The results that detail the area and associated resources (land cover, population, and infrastructure) vulnerable to a 1.18-m sea-level rise by the year 2100 are reported as a range of values (at the 95% confidence level) to account for the vertical uncertainty in the base data. Examination of the tabulated statistics about land cover, population, and infrastructure in the minimum and maximum vulnerable areas shows that these resources are not uniformly distributed throughout the overall vulnerable zone. The methods demonstrated in the Mobile Bay analysis provide an example of how to consider and properly account for vertical uncertainty in elevation-based sea-level rise vulnerability assessments, and the advantages of doing so.

The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients.

PubMed

Lee, Bun-Hee; Kim, Yong-Ku

2006-06-01

Hyperprolactinemia can be induced by dopamine D2 receptor-binding drugs such as antipsychotic drugs. The author investigated the relationship between changes in prolactin (PRL) and clinical efficacy of risperidone. In this study, 27 acute psychotic inpatients completed a 12-week trial of risperidone. At baseline and at 2, 4, 8, and 12 weeks after beginning medication, the author measured PRL, assessed hyperprolactinemia-related symptoms, and administered the Brief Psychotic Rating Scale (BPRS). Risperidone treatment significantly elevated serum PRL level (range: 26.9 ng/ml-320.0 ng/ml). The increases of PRL in females were higher than males. The changes in serum PRL levels were not significantly correlated with the improvements in total BPRS scores. PRL-related symptoms such as irregular menstruation, galactorrhea, or erectile dysfunction occurred in nine subjects (7 females and 2 males) whose serum PRL levels increase very highly after 2 weeks of risperidone. In conclusion, our study suggests that the changes in serum PRL levels were not significantly correlated with clinical efficacy of risperidone.

Tidal Marshes across a Chesapeake Bay Subestuary Are Not Keeping up with Sea-Level Rise

PubMed Central

Beckett, Leah H.; Baldwin, Andrew H.; Kearney, Michael S.

2016-01-01

Sea-level rise is a major factor in wetland loss worldwide, and in much of Chesapeake Bay (USA) the rate of sea-level rise is higher than the current global rate of 3.2 mm yr-1 due to regional subsidence. Marshes along estuarine salinity gradients differ in vegetation composition, productivity, decomposition pathways, and sediment dynamics, and may exhibit different responses to sea-level rise. Coastal marshes persist by building vertically at rates at or exceeding regional sea-level rise. In one of the first studies to examine elevation dynamics across an estuarine salinity gradient, we installed 15 surface elevation tables (SET) and accretion marker-horizon plots (MH) in tidal freshwater, oligohaline, and brackish marshes across a Chesapeake Bay subestuary. Over the course of four years, wetlands across the subestuary decreased 1.8 ± 2.7 mm yr-1 in elevation on average, at least 5 mm yr-1 below that needed to keep pace with global sea-level rise. Elevation change rates did not significantly differ among the marshes studied, and ranged from -9.8 ± 6.9 to 4.5 ± 4.3 mm yr-1. Surface accretion of deposited mineral and organic matter was uniformly high across the estuary (~9–15 mm yr-1), indicating that elevation loss was not due to lack of accretionary input. Position in the estuary and associated salinity regime were not related to elevation change or surface matter accretion. Previous studies have focused on surface elevation change in marshes of uniform salinity (e.g., salt marshes); however, our findings highlight the need for elevation studies in marshes of all salinity regimes and different geomorphic positions, and warn that brackish, oligohaline, and freshwater tidal wetlands may be at similarly high risk of submergence in some estuaries. PMID:27467784

Feed intake and behavior of dairy goats when offered an elevated feed bunk.

