Time-dependent expression of cytochrome p450 epoxygenases during human prenatal development

There is growing evidence that some members of cytochrome P450 enzymes contribute to regulation of normal prenatal development. CYP epoxygenases (CYP2C and CYP2J subfamilies) convert arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active molecules involved in mitogenesis and cell signaling. Almost nothing is known about localization of their expression in tissues during human prenatal development. The spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2C19 and CYP2J2 in human embryonic/fetal intestines, liver, and kidney was investigated by immunohistochemical method. CYP epoxygenases are expressed already in early stages of development in these embryonic/fetal tissues (as early as 7th week of IUD in the intestines, 5th week of IUD in the liver, and 6th week of IUD in the kidney). In kidney, CYP epoxygenases are expressed in the metanephrogenic blastema (but not in the uninduced mesenchyme) and in the tubular system. In the intestines, diverse CYP epoxygenases distribution along crypt-villus axis could suggest role in cell differentiation. Moreover, we detected higher CYP2J2 level in these organs than in adult tissue samples.     

Inhibition of an IUD-induced precocious luteolysis by prostaglandin E1 (PGE1) in sheep

Fifteen ewes were assigned as they came into estrus to one of three randomized treatment groups: 1. Sham IUD + Vehicle, 2. IUD + Vehicle or 3. IUD + PGE1 in vehicle. An IUD was inserted adjacent to the luteal-bearing ovary on day 3 postestrus. Prostaglandin E1 (500 micrograms) in vehicle (Na2CO3) or vehicle was given intrauterine through an indwelling uterine cannula every four hours from day 3 postestrus until ewes returned to estrus. Precocious estrus was induced in both the sham IUD and IUD groups receiving vehicle. Prostaglandin E1 prevented an IUD-induced premature luteolysis based on daily concentrations of progesterone in peripheral blood and the interestrous interval. It is concluded that an IUD-induced premature luteolysis is not necessarily via physical distention by the IUD. It is also concluded that chronic intrauterine infusions of PGE1 can prevent an IUD-induced premature luteolysis.     

Time-dependent expression of cytochrome p450 epoxygenases during human prenatal development

There is growing evidence that some members of cytochrome P450 enzymes contribute to regulation of normal prenatal development. CYP epoxygenases (CYP2C and CYP2J subfamilies) convert arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active molecules involved in mitogenesis and cell signaling. Almost nothing is known about localization of their expression in tissues during human prenatal development. The spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2C19 and CYP2J2 in human embryonic/fetal intestines, liver, and kidney was investigated by immunohistochemical method. CYP epoxygenases are expressed already in early stages of development in these embryonic/fetal tissues (as early as 7th week of IUD in the intestines, 5th week of IUD in the liver, and 6th week of IUD in the kidney). In kidney, CYP epoxygenases are expressed in the metanephrogenic blastema (but not in the uninduced mesenchyme) and in the tubular system. In the intestines, diverse CYP epoxygenases distribution along crypt-villus axis could suggest role in cell differentiation. Moreover, we detected higher CYP2J2 level in these organs than in adult tissue samples.     

Inhibition of an IUD-induced precocious luteolysis by prostaglandin E1 (PGE1) in sheep

Fifteen ewes were assigned as they came into estrus to one of three randomized treatment groups: 1. Sham IUD + Vehicle, 2. IUD + Vehicle or 3. IUD + PGE₁ in vehicle. An IUD was inserted adjacent to the luteal-bearing ovary on day 3 postestrus. Prostaglandin E₁ (500 μg) in vehicle (Na₂CO₃) or vehicle was given intrauterine through an indwelling uterine cannula every four hours from day 3 postestrus until ewes returned to estrus. Precocious estrus was induced in both the sham IUD groups receiving vehicle. Prostaglandin E₁ prevented an IUD-induced premature luteolysis based on daily concentrations of progesterone in peripheral blood and the interestrous interval. It is concluded that an IUD-induced premature luteolysis is not necessarily via physical distention by the IUD. It is also concluded that chronic intrauterine infusions of PGE₁ can prevent an IUD-induced premature luteolysis.     

