Neglected diseases caused by arenaviruses such as Lassa (LASV) and filoviruses like Ebola (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in virus entry. We hypothesize that repurposing combinations of orally administered approved drugs provides effective suppression of arenaviruses. In this report, we demonstrate that arbidol, an approved influenza antiviral previously shown to inhibit EBOV, LASV, and many other viruses, inhibits murine leukemia (MLV) reporter viruses pseudotyped with the fusion glycoproteins (GP) of other arenaviruses [Junin (JUNV), lymphocytic choriomeningitis virus (LCMV), and Pichinde (PICV)]. Arbidol and other approved drugs including aripiprazole, amodiaquine, sertraline, and niclosamide also inhibit infection of cells by infectious PICV, and arbidol, sertraline and niclosamide inhibit infectious LASV. Combining arbidol with aripiprazole or sertraline results in synergistic suppression of LASV and JUNV GP-bearing pseudoviruses. This proof-of-concept study shows that arenavirus infection in vitro can be synergistically inhibited by combinations of approved drugs. This approach may lead to a proactive strategy with which to prepare for and control known and new arenavirus outbreaks.
Background Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. Methods We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1β, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. Results We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4–10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1β (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). Conclusions We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.
Objectives: Heightened systemic inflammation is common in obese individuals and persons with HIV (PWH) and is independently associated with an increased risk of cardiovascular diseases (CVDs). We investigated the combined effect of central obesity, a surrogate measure of visceral fat and HIV on circulating levels of inflammatory cytokines among Kenyan adults. Design: A cross-sectional study. Methods: We analysed and compared data from 287 virally suppressed PWH and 277 noninfected Kenyan adults, including biomarkers of gut epithelial dysfunction (intestinal fatty acid binding protein), monocyte activation (soluble CD163 and CD14) and inflammation [interleukin (IL)-1β, IL-6, TNF-α and hsCRP] by HIV/central obesity status (HIV-positive/obese, HIV-negative/obese, HIV-positive/nonobese and HIV-negative/nonobese). Central obesity was defined as waist circumference more than 80 cm for women and more than 94 cm for men. We assessed the association of HIV/obesity status with elevated biomarkers (>75th percentile) using logistic regression. Results: Median age for participants was 44 years and 37% were centrally obese. Levels of all biomarkers were higher among the HIV-positive/obese compared with the HIV-negative/nonobese ( P < 0.05 for all comparisons). The HIV-positive/obese group had the greatest odds of having elevated inflammatory biomarkers compared with other groups even after adjustment of age, BMI and other conventional CVD risk factors ( P < 0.05 for all). Additional adjustment for sCD163 in the multivariate model substantially attenuated the association for HIV-positive/obesity with IL-1β, IL-6 and TNF-α but not hsCRP. The contribution of HIV-positive/obesity to inflammation was independent of the degree of immunosuppression. Conclusion: Central obesity is prevalent among virally suppressed African PWH and is associated with greater inflammation and monocyte activation independent of other comorbidities and HIV-specific factors.
Table 1: several rows in panels C and D were mislabeled with the wrong drug names, and two values in the "Obs" column of panel C were incorrect. The correct table is shown below.
Humans are all exposed to many different forms of radiation -radio waves, microwaves, ultraviolet, Xrays, etc. The form of radiation involved in Nuclear Medicine is called ionising radiation. This poster will provide advice to haemodialysis staff that may have to carry out dialysis on patients who have received ionising radiation as part of a medical investigation. All patients who are referred to the Nuclear Medicine Department for imaging procedures are given an injection of a pharmaceutical preparation with a radioactive compound attached to it. The vast majority of the patients are studied using Technetium -99m as a radioactive tag but on occasions, compounds like Iodine -123 and Gallium-67 are also used. The different radioactive materials have different physical decay rates. Following administration of the pharmaceutical agent, the patient is deemed "radioactive". For this reason, unless it is clinically justified, haemodialysis should not be performed on patients in the 24 h period after a nuclear medicine injection. However, if haemodialysis is required, certain protocols must be carried out, because some risks are associated with the procedure. The main risks associated with these patients are external irradiation, internal contamination and fluid over load. Due to the short half-life of the radioactivity, these risks, in general, only warrant control in the 24 h period following the radioactive injection.
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