PubMed

Neave, Heather W; von Keyserlingk, Marina A G; Weary, Daniel M; Zobel, Gosia

2018-04-01

Goats are browsers and select vegetation at various heights when foraging. On commercial farms, dairy goats are typically fed from low-level feed bunks. The objective of this study was to determine how feed intake and feeding behavior vary when goats are offered feed at variable heights, with the potential of evaluating the benefits of offering an elevated feeder to dairy goats. Thirteen Saanen X dairy goats were housed in a home pen with a lying area of wood shavings, where they were pre-exposed for 24 d to 3 feeder heights designed to result in differences in head height while feeding: floor level (head lowered relative to body), head level (head level relative to body), and elevated level (head and neck angled upward). Nine groups of 3 goats each were randomly selected and housed for 24 h in a test pen identical to the home pen except that it contained 1 of each of the 3 feeder heights. Each feeder contained ad libitum chopped alfalfa silage and a top-dressed corn-based supplement, refreshed twice daily. Refusals from inside and under each feeder were weighed to calculate intake. Feed intake increased with increasing feeder height (mean ± SE; 0.18, 0.29, and 0.34 ± 0.04 kg of DM/goat for floor-level, head-level, and elevated-level feeders, respectively). Total feeding time did not vary with feeder height, but feeding rate tended to be faster at the elevated-level feeder (14.5 ± 2.1 g of DM/min) compared with head-level (9.2 ± 2.3 g of DM/min) and floor-level (8.9 ± 2.1 g of DM/min) feeders. Goats visited the floor-level feeder (36.4 ± 8.4 visits/goat) less than the head-level (79.4 ± 8.4 visits/goat) and elevated-level (74.8 ± 8.4 visits/goat) feeders. The number of displacements per minute of feeding time (physical removal of another goat from the feeding place) was greater at the elevated-level feeder (0.46 ± 0.06 displacements/min) compared with the floor-level feeder (0.23 ± 0.06 displacements/min) and tended to differ from the head-level feeder (0.27 ± 0.06 displacements/min). We conclude that goats eat more from an elevated feeder and compete more to access this feeder. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

An In Vivo Analysis of the Effect of Season-Long Open-Air Elevation of Ozone to Anticipated 2050 Levels on Photosynthesis in Soybean1

PubMed Central

Morgan, Patrick B.; Bernacchi, Carl J.; Ort, Donald R.; Long, Stephen P.

2004-01-01

Rising atmospheric carbon dioxide concentration ([CO2]) is widely recognized, but less appreciated is a concomitant rise in tropospheric ozone concentration ([O3]). In industrialized countries, [O3] has risen by 0.5% to 2.5% per year. Tropospheric [O3] is predicted to reach a global mean of >60 nL L−1 by 2050 with greater averages locally. Previous studies in enclosures suggest that this level of [O3] will decrease leaf photosynthesis, thereby limiting growth and yield of Glycine max L. Merr. SoyFACE (Soybean Free Air gas Concentration Enrichment) is the first facility to elevate atmospheric [O3] (approximately 1.2× current) in replicated plots under completely open-air conditions within an agricultural field. Measurements of gas exchange (assimilation versus light and assimilation versus intercellular [CO2]) were made on excised leaves from control and treatment plots (n = 4). In contrast to expectations from previous chamber studies, elevated [O3] did not alter light-saturated photosynthesis (Asat, P = 0.09), carboxylation capacity (Vc,max, P = 0.82), or maximum electron transport (Jmax, P = 0.66) for the topmost most recently fully expanded leaf at any stage of crop development. Leaves formed during the vegetative growth stage did not show a significant ozone-induced loss of photosynthetic capacity as they aged. Leaves formed during flowering did show a more rapid loss of photosynthetic capacity as they aged in elevated [O3]. Asat, Vc,max, and Jmax (P = 0.04, 0.004, and 0.002, respectively) were decreased 20% to 30% by treatment with ozone. This is noteworthy since these leaves provide photosynthate to the developing grain. In conclusion, a small (approximately 20%) increase in tropospheric [O3] did not significantly alter photosynthetic capacity of newly expanded leaves, but as these leaves aged, losses in photosynthetic carbon assimilation occurred. PMID:15299126

A Behavioral Measure of Costly Helping: Replicating and Extending the Association with Callous Unemotional Traits in Male Adolescents

PubMed Central

Sakai, Joseph T.; Dalwani, Manish S.; Mikulich-Gilbertson, Susan K.; McWilliams, Shannon K.; Raymond, Kristen M.; Crowley, Thomas J.