Association of amoebae and actinomyces in an intrauterine contraceptive device user

A patient wearing an intrauterine contraceptive device (IUD) was diagnosed as being colonized by Actinomyces and amoebae by examination of a routine Papanicolaou smear. The patient received vaginal treatment with metronidazole, which temporarily eliminated the protozoa; however, it was necessary to remove the IUD to definitively eradicate the microorganisms. Follow-up Papanicolaou smears taken after removal of the IUD have been normal and free of both microorganisms.     

IUD appendicitis during pregnancy.

This case shows that abdominal and pelvic x-ray examinations may not adequately show a misplaced IUD in a gravid woman, and further workup is necessary after delivery if the IUD is not clearly visible on the initial x-ray films. It also shows that chronic inflammation may develop in the area of a misplaced IUD, producing chronic abdominal pain and complications, even after several years have transpired. Finally, patients may still be at risk for complications after an IUD has been removed because of the dense adhesions that develop due to the chronic inflammatory response elicited by the IUD.     

Fertility control using intrauterine devices: an alternative for population control in wild horses

The purpose of this study was to develop a contraceptive method for feral horses. The feral horse population has increased significantly in recent years despite attempts to control numbers. As in most wild animal population control programs, contraceptive methods must be easy to apply, cause minimal disruption to the social structure and be fully reversible. In the present study, we tested the effectiveness of an intrauterine device (IUD) for fertility control in mares. Six mares were fitted with a silastic O-ring-shaped IUD on July 1 of Year 1. The IUD-treated mares were turned out with 12 nontreated mares and a fertile stallion in a large pasture until October 20 (112 d). None of the IUD-treated mares and all the nontreated mares became pregnant. The IUD-treated mares were maintained separately from the stallion during the winter. Following removal of the IUD on April 27 of Year 2, the mares were again introduced to the pasture with the stallion together with 6 nontreated mares. For the 6 mares previously treated with an IUD, the mean interval from introduction to the stallion to conception was 17.5 +/- 5 d or 1.3 cycles per pregnancy, and all mares produced a normal foal at term. Subsequently, 19 recorded mare breeding seasons resulted in 18 foals. Uterine cytology and histopathology indicate that the IUD causes mild chronic endometritis without permanent changes in the endometrium. We conclude that based on our observations, the O-ring-shaped IUD is an effective, safe and practical contraceptive method for mares.     

Retention function of all segments of IUD usage: a compound distribution.

The distribution of the all segments of IUD use consists of two components: the distribution of the length of each segment and the distribution of the number of segments. In this article, a compound distribution of all segments of IUD, developed by the authors is described. The distribution assumes that each segment of IUD use is a mixed exponential distribution and the number of segments experienced by women is a truncated Poisson distribution. This distribution is useful in estimating the demographic impact of an IUD and IUD program.     

Comparing the effectiveness of copper intrauterine devices available in Canada. Is FlexiT non-inferior to NovaT when inserted immediately after first-trimester abortion? Study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: We describe the rationale and protocol for a randomized noninferiority controlled trial (RCT) to determine if the Flexi-T380(+) copper intrauterine contraceptive device (IUD) is comparable in terms of effectiveness and expulsion rates to the most common Canadian IUD currently in use, NovaT-200, when placed immediately after a first-trimester abortion. METHODS: Consenting women choosing to use an IUD after an abortion for a pregnancy of less than 12 weeks of gestation will be randomized to device-type groups to receive immediate post-abortion placement of either a Flexi-T380(+) IUD, a device for which no current evidence on expulsion or effectiveness rates is available, or the Nova-T200 IUD, the only other brand of copper IUD available in Canada at the time of study initiation. The primary outcome measure is IUD expulsion rate at 1 year. Secondary outcomes include: pregnancy rate, method continuation rate, complication rates (infection, perforation), and satisfaction with contraceptive method. A non-intervention group of consenting women choosing a range of other post-abortion contraception methods, including no contraception, will be included for comparison of secondary outcomes. Web-based contraception satisfaction questionnaires, clinical records, and government-linked health administrative databases will be used to assess primary and secondary outcomes. DISCUSSION: The RCT design, combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry, and hospital records, offers a unique opportunity to determine if a novel IUD has a comparable expulsion rate to that of the current standard IUD in Canada, in addition to the first opportunity to determine pregnancy rate and method satisfaction at 1 year post-abortion for women choosing a range of post-abortion contraceptive options. We highlight considerations of design, implementation, and evaluation of the first trial to provide rigorous evidence for the effectiveness of current Canadian IUDs when inserted after first-trimester abortion.Trial registrationClinicalTrials.gov Identifier NCT01174225.     

