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News Article | April 27, 2017
Site: www.eurekalert.org

Boston, MA-- A new study led by researchers at Brigham and Women's Hospital has found that a single measurement of plasma glycated CD59 (GCD59), a novel biomarker for diabetes, at weeks 24-28 of gestation identified, with high sensitivity and specificity, women who failed the glucose challenge test as well as women with gestational diabetes. Plasma levels of GCD59 were also associated with the probability of delivering a large-for-gestational-age newborn. These findings are published in Diabetes Care. Gestational diabetes is a type of diabetes that occurs during a woman's pregnancy, increasing the mother's risk of delivering a large-for-gestational-age baby, which can lead to pre-term birth, fetal injury, perinatal mortality and cesarean delivery. Gestational diabetes is also a risk factor for preeclampsia and gestational hypertension. Since treatment of gestational diabetes can lessen the risk of adverse pregnancy outcomes, practice guidelines recommend screening all non-diabetic, pregnant women for the disease. The current standard of care to both screen and diagnose gestational diabetes predominantly involves a two-step approach. The first step, known as the glucose challenge test, includes administration of a sugary drink followed by a blood sugar measurement one hour later. Women who fail this screening are then sent for a longer test, called the oral glucose tolerance test, which requires fasting overnight, drinking a more concentrated sugar solution and undergoing baseline and hourly blood draws for three hours. These glucose tests, or variations thereof, are currently the only methods used to screen pregnant women for or diagnose gestational diabetes. They are time consuming, cumbersome, uncomfortable for mothers and have poor reported reproducibility. The research team's primary goal was to assess the accuracy of the diabetes biomarker, GCD59, in predicting the results of the standard of care glucose challenge test used to screen for gestational diabetes. The team conducted a case-control study of 1,000 pregnant women who were receiving standard prenatal care at BWH: 500 women who had a normal glucose challenge test (control subjects) and 500 women who failed the glucose challenge test and required a subsequent oral glucose tolerance test (case patients). Researchers found that, when compared with the control subjects, the median plasma GCD59 value was 8.5-fold higher in the patients who failed the glucose challenge test and 10-fold higher in the subset of these patients who met diagnostic criteria for gestational diabetes in the subsequent oral glucose tolerance test. "This is the first study to demonstrate that a single measurement of plasma GCD59 can be used as a simplified method to identify women who are at risk for failing the glucose challenge test and are at higher risk for developing gestational diabetes," says Jose Halperin, MD, a physician and researcher, Director of the Hematology Laboratory for Translational Research at BWH and senior author of the publication. The researchers also found that higher plasma GCD59 levels at gestational week 24-28 were associated with higher prevalence of large-for-gestational-age newborns, with the higher the level, the higher the risk (4 percent higher risk for patients in the lowest quartile of GCD59 plasma levels, and 14 percent in the highest quartile). Out of the 58 large-for-gestational-age babies born to mothers that failed the glucose challenge test in this study, 80 percent were born to mothers who did not meet oral glucose tolerance test criteria for gestational diabetes, but had median plasma GCD59 levels 7-fold higher than control women with a normal glucose challenge test. These findings are consistent with other studies showing that women who fail the glucose challenge test, but do not meet criteria for gestational diabetes, are still at a higher risk of abnormal pregnancy outcomes, including delivering large for gestational age babies. Currently there are no practice guidelines for the management of women who fall between normal and abnormal glucose tolerance levels, and, therefore, their management is the same as that for women with a normal glucose challenge test results. "These results suggest that a single measurement of plasma GCD59 during weeks 24-28 may also help stratify the risk for delivering larger infants among women with gestational glucose intolerance." says Halperin. "Our studies opened an avenue for larger multicenter studies to further assess the clinical utility of plasma GCD59 for screening and diagnosis of gestational diabetes among the general population of the United States. If our results are confirmed, we're hopeful that the GCD59 test could be available in clinical practices within the next few years." Jose Halperin and Michael Chorev have a financial interest in Mellitus, LLC, which is developing diagnostic tools for diabetes, including the test described in this research under a license agreement from Harvard University. This project was supported by the National Institutes of Health grants DK-095429, DK-62994, DK-089206, DK-101442, DK-107407, and HL-111771. It was also funded by the Harvard University Accelerator Fund, now known as the Blavatnik Biomedical Accelerator at Harvard University and the Doris Duke Charitable Foundation. Paper cited: Halperin et al. "Plasma Glycated CD59, a Novel Biomarker for Detection of Pregnancy-Induced Glucose Intolerance." Diabetes Care DOI: 10.2337/dc16-2598. Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.


