Minimal shedding of the glycocalyx layer during abdominal hysterectomy

Funding Information: This project was funded by the Stockholm City Council, the Kleberg Foundation and Riga Stradins University. Publisher Copyright: © 2017 The Author(s).Background: Surgery with and without hypervolaemia may cause shedding (breakdown) of the endothelial glycocalyx layer, but the severity of this problem is unclear. Methods: In this preliminary report of a larger clinical trial, the plasma and urine concentrations of three biomarkers of glycocalyx shedding (syndecan-1, hyaluronic acid and heparan sulfate) were measured in seven patients before, during, and after open hysterectomy. The fluid therapy consisted of 25ml/kg (approximately 2l) of Ringer's lactate, which was infused over 30min when the surgery started. The resulting plasma volume expansion at the end of the infusion was estimated from the haemodilution. Results: The mean plasma concentration of syndecan-1 was 21.7ng/ml before surgery and averaged 19.7ng/ml during and after the surgery. The plasma concentration of hyaluronic acid decreased from 38.0 to 27.7ng/ml (P<0.05), while heparan sulfate increased from 3.4 to 5.5μg/ml (P<0.05). The urine concentrations of syndecan-1 decreased significantly, while they increased for hyaluronic acid and heparan sulfate. Despite the vigorous fluid load, the urine flow did not exceed 1ml/min. Conclusions: No clear evidence was found for shedding of the endothelial glycocalyx layer when 2l of Ringer's lactate was infused over 30min during abdominal hysterectomy. Urine analyses yielded patterns of changes that differed from those in plasma. Trial registration:ISRCTN81005631. Registered May 17, 2016.publishersversionPeer reviewe

Impact of storage conditions on preparation of activated carbon from sheep wool fibres

Received: January 31st, 2023 ; Accepted: June 16th, 2023 ; Published: July 6th, 2023 ; Correspondence: [email protected] the European Union, up to 200 thousand tons (Zoccola et al., 2015) of sheep wool fibres, that are not used for textile fabrication, are a secondary by-product with wide field of application possibilities, including preparation of activated carbon. Taking into account, that wool fibres can be stored for long time, under impact of the local climate conditions (including low temperatures) before their application, for example, under variety of temperature, presence of air and light, different moisture conditions, it is necessary to estimate the impact of wool’s storage conditions on the preparation of activated carbon. In the present work, various parameters, such as, temperature, presence of air and daylight as well as humidity, were selected for comparison. After storage of wool fibres under selected various conditions, thermogravimetry/differential thermal analysis (TG/DTA) followed by with Fourier transform infrared (FTIR) spectrometry were used in order to estimate the impact of each parameter on the thermal decomposition processes: release of moisture, sulphur and nitrogen containing compounds and oxidative degradation followed by release of carbon dioxide. It was estimated, that one year of storage under varying conditions does not significantly affect the thermal decomposition properties of the wool fibres. However, minor impact of humidity absorbed from air on wool is observed. Wool samples that were stored at elevated humidity gave higher residual carbon yield (R) in comparison to the fibres stored in dry conditions. The obtained results are used to develop recommendations for preparation of activated carbon from wool fibres and for its application in air filtrating systems

A Forum for Business Growth and Workforce Development: Findings and Recommendations

In the fall of 2008, Illinois State University – Extended University (EU) and the Economic Development Council of the Bloomington-Normal Area (EDC) initiated discussions about a community partnership project to identify workforce opportunities and challenges related to economic stabilization and growth in order to gain a better understanding of the state of workforce preparedness in the area. Rapidly changing dynamics in the economy made previous assessments obsolete. Organizations who work toward the promotion of a strong workforce were approached to participate in the project. EU and the EDC were joined in sponsoring a community event by Heartland Community College, Illinois Wesleyan University, Lincoln College – Normal, Regional Office of Education 17, McLean County Chamber of Commerce, CareerLink 16, and the Small Business Development Center at Illinois State University. Project partners designed and developed a series of discussion forums for eight sectors: Agriculture and Energy, Manufacturing, Small Business Retail, Service, Financial Services, Information Technology, Healthcare, and Construction. The Forum for Business Growth and Workforce Development was held from June 8 – 12, 2009 at Illinois State University. Each sector panel discussion was moderated over a ninety minute period and included two to seven panelists from area businesses

