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Invasive group B streptococcal infection in infants in Shenzhen, China.

2017-05-30

To compare the 2-year effects of raloxifene (Rlx) with oral postmenopausal hormone therapy (HT) on serum markers of brain and whole-body cholesterol metabolism.

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.

Long-term care facilities.

Raloxifene significantly shortened the time to return of chronic pelvic pain. Because recurrence of endometriosis lesions did not correlate with return of pain, other factors are implicated in pelvic pain.

Ovarian steroids, particularly oestrogen, are important factors for fibroid growth. This has provided a rationale for the investigation of hormonal therapies for women with fibroids. This chapter will assess the role of hormonal therapies for pre-menopausal women with fibroids. A comprehensive search of MEDLINE and EMBASE was undertaken in December 2006. Twenty-nine relevant randomized controlled trials and two systematic reviews were found. The included studies assessed gonadotrophin-releasing hormone analogues (GnRHa) alone, GnRHa plus add-back (with either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene) and GnRHa given for at least 3 months prior to surgery for fibroids. Two trials assessed the effects of raloxifene alone. One trial assessed the effects of low-dose mifepristone, and a pilot study assessed the role of the selective progesterone receptor modulator, asoprisinil. GnRHa reduce fibroid and uterine volume and heavy bleeding but are associated with menopausal symptoms and bone loss, which limit long-term use. There is some evidence that add-back therapy, either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene, can reduce the menopausal symptoms associated with GnRHa and/or loss of bone density, but there is insufficient good-quality research to make definitive conclusions. GnRHa given for at least 3 months before fibroid surgery improve pre-operative haemoglobin concentration and haematocrit, reduce uterine and pelvic symptoms, and reduce the rate of vertical incisions during laparotomy. Women undergoing hysterectomy are more likely to have a vaginal than an abdominal procedure. Limited evidence suggests that raloxifene may be useful in older premenopausal women with lower concentrations of background oestradiol. Limited short-term evidence of two progestogenic therapies indicates that low-dose mifepristone may improve quality of life and bleeding in the short term, and asoprisinil may improve bleeding and fibroid-related symptoms. In conclusion, more research is required on the role of hormonal therapies for women with fibroids, particularly add-back options and selective oestrogen and progesterone receptor modulators. No definitive conclusions can be reached on the basis of the limited evidence found.

Raloxifene, a selective estrogen receptor modulator used for the treatment of osteoporosis, undergoes extensive conjugation to the 6-beta- and 4'-beta-glucuronides in vivo. This paper investigated raloxifene glucuronidation by human liver and intestinal microsomes and identified the responsible UDP-glucuronosyltransferases (UGTs). UGT1A1 and 1A8 were found to catalyze the formation of both the 6-beta- and 4'-beta-glucuronides, whereas UGT1A10 formed only the 4'-beta-glucuronide. Expressed UGT1A8 catalyzed 6-beta-glucuronidation with an apparent K(m) of 7.9 microM and a V(max) of 0.61 nmol/min/mg of protein and 4'-beta-glucuronidation with an apparent K(m) of 59 microM and a V(max) of 2.0 nmol/min/mg. Kinetic parameters for raloxifene glucuronidation by expressed UGT1A1 could not be determined due to limited substrate solubility. Based on rates of raloxifene glucuronidation and known extrahepatic expression, UGT1A8 and 1A10 appear to be primary contributors to raloxifene glucuronidation in human jejunum microsomes. For human liver microsomes, the variability of 6-beta- and 4'-beta-glucuronide formation was 3- and 4-fold, respectively. Correlation analyses revealed that UGT1A1 was responsible for 6-beta- but not 4'-beta-glucuronidation in liver. Treatment of expressed UGTs with alamethicin resulted in minor increases in enzyme activity, whereas in human intestinal microsomes, maximal increases of 8-fold for the 6-glucuronide and 9-fold for the 4'-glucuronide were observed. Intrinsic clearance values in intestinal microsomes were 17 microl/min/mg for the 6-glucuronide and 95 microl/min/mg for the 4'-isomer. The corresponding values for liver microsomes were significantly lower, indicating that intestinal glucuronidation may be a significant contributor to the presystemic clearance of raloxifene in vivo.