bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric Oxide Scavenging by Red Blood Cell Microparticles and Cell-Free Hemoglobin as a Mechanism for the Red Cell Storage Lesion
Authors: Donadee Chenell , Raat Nicolaas J.H. , Kanias Tamir , Tejero Jesús , Lee Janet S. , Kelley Eric E. , Zhao Xuejun , Liu Chen , Reynolds Hannah , Azarov Ivan , Frizzell Sheila , Meyer E. Michael , Donnenberg Albert D. , Qu Lirong , Triulzi Darrel , Kim-Shapiro Daniel B. , Gladwin Mark T. 
Published: July 2011

Background—
Intravascular red cell hemolysis impairs nitric oxide (NO)–redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood.

Methods and Results—
We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 μmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis.

Conclusions—
The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis.
Altered Mitochondrial Dynamics Contributes to Endothelial Dysfunction in Diabetes Mellitus
Authors: Shenouda Sherene M. , Widlansky Michael E. , Chen Kai , Xu Guoquan , Holbrook Monika , Tabit Corey E. , Hamburg Naomi M. , Frame Alissa A. , Caiano Tara L. , Kluge Matthew A. , Duess Mai-Ann , Levit Aaron , Kim Brian , Hartman Mor-Li , Joseph Lija , Shirihai Orian S. , Vita Joseph A. 
Published: July 2011

Background—
Endothelial dysfunction contributes to the development of atherosclerosis in patients with diabetes mellitus, but the mechanisms of endothelial dysfunction in this setting are incompletely understood. Recent studies have shown altered mitochondrial dynamics in diabetes mellitus with increased mitochondrial fission and production of reactive oxygen species. We investigated the contribution of altered dynamics to endothelial dysfunction in diabetes mellitus.

Methods and Results—

We observed mitochondrial fragmentation (
P
=0.002) and increased expression of fission-1 protein (Fis1;
P
<0.0001) in venous endothelial cells freshly isolated from patients with diabetes mellitus (n=10) compared with healthy control subjects (n=9). In cultured human aortic endothelial cells exposed to 30 mmol/L glucose, we observed a similar loss of mitochondrial networks and increased expression of Fis1 and dynamin-related protein-1 (Drp1), proteins required for mitochondrial fission. Altered mitochondrial dynamics was associated with increased mitochondrial reactive oxygen species production and a marked impairment of agonist-stimulated activation of endothelial nitric oxide synthase and cGMP production. Silencing Fis1 or Drp1 expression with siRNA blunted high glucose–induced alterations in mitochondrial networks, reactive oxygen species production, endothelial nitric oxide synthase activation, and cGMP production. An intracellular reactive oxygen species scavenger provided no additional benefit, suggesting that increased mitochondrial fission may impair endothelial function via increased reactive oxygen species.

Conclusion—
These findings implicate increased mitochondrial fission as a contributing mechanism for endothelial dysfunction in diabetic states.
Detection of Intracoronary Thrombus by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction
Authors: Jansen C.H.P. , Perera D. , Makowski M.R. , Wiethoff A.J. , Phinikaridou A. , Razavi R.M. , Marber M.S. , Greil G.F. , Nagel E. , Maintz D. , Redwood S. , Botnar R.M. 
Published: July 2011

Background—
Persistent intracoronary thrombus after plaque rupture is associated with an increased risk of subsequent myocardial infarction and mortality. Coronary thrombus is usually visualized invasively by x-ray coronary angiography. Non–contrast-enhanced T1-weighted magnetic resonance (MR) imaging has been useful for direct imaging of carotid thrombus and intraplaque hemorrhage by taking advantage of the short T1 of methemoglobin present in acute thrombus and intraplaque hemorrhage. The aim of this study was to investigate the use of non–contrast–enhanced MR for direct thrombus imaging (MRDTI) in patients with acute myocardial infarction.

Methods and Results—

Eighteen patients (14 men; age, 61±9 years) underwent MRDTI within 24 to 72 hours of presenting with an acute coronary syndrome before invasive x-ray coronary angiography; MRDTI was performed with a T1-weighted, 3-dimensional, inversion-recovery black-blood gradient-echo sequence without contrast administration. Ten patients were found to have intracoronary thrombus on x-ray coronary angiography (left anterior descending, 4; left circumflex, 2; right coronary artery, 4; and right coronary artery–posterior descending artery, 1), and 8 had no visible thrombus. We found that MRDTI correctly identified thrombus in 9 of 10 patients (sensitivity, 91%; posterior descending artery thrombus not detected) and correctly classified the control group in 7 of 8 patients without thrombus formation (specificity, 88%). The contrast-to-noise ratio was significantly greater in coronary segments containing thrombus (n=10) compared with those without visible thrombus (n=131; mean contrast-to-noise ratio, 15.9 versus 2.6;
P
<0.001).