2016-01-01

Background Some conduct-disordered youths have high levels of callous unemotional traits and meet the DSM-5’s “with limited prosocial emotions” (LPE) specifier. These youths often do aggressive, self-benefitting acts that cost others. We previously developed a task, the AlAn’s game, which asks participants to repeatedly decide whether to accept or reject offers in which they will receive money but a planned charity donation will be reduced. In our prior work, more "costly helping" (i.e., rejecting the offered money and protecting the donation) was associated with lower callous unemotional traits. Here we extend that prior work in a larger sample of adolescent male patients with serious conduct problems and controls, and test whether this association is mediated specifically by a Moral Elevation response (i.e., a positive emotional response to another’s act of virtue). Methods The adolescent male participants were: 45 patients (23 with LPE) and 26 controls, who underwent an extensive phenotypic assessment including a measure of Moral Elevation. About 1 week later participants played the AlAn’s game. Results All AlAn’s game outcomes demonstrated significant group effects: (1) money taken for self (p = 0.02); (2) money left in the charitable donation (p = 0.03); and, (3) costly helping (p = 0.047). Controls took the least money and did the most costly helping, while patients with LPE took the most money and did the least costly helping. Groups also significantly differed in post-stimulus Moral Elevation scores (p = 0.005). Exploratory analyses supported that the relationship between callous unemotional traits and costly helping on the AlAn’s game may be mediated in part by differences in Moral Elevation. Conclusions The AlAn's game provides a standardized behavioral measure associated with callous unemotional traits. Adolescents with high levels of callous unemotional traits engage in fewer costly helping behaviors, and those differences may be related to blunting of positive emotional responses. PMID:26977935

Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkB, Akt, and Glut-2 in livers of Zucker diabetic fatty rats

PubMed Central

Jain, Sushil K.; Croad, Jennifer L.; Velusamy, Thirunavukkarasu; Rains, Justin L.; Bull, Rebeca

2011-01-01

Aim Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in ZDF rats. Methods Starting at the age of 6 wks, ZDF rats were supplemented orally (daily gavages for 8 more wks) with saline-placebo (D) or chromium (400µg Cr/KgBW) as chromium-dinicocysteinate (CDNC), chromium-dinicotinate (CDN), or chromium-picolinate (CP) or equimolar L-cysteine (LC, img/Kg BW), and fed Purina 5008 diet for 8 wks. ZDF rats of 6 wks age before any supplementations and onset of diabetes were considered as baseline (BL). Results D rats showed elevated levels of fasting blood glucose, HbA1, CRP, MCP-1, ICAM-1 and oxidative stress (LP) and lower adiponectin and vitamin C, when compared to BL rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA1, CRP, MCP-1, ICAM-1 and LP and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkB, Akt and GLUT-2 levels were decreased, IRS-1 activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. Conclusions CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats. PMID:20306473

A study of the prostate, androgens and sexual activity of male rats

PubMed Central

Hernandez, Maria Elena; Soto-Cid, Abraham; Aranda-Abreu, Gonzalo E; Díaz, Rosaura; Rojas, Fausto; Garcia, Luis I; Toledo, Rebeca; Manzo, Jorge