"We look forward to collaborating with our colleagues and partners at AACC this year to further relationships and deepen understanding. We know that, as significant changes occur in the healthcare landscape, our clinical partners face a host of challenges that require new ways of thinking," said Arnd Kaldowski, president, Beckman Coulter Diagnostics and Group Executive Diagnostics for Danaher. "We believe that patient care begins with the clinical laboratory. Helping serve patients in the safest and most efficient manner is our job, and, in fact, it is our vision to advance healthcare for every person." At the heart of the Beckman Coulter Diagnostics Difference, are the company's comprehensive high-quality clinical diagnostics solutions—exemplified by several new products featured in the booth this year, including the: The launch of these new products further expands portfolio spanning multiple disciplines, further expands the clinical diagnostic solutions available to customers through Danaher Corporation's network of companies, which include Beckman Coulter, Cepheid, Leica Biosystems, Radiometer and SCIEX Diagnostics. The breadth of offerings extends from established to highly advanced diagnostic technologies for clinical and anatomic pathology laboratories and point-of-care testing. With a rich history and tradition of innovation, the diagnostic companies of Danaher remain committed to helping healthcare systems build comprehensive and efficient diagnostic services to meet the evolving demands of highly integrated and coordinated healthcare delivery models. Laboratorians and healthcare professionals can learn more about Beckman Coulter Diagnostics solutions by participating in the company-hosted educational programs and in-booth presentations listed below. Detailed information is available here. Tuesday, August 1, 1:00 to 2:00 pm Sepsis and the Hematology Laboratory In this session, the clinical and laboratory-related characteristics of sepsis are described, with special emphasis on hematologic manifestations of sepsis. Speaker: Mike Samoszuk, M.D., Beckman Coulter Wednesday, August 2, 10:30 am to 12:00 pm The ASSESS Trial: A Multi-instrument Evaluation of 13 Commercial Troponin Assays, Sample Analysis in a Common Cohort of Samples Moderator: Robert Christenson, Ph.D., University of Maryland School of Medicine Speakers: Allison Chambliss, Ph.D., Keck School of Medicine of University of Southern California; Paramjit Sandhu, M.D., MPH, Centers for Disease Control and Prevention; Alan Wu, Ph.D., University of California San Francisco General Hospital Procalcitonin and its Role as a Biomarker for the Management of Sepsis                  Sherry Faye, Ph.D.      Tuesday, August 1, 12:00 pm New Challenges for Microbiology Laboratories in Antibiotic Susceptibility Testing Barbara Zimmer, Ph.D.             Tuesday, August 1, 1:00 pm H&H Testing: The Rule of Three Is Still Relevant Ahmed Bentahar M.D., Ph.D. Tuesday, August 1, 2:00 pm High-sensitivity Cardiac Troponin: What Does It Mean for Your Laboratory, Your Clinicians and Your Patients? Peter Kavsak Ph.D., FCACB, FACB, FCCS                 Tuesday, August 1, 3:00 pm Leveraging Service and Care Through Real-time Analysis of Provider Relationships and Behavior   Connor Billing Thursday, August 3, 10:00 am 9:30 am to 5:00 pm │ Tuesday, August 1 or Wednesday, August 2 Authors will be available at posters from 12:30 to 1:30 pm for discussion with attendees. A Prospective Observational Study of the Clinical Decision Impact on the Prostate Health Index (phi) Test in a Urology Practice Setting (A-141) A Comparison of the New Beckman Coulter DxC 700 AU Clinical Chemistry System to the UniCel DxC 800 Synchron Clinical Systems (B-440) Characteristics of the New Beckman Coulter Access hsTnI Assay (TBD) Biomarker Changes in Adult Men with Low Testosterone (low-T) (A-172) Improvement to Workflow in Reagent Dispense System Design in the New Beckman Coulter DxM MicroScan WalkAway System (B-075) Multicenter Evaluation of Imipenem MIC Results for Gram Negative Bacilli Using MicroScan Dried Gram Negative MIC Panels (A-123) Easy as 1, 2, 3? Trimester-specific TSH Reference Intervals in a Well-Characterized Population Using the Beckman Coulter (3rd IS) Immunoassay (TBD) Early Development of DxONE Insights, a Tool to Enhance Data-Driven Decision Making to Improve Laboratory Efficiency (B-028) Beckman Coulter Diagnostics helps healthcare and laboratory professionals provide better patient care by delivering the accurate diagnostic information they need, when they need it. For more than 80 years, Beckman Coulter has been the partner of choice for healthcare organizations. Our scalable instruments, comprehensive diagnostic tests and business management services are trusted by hospitals, laboratories and other critical care settings around the world. We share in our customers' mission toward continuous improvement and quality patient care, because we believe when efficiency and clinical outcomes are improved, patients benefit, and we can move healthcare forward for every person. Beckman Coulter, the stylized logo and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. *Pending 510(k) clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostic use in the United States. **Under development. The performance characteristics of this product have not been established. ***Not yet available for in vitro diagnostic use. Pending achievement of CE compliance, Canadian Licensure and other regulatory registrations. REMISOL Advance is a trademark or registered trademark of Normand-Info SAS in the United States and other countries. Used under license. Cepheid and GeneXpert are trademarks of Cepheid in the United States and other countries.