Conclusion—
Use of MRDTI allows selective visualization of coronary thrombus in a patient population with a high probability of intracoronary thrombosis.
Real time continuous glucose monitoring: how does it work in real life?
Authors: Geelhoed-Duijvestijn Petronella H. , Box Fieke , Diamant Michaela , Otoide-Vree Marleen , Van Niel Judith 
Published: July 2011

Patients (>90% type 1 diabetes) using real time- continuous glucose monitoring (RT-CGM) for more than 3 months were asked to complete a questionnaire on type and duration of diabetes, self-reported complications, subjective reasons for RT-CGM use, source of payment for RT-CGM, personal income, time on the sensor, but also information such as perceived burden of diabetes, admissions for severe hypoglycaemia or ketoacidosis before and since commencing RT-CGM use. Of the 150 patients supplied with the questionnaire it was completed by 89%. Compliance was high with 77% reporting RT-CGM use ≥75% of the time. The proportion of patients having an HbA1c of ≤7% increased from 33% to 73% (p<0.001). Severe hypoglycaemia and hospital admissions for hypoglycaemia and ketoacidosis also decreased significantly. Patient satisfaction with the device was high. The impact of living with diabetes in daily life improved from 4.1 to 3.4 (p<0.001). The hypoglycaemia alarm was most appreciated. In summary, we confirm that RT-CGM can be a valuable tool to support patients in the self-management of their type 1 diabetes in real life practice if they are willing and able to use the device at least 75% of the time.
Is sleep apnoea a specialist condition? The role of general practitioners
Authors: Martínez-García M.A. , Catalán Serra P. 
Published: July 2011

Educational aimsTo identify obstructive sleep apnoea (OSA) as a public health problem of the first order that requires involvement at all levels of care, from primary to specialist.To pay special attention to aspects of OSA less familiar to primary care, particularly its relationship with cardiovascular diseases.To analyse the expected role of primary care in the diagnosis, treatment and follow-up of patients with OSA and its risk factors.To make clear that treatment with continuous positive airway pressure (CPAP) is not the exclusive domain of specialist care, as many of the problems associated with OSA can be monitored in primary care.SummaryThere is no doubt that OSA is a public health problem, on account of its great prevalence and significant negative effects on health, in both the short and long term. These effects stem from the association observed between OSA and traffic and workplace accidents, as well as its association with various cardiovascular pathologies and diseases. The growing number of patients being diagnosed and treated makes it increasingly difficult for specialists to monitor and follow them up on their own. There is therefore a growing need to involve primary care staff in the attention given to these patients. As in the case of other public health problems such as obesity and diabetes, the primary care physician must acquire sufficient knowledge and expertise both to refer a patient with suspected osa to the suitable specialist and to conduct a basic follow-up, regardless of whether the patient has been prescribed treatment with CPAP.
Calcium/calmodulin kinase1 and its relation to thermotolerance and HSP90 in Sporothrix schenckii: an RNAi and yeast two-hybrid study
Authors: Rodriguez-Caban Jorge , Gonzalez-Velazquez Waleska , Perez-Sanchez Lizaida , Gonzalez-Mendez Ricardo , Valle Nuri Rodriguez-del 
Published: July 2011

Abstract

Background

Sporothrix schenckii is a pathogenic dimorphic fungus of worldwide distribution. It grows in the saprophytic form with hyaline, regularly septated hyphae and pyriform conidia at 25°C and as the yeast or parasitic form at 35°C. Previously, we characterized a calcium/calmodulin kinase in this fungus. Inhibitors of this kinase were observed to inhibit the yeast cell cycle in S. schenckii.

Results
The presence of RNA interference (RNAi) mechanism in this fungus was confirmed by the identification of a Dicer-1 homologue in S. schenckii DNA. RNAi technology was used to corroborate the role of calcium/calmodulin kinase I in S. schenckii dimorphism. Yeast cells were transformed with the pSilent-Dual2G (pSD2G) plasmid w/wo inserts of the coding region of the calcium/calmodulin kinase I (sscmk1) gene. Transformants were selected at 35°C using resistance to geneticin. Following transfer to liquid medium at 35°C, RNAi transformants developed as abnormal mycelium clumps and not as yeast cells as would be expected. The level of sscmk1 gene expression in RNAi transformants at 35°C was less than that of cells transformed with the empty pSD2G at this same temperature. Yeast two-hybrid analysis of proteins that interact with SSCMK1 identified a homologue of heat shock protein 90 (HSP90) as interacting with this kinase. Growth of the fungus similar to that of the RNAi transformants was observed in medium with geldanamycin (GdA, 10 μM), an inhibitor of HSP90.

