scholarly journals Enhanced HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women correlates with increased inflammatory responses

2011 ◽  
Vol 4 (6) ◽  
pp. 671-681 ◽  
Author(s):  
C Rollenhagen ◽  
S N Asin
Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 231
Author(s):  
Carolina Herrera ◽  
Mike D. McRaven ◽  
Ken G. Laing ◽  
Jayne Dennis ◽  
Thomas J. Hope ◽  
...  

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242774
Author(s):  
Alexander Tacey ◽  
Cassandra Smith ◽  
Mary N. Woessner ◽  
Paul Chubb ◽  
Christopher Neil ◽  
...  

Background There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits. Methods In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions. Results ucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p < 0.05), particularly in women (p < 0.01). In all participants, higher ucOC was associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p > 0.05). Conclusion Increased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo, has direct or indirect effects on blood vessel function.


2017 ◽  
Author(s):  
Christopher J. Nicholson ◽  
Michèle Sweeney ◽  
Stephen C. Robson ◽  
Michael J. Taggart

AbstractThe beneficial role of oestrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of oestrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of the menopause and ageing on the acute vasodilatory effects of oestrogen in ex vivo uterine resistance arteries.Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre-(42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Ageing was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodelling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-oestradiol (non-specific oestrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by ageing and the menopause. However, the impairment of oestrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that adverse resistance arterial ageing is a dominant factor leading to weakened vasodilatory action of oestrogenic compounds.


1976 ◽  
Vol 35 (02) ◽  
pp. 403-414 ◽  
Author(s):  
Terence Davies ◽  
Gillian Fieldhouse ◽  
George P. McNicol

SummaryThe effects on the haemostatic mechanism of oestrogen therapy, given to prevent bone loss in post-menopausal women, have been investigated. Oestriol succinate was given orally to 10 women at a level of 2 mg/day for 1 month and for a further 3 months with incremental increase of 2 mg each month. 6 of the 10 women were subsequently treated with 25 μg/day orally of ethinyl oestradiol. Oestriol succinate therapy resulted in a small increase in the level of factor VII, a decrease in factor VIII concentration and increased sensitivity of platelets to aggregating agents. Ethinyl oestradiol treatment resulted in much more widespread changes with marked increases in coagulation factors VII, VIII, IX and X, decreased levels of antithrombin and dramatic increases in circulating plasminogen levels and euglobulin lysis activity. The data suggested that the nature of oestrogens employed therapeutically is important in determining the qualitative and quantitative effect of oestrogen therapy on components of the haemostatic mechanism.


2016 ◽  
Author(s):  
Antimo Moretti ◽  
Sire Alessandro de ◽  
Dario Calafiore ◽  
Raffaele Gimigliano ◽  
Francesca Gimigliano ◽  
...  

2016 ◽  
Author(s):  
Fernando Blanco-Rodriguez ◽  
Nicole Ellis-Infante ◽  
Victor Lopez-Rivas ◽  
Sherlin May-Kim ◽  
Charlotte Pickett ◽  
...  

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