2007-01-01

Background The prostate is a sexual gland that produces important substances for the potency of sperm to fertilize eggs within the female reproductive tract, and is under complex endocrine control. Taking advantage of the peculiar behavioral pattern of copulating male rats, we developed experimental paradigms to determine the influence of sexual behavior on the level of serum testosterone, prostate androgen receptors, and mRNA for androgen receptors in male rats displaying up to four consecutive ejaculations. Methods The effect of four consecutive ejaculations was investigated by determining levels of (i) testosterone in serum by solid phase RIA, (ii) androgen receptors at the ventral prostate with Western Blots, and (iii) androgen receptors-mRNA with RT-PCR. Data were analyzed with a one-way ANOVA followed by a post hoc application of Dunnett's test if required. Results The constant execution of sexual behavior did not produce any change in the weight of the ventral prostate. Serum testosterone increased after the second ejaculation, and remained elevated even after four ejaculations. The androgen receptor at the ventral prostate was higher after the first to third ejaculations, but returned suddenly to baseline levels after the fourth ejaculation. The level of mRNA increased after the first ejaculation, continued to increase after the second, and reached the highest peak after the third ejaculation; however, it returned suddenly to baseline levels after the fourth ejaculation. Conclusion Four consecutive ejaculations by sexually experienced male rats had important effects on the physiological responses of the ventral prostate. Fast responses were induced as a result of sexual behavior that involved an increase and decrease in androgen receptors after one and four ejaculations, respectively. However, a progressive response was observed in the elevation of mRNA for androgen receptors, which also showed a fast decrease after four ejaculations. All of these changes with the prostate gland occurred in the presence of a sustained elevation of testosterone in the serum that started after two ejaculations. A consideration of these fast-induced changes suggests that the nerve supply plays a key role in prostate physiology during the sexual behavior of male rats. PMID:17367532

The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection

PubMed Central

Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre

2016-01-01

Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377

Drought response transcriptomes are altered in poplar with reduced tonoplast sucrose transporter expression

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

Xue, Liang-Jiao; Frost, Christopher J.; Tsai, Chung-Jui

Transgenic Populus tremula x alba (717-1B4) plants with reduced expression of a tonoplast sucrose efflux transporter, PtaSUT4, exhibit reduced shoot growth compared to wild type (WT) under sustained mild drought. The present study was undertaken to determine whether SUT4-RNAi directly or indirectly altered poplar predisposition and/or response to changes in soil water availability. While sucrose and hexose levels were constitutively elevated in shoot organs, expression responses to drought were most altered in the root tips of SUT4-RNAi plants. Prior to any drought treatment, constitutively elevated transcript levels of abscisic acid biosynthetic genes and bark/vegetative storage proteins suggested altered metabolism inmore » root tips of RNAi plants. Stronger drought-stimulation of stress-inducible genes encoding late-embryogenesis-abundant proteins in transgenic roots was consistent with increased vulnerability to soil drying. Transcript evidence suggested an RNAi effect on intercellular water trafficking by aquaporins in stem xylem during soil drying and recovery. Co-expression network analysis predicted altered integration of abscisic acid sensing/signaling with ethylene and jasmonate sensing/signaling in RNAi compared to WT roots. The overall conclusion is that steepened shoot-root sugar gradient in RNAi plants increased sensitivity of root tips to decreasing soil water availability.« less

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

PubMed

Zaahkouk, A M S; Abdel Aziz, M T; Rezq, A M; Atta, H M; Fouad, H H; Ahmed, H H; Sabry, D; Yehia, M H

2015-01-01

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κβ and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κβ, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κβ, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Drought response transcriptomes are altered in poplar with reduced tonoplast sucrose transporter expression

DOE PAGES

Xue, Liang-Jiao; Frost, Christopher J.; Tsai, Chung-Jui; ...

