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  • 1
    Online Resource
    Online Resource
    Use of the NP-40 Detergent-Mediated Assay in Discovery of Inhibitors of β-Hematin Crystallization
    American Society for Microbiology ; 2011
    In:  Antimicrobial Agents and Chemotherapy Vol. 55, No. 7 ( 2011-07), p. 3363-3369
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 55, No. 7 ( 2011-07), p. 3363-3369
    Abstract: The protozoan parasite responsible for malaria affects over 500 million people each year. Current antimalarials have experienced decreased efficacy due to the development of drug-resistant strains of Plasmodium spp., resulting in a critical need for the discovery of new antimalarials. Hemozoin, a crystalline by-product of heme detoxification that is necessary for parasite survival, serves as an important drug target. The quinoline antimalarials, including amodiaquine and chloroquine, act by inhibiting the formation of hemozoin. The formation of this crystal does not occur spontaneously, and recent evidence suggests crystallization occurs in the presence of neutral lipid particles located in the acidic digestive vacuole of the parasite. To mimic these conditions, the lipophilic detergent NP-40 has previously been shown to successfully mediate the formation of β-hematin, synthetic hemozoin. Here, an NP-40 detergent-based assay was successfully adapted for use as a high-throughput screen to identify inhibitors of β-hematin formation. The resulting assay exhibited a favorable Z ′ of 0.82 and maximal drift of less than 4%. The assay was used in a pilot screen of 38,400 diverse compounds at a screening concentration of 19.3 μM, resulting in the identification of 161 previously unreported β-hematin inhibitors. Of these, 48 also exhibited ≥90% inhibition of parasitemia in a Plasmodium falciparum whole-cell assay at a screening concentration of 23 μM. Eight of these compounds were identified to have nanomolar 50% inhibitory concentration values near that of chloroquine in this assay.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00121-11
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Association of Obesity and Diabetes With SARS-CoV-2 Infection and Symptoms in the COVID-19 Community Research Partnership
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 6 ( 2023-05-17), p. e295-e305
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 6 ( 2023-05-17), p. e295-e305
    Abstract: Obesity and diabetes are established risk factors for severe SARS-CoV-2 outcomes, but less is known about their impact on susceptibility to COVID-19 infection and general symptom severity. Objective We hypothesized that those with obesity or diabetes would be more likely to self-report a positive SARS-CoV-2 test, and, among those with a positive test, have greater symptom severity and duration. Methods Among 44 430 COVID-19 Community Research Partnership participants, we evaluated the association of self-reported and electronic health record obesity and diabetes with a self-reported positive COVID-19 test at any time. Among the 2663 participants with a self-reported positive COVID-19 test during the study, we evaluated the association of obesity and diabetes with self-report of symptom severity, duration, and hospitalization. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and health care worker status. Results We found a positive graded association between body mass index (BMI) category and positive COVID-19 test (overweight odds ratio [OR] 1.14 [1.05-1.25] ; obesity I OR 1.29 [1.17-2.42]; obesity II OR 1.34 [1.19-1.50] ; obesity III OR 1.53 [1.35-1.73]), and a similar but weaker association with COVID-19 symptoms and severity among those with a positive test. Diabetes was associated with COVID-19 infection but not symptoms after adjustment, with some evidence of an interaction between obesity and diabetes. Conclusion While the limitations of this health system convenience sample include generalizability and selection around test seeking, the strong graded association of BMI and diabetes with self-reported COVID-19 infection suggests that obesity and diabetes may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic factors.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgac715
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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