Conclusions
Using the RNAi technology we silenced the expression of sscmk1 gene in this fungus. RNAi transformants were unable to grow as yeast cells at 35°C showing decreased tolerance to this temperature. The interaction of SSCMK1 with HSP90, observed using the yeast two-hybrid assay suggests that this kinase is involved in thermotolerance through its interaction with HSP90. SSCMK1 interacted with the C terminal domain of HSP90 where effector proteins and co-chaperones interact. These results confirmed SSCMK1 as an important enzyme involved in the dimorphism of S. schenckii, necessary for the development of the yeast phase of this fungus. Also this study constitutes the first report of the transformation of S. schenckii and the use of RNAi to study gene function in this fungus.
Regulation of bombesin-stimulated cyclooxygenase-2 expression in prostate cancer cells
Authors: Wen Xiaodong , Chao Celia , Ives Kirk , Hellmich Mark R 
Published: July 2011

Abstract

Background
Cyclooxygenase-2 (COX-2) and the bombesin (BBS)-like peptide, gastrin-releasing peptide (GRP), have been implicated in the progression of hormone-refractory prostate cancer; however, a mechanistic link between the bioactive peptide and COX-2 expression in prostate cells has not been made.

Results
We report that BBS stimulates COX-2 mRNA and protein expression, and the release of prostaglandin E2 from the GRP receptor (GRPR)-positive, androgen-insensitive prostate cancer cell line, PC-3. BBS-stimulated COX-2 expression is mediated, in part, by p38MAPK and PI3 kinase (PI3K)/Akt pathways, and blocked by a GRPR antagonist. The PI3K/Akt pathway couples GRPR to the transcription factor, activator protein-1 (AP-1), and enhanced COX-2 promoter activity. Although BBS stimulates nuclear factor-kappaB (NF-κB) in PC-3, NF-κB does not regulate GRPR-mediated COX-2 expression. The p38MAPK pathway increases BBS-stimulated COX-2 expression by slowing the degradation of COX-2 mRNA. Expression of recombinant GRPR in the androgen-sensitive cell line LNCaP is sufficient to confer BBS-stimulated COX-2 expression via the p38MAPK and PI3K/Akt pathways.

Conclusions
Our study establishes a mechanistic link between GRPR activation and enhanced COX-2 expression in prostate cancer cell lines, and suggests that inhibiting GRPR may, in the future, provide an effective therapeutic alternative to non-steroidal anti-inflammatory drugs for inhibiting COX-2 in patients with recurrent prostate cancer.
Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart
Authors: Ajmani Preeti , Yadav Harlokesh N , Singh Manjeet , Sharma Pyare L 
Published: July 2011

Abstract

Background
Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat.

Methods
Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, i.p,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent.

Results
IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito KATP channel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination.

Conclusions
Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS.
The epidemiology of alcohol utilization during pregnancy: an analysis of the Canadian Maternity Experiences Survey (MES)
Authors: Walker Meghan J , Al-Sahab Ban , Islam Farah , Tamim Hala 
Published: July 2011