Zouari R.,University of Sfax | Hamden K.,University of Sfax | Feki A.E.,University of Sfax | Chaabouni K.,Biochemistry Laboratory | And 5 more authors.
Biomedicine and Pharmacotherapy | Year: 2016

This study was aimed to assess the plausible anti-obesity effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant on high fat high fructose diet-fed rats (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet (CD), HFFD, HFFD supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD + Bios1, 10 mg/kg/day), HFFD receiving standard drug (HFFD + Torva, 10 mg/kg/day) or SPB1 biosurfactant (HFFD + Bios2, 10 mg/kg/day) during the last 4 weeks of the study. The results showed an increase in body weight of HFFD by ∼19% as compared to controls (CD). Moreover, serum lipase activity underwent a threefold increase which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG) and LDL-cholesterol (LDL-Ch) in serum of untreated HFFD, as well as a rise in the calculated atherogenic index (AI). Furthermore, liver dysfunction indices such as AST, ALT, CPK, LDH, GGT, ALP and T-Bilirubins exhibited remarkable increases in serum of HFFD as compared to controls (CD). Whereas, the administration of Bacillus subtilis SPB1 biosurfactant to HFFD improved the body weight gain and serum lipids profile and reverted back near normal the activities of lipase and liver toxicity indicators. In addition, notable protective and curative effects were reported in liver tissues. Overall, these results suggest that the lipopeptides biosynthesized by Bacillus subtilis SPB1 achieved an anti-obesity effect through the inhibition of lipid digestive and liver dysfunction enzymes. © 2016


Tatour M.,Thrombosis and Hemostasis Unit | Shapira M.,Hillel Yaffe Medical Center | Axelman E.,Thrombosis and Hemostasis Unit | Ghanem S.,Thrombosis and Hemostasis Unit | And 4 more authors.
Thrombosis and Haemostasis | Year: 2017

Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells. Platelets and granulocytes were purified from pooled normal plasma and were incubated with ATP, ADP, epinephrine, collagen, ristocetin, arachidonic acid, serotonin, LPS and thrombin. Heparanase levels were assessed by ELISA, heparanase procoagulant activity assay and western blot analysis. The effects of selective protease-activated receptor (PAR)-1 and 2 inhibitors and PAR-1 and 4 activators were studied. An in-house synthesised inhibitory peptide to heparanase was used to evaluate platelet heparanase involvement in activation of the coagulation system. Heparanase was released from platelets only by thrombin induction while other inducers exerted no such effect. The heparanase level in a platelet was found to be 40 % higher than in a granulocyte. Heparanase released from platelets or granulocytes increased factor Xa generation by three-fold. PAR-1 activation via ERK intracellular pathway was found to induce heparanase release. In conclusion, heparanase is selectively released from platelets and granulocytes by thrombin interacting with PAR-1. Heparanase derived from platelets and granulocytes is involved in activation of the extrinsic coagulation pathway. The present study implies on a potential anticoagulant effect, in addition to anti-platelet effect, of the new clinically studied PAR-1 inhibitors. © Schattauer 2017.


PubMed | Biochemistry Laboratory, University of Sfax and Hematology Laboratory
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016

This study was aimed to assess the plausible anti-obesity effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant on high fat high fructose diet-fed rats (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet (CD), HFFD, HFFD supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD+Bios1, 10mg/kg/day), HFFD receiving standard drug (HFFD+Torva, 10mg/kg/day) or SPB1 biosurfactant (HFFD+Bios2, 10mg/kg/day) during the last 4 weeks of the study. The results showed an increase in body weight of HFFD by 19% as compared to controls (CD). Moreover, serum lipase activity underwent a threefold increase which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG) and LDL-cholesterol (LDL-Ch) in serum of untreated HFFD, as well as a rise in the calculated atherogenic index (AI). Furthermore, liver dysfunction indices such as AST, ALT, CPK, LDH, GGT, ALP and T-Bilirubins exhibited remarkable increases in serum of HFFD as compared to controls (CD). Whereas, the administration of Bacillus subtilis SPB1 biosurfactant to HFFD improved the body weight gain and serum lipids profile and reverted back near normal the activities of lipase and liver toxicity indicators. In addition, notable protective and curative effects were reported in liver tissues. Overall, these results suggest that the lipopeptides biosynthesized by Bacillus subtilis SPB1 achieved an anti-obesity effect through the inhibition of lipid digestive and liver dysfunction enzymes.