2016-09-19

Transgenic Populus tremula x alba (717-1B4) plants with reduced expression of a tonoplast sucrose efflux transporter, PtaSUT4, exhibit reduced shoot growth compared to wild type (WT) under sustained mild drought. The present study was undertaken to determine whether SUT4-RNAi directly or indirectly altered poplar predisposition and/or response to changes in soil water availability. While sucrose and hexose levels were constitutively elevated in shoot organs, expression responses to drought were most altered in the root tips of SUT4-RNAi plants. Prior to any drought treatment, constitutively elevated transcript levels of abscisic acid biosynthetic genes and bark/vegetative storage proteins suggested altered metabolism inmore » root tips of RNAi plants. Stronger drought-stimulation of stress-inducible genes encoding late-embryogenesis-abundant proteins in transgenic roots was consistent with increased vulnerability to soil drying. Transcript evidence suggested an RNAi effect on intercellular water trafficking by aquaporins in stem xylem during soil drying and recovery. Co-expression network analysis predicted altered integration of abscisic acid sensing/signaling with ethylene and jasmonate sensing/signaling in RNAi compared to WT roots. The overall conclusion is that steepened shoot-root sugar gradient in RNAi plants increased sensitivity of root tips to decreasing soil water availability.« less

Triggering Interventions for Influenza: The ALERT Algorithm

PubMed Central

Reich, Nicholas G.; Cummings, Derek A. T.; Lauer, Stephen A.; Zorn, Martha; Robinson, Christine; Nyquist, Ann-Christine; Price, Connie S.; Simberkoff, Michael; Radonovich, Lewis J.; Perl, Trish M.

2015-01-01

Background. Early, accurate predictions of the onset of influenza season enable targeted implementation of control efforts. Our objective was to develop a tool to assist public health practitioners, researchers, and clinicians in defining the community-level onset of seasonal influenza epidemics. Methods. Using recent surveillance data on virologically confirmed infections of influenza, we developed the Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm, a method to identify the period of highest seasonal influenza activity. We used data from 2 large hospitals that serve Baltimore, Maryland and Denver, Colorado, and the surrounding geographic areas. The data used by ALERT are routinely collected surveillance data: weekly case counts of laboratory-confirmed influenza A virus. The main outcome is the percentage of prospective seasonal influenza cases identified by the ALERT algorithm. Results. When ALERT thresholds designed to capture 90% of all cases were applied prospectively to the 2011–2012 and 2012–2013 influenza seasons in both hospitals, 71%–91% of all reported cases fell within the ALERT period. Conclusions. The ALERT algorithm provides a simple, robust, and accurate metric for determining the onset of elevated influenza activity at the community level. This new algorithm provides valuable information that can impact infection prevention recommendations, public health practice, and healthcare delivery. PMID:25414260

Metabolic effects of polycystic ovary syndrome in adolescents

PubMed Central

Han, Yejin; Lee, Hye-Jin; Oh, Jee-Young; Sung, Yeon-Ah

2015-01-01

Purpose Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS. Methods Anthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI)-matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile. Results Hemoglobin, gamma-glutamyl transferase (r-GT), total cholesterol, low-density lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%. Conclusion PCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents. PMID:26512349

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

PubMed

Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

2007-03-01

Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. Copyright 2007 Prous Science.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Endocrine antecedents of polycystic ovary syndrome (PCOS) in fetal and infant prenatally androgenized female rhesus monkeys

PubMed Central

Abbott, David H; Barnett, Deborah K; Levine, Jon E; Padmanabhan, Vasantha; Dumesic, Daniel A; Jacoris, Steve; Tarantal, Alice F

2008-01-01

Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels mostly normalized, while serum androstenedione levels in PA infants were elevated. TP injections did not increase estrogen levels in the dams, PA fetuses and infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally-induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants, and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood. PMID:18385445

Effect of sulfonylureas administered centrally on the blood glucose level in immobilization stress model.

PubMed

Sharma, Naveen; Sim, Yun-Beom; Park, Soo-Hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

2015-05-01

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Evaluation of a childhood lead questionnaire in predicting elevated blood lead levels in a rural community.

