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  1. Article ; Online: Old drug, new Trick? The rationale for the treatment of COVID-19 with activated protein C.

    Pestka, Steven B

    Medical hypotheses

    2021  Volume 149, Page(s) 110537

    Abstract: As the COVID-19 pandemic continues, researchers seek to identify efficacious treatments. Current approaches to COVID-19 therapeutics focus on antiviral agents, convalescent plasma, monoclonal antibodies, immunomodulators and more traditional therapies ... ...

    Abstract As the COVID-19 pandemic continues, researchers seek to identify efficacious treatments. Current approaches to COVID-19 therapeutics focus on antiviral agents, convalescent plasma, monoclonal antibodies, immunomodulators and more traditional therapies such as steroids [1-6]. Reversing disturbances in coagulation has also been identified as a priority area for candidate therapies, such as through the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 adaptive clinical trial (ACTIV-4) which is currently evaluating aspirin, heparins and apixaban [7]. Since there is a clear relationship between mechanisms of coagulation and the immune response, it is possible that reversing disturbances in coagulation may diminish the dysregulated immune response observed in COVID-19. The basis for this hypothesis is described below and is followed by discussion of a proposed candidate therapy - activated protein C. By treating COVID-19 patients using a novel approach, which does not focus on immune-based or antiviral treatments, but instead which addresses both the anti-thrombotic and inflammatory consequences of infection, the hope is that new therapeutic targets can be considered and new candidate therapies, such as activated protein C, may be evaluated.
    MeSH term(s) Animals ; Antiviral Agents/therapeutic use ; Blood Coagulation/drug effects ; COVID-19/drug therapy ; Fibrinolytic Agents/therapeutic use ; Humans ; Inflammation/drug therapy ; Models, Theoretical ; Protein C/therapeutic use ; Recombinant Proteins/therapeutic use ; Sepsis/immunology ; Sepsis/therapy
    Chemical Substances Antiviral Agents ; Fibrinolytic Agents ; Protein C ; Recombinant Proteins ; drotrecogin alfa activated (JGH8MYC891)
    Language English
    Publishing date 2021-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2021.110537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1132: Show issues Location:
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  2. Article: Patient Experiences With Transfer for Community Hospital Inpatient Admission From an Academic Emergency Department.

    Sonis, Jonathan D / Berlyand, Yosef / Yun, Brian J / Aaronson, Emily L / Raja, Ali S / Brown, David F M / Pestka, Steven B / White, Benjamin A

    Journal of patient experience

    2020  Volume 7, Issue 6, Page(s) 946–950

    Abstract: Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a ... ...

    Abstract Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a survey-based retrospective cohort study, we aimed to assess the patient experience for those who agreed to transfer and admission to an affiliated community hospital from a large, academic center's ED. In all, 85% of participants rated their overall experience as either great or good, 92% did not find it hard to make the decision to be transferred, and 95% found the transfer process itself to be easy.
    Language English
    Publishing date 2020-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2857285-3
    ISSN 2374-3743 ; 2374-3735
    ISSN (online) 2374-3743
    ISSN 2374-3735
    DOI 10.1177/2374373520949168
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  3. Article ; Online: Patient Experiences With Transfer for Community Hospital Inpatient Admission From an Academic Emergency Department

    Jonathan D Sonis MD, MHCM / Yosef Berlyand MD / Brian J Yun MD, MBA, MPH / Emily L Aaronson MD, MPH / Ali S Raja MD, MBA, MPH / David F M Brown MD / Steven B Pestka MD / Benjamin A White MD

    Journal of Patient Experience, Vol

    2020  Volume 7

    Abstract: Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a ... ...

    Abstract Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a survey-based retrospective cohort study, we aimed to assess the patient experience for those who agreed to transfer and admission to an affiliated community hospital from a large, academic center’s ED. In all, 85% of participants rated their overall experience as either great or good, 92% did not find it hard to make the decision to be transferred, and 95% found the transfer process itself to be easy.
    Keywords Medicine (General) ; R5-920
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine.

    Wu, Wenda / Zhou, Hui-Ren / Bursian, Steven J / Link, Jane E / Pestka, James J

    Archives of toxicology

    2016  Volume 90, Issue 4, Page(s) 997–1007

    Abstract: ... Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis ...

