Characterization of copper in uterine fluids of patients who use the copper T-380A intrauterine device.
ABSTRACT The copper intrauterine device (IUD) is a highly effective method of contraception that requires the dissolution of the copper into uterine cavity. However, there is little information about the amount and form of copper in the fluid and whether the presence of this element produces any change in the protein concentration.
Twenty-seven women were divided into three groups that had used IUD for about 6 months, 1 year and > or =3 years. The samples were collected during the proliferative phase (Pp), secretory phase (Sp) and menstruation (M). Square-wave anodic stripping voltammetry (SWASV), cyclic voltammetry (CV), high performance liquid chromatography (HPLC) and atomic absorption spectrometry (AAS) were used in this study.
Total copper concentrations were between 3.9 and 19.1 micro g/ml. The mean and standard deviations were as follows: 6 months, 11.4+/-4.7 micro g/ml of copper; 1 year, 11.5+/-7.0 micro g/ml of copper; and 3 years, 6.2+/-1.5 micro g/ml of copper. Total proteins were quantified by measuring the area under the chromatographic peaks. The mean areas obtained with uterine fluid samples from women who used IUDs for 6 months, 1 year and 3 years were 290,013, 538,934 and 201,863 arbitrary units (AU), respectively. The control sample was only 22323.
The amount of copper released from IUD, although high, is in the form of complexes with proteins. IUDs have a constant copper release for at least 6-12 months. Copper(I) was not detected in the fluid. Copper induces a change in the total protein concentration. The amount of copper released and the amount of proteins is slightly larger during the menstrual stage.
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ABSTRACT: A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P<0.05) was identified when the observation period was terminated, and the changes of nano-Cu/LDPE on these parameters were less remarkable than those of the Cu group (P<0.05). The damage to the endometrial morphology caused by the nano-Cu/LDPE composite was much less than that caused by bulk copper. The nano-Cu/LDPE composite might be a potential substitute for conventional materials for intrauterine devices in the future because of its decreased adverse effects on the endometrial microenvironment.International Journal of Nanomedicine 01/2014; 9:1127-38. · 4.20 Impact Factor
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ABSTRACT: Devices and materials intended for clinical applications as medical and implant devices should be evaluated to determine their biocompatibility in physiological systems. This article presents results from cytotoxicity assay of L929 mouse fibroblasts culture, tests for skin irritation, intracutaneous reactivity and sensitization, and material implantation tests for the novel copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD) with potential for future clinical utilization. Cytotoxicity test in vitro was conducted to evaluate the change in morphology, growth and proliferation of cultured L929 mouse fibroblasts, which in vivo examination for skin irritation (n = 6) and intracutaneous reactivity (n = 6) were carried out to explore the irritant behavior in New Zealand White rabbits. Skin sensitization was implemented to evaluate the potential skin sensitizing in Hartley guinea pigs (n = 35). The materials were implanted into the spinal muscle of rabbits (n = 9). The cytotoxicity grade of the nano-Cu/LDPE IUD was 0-1, suggested that the composite was nontoxic or mildly cytotoxic; no irritation reaction and skin sensitization were identified in any animals of specific extracts prepared from the material under test; similarly to the control sides, the inflammatory reaction was observed in the rabbits living tissue of the implanted material in intramuscular implantation assay. They indicated that the novel composite intrauterine device presented potential for this type of application because they meet the requirements of the standard practices recommended for evaluating the biological reactivity. The nano-Cu/LDPE IUD has good biocompatibility, which is biologically safe for the clinical research as a novel contraceptive device.PLoS ONE 01/2013; 8(9):e74128. · 3.53 Impact Factor
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ABSTRACT: There are multiple advantages to “extended use” of the intrauterine device (IUD) use beyond the manufacturer-approved time period, including prolongation of contraceptive and non-contraceptive benefits. We performed a literature review of studies that have reported pregnancy outcomes associated with extended use of IUDs, including copper IUDs and the levonorgestrel intrauterine system (LNG-IUS). Among parous women who are at least 25 years old at the time of IUD insertion, there is good evidence to support extended use of the following devices: the TCu380A and the TCu220 for 12 years, the Multiload Cu-375 for 10 years, the frameless GyneFix® (330 mm2) for 9 years, the levonorgestrel intrauterine system 52 mg (Mirena®) for 7 years and the Multiload Cu-250 for 4 years. Women who are at least 35 years old at the time of insertion of a TCu380A IUD can continue use until menopause with a negligible risk of pregnancy. We found no data to support use of the LNG-IUS 13.5 mg (Skyla®) beyond 3 years. When counseling about extended IUD use, clinicians should consider patient characteristics and preferences, as well as country- and community-specific factors. Future research is necessary to determine the risk of pregnancy associated with extended use of the copper IUD and the LNG-IUS among nulliparous women and women less than 25 years old at the time of IUD insertion. More data are needed on the potential effect of overweight and obesity on the long-term efficacy of the LNG-IUS.Contraception 01/2014; · 3.09 Impact Factor