Preinduction cervical priming with PGE2 vaginal film in primigravidae--a randomised, double blind, placebo controlled study

Previous reports with an 850 micrograms prostaglandin E2 film for cervical ripening before induction of labour in term pregnancy have been favourable. These studies however had no controls. The present study compares this PGE2 vaginal film with a nonmedicated similar vaginal film (placebo) for preinduction cervical ripening in primigravid women at term. A total of 69 women with modified Bishop's cervical scores 1-5 were assigned randomly to either the PGE2 group (33 women) or placebo group (36 women). Cervical score assessments were made at 12 and 24 hours after which labour was induced by amniotomy and oxytocin infusion. Although the cervical scores between placebo and PGE2 groups at 12 and 24 hours were not significantly different, the scores were marginally better with the prostaglandin film. Pregnancy outcome was satisfactory in both groups with no perinatal or maternal mortality and morbidity. The caesarean rate was 30.6% in the placebo group and 24.2% in the PGE2 group. This study emphasizes the need for a control group when studying the success of agents used for ripening the pregnant cervix at term.     

Comparative study of a two dose schedule of PGE2 3 mg pessary and 1700 micrograms film for induction of labour in nulliparae with poor cervical score

Efficacy of a two dose schedule of 3 mg pessary or 1700 micrograms film of PGE2 for induction of labour was compared in nulliparae with poor cervical score. Patient characteristics in the two groups (43 in 3 mg and 40 in 1700 micrograms group) were comparable in age, period of gestation, indications for induction of labour and in their initial cervical score. The number of patients who started labour with a two dose schedule 4 hours apart were similar in each group. The improvement of cervical score, length of labour, mode of delivery and the neonatal outcome were not different in the two groups. There was no advantage of using a film preparation over that in the form of a pessary and the use of 3 mg dose did not give significantly better results compared with the 1700 micrograms dose, in terms of obstetric or neonatal outcome.     

An alternative receptor to poly I:C on cell surfaces for interferon induction

Not‐self or denatured nucleic acids are recognized by pattern recognition receptors localized mainly in endosomes and cytoplasm, such as Toll‐like receptor (TLR) 3, TLR7, TLR9, retinoic acid‐inducible gene‐I, DNA‐dependent activator of IFN‐regulatory factors and other receptors. The binding of polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that robustly induces type I interferon, to a putative cell‐surface receptor on a rabbit kidney cell line, RK13, has been analyzed by the authors and RK13 cells found to capture poly I:C in a specific fashion with sufficient affinity. These findings suggest that an alternative receptor to poly I:C participates in the induction of type 1 interferon, which localizes on cell surfaces. Although the nature of this molecule has not yet been identified, accumulating evidence has led the present authors to speculate that there are undefined classes of RNA‐recognition molecules on cell surfaces and that these are unlikely to be categorized as previously reported dsRNA receptors. Although many years have passed since this possibility was first reported by the present authors, it remains attractive. In this article, previously reported cell‐surface dsRNA receptors are reviewed in comparison with other receptors reported to date that are firmly involved in the innate immune‐sensing of nucleic acids.     

阴道微生态与宫颈疾病发生发展的相关性研究

微生态学是近年新兴的学科,女性生殖道是一个重要的微生态区域。生殖道微生态体系是由正常的解剖结构、生殖道各种菌群、周期性内分泌变化、局部免疫系统四个部分组成。随着阴道微生态平衡理论的提出和发展,阴道微生态和HPV感染、宫颈上皮内瘤变、宫颈癌的内在关联引起了极大的重视。阴道微生态与宫颈疾病的发生发展相关,宫颈病变影响了阴道微生态环境,长期的阴道菌群失调也会反作用于宫颈,导致宫颈的病变加重甚至恶化,如此形成恶性循环。因此阴道微生态对宫颈疾病的诊断、治疗和预防将具有重要的临床意义。     

Immunofluorescence with monoclonal antibodies on poly-L-lysine coated slides: an alternative to conventional methods

It is sometimes difficult to perform immunofluorescence tests because of low cell numbers. Therefore a simple method using poly-L-lysine coated slides was applied to immunofluorescence and compared with the routine suspension method. Peripheral blood lymphocytes from normal persons, samples of normal bone marrow, thymus and tonsil as well as samples from patients with leukemia or lymphoma were tested with these two methods using 20 different monoclonal antibodies. The PLL-slide method was shown to be comparable with the suspension method and is an alternative in case of low cell numbers, since as few as 3 X 10(4) cells can be tested for one antigen.     