    Abstract Trichothecene mycotoxins are a family of potent translational inhibitors that are associated with foodborne outbreaks of human and animal gastroenteritis in which vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis in the mink (Neovison vison), and this response has been directly linked to secretion of both the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5-hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes that contaminate cereals, and further compared these effects to those of emetine, a natural alkaloid that is used medicinally and also well known to block translation and cause vomiting. Following intraperitoneal (IP) and oral exposure, all three agents caused vomiting with evident dose-dependent increases in both duration and number of emetic events as well as decreases in latency to emesis. T-2 and HT-2 doses causing emesis in 50 % of treated animals (ED50s) were 0.05 and 0.02 mg/kg BW following IP and oral administration, respectively, whereas the ED50s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure, respectively. Importantly, oral administration of all three toxins elicited marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded to emesis. Taken together, the results suggest that T-2 and HT-2 were much more potent than emetine and that emesis induction by all three translational inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT.
    MeSH term(s) Administration, Oral ; Animals ; Dose-Response Relationship, Drug ; Emetics/administration & dosage ; Emetics/pharmacology ; Emetics/toxicity ; Emetine/administration & dosage ; Emetine/pharmacology ; Emetine/toxicity ; Female ; Mink ; Peptide Fragments/blood ; Peptide YY/blood ; Serotonin/blood ; T-2 Toxin/administration & dosage ; T-2 Toxin/analogs & derivatives ; T-2 Toxin/toxicity ; Vomiting/chemically induced
    Chemical Substances Emetics ; Peptide Fragments ; Peptide YY (106388-42-5) ; peptide YY (3-36) (123583-37-9) ; Serotonin (333DO1RDJY) ; T-2 Toxin (I3FL5NM3MO) ; HT-2 toxin (NC6C26RM46) ; Emetine (X8D5EPO80M)
    Language English
    Publishing date 2016-04
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-015-1508-7
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  5. Article ; Online: Peptide YY3-36 and 5-hydroxytryptamine mediate emesis induction by trichothecene deoxynivalenol (vomitoxin).

    Wu, Wenda / Bates, Melissa A / Bursian, Steven J / Flannery, Brenna / Zhou, Hui-Ren / Link, Jane E / Zhang, Haibin / Pestka, James J

    Toxicological sciences : an official journal of the Society of Toxicology

    2013  Volume 133, Issue 1, Page(s) 186–195

    Abstract: Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset ... ...

    Abstract Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset of emesis, the mechanisms for this adverse effect are not fully understood. Recently, our laboratory has demonstrated that the mink (Neovison vison) is a suitable small animal model for investigating trichothecene-induced emesis. The goal of this study was to use this model to determine the roles of two gut satiety hormones, peptide YY3-36 (PYY3-36) and cholecystokinin (CCK), and the neurotransmitter 5-hydroxytryptamine (5-HT) in DON-induced emesis. Following ip exposure to DON at 0.1 and 0.25mg/kg bw, emesis induction ensued within 15-30min and then persisted up to 120min. Plasma DON measurement revealed that this emesis period correlated with the rapid distribution and clearance of the toxin. Significant elevations in both plasma PYY3-36 (30-60min) and 5-HT (60min) but not CCK were observed during emesis. Pretreatment with the neuropeptide Y2 receptor antagonist JNJ-31020028 attenuated DON- and PYY-induced emesis, whereas the CCK1 receptor antagonist devezapide did not alter DON's emetic effects. The 5-HT3 receptor antagonist granisetron completely suppressed induction of vomiting by DON and the 5-HT inducer cisplatin. Granisetron pretreatment also partially blocked PYY3-36-induced emesis, suggesting a potential upstream role for this gut satiety hormone in 5-HT release. Taken together, the results suggest that both PYY3-36 and 5-HT play contributory roles in DON-induced emesis.
    MeSH term(s) Animals ; Antiemetics/administration & dosage ; Antiemetics/pharmacology ; Antiemetics/therapeutic use ; Benzamides/administration & dosage ; Benzamides/pharmacology ; Benzamides/therapeutic use ; Cholecystokinin/antagonists & inhibitors ; Cholecystokinin/blood ; Cholecystokinin/metabolism ; Devazepide/administration & dosage ; Devazepide/pharmacology ; Devazepide/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Granisetron/administration & dosage ; Granisetron/pharmacology ; Granisetron/therapeutic use ; Mink ; Peptide Fragments/antagonists & inhibitors ; Peptide Fragments/blood ; Peptide Fragments/metabolism ; Peptide YY/antagonists & inhibitors ; Peptide YY/blood ; Peptide YY/metabolism ; Piperazines/administration & dosage ; Piperazines/pharmacology ; Piperazines/therapeutic use ; Serotonin/blood ; Serotonin/metabolism ; Serotonin Antagonists/administration & dosage ; Serotonin Antagonists/pharmacology ; Serotonin Antagonists/therapeutic use ; Time Factors ; Trichothecenes/blood ; Trichothecenes/toxicity ; Vomiting/blood ; Vomiting/chemically induced ; Vomiting/metabolism ; Vomiting/prevention & control
    Chemical Substances Antiemetics ; Benzamides ; JNJ-31020028 ; Peptide Fragments ; Piperazines ; Serotonin Antagonists ; Trichothecenes ; Peptide YY (106388-42-5) ; peptide YY (3-36) (123583-37-9) ; Serotonin (333DO1RDJY) ; Cholecystokinin (9011-97-6) ; Devazepide (JE6P7QY7NH) ; deoxynivalenol (JT37HYP23V) ; Granisetron (WZG3J2MCOL)
    Language English
    Publishing date 2013-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kft033
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1709: Show issues Location:
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  6. Article: Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus.