PubMed

Muñiz, Marco A; Dundas, Robert; Mahoney, Martin C

2003-01-01

The accuracy of a lead screening questionnaire in predicting elevated blood lead levels was examined in a pediatric practice in a rural part of New York state. A retrospective chart review was used to collect data on children ages 9 to 24 months who presented for well-child visits. Children with both questionnaire and lead level results available in the chart were included in the study (n = 171). The mean blood lead level among all children was 1.6 microg/dl (median = 2.0 microg/dl, range 0 to 24 microg/dl). Four children (2.3%) had elevated lead levels (greater than 10 microg/dl), with levels for two of these children being greater than 20 microg/dl. Although our lead screening questionnaire was expanded from the standard 1991 CDC questionnaire by the inclusion of six additional items, it was not especially useful in predicting elevated blood lead levels above 10 microg/dl. However, the questionnaire exhibited some utility in predicting marked elevations in blood lead levels (over 20 microg/dl). Although results in other geographic areas might differ, the lead questionnaire may have value by enhancing parents' awareness of potential lead hazards in their children's environment and may prove to be more useful in areas of high risk to lead exposure.

Plasma Uric Acid Levels Correlate with Inflammation and Disease Severity in Malian Children with Plasmodium falciparum Malaria

PubMed Central

Lopera-Mesa, Tatiana M.; Mita-Mendoza, Neida K.; van de Hoef, Diana L.; Doumbia, Saibou; Konaté, Drissa; Doumbouya, Mory; Gu, Wenjuan; Traoré, Karim; Diakité, Seidina A. S.; Remaley, Alan T.; Anderson, Jennifer M.; Rodriguez, Ana; Fay, Michael P.; Long, Carole A.; Diakité, Mahamadou; Fairhurst, Rick M.

2012-01-01

Background Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs) and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of ‘parasite-derived’ UA stimulate immune cells to produce inflammatory cytokines in vitro. Methods and Findings We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β) in 470 Malian children presenting with uncomplicated malaria (UM), non-cerebral severe malaria (NCSM) or cerebral malaria (CM). UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09–1.35, n = 23, p = 0.0007) and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97–1.41, n = 9, p = 0.0890) compared to those with UM (median 4.60 mg/dl, n = 438). In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001), IL-10 (r = 0.242, p<0.00001), sTNFRII (r = 0.221, p<0.00001), MCP-1 (r = 0.220, p<0.00001), IL-8 (r = 0.147, p = 0.002), TNFα (r = 0.132, p = 0.006) and IP-10 (r = 0.120, p = 0.012)]. In 39 children, UA levels were 1.49-fold (95% CI 1.34–1.65; p<0.0001) higher during their malaria episode [geometric mean titer (GMT) 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl). Conclusions Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA and renal function may be involved. Defining pathogenic roles for parasite-derived UA precipitates, which we have not directly studied here, requires further investigation. Trial Registration ClinicalTrials.gov NCT00669084 PMID:23071567

Elevated voltage level I.sub.DDQ failure testing of integrated circuits

DOEpatents

Righter, Alan W.

1996-01-01

Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

Impact of elevated levels of atmospheric CO2 and herbivory on flavonoids of soybean (Glycine max Linnaeus).

PubMed

O'Neill, Bridget F; Zangerl, Arthur R; Dermody, Orla; Bilgin, Damla D; Casteel, Clare L; Zavala, Jorge A; DeLucia, Evan H; Berenbaum, May R