Caprylic acid precipitation method for impurity reduction: An alternative to conventional chromatography for monoclonal antibody purification

We report the use of caprylic acid based impurity precipitation as (1) an alternative method to polishing chromatography techniques commonly used for monoclonal antibody purification and (2) an impurity reduction step prior to harvesting the bioreactor. This impurity reduction method was tested with protein A purified antibodies and with cell culture fluid. First, the operational parameters influencing precipitation of host cell proteins and high molecular weight aggregate in protein A pools were investigated. When used as a polishing step, the primary factor affecting purification and yield was determined to be pH. Caprylic acid precipitation was comparable to polishing IEX chromatography in reducing host cell protein and aggregate levels. A virus reduction study showed complete clearance of a model retrovirus during caprylic acid precipitation of protein A purified antibody. Caprylic acid mediated impurity precipitation in cell culture showed that the impurity clearance was generally insensitive to pH and caprylic acid concentration whereas yield was a function of caprylic acid concentration. Protein A purification of caprylic acid precipitated cell culture fluid generated less turbid product pool with reduced levels of host cell proteins and high molecular weight aggregate. The results of this study show caprylic acid precipitation to be an effective purification method that can be incorporated into a production facility with minimal cost as it utilizes existing tanks and process flow. Eliminating flow through chromatography polishing step can provide process intensification by avoiding the process tank volume constraints for high titer processes. Biotechnol. Bioeng. 2012; 109: 2589–2598. © 2012 Wiley Periodicals, Inc.     

CERNA2: A predictor for clinical progression and poor prognosis in cervical carcinoma

Competing long noncoding RNA 2 (lncRNA 2) for microRNA let-7b (CERNA2) has emerged as an important regulator of tumorigenesis and cancer progression but the clinical value and regulatory function of CERNA2 is yet to be investigated in cervical carcinoma. In our study, we found the CERNA2 expression was obviously increased in cervical carcinoma tissues compared with adjacent normal cervical tissues. In addition, we observed that metastatic lymph nodes exhibited high levels of CERNA2 expression in contrast to primary cervical carcinoma tissues. Furthermore, high CERNA2 expression was associated with advanced clinical stage, lymph node metastasis, distant metastasis poor histological grade, and short overall survival in cervical carcinoma patients. Moreover, high CERNA2 expression acted as an independent unfavorable predictor for overall survival in cervical carcinoma patients. The cell migration and invasion assays in vitro suggested that knockdown of CERNA2 remarkably inhibited cell migration and invasion in cervical carcinoma. In conclusion, CERNA2 functions as an oncogenic lncRNA and may be as a potential therapeutic target in cervical carcinoma.     

Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1

Peripheral inflammation involves an increase in cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) synthesis in the central nervous system (CNS), which contributes to allodynia and hyperalgesia. In the present study we have determined the changes in prostanoid tissue levels and in expression of terminal prostanoid synthases in both the CNS and inflamed peripheral tissue during carrageenan-induced paw inflammation in the rat. Prostanoid levels were measured by liquid chromatography-mass spectrometry and enzyme expression at the RNA level by quantitative PCR analysis during both the early (1-6 h) and late (12 and 24 h) phases of the inflammatory response. In the paw, the early phase was associated with increases in PGE(2) and thromboxane (TX)B(2) levels and with a peak of COX-2 expression that preceded that of microsomal prostaglandin-E(2) synthase-1 (mPGES-1). COX-2 and mPGES-1 remained elevated during the late phase, and PGE(2) continued to further increase through 24 h. The cytosolic PGE(2) synthase (cPGES) showed a small transient increase during the early phase, whereas mPGES-2 expression was not affected by inflammation. In the cerebrospinal fluid, elevated levels of PGE(2), 6-keto-PGF(1alpha), PGD(2), and TXB(2) were detected during the early phase. PGE(2) levels also increased in the spinal cord and, to a lesser extent, in the brain and remained elevated in both the cerebrospinal fluid and the spinal cord during the late phase. The expression of mPGES-1 was strongly up-regulated in the brain and spinal cord during inflammation, whereas no change was detected for the expression of cPGES, mPGES-2, COX-1, and terminal PGD, TX, or PGI synthases. The results show that the carrageenan-induced edema in the paw elicits an early phase of COX-2 induction in the CNS leading to an increase synthesis in PGD(2), 6-keto-PGF(1alpha), and TXB(2) in addition to the major PGE(2) response. The data also indicate that the up-regulation of mPGES-1 contributes to COX-2-mediated PGE(2) production in the CNS during peripheral inflammation.     