AbstractBackgroundMaternal alcohol consumption during pregnancy may potentially constitute a major public health concern in Canada but despite this, the available epidemiological data on both rates and predictors of alcohol consumption during pregnancy is limited. The present study assessed the prevalence and predictors of maternal alcohol consumption during pregnancy of women living in Canada from 2005-2006 who had a singleton live birth and whose child remained in their care 5-9 months following birth. Prevalence of maternal alcohol consumption was examined across the Canadian provinces.MethodsThe analysis was based on the Maternity Experience Survey (MES), a population-based survey that assessed pregnancy, delivery and postnatal experiences of mothers and their children between November 2005 and May 2006. The main outcome variable assessed was ever drinking alcohol during pregnancy. The sample of mothers who drank during pregnancy consisted mainly of low to moderate level-alcohol drinkers (95.8%), while only 1.7% of the sample were heavy drinkers (>1 drink per day). Socio-economic factors, demographic factors, maternal characteristics, and pregnancy related factors that proved to be significant at the bivariate level were considered for a logistic regression analysis. Bootstrapping was performed to account for the complex sampling design.ResultsAnalysis of 5882 mothers, weighted to represent 72,767 Canadian women, found that 10.8% of women drank alcohol at some point during their pregnancies. This mainly reflects prevalence of low to moderate maternal alcohol consumption. Prevalence of drinking alcohol during pregnancy was 13.8% in Eastern-Central provinces, 7.8% in Western Provinces-British Columbia, 4.1% in Eastern-Atlantic provinces and 4.0% in Western-Prairie Provinces. Utilizing alcohol during gestation was significantly associated with several important factors including marital status, smoking status, reaction to the pregnancy and immigrant status. While being an immigrant to Canada appeared to confer a protective effect, women who have partners (odds ratio (OR) = 2.00; 95% confidence interval (CI): 1.20, 3.31) and smoked during pregnancy (OR = 1.54; 95% CI: 1.12, 1.87) were significantly more likely to drink alcohol during their pregnancies. Perhaps most importantly, pregnant women who reported indifference or being unhappy/very unhappy in regards to their pregnancies exhibited 1.89- and 2.5-fold increased risk of drinking alcohol during their pregnancies, respectively.ConclusionA number of important factors associated with maternal alcohol utilization during pregnancy have been identified, indicating areas where increased focus may serve to reduce maternal and pediatric morbidity and mortality.
A study on trypsin, Aspergillus flavus and Bacillus sp. protease inhibitory activity in Cassia tora (L.) syn Senna tora (L.) Roxb. seed extract
Authors: Tripathi Vinayak R , Kumar Shailendra , Garg Satyendra K 
Published: July 2011

Abstract

Background
Proteases play an important role in virulence of many human, plant and insect pathogens. The proteinaceous protease inhibitors of plant origin have been reported widely from many plant species. The inhibitors may potentially be used for multiple therapeutic applications in viral, bacterial, fungal diseases and physiological disorders. In traditional Indian medicine system, Cassia tora (Senna tora) is reportedly effective in treatment of skin and gastrointestinal disorders. The present study explores the protease inhibitory activity of the above plant seeds against trypsin, Aspergillus flavus and Bacillus sp. proteases.

Methods
The crushed seeds of Cassia tora were washed thoroughly with acetone and hexane for depigmentation and defatting. The proteins were fractionated by ammonium sulphate (0-30, 30-60, 60-90%) followed by dialysis and size exclusion chromatography (SEC). The inhibitory potential of crude seed extract and most active dialyzed fraction against trypsin and proteases was established by spot test using unprocessed x-ray film and casein digestion methods, respectively. Electrophoretic analysis of most active fraction (30-60%) and SEC elutes were carried employing Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Gelatin SDS-PAGE. Inhibition of fungal spore germination was studied in the presence of dialyzed active inhibitor fraction. Standard deviation (SD) and ANOVA were employed as statistical tools.

Results
The crude seeds' extract displayed strong antitryptic, bacterial and fungal protease inhibitory activity on x-ray film. The seed protein fraction 30-60% was found most active for trypsin inhibition in caseinolytic assay (P < 0.001). The inhibition of caseinolytic activity of the proteases increased with increasing ratio of seed extract. The residual activity of trypsin, Aspergillus flavus and Bacillus sp. proteases remained only 4, 7 and 3.1%, respectively when proteases were incubated with 3 mg ml-1 seed protein extract for 60 min. The inhibitory activity was evident in gelatin SDS-PAGE where a major band (~17-19 kD) of protease inhibitor (PI) was detected in dialyzed and SEC elute. The conidial germination of Aspergillus flavus was moderately inhibited (30%) by the dialyzed seed extract.

Conclusions

Cassia tora seed extract has strong protease inhibitory activity against trypsin, Aspergillus flavus and Bacillus sp. proteases. The inhibitor in Cassia tora may attenuate microbial proteases and also might be used as phytoprotecting agent.
Fabrication of ultrahigh-density nanowires by electrochemical nanolithography
Authors: Chen Feng , Jiang Hongquan , Kiefer Arnold M , Clausen Anna M , Ting Yuk-Hong , Wendt Amy E , Ding Bingjun , Lagally Max G 
Published: July 2011

Abstract
An approach has been developed to produce silver nanoparticles (AgNPs) rapidly on semiconductor wafers using electrochemical deposition. The closely packed AgNPs have a density of up to 1.4 × 1011 cm-2 with good size uniformity. AgNPs retain their shape and position on the substrate when used as nanomasks for producing ultrahigh-density vertical nanowire arrays with controllable size, making it a one-step nanolithography technique. We demonstrate this method on Si/SiGe multilayer superlattices using electrochemical nanopatterning and plasma etching to obtain high-density Si/SiGe multilayer superlattice nanowires.