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  1. Article ; Online: Chloroquine and COVID-19 - a potential game changer?

    Sturrock, Beattie Rh / Chevassut, Timothy Jt

    Clinical medicine (London, England)

    2020  Volume 20, Issue 3, Page(s) 278–281

    Abstract: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for ... ...

    Abstract The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-05-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2020-0129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article: Chloroquine and COVID-19 - a potential game changer?

    Sturrock, Beattie Rh / Chevassut, Timothy Jt

    Abstract: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for ... ...

    Abstract The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #72336
    Database COVID19

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  3. Article ; Online: The renin-angiotensin system - a therapeutic target in COVID-19?

    Sturrock, Beattie Rh / Milne, Kate M / Chevassut, Timothy Jt

    Clinical medicine (London, England)

    2020  Volume 20, Issue 4, Page(s) e72–e75

    Abstract: COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of ...

    Abstract COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans. We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials. Here we give an overview of the RAS pathway with respect to COVID-19 and argue that strategies which manipulate this pathway might reduce the destructive lung manifestations of COVID-19 and improve patient outcomes.
    MeSH term(s) Amides/therapeutic use ; Angiotensin II/metabolism ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Antihypertensive Agents/therapeutic use ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Fumarates/therapeutic use ; Humans ; Lung Injury/metabolism ; Lung Injury/virology ; Mice ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; Renin-Angiotensin System ; SARS-CoV-2 ; Virus Internalization
    Chemical Substances Amides ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Fumarates ; Angiotensin II (11128-99-7) ; aliskiren (502FWN4Q32) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-05-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2020-0146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: The renin-angiotensin system - a therapeutic target in COVID-19?

    Sturrock, Beattie Rh / Milne, Kate / Chevassut, Timothy Jt

    Abstract: COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of ...

    Abstract COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans. We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials. Here we give an overview of the RAS pathway with respect to COVID-19 and argue that strategies which manipulate this pathway might reduce the destructive lung manifestations of COVID-19 and improve patient outcomes.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32414711
    Database COVID19

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  5. Article ; Online: Thrombotic risk in COVID-19: a case series and case-control study.

    Stoneham, Simon M / Milne, Kate M / Nuttall, Elisabeth / Frew, Georgina H / Sturrock, Beattie Rh / Sivaloganathan, Helena / Ladikou, Eleni E / Drage, Stephen / Phillips, Barbara / Chevassut, Timothy Jt / Eziefula, Alice C

    Clinical medicine (London, England)

    2020  Volume 20, Issue 4, Page(s) e76–e81

    Abstract: Background: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are ... ...

    Abstract Background: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are extremely limited.
    Methods: We describe three cases of thromboembolism refractory to heparin treatment, the incidence of VTE in an inpatient cohort, and a case-control study to identify risk factors associated with VTE.
    Results: We identified 274 confirmed (208) or probable (66) COVID-19 patients. 21 (7.7%) were diagnosed with VTE. D-dimer was elevated in both cases (confirmed VTE) and controls (no confirmed VTE) but higher levels were seen in confirmed VTE cases (4.1 vs 1.2 μg/mL, p<0.001).
    Conclusion: Incidence of VTE is high in patients hospitalised with COVID-19. Urgent clinical trials are needed to evaluate the role of anticoagulation in COVID-19. Monitoring of D-dimer and anti-factor Xa levels may be beneficial in guiding management.
    MeSH term(s) Aged ; Aged, 80 and over ; Anticoagulants/therapeutic use ; Betacoronavirus ; Biomarkers/blood ; COVID-19 ; Case-Control Studies ; Coronavirus Infections/blood ; Coronavirus Infections/complications ; Female ; Fibrin Fibrinogen Degradation Products/metabolism ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Incidence ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/complications ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; Venous Thromboembolism/blood ; Venous Thromboembolism/drug therapy ; Venous Thromboembolism/epidemiology ; Venous Thromboembolism/virology
    Chemical Substances Anticoagulants ; Biomarkers ; Fibrin Fibrinogen Degradation Products ; Heparin, Low-Molecular-Weight ; fibrin fragment D
    Keywords covid19
    Language English
    Publishing date 2020-05-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2020-0228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: A dynamic multi-compartmental model of DNA methylation with demonstrable predictive value in hematological malignancies

    McGovern, Andrew P / Powell, Benjamin E / Chevassut, Timothy J.T

    Journal of theoretical biology. 2012 Oct. 7, v. 310

    2012  

    Abstract: Recent advances have highlighted the central role of DNA methylation in leukemogenesis and have led to clinical trials of epigenetic therapy, notably hypomethylating agents, in myelodysplasia and acute myeloid leukemia. However, despite these advances, ... ...

