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Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives.
Achilles, SL, Meyn, LA, Mhlanga, FG, Matubu, AT, Stoner, KA, Beamer, MA, Chirenje, ZM, Hillier, SL
American journal of reproductive immunology (New York, N.Y. : 1989). 2020;(3):e13287
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Abstract
PROBLEM Contraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods. METHOD OF STUDY We collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge. RESULTS Compared to baseline, the number of cervical HIV target cells (#CD4 cells P < .04 and #CD11c cells P < .04), the concentration of the inflammatory cytokine IL-1β (P < .01), and the innate in vitro anti-HIV activity (P < .001) significantly decreased following DMPA initiation. In Cu-IUD users, genital HIV target cells increased (#CD4 cells P < .001, #CD4CCR5 cells P = .02, #CD4CD69 cells P < .001, #CD8CD69 P = .01, and #CD11c cells P = .003) at day 30 and resolved by day 180. IFN-γ (P < .001), IL-1β (P < .001), IL-6 (P < .001), IL-8 (P < .001), IL-10 (P < .01), and RANTES (P < .001) were also significantly increased at day 30. Minimal alterations were observed following initiation of subdermal implantable contraceptives. CONCLUSIONS This head-to-head study compared six contraceptives and found increased HIV target cells and cervical inflammation temporally associated with Cu-IUD initiation. Use of hormonal contraception, including DMPA, did not increase cervical HIV target cells or inflammation. Clinical Trial Number: NCT02038335.
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Steroidogenesis in the skin: implications for local immune functions.
Slominski, A, Zbytek, B, Nikolakis, G, Manna, PR, Skobowiat, C, Zmijewski, M, Li, W, Janjetovic, Z, Postlethwaite, A, Zouboulis, CC, et al
The Journal of steroid biochemistry and molecular biology. 2013;:107-23
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Abstract
The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7Δ-steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases. This article is part of a Special Issue entitled 'CSR 2013'.
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Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis.
Davison, C, Ventre, KM, Luchetti, M, Randolph, AG
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2004;(5):482-9
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Abstract
BACKGROUND Viral bronchiolitis is the leading cause of respiratory failure among infants in the United States. Currently, the mainstay of treatment is supportive care. The effectiveness of treatments used for mechanically ventilated infants with bronchiolitis is unclear. OBJECTIVE To evaluate the strength of the evidence supporting the use of currently available treatments for critically ill infants with bronchiolitis. DATA SOURCE We searched PubMed, citations of relevant articles, personal files, and conference proceedings, and we contacted experts in the field. STUDY SELECTION Randomized, controlled trials evaluating any therapy for bronchiolitis that included children in an intensive care unit. DATA EXTRACTION Two reviewers independently extracted data and assessed methodologic quality. DATA SYNTHESIS A total of 2,319 citations were screened, and 16 randomized, controlled trials were included. There were three trials of surfactant, three of ribavirin, three of immune globulin, three of systemic corticosteroids, and one each of vitamin A, interferon, erythropoietin, and heliox. A meta-analysis of the three surfactant studies showed a strong trend toward a decrease in duration of mechanical ventilation of 2.58 days (95% confidence interval, -5.34 to 0.18 days; p =.07) and a significant decrease of 3.3 intensive care unit days (95% confidence interval, -6.38 to -0.23 days; p =.04). A meta-analysis of the three systemic corticosteroid studies showed no overall effect on duration of mechanical ventilation when all three trials were combined (-0.62 day; 95% confidence interval, -2.78 to 1.53 days; p =.57). We identified one published meta-analysis of three ribavirin studies showing a significant decrease in ventilator days with ribavirin (-1.2 days; 95% confidence interval, -0.2 to -3.4 days; p =.2). CONCLUSIONS Currently, there are no clearly effective interventions available to improve the outcome of critically ill infants with bronchiolitis. Surfactant seems to be a promising intervention, and corticosteroids or ribavirin may also be beneficial.