Antioxidant-mediated inhibition of the heat shock response leads to apoptosis

AbstractWe examined the hypothesis that reactive oxygen species (ROS) contribute to the induction of heat shock proteins (hsps) during stress response. Exposure of HL-60 human myelocytic cells to 42°C induced both hsp72 and hsp27. In the presence of the antioxidant molecules pyrrolidine dithiocarbamate or 1,10-phenanthroline induction of hsp72 and 27 was significantly decreased, while N-acetyl-l-cysteine caused a slight reduction. Prevention of hsp induction was associated with heat sensitization and increased caspase activity, indicating that the cells were undergoing apoptosis. These data suggest that ROS contribute to the induction of hsps and furthermore, that hsp induction and apoptosis are mutually exclusive events within the same cell

A critical role for Thioredoxin- Interacting protein in diabetes-related impairment of angiogenesis

Impaired angiogenesis in ischemic tissue is a hallmark of diabetes. Thioredoxin-interacting protein (TXNIP) is an exquisitely glucose-sensitive gene that is overexpressed in diabetes. As TXNIP modulates the activity of the key angiogenic cytokine vascular endothelial growth factor (VEGF), we hypothesized that hyperglycemia-induced dysregulation of TXNIP may play a role in the pathogenesis of impaired angiogenesis in diabetes. In the current study, we report that high glucose– mediated overexpression of TXNIP induces a widespread impairment in endothelial cell (EC) function and survival by reducing VEGF production and sensitivity to VEGF action, findings that are rescued by silencing TXNIP with small interfering RNA. High glucose–induced EC dysfunction was recapitulated in normal glucose conditions by overexpressing either TXNIP or a TXNIP C247S mutant unable to bind thioredoxin, suggesting that TXNIP effects are largely independent of thioredoxin activity. In streptozotocin-induced diabetic mice, TXNIP knockdown to nondiabetic levels rescued diabetes-related impairment of angiogenesis, arteriogenesis, blood flow, and functional recovery in an ischemic hindlimb. These findings were associated with in vivo restoration of VEGF production to nondiabetic levels. These data implicate a critical role for TXNIP in diabetes-related impairment of ischemia-mediated angiogenesis and identify TXNIP as a potential therapeutic target for the vascular complications of diabetes.Louise L. Dunn, Philippa J.L. Simpson, Hamish C. Prosser, Laura Lecce, Gloria S.C. Yuen, Andrew Buckle, Daniel P. Sieveking, Laura Z. Vanags, Patrick R. Lim, Renee W.Y. Chow, Yuen Ting Lam, Zoe Clayton, Shisan Bao, Michael J. Davies, Nadina Stadler, David S. Celermajer, Roland Stocker, Christina A. Bursill, John P. Cooke, and Martin K.C. N

BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families

Background: The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5-10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.Methods: 50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.Results: Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.Conclusions: Molecular screening of sequential cancer patients is an important tool to identify HBOC families.publishersversionPeer reviewe

Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia

<p>Abstract</p> <p>Background</p> <p>Mutations in the high penetrance breast and ovarian cancer susceptibility gene <it>BRCA1 </it>account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of <it>BRCA1 </it>mutations located in different parts of the <it>BRCA1 </it>gene have been described previously; however, phenotypic differences of specific <it>BRCA1 </it>mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the <it>BRCA1 </it>c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.</p> <p>Methods</p> <p>We investigated the prevalence of the <it>BRCA1 </it>founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the <it>BRCA1 </it>mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.</p> <p>Results</p> <p>We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1^stand 2^nddegree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.</p> <p>Conclusions</p> <p>Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.</p

PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

Background: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.publishersversionPeer reviewe

Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery

Publisher Copyright: © 2015 Ozolina et al.Background: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.publishersversionPeer reviewe

A model of the PI cycle reveals the regulating roles of lipid-binding proteins and pitfalls of using mosaic biological data

The phosphatidylinositol (PI) cycle is central to eukaryotic cell signaling. Its complexity, due to the number of reactions and lipid and inositol phosphate intermediates involved makes it difficult to analyze experimentally. Computational modelling approaches are seen as a way forward to elucidate complex biological regulatory mechanisms when this cannot be achieved solely through experimental approaches. Whilst mathematical modelling is well established in informing biological systems, many models are often informed by data sourced from multiple unrelated cell types (mosaic data) or from purified enzyme data. In this work, we develop a model of the PI cycle informed by experimental and omics data taken from a single cell type, namely platelets. We were able to make a number of predictions regarding the regulation of PI cycle enzymes, the importance of the number of receptors required for successful GPCR signaling and the importance of lipid- and protein-binding proteins in regulating second messenger outputs. We then consider how pathway behavior differs, when fully informed by data for HeLa cells and show that model predictions remain consistent. However, when informed by mosaic experimental data model predictions greatly vary illustrating the risks of using mosaic datasets from unrelated cell types