Jordheim L.P.,French Institute of Health and Medical Research | Jordheim L.P.,University of Lyon | Seve P.,French Institute of Health and Medical Research | Seve P.,University of Lyon | And 5 more authors.
The Lancet Oncology | Year: 2011

The large subunit of human ribonucleotide reductase, RRM1, is involved in the regulation of cell proliferation, cell migration, tumour and metastasis development, and the synthesis of deoxyribonucleotides for DNA synthesis. It is also a cellular target for the chemotherapeutic agent, gemcitabine. RRM1 has been studied in a large number of patients with different types of cancer, such as non-small-cell lung cancer, pancreatic cancer, breast cancer, and biliary tract cancer, to establish its prognostic or predictive value when patients were treated with gemcitabine, and mRNA expression and genetic variants as determined by genotyping have in some cases been associated with clinical outcome of patients with cancer. Here, we review preclinical and clinical studies of RRM1 assessment and discuss the further steps in the development of this clinically pertinent biomarker. © 2011 Elsevier Ltd.


PubMed | Hematology laboratory, Internal Medicine Unit, Infectious Diseases Unit, GHER Hospital and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016

It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.


Eimer S.,University of Bordeaux Segalen | Dugay F.,Pontchailloux University Hospital | Airiau K.,French Institute of Health and Medical Research | Avril T.,Eugene Marquis Center | And 6 more authors.
Neuro-Oncology | Year: 2012

Putative cancer stem cells have been identified in glioblastoma (GBM), associated with resistance to conventional therapies. Overcoming this resistance is a major challenge to manage this deadly brain tumor. Epidermal growth factor receptor (EGFR) is commonly amplified, over-expressed, and/or mutated in GBM, making it a compelling target for therapy. This study investigates the behavior of 3 primary neurosphere (NS) cell lines and their adherent counterparts originated from human GBM resections, when treated with EGFR-tyrosine kinase inhibitor erlotinib, associated or not with cyclopamine, a hedgehog pathway inhibitor. Adherent cells cultured in the presence of serum expressed the glial fibrillary acidic protein, whereas NS-forming cells cultured in serum-free medium expressed CD133, nestin, and Oct-4, markers of neural stem and progenitor cells. For the 3 adherent cell lines, erlotinib has a moderate effect (50 inhibitory concentration [IC50], >10 μM). Conversely, erlotinib induced a strong cell growth inhibition (IC50, <1 μM) on NS-forming cells, related to the EGFR gene amplification and EGFR protein expression. A short exposure to erlotinib reduced nestin-positive cell proliferation, but NS-initiating activity and self-renewal were not altered. EGFR pathway seems essential for GBM progenitor cell proliferation but dispensable for cancer stem-like cell self-renewal. Inhibition of hedgehog pathway with cyclopamine was evaluated in association with erlotinib on NS growth. Although each drug separately had no effect on sphere initiation, their combination significantly decreased the sphere number (P <. 001). Our findings show synergic efficiency for erlotinib-cyclopamine association and provide a suitable in vitro model to explore drug combinations on GBM cells. © 2012 The Author(s).


Jordheim L.P.,French Institute of Health and Medical Research | Jordheim L.P.,Hematology Laboratory | Durantel D.,French Institute of Health and Medical Research | Zoulim F.,Hematology Laboratory | And 3 more authors.
Nature Reviews Drug Discovery | Year: 2013

Nucleoside analogues have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with cancer or viral infections. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Here, we review new nucleoside analogues and associated compounds that are currently in preclinical or clinical development for the treatment of cancer and viral infections, and that aim to provide increased response rates and reduced side effects. We also highlight the different approaches used in the development of these drugs and the potential of personalized therapy.


Bonello L.,Hopital University Nord | Bonello L.,French Institute of Health and Medical Research | Bonello N.,Hopital de la Timone Enfant | Grosdidier C.,French Institute of Health and Medical Research | And 2 more authors.
Clinical Pharmacology and Therapeutics | Year: 2011

Clopidogrel is an important antiplatelet agent, but a considerable variability in the biological effect of the drug has been observed. Additionally, patients with insufficient platelet reactivity inhibition following a loading dose (LD) of clopidogrel have a poor outcome. The mechanisms of variability are dependent on genetic polymorphisms of enzymes involved in clopidogrel metabolism. Paraoxonase 1 has been identified as the main determinant of the biological and clinical efficacy of clopidogrel. This finding could enable the use of pharmacogenomics to tailor antiplatelet agents. © 2011 American Society for clinical Pharmacology and Therapeutics.

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