21例人流术后节育器嵌顿致滞留或残留于宫内取出的临床分析

目的探讨带器妊娠行人工流产术后节育器嵌顿致滞留或残留于宫内患者取出节育器的效果。方法回顾性分析2006年2月～2009年12月期间在永康市计划生育指导站21例患者的临床资料。结果21例在B超引导下,均成功取出。结论对放置IUD的妇女要定期复查,对放置IUD避孕失败的妇女,明确宫腔内是否有IUD,做到早发现,早诊断,及时正确地处理。     

Incidence of actinomycetes infection in women using intrauterine contraceptive devices

Pancervicovaginal smears taken from 350 women using an intrauterine contraceptive device (IUD) were screened for the presence of actinomycetes organisms. Of the 12 cases in which actinomycetes-like organisms were seen in Papanicolaou-stained smears, the presence of actinomycetes organisms was confirmed by immunofluorescence in 10 cases. The prevalence of actinomycetes infection was thus 2.8% (10 of 350 cases) in the IUD users. Eight (4.3%) of 173 symptomatic subjects had actinomycetes infections. Two of the positive cases were asymptomatic. Eight of the ten patients with confirmed actinomycetes infection were using the Cu T device while two were wearing the Lippes Loop IUD. Seven of the ten patients had been using an IUD for more than two years. The time of insertion of the IUD (postpuerperal, postmenstrual or after medical termination of pregnancy) did not show any correlation with the presence of actinomycetes infection. Actinomyces israelii was responsible for the infection in eight cases while Arachnia propionica was seen in two cases. The organisms could not be grown in culture.     

Pelvic inflammatory disease and the intrauterine device: findings in a large cohort study.

The incidence of pelvic inflammatory disease was investigated among parous women taking part in the Oxford-Family Planning Association contraceptive study. Hospital admission rates for "acute definite" disease were 1.51 per 1000 woman-years among those currently using an intrauterine device (IUD) and 0.14 per 1000 woman-years among those using other methods of birth control (age-standardised relative risk 10.5 to 1 with 95% confidence limits of 5.4 to 1 and 32 to 1). There was little evidence of an increased risk of such disease in ex-users of an IUD. Hospital admission for "chronic definite" disease, on the other hand, was commoner in ex-users of an IUD than in current users. Acute definite disease occurred somewhat more frequently during the early months of use of an IUD than during the later months. While the rate of such disease was increased in users of each type of device, the highest rate (8.1 per 1000 woman-years) was observed in users of the Dalkon shield. This rate, however, was based on only three affected women.     

Inhibition of DNA synthesis in isolated human endometrial cells by a levonorgestrel-releasing intrauterine device

OBJECTIVE: To estimate the effect of an intrauterine device (IUD) releasing 20 micrograms levonorgestrel (LNG) per 24 hours on DNA synthesis in human endometrial cells before and after 12 months of use. STUDY DESIGN: Endometrial specimens were collected from the anterior or posterior wall of the miduterus from 6 females on cycle day 10-12 before insertion of the IUD and after 12 months of use. RESULTS: Previous results from our group did not reveal any influence on endometrial DNA cell content when a levonorgestrel IUD releasing 2 micrograms/24 h was used for 12 months in a group of fertile females. In this study, the IUD release rate, 20 micrograms LNG/24 h, was statistically significantly different from the results in the previous studies. The effect of the levonorgestrel IUD on endometrial proliferation was dose dependent, and a significant correlation could be found between continuous exposure to LNG and inhibition of DNA synthesis in endometrial cells. CONCLUSION: Inhibition of proliferative activity in endometrial cells seems to be reflected by a decrease in DNA synthesis per cell nucleus and contributes to the clinical performance of the LNG-releasing IUD.     

