IMPAACT P1097 was a multicenter trial to determine washout pharmacokinetics and safety of in utero/intrapartum exposure to raltegravir in infants born to HIV-infected pregnant women receiving raltegravir-based antiretroviral therapy. Twenty-two mother-infant pairs were enrolled; evaluable pharmacokinetic data was available from 19 mother-infant pairs. Raltegravir readily crossed the placenta, with median cord blood/maternal delivery plasma raltegravir concentration ratio 1.48 (range, 0.32–4.33). Raltegravir elimination was highly variable and extremely prolonged in some infants; [median t½ 26.6 hours (range 9.3–184 hours)]. Prolonged raltegravir elimination likely reflects low neonatal UGT1A1 enzyme activity and enterohepatic recirculation. Excessive raltegravir concentrations must be avoided in the neonate, since raltegravir at high plasma concentrations may increase the risk of bilirubin neurotoxicity. Sub-therapeutic concentrations, which could lead to inadequate viral suppression and development of raltegravir resistance, must be avoided as well. Two ongoing IMPAACT studies are investigating further the pharmacology of raltegravir in neonates.

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This study investigates whether goserelin can inhibit ovarian cancer proliferation and protect ovarian function from cisplatin (CDDP). We evaluated proliferation and AKT phosphorylation in goserelin-treated ES-2 and SKOV3-ip ovarian cancer cells. Anti-Müllerian hormone (AMH) in human granulosa cells (hGCs) cotreated with goserelin and CDDP was measured by ELISA. Tumour volumes, Ki-67 expression, estrus, follicles, ovarian volumes, and serum AMH were compared in nude mice bearing transplanted tumours treated with goserelin and/or CDDP. Our results showed that goserelin inhibited cellular proliferation and AKT phosphorylation in vitro, and inhibited tumour growth and Ki-67 expression in vivo. Goserelin and CDDP cotreatment decreased the estrus cycles of the nude mice and prolonged estrus duration. Goserelin abrogated the CDDP-induced down-regulation of primary and preantral follicle percentage and ovarian volume. Goserelin increased AMH secretion in vitro and in vivo. In conclusion, goserelin inhibited ovarian cancer proliferation and simultaneously protected ovarian function from CDDP.

Objectives Our study purpose was to detect the distribution of anti-nuclear antibody (ANA) IgG subclasses in patients with systemic lupus erythematosus (SLE) and to evaluate their influence on the inflammatory process in SLE. Methods We determined the serum levels of ANA IgG subclasses from 70 SLE patients, 25 patients with other autoimmune diseases (OAD), and 25 healthy controls using ELISA. The serum level of total ANA IgG and the avidity of ANA IgG, dsDNA IgG, and dsDNA IgG subclasses were analysed by ELISA. Results The results indicated that levels of four ANA IgG subclasses (IgG1, IgG2, IgG3 and IgG4) and total IgG were significantly higher in SLE patients than in OAD patients and healthy controls ( p < 0.001). Moreover, the level of each ANA IgG subclass and the prevalence of high-avidity IgG ANAs (HA IgG ANAs) were significantly higher in the active cases than in the inactive cases of SLE and LN. Furthermore, level of ANA IgG subclasses decreased as level of dsDNA IgG subclasses decreased in 30 patients with SLE. In comparison, ANA IgG3 was significantly effective in high-dose prednisone combined with hydroxychloroquine ( p = 0.025). Additionally, it revealed that level of dsDNA IgG had a significant influence on four ANA IgG subclasses, especially on ANA IgG3 (β coefficient = 0.649, p < 0.001). Level of ANA IgG3 was also positively related to the serum level of dsDNA IgG (r = 0.729, p < 0.001) and RAI of HA IgG ANAs (r = 0.504, p < 0.001). However, the level of ANA IgG4 was positively related to the serum level of albumin (r = 0.572, p < 0.001) and RAI of HA IgG ANAs (r = 0.549, p < 0.001). Moreover, the results revealed that cutaneous and renal involvement were mainly associated with the ANA IgG1 and IgG4 subclasses. Although, arthritic involvement was mainly associated with ANA IgG3. Conclusions First, we demonstrated that the ANA IgG subclasses were diagnostic tools in SLE patients. Furthermore, HA IgG ANAs might affect the distribution of ANA IgG3 and IgG4. Moreover, ANA IgG3 might play a particular role in the activity of SLE disease and therapy. Therefore, an altered ANA IgG subclass distribution might be a risk factor influencing the inflammatory process in SLE.