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1.
Bioconjug Chem ; 33(8): 1574-1583, 2022 08 17.
Article in English | MEDLINE | ID: covidwho-1977960

ABSTRACT

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.


Subject(s)
Thrombocytopenia , Antibodies, Monoclonal/therapeutic use , Anticoagulants/adverse effects , Fondaparinux/adverse effects , Heparin/adverse effects , Humans , Platelet Factor 4/metabolism , Platelet Factor 4/therapeutic use , Polysaccharides , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
2.
Front Public Health ; 10: 787299, 2022.
Article in English | MEDLINE | ID: covidwho-1775992

ABSTRACT

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.


Subject(s)
Acne Vulgaris , Drug Resistance, Bacterial , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Drug Resistance, Bacterial/genetics , Humans , Macrolides/pharmacology , Macrolides/therapeutic use , Microbial Sensitivity Tests
3.
Life (Basel) ; 11(8)2021 Aug 13.
Article in English | MEDLINE | ID: covidwho-1376885

ABSTRACT

Cancer cells circulating in blood vessels activate platelets, forming a cancer cell encircling platelet cloak which facilitates cancer metastasis. Heparin (H) is frequently used as an anticoagulant in cancer patients but up to 5% of patients have a side effect, heparin-induced thrombocytopenia (HIT) that can be life-threatening. HIT is developed due to a complex interaction among multiple components including heparin, platelet factor 4 (PF4), HIT antibodies, and platelets. However, available information regarding the effect of HIT components on cancers is limited. Here, we investigated the effect of these materials on the mechanical property of breast cancer cells using atomic force microscopy (AFM) while cell spreading was quantified by confocal laser scanning microscopy (CLSM), and cell proliferation rate was determined. Over time, we found a clear effect of each component on cell elasticity and cell spreading. In the absence of platelets, HIT antibodies inhibited cell proliferation but they promoted cell proliferation in the presence of platelets. Our results indicate that HIT complexes influenced the development of breast cancer cells.

4.
Int J Environ Res Public Health ; 17(9)2020 04 28.
Article in English | MEDLINE | ID: covidwho-133668

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic aroused global public concern and became a major medical issue. This study aims to investigate the global research routine and trends of coronavirus over the last twenty years based on the production, hotspots, and frontiers of published articles as well as to provide the global health system with a bibliometric reference. The Web of Science core collection database was retrieved for coronavirus articles published from 1 January 2000 to 17 March 2020. Duplicates and discrete papers were excluded. Analysis parameters including time, regions, impact factors, and citation times were processed through professional software. A total of 9043 coronavirus articles originated from 123 countries and were published in 1202 journals. The USA contributed most articles (3101) followed by China (2230). The research was published in specialized journals including the Journal of Virology. Universities were the main institutions of science progress. High-impact articles covered fields of basic science and clinical medicine. There were two sharp increases in research yields after the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) outbreaks. International collaborations promoted study progress, and universities and academies act as the main force in coronavirus research. More research on prevention and treatment is needed according to an analysis of term density.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus , Global Health/trends , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome/epidemiology , Betacoronavirus , Bibliometrics , COVID-19 , Disease Outbreaks , Humans , SARS-CoV-2
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