Morphological,Molecular and Pathological Characterization of Phytophthora amaranthi sp. nov. from Amaranth in Taiwan

In the spring of 2007, a serious disease on amaranth was noticed in several farms in the major amaranth production area in central Taiwan. Abundant oospores were found in the disease tissues. A species of Phytophthora was consistently isolated from disease tissues. The organism formed abundant oospores with smooth walls and with amphigynous antheridia in single culture. Sporangia were partially deciduous with short‐ to medium‐length pedicels. Morphological characteristics of this organism did not match any reported Phytophthora species, and the organism was named Phytophthora amaranthi. Pathogenicity tests and molecular characterization confirmed the identity of the organism as a new pathogen of amaranth and a new species of Phytophthora.     

Mechanisms behind intrauterine device-induced luteal persistence in mares

Intrauterine glass balls are used to prevent oestrous signs in sports mares, but the mechanism of action is unknown. It has been suggested that the glass ball can mimic an embryo or act via an induced chronic uterine inflammation and absent or continuous low-grade prostaglandin (PG) release. The purpose of this study was to induce prolonged luteal function in mares using a small intrauterine device (IUD) and to study the mechanisms behind prolonged IUD-induced luteal function. A uterine swab and a biopsy specimen were obtained in early oestrus. A water-filled plastic ball, diameter 20mm and weight 3.6g, was inserted into the uterus 2-4 days after ovulation; the control mares underwent similar cervical manipulation without ball insertion. The mares were examined three times per week until day 23 and twice weekly thereafter until they returned to oestrus (transrectal palpation, ultrasonography and progesterone determination). The location of the IUD was recorded and ultrasound scans were video-recorded to assess the frequency of uterine contractions. When the mare returned to oestrus, a uterine swab and biopsy specimen were obtained and the bacteriological, cytological and histological (inflammation and glandular dilation) results compared with the samples obtained before the IUD insertion. The PG F(2alpha) metabolite levels were measured in the plasma of four control mares and eight IUD mares on days 11-16. The IUD induced a prolonged luteal phase in 75% of the mares (9/12; IUD-P); the mean dioestrous length was 57.0 days. The three mares that did not respond to the IUD (IUD-N) showed a mean dioestrous length of 15.7 days and the 12 control mares 16.1 days. The inflammation and glandular dilation scores were not significantly different in pre- and post-manipulation biopsy specimens. Although locational changes of the IUD were observed, they occurred over very small distances and were mostly limited within the body-bifurcation area. The IUD-N and control mares showed increased uterine contractility 11-16 days post-ovulation, whereas the IUD-P mares did not. The control mares (n=4) and IUD-N mares (n=2) showed increased PG levels from day 14 post-ovulation, while the IUD-P mares (n=6) showed basal levels only. We concluded that the IUD did not cause continuous PG release and suggest that close contact of the IUD with the endometrium may prevent the endometrial cells from releasing PGF(2alpha).     

Efficacy of a Y-Design Silastic Elastomer Intrauterine Device as a Horse Contraceptive