2010-01-01

Atmospheric levels of carbon dioxide (CO2) have been increasing steadily over the last century. Plants grown under elevated CO2 conditions experience physiological changes, particularly in phytochemical content, that can influence their suitability as food for insects. Flavonoids are important plant defense compounds and antioxidants that can have a large effect on leaf palatability and herbivore longevity. In this study, flavonoid content was examined in foliage of soybean (Glycine max Linnaeus) grown under ambient and elevated levels of CO2 and subjected to damage by herbivores in three feeding guilds: leaf skeletonizer (Popillia japonica Newman), leaf chewer (Vanessa cardui Linnaeus), and phloem feeder (Aphis glycines Matsumura). Flavonoid content also was examined in foliage of soybean grown under ambient and elevated levels of O3 and subjected to damage by the leaf skeletonizer P. japonica. The presence of the isoflavones genistein and daidzein and the flavonols quercetin and kaempferol was confirmed in all plants examined, as were their glycosides. All compounds significantly increased in concentration as the growing season progressed. Concentrations of quercetin glycosides were higher in plants grown under elevated levels of CO2. The majority of compounds in foliage were induced in response to leaf skeletonization damage but remained unchanged in response to non-skeletonizing feeding or phloem-feeding. Most compounds increased in concentration in plants grown under elevated levels of O3. Insects feeding on G. max foliage growing under elevated levels of CO2 may derive additional antioxidant benefits from their host plants as a consequence of the change in ratios of flavonoid classes. This nutritional benefit could lead to increased herbivore longevity and increased damage to soybean (and perhaps other crop plants) in the future.

Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip.

PubMed

Kolecki, Radek; Dammavalam, Vikalpa; Bin Zahid, Abdullah; Hubbard, Molly; Choudhry, Osamah; Reyes, Marleen; Han, ByoungJun; Wang, Tom; Papas, Paraskevi Vivian; Adem, Aylin; North, Emily; Gilbertson, David T; Kondziolka, Douglas; Huang, Jason H; Huang, Paul P; Samadani, Uzma

2018-03-01

OBJECTIVE The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip. METHODS Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP. RESULTS Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and ≥ 12 mm Hg was 0.798. To discriminate an ICP < 15 from ≥ 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from ≥ 20 mm Hg the AUC was 0.889. CONCLUSIONS Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

Is moral elevation an approach-oriented emotion?

PubMed Central

Van de Vyver, Julie; Abrams, Dominic

2017-01-01

Abstract Two studies were designed to test whether moral elevation should be conceptualized as an approach-oriented emotion. The studies examined the relationship between moral elevation and the behavioral activation and inhibition systems. Study 1 (N = 80) showed that individual differences in moral elevation were associated with individual differences in behavioral activation but not inhibition. Study 2 (N = 78) showed that an elevation-inducing video promoted equally high levels of approach orientation as an anger-inducing video and significantly higher levels of approach orientation than a control video. Furthermore, the elevation-inducing stimulus (vs. the control condition) significantly promoted prosocial motivation and this effect was sequentially mediated by feelings of moral elevation followed by an approach-oriented state. Overall the results show unambiguous support for the proposal that moral elevation is an approach-oriented emotion. Applied and theoretical implications are discussed. PMID:28191027

The Encoding of Sound Source Elevation in the Human Auditory Cortex.

PubMed

Trapeau, Régis; Schönwiesner, Marc

2018-03-28

Spatial hearing is a crucial capacity of the auditory system. While the encoding of horizontal sound direction has been extensively studied, very little is known about the representation of vertical sound direction in the auditory cortex. Using high-resolution fMRI, we measured voxelwise sound elevation tuning curves in human auditory cortex and show that sound elevation is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. We changed the ear shape of participants (male and female) with silicone molds for several days. This manipulation reduced or abolished the ability to discriminate sound elevation and flattened cortical tuning curves. Tuning curves recovered their original shape as participants adapted to the modified ears and regained elevation perception over time. These findings suggest that the elevation tuning observed in low-level auditory cortex did not arise from the physical features of the stimuli but is contingent on experience with spectral cues and covaries with the change in perception. One explanation for this observation may be that the tuning in low-level auditory cortex underlies the subjective perception of sound elevation. SIGNIFICANCE STATEMENT This study addresses two fundamental questions about the brain representation of sensory stimuli: how the vertical spatial axis of auditory space is represented in the auditory cortex and whether low-level sensory cortex represents physical stimulus features or subjective perceptual attributes. Using high-resolution fMRI, we show that vertical sound direction is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. In addition, we demonstrate that the shape of these tuning functions is contingent on experience with spectral cues and covaries with the change in perception, which may indicate that the tuning functions in low-level auditory cortex underlie the perceived elevation of a sound source. Copyright © 2018 the authors 0270-6474/18/383252-13$15.00/0.