    Abstract Recent advances have highlighted the central role of DNA methylation in leukemogenesis and have led to clinical trials of epigenetic therapy, notably hypomethylating agents, in myelodysplasia and acute myeloid leukemia. However, despite these advances, our understanding of the dynamic regulation of the methylome remains poor. We have attempted to address this shortcoming by producing a dynamic, six-compartmental model of DNA methylation levels based on the activity of the Dnmt methyltransferase proteins. In addition, the model incorporates the recently discovered Tet family proteins which enzymatically convert methylcytosine to hydroxymethylcytosine. A set of first order, partial differential equations comprise the model and were solved via numerical integration. The model is able to predict the relative abundances of unmethylated, hemimethylated, fully methylated, and hydroxymethylated CpG dyads in the DNA of cells with fully functional Dnmt and Tet proteins. In addition, the model accurately predicts the experimentally measured changes in these abundances with disruption of Dnmt function. Furthermore, the model reveals the mechanism whereby CpG islands are maintained in a hypomethylated state via local modulation of Dnmt and Tet activities without any requirement for active demethylation. We conclude that this model provides an accurate depiction of the major epigenetic processes involving modification of DNA.
    Keywords DNA ; DNA methylation ; clinical trials ; epigenetics ; equations ; genomic islands ; models ; myeloid leukemia ; proteins ; therapeutics
    Language English
    Dates of publication 2012-1007
    Size p. 14-20.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2012.06.018
    Database NAL-Catalogue (AGRICOLA)

    Full text online

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    In stock of ZB MED Bonn / Germany

    Z 70/159: Show issues

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  7. Article: Thrombotic risk in COVID-19: a case series and case-control study

    Stoneham, Simon M / Milne, Kate M / Nuttall, Elisabeth / Frew, Georgina H / Sturrock, Beattie Rh / Sivaloganathan, Helena / Ladikou, Eleni E / Drage, Stephen / Phillips, Barbara / Chevassut, Timothy Jt / Eziefula, Alice C

    Clin Med (Lond)

    Abstract: BACKGROUND: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are ... ...

    Abstract BACKGROUND: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are extremely limited. METHODS: We describe three cases of thromboembolism refractory to heparin treatment, the incidence of VTE in an inpatient cohort, and a case-control study to identify risk factors associated with VTE. RESULTS: We identified 274 confirmed (208) or probable (66) COVID-19 patients. 21 (7.7%) were diagnosed with VTE. D-dimer was elevated in both cases (confirmed VTE) and controls (no confirmed VTE) but higher levels were seen in confirmed VTE cases (4.1 vs 1.2 µg/mL, p<0.001). CONCLUSION: Incidence of VTE is high in patients hospitalised with COVID-19. Urgent clinical trials are needed to evaluate the role of anticoagulation in COVID-19. Monitoring of D-dimer and anti-factor Xa levels may be beneficial in guiding management.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #305971
    Database COVID19

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  8. Article: dynamic multi-compartmental model of DNA methylation with demonstrable predictive value in hematological malignancies

    McGovern, Andrew P. / Powell, Benjamin E. / Chevassut, Timothy J.T.

    Journal of theoretical biology

    Volume v. 310

    Abstract: Recent advances have highlighted the central role of DNA methylation in leukemogenesis and have led to clinical trials of epigenetic therapy, notably hypomethylating agents, in myelodysplasia and acute myeloid leukemia. However, despite these advances, ... ...

    Abstract Recent advances have highlighted the central role of DNA methylation in leukemogenesis and have led to clinical trials of epigenetic therapy, notably hypomethylating agents, in myelodysplasia and acute myeloid leukemia. However, despite these advances, our understanding of the dynamic regulation of the methylome remains poor. We have attempted to address this shortcoming by producing a dynamic, six-compartmental model of DNA methylation levels based on the activity of the Dnmt methyltransferase proteins. In addition, the model incorporates the recently discovered Tet family proteins which enzymatically convert methylcytosine to hydroxymethylcytosine. A set of first order, partial differential equations comprise the model and were solved via numerical integration. The model is able to predict the relative abundances of unmethylated, hemimethylated, fully methylated, and hydroxymethylated CpG dyads in the DNA of cells with fully functional Dnmt and Tet proteins. In addition, the model accurately predicts the experimentally measured changes in these abundances with disruption of Dnmt function. Furthermore, the model reveals the mechanism whereby CpG islands are maintained in a hypomethylated state via local modulation of Dnmt and Tet activities without any requirement for active demethylation. We conclude that this model provides an accurate depiction of the major epigenetic processes involving modification of DNA.
    Keywords models ; therapeutics ; genomic islands ; myeloid leukemia ; epigenetics ; DNA methylation ; DNA ; equations ; clinical trials ; proteins
    Language English
    Document type Article
    ISSN 0022-5193
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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