To successfully manage population growth rates of free-roaming horses (Equus ferus caballus), an effective, long-acting contraceptive could be beneficial. We evaluated the efficacy and safety of an intrauterine device (IUD) in a breeding trial using seasonal pasture assemblages of 2 males individually pastured in large enclosures (~81 ha) each with 10 females per male. The study took place at a large animal research facility at Oklahoma State University in Stillwater, Oklahoma, USA. Specific objectives of the study were to evaluate the effectiveness of IUDs in preventing pregnancy over 20.5 months with return to fertility assessed over the subsequent 6 months and to evaluate potential effects of this IUD on ovarian function and uterine health (e.g., endometrial inflammation, infection, fibrosis). We developed a Y-design IUD, made of silastic elastomer, and set the desired retention rate at 75%. After procurement of endometrial biopsies, we inserted IUDs into the uteri of 20 females and examined them via transrectal ultrasound every 2 weeks for detection of the device and assessment of uterine health. After 20.5 months we removed the remaining 15 IUDs, obtained a second endometrial biopsy for comparision, and returned the females to their respective males for continued breeding in efforts to assess uterine return to health as indicated by pregnancy rates. The Y-design IUD met the 75% retention rate goal, with 100% contraception in females that retained the device; 12 of 20 treated females became pregnant (i.e. returned to fertility) after removal of the IUD. Based on these results, we conclude that the Y-design IUD is a safe and effective device to control fertility in free-roaming horses. © 2021 The Wildlife Society.     

Prostaglandin mediated action of IUD's (II) F-prostaglandins (PGF) in the uterine horn of pregnant rats and hamsters with intrauterine devices

The present investigation clearly shows that the presence of an IUD is associated with uterine hypertrophy and an increased production of F-prostaglandins.In the hamster, a bilateral IUD produced a significant increase in peripheral plasma PGF, presumably of uterine origin and an increased uterine PGF content at 2230 – 2300 h of day 4 of pregnancy. Earlier sampling (1530 – 1600 h) on the same day of pregnancy did not reveal any significant difference.In the rat, uterine PGF content and concentration, as well as PGF levels in uterine venous plasma were all increased in the IUD bearing horn from day 4 pregnant animals at 1530 – 1630 h in comparison to the contralateral control horn.     

Source and Portal of Entry of Bacteria Found in Bruised Poultry Tissue

Bacteriological studies revealed that normal tissue, air sacs, feathers, skin of birds, poultry feed, gut, and chicken droppings were sources of the predominant organisms, including staphylococci, found in bruised poultry tissue. Further investigation of normal tissue revealed that after the intramuscular injection of Staphylococcus aureus, marker strain (MS), the organism was eliminated from these tissues within 7 days. However, when these tissues were traumatized 3 days after injection, the number of the test organism increased, and the organism was present on the 7th day after inoculation. Poultry feed and fecal material contained a large number of staphylococci identical to those isolated from bruised tissue (McCarthy, Brown, and Hamdy, 1963), thereby implicating the gut as a possible portal of entry. When a pathogenic marker strain of S. aureus was established in the intestinal tract of chickens by administering an active culture of this organism either in their drinking water or by gavage, it was recovered from the traumatized tissue. The incidence of positive culture of S. aureus MS in these tissues correlated with age of bruise, reaching 22 to 33% immediately after contusion and at the early stages of healing (1 to 3 days post bruise) and decreasing thereafter from 11 to 0% on the 4th through 6th days after bruise infliction. The air sac was also found to be a site by which bacteria may enter the traumatized tissues, but to a limited extent.     

Cooperation between p53 mutation and high telomerase transgenic expression in spontaneous cancer development

Telomerase reintroduction in adult somatic tissues is envisioned as a way to extend their proliferative capacity. It is still a question, however, whether constitutive telomerase expression in adult tissues impacts the normal aging and spontaneous cancer incidence of an organism. Here, we studied the aging and spontaneous cancer incidence of mice with transgenic telomerase expression in a wide range of adult tissues, K5-Tert mice. For this, we maintained large colonies of K5-Tert mice for more than 2 years. K5-Tert mice showed a decreased life span compared to wild-type cohorts associated with a higher incidence of preneoplastic and neoplastic lesions in various tissue types. Neoplasias in K5-Tert mice were coincident with transgene expression in the affected tissues. These observations suggest that high telomerase activity may cooperate with genetic alterations that occur with age to promote tumorigenesis. Indeed, we demonstrate here that increased cancer incidence and the reduced viability of K5-Tert mice are aggravated in a p53(+/-) genetic background, indicating that telomerase cooperates with loss of p53 function in inducing tumorigenesis. Altogether, these results demonstrate that constitutive high levels of telomerase activity result in a decreased life span associated with an increased incidence of neoplasias as the organism ages.