Functional role of long-lived flowers in preventing pollen limitation in a high elevation outcrossing species

PubMed Central

Pacheco, Diego Andrés; Dudley, Leah S

2017-01-01

Abstract Low pollinator visitation in harsh environments may lead to pollen limitation which can threaten population persistence. Consequently, avoidance of pollen limitation is expected in outcrossing species subjected to habitually low pollinator service. The elevational decline in visitation rates on many high mountains provides an outstanding opportunity for addressing this question. According to a recent meta-analysis, levels of pollen limitation in alpine and lowland species do not differ. If parallel trends are manifested among populations of alpine species with wide elevational ranges, how do their uppermost populations contend with lower visitation? We investigated visitation rates and pollen limitation in high Andean Rhodolirium montanum. We test the hypothesis that lower visitation rates at high elevations are compensated for by the possession of long-lived flowers. Visitation rates decreased markedly over elevation as temperature decreased. Pollen limitation was absent at the low elevation site but did occur at the high elevation site. While initiation of stigmatic pollen deposition at high elevations was not delayed, rates of pollen arrival were lower, and cessation of pollination, as reflected by realized flower longevity, occurred later in the flower lifespan. Comparison of the elevational visitation decline and levels of pollen limitation indicates that flower longevity partially compensates for the lower visitation rates at high elevation. The functional role of flower longevity, however, was strongly masked by qualitative pollen limitation arising from higher abortion levels attributable to transference of genetically low-quality pollen in large clones. Stronger clonal growth at high elevations could counterbalance the negative fitness consequences of residual pollen limitation due to low visitation rates and/or difficult establishment under colder conditions. Visitation rates on the lower part of the elevational range greatly exceeded community rates recorded several decades ago when the planet was cooler. Current pollen limitation for some species in some habitats might underestimate historical levels. PMID:29225762

Base (100-year) flood elevations for selected sites in Marion County, Missouri

USGS Publications Warehouse

Southard, Rodney E.; Wilson, Gary L.

1998-01-01

The primary requirement for community participation in the National Flood Insurance Program is the adoption and enforcement of floodplain management requirements that minimize the potential for flood damages to new construction and avoid aggravating existing flooding conditions. This report provides base flood elevations (BFE) for a 100-year recurrence flood for use in the management and regulation of 14 flood-hazard areas designated by the Federal Emergency Management Agency as approximate Zone A areas in Marion County, Missouri. The one-dimensional surface-water flow model, HEC-RAS, was used to compute the base (100-year) flood elevations for the 14 Zone A sites. The 14 sites were located at U.S., State, or County road crossings and the base flood elevation was determined at the upstream side of each crossing. The base (100-year) flood elevations for BFE 1, 2, and 3 on the South Fork North River near Monroe City, Missouri, are 627.7, 579.2, and 545.9 feet above sea level. The base (100-year) flood elevations for BFE 4, 5, 6, and 7 on the main stem of the North River near or at Philadelphia and Palmyra, Missouri, are 560.5, 539.7, 504.2, and 494.4 feet above sea level. BFE 8 is located on Big Branch near Philadelphia, a tributary to the North River, and the base (100-year) flood elevation at this site is 530.5 feet above sea level. One site (BFE 9) is located on the South River near Monroe City, Missouri. The base (100-year) flood elevation at this site is 619.1 feet above sea level. Site BFE 10 is located on Bear Creek near Hannibal, Missouri, and the base (100-year) elevation is 565.5 feet above sea level. The four remaining sites (BFE 11, 12, 13, and 14) are located on the South Fabius River near Philadelphia and Palmyra, Missouri. The base (100-year) flood elevations for BFE 11, 12, 13, and 14 are 591.2, 578.4, 538.7, and 506.9 feet above sea level.