    Miranda, Tina Branscombe / Khusial, Permanan / Cook, Jeffry R / Lee, Jin-Hyung / Gunderson, Samuel I / Pestka, Sidney / Zieve, Gary W / Clarke, Steven

    Biochemical and biophysical research communications

    2004  Volume 323, Issue 2, Page(s) 382–387

    Abstract: We report a novel modification of spliceosome proteins Sm D1, Sm D3, and Sm B/B'. L292 mouse ... fibroblasts were labeled in vivo with [3H]methionine. Sm D1, Sm D3, and Sm B/B' were purified ... The isolated Sm D1, Sm D3 or Sm B/B' proteins were hydrolyzed to amino acids and the products were analyzed ...

    Abstract We report a novel modification of spliceosome proteins Sm D1, Sm D3, and Sm B/B'. L292 mouse fibroblasts were labeled in vivo with [3H]methionine. Sm D1, Sm D3, and Sm B/B' were purified from either nuclear extracts, cytosolic extracts or a cytosolic 6S complex by immunoprecipitation of the Sm protein-containing complexes and then separation by electrophoresis on a polyacrylamide gel containing urea. The isolated Sm D1, Sm D3 or Sm B/B' proteins were hydrolyzed to amino acids and the products were analyzed by high-resolution cation exchange chromatography. Sm D1, Sm D3, and Sm B/B' isolated from nuclear fractions were all found to contain omega-NG-monomethylarginine and symmetric omega-NG,NG'-dimethylarginine, modifications that have been previously described. In addition, Sm D1, Sm D3, and Sm B/B' were also found to contain asymmetric omega-NG,NG-dimethylarginine in these nuclear fractions. Analysis of Sm B/B' from cytosolic fractions and Sm B/B' and Sm D1 from cytosolic 6S complexes showed only the presence of omega-NG-monomethylarginine and symmetric omega-NG,NG'-dimethylarginine. These results indicate that Sm D1, Sm D3, and Sm B/B' are asymmetrically dimethylated and that these modified proteins are located in the nucleus. In reactions in which Sm D1 or Sm D3 was methylated in vitro with a hemagglutinin-tagged PRMT5 purified from HeLa cells, we detected both symmetric omega-NG,NG'-dimethylarginine and asymmetric omega-NG,NG-dimethylarginine when reactions were done in a Tris/HCl buffer, but only detected symmetric omega-NG,NG'-dimethylarginine when a sodium phosphate buffer was used. These results suggest that the activity responsible for the formation of asymmetric dimethylated arginine residues in Sm proteins is either PRMT5 or a protein associated with it in the immunoprecipitated complex.
    MeSH term(s) Amino Acid Sequence ; Animals ; Arginine/chemistry ; Arginine/metabolism ; Binding Sites ; Cell Extracts/chemistry ; Cell Line ; Cell Nucleus/chemistry ; Cell Nucleus/metabolism ; Fibroblasts/metabolism ; Fibroblasts/ultrastructure ; HeLa Cells ; Humans ; Methylation ; Mice ; Molecular Sequence Data ; Protein Binding ; Ribonucleoproteins, Small Nuclear/chemistry ; Ribonucleoproteins, Small Nuclear/metabolism ; Spliceosomes/chemistry ; Spliceosomes/metabolism ; Structure-Activity Relationship
    Chemical Substances Cell Extracts ; Ribonucleoproteins, Small Nuclear ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2004-10-15
    Publishing country United States
    Document type Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2004.08.107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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