The Wae to repair: prostaglandin E2 (PGE2) triggers intestinal wound repair

Accurate wound repair is a crucial step to protect organisms from environmental damage, for example infection and toxin exposure. In this issue of The EMBO Journal, Miyoshi et al ( 2017 ) have elucidated a new mechanism underpinning this process within the intestine where mesenchymal prostaglandin E2 produced following damage drives intestinal regeneration.     

MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib

Untreated chronic myeloid leukemia (CML) progresses from chronic phase to blastic crisis (BC). Increased genomic instability, deregulated proliferation, and loss of differentiation appear associated to BC, but the molecular alterations underlying the progression of CML are poorly characterized. MYC oncogene is frequently deregulated in human cancer, often associated with tumor progression. Genomic instability and induction of aberrant DNA replication are described as effects of MYC. In this report, we studied MYC activities in CML cell lines with conditional MYC expression with and without exposure to imatinib, the front-line drug in CML therapy. In cells with conditional MYC expression, MYC did not rescue the proliferation arrest mediated by imatinib but provoked aberrant DNA synthesis and accumulation of cells with 4C content. We studied MYC mRNA expression in 66 CML patients at different phases of the disease, and we found that MYC expression was higher in CML patients at diagnosis than control bone marrows or in patients responding to imatinib. Further, high MYC levels at diagnosis correlated with a poor response to imatinib. MYC expression did not directly correlate with BCR-ABL levels in patients treated with imatinib. Overall our study suggests that, as in other tumor models, MYC-induced aberrant DNA synthesis in CML cells is consistent with MYC overexpression in untreated CML patients and nonresponding patients and supports a role for MYC in CML progression, possibly through promotion of genomic instability.     

The germ layer origin of mouse vaginal epithelium restricts its responsiveness to mesenchymal inductors: uterine induction

The epithelium of the mammalian vagina arises from two distinct germ layers, endoderm from the urogenital sinus and mesoderm from the lower fused Müllerian ducts. While previously it has been reported that neonatal vaginal epithelium can be induced to differentiate as uterus, which normally develops from the middle portion of the Müllerian ducts, it has not been determined whether this ability is shared by both mesoderm- and endoderm-derived vaginal epithelia. To test if germ layer origin influences the ability of vaginal epithelium to undergo uterine differentiation, we have isolated sinus-derived and Müllerian-derived vaginal epithelia from newborn mice, combined them with uterine mesenchyme, and grown them for 4 weeks in female mice. Mesoderm-derived Müllerian vaginal epithelium in combination with uterine mesenchyme formed the simple columnar epithelium typical of uterus. Similar results were obtained with neonatal cervical epithelium, another mesodermal Müllerian duct derivative. On the other hand, sinus vaginal epithelium combined with uterine mesenchyme formed small cysts lined by a stratified squamous vaginal-like epithelium. This epithelium never showed evidence of cycling between the cornified and mucified states as is typically seen in vaginal epithelium combined with vaginal stroma. These results indicate that the ability of epithelium to form uterus is limited to mesoderm-derived epithelia and suggest that endoderm-derived sinus vaginal epithelium cannot undergo the typical differentiative modifications in response to the hormonal fluctuations of the estrous cycle when associated with uterine stroma.     

The concurrent in vitro and in vivo release of PGE2 from a controlled-release hydrogel polymer pessary for cervical ripening

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pessary containing 10 mg prostaglandin E2 (PGE2), designed to release 0.6 mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63 mg/hr. to 1.23 mg/hr. This compared with a concomitant release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE2 release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE2 release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.     

An alternative method to determine maximal accumulated O2 deficit in runners

An accepted measure of anaerobic capacity is the maximal O2 deficit. But it is not feasible to use O2 deficit if > or =10 submaximal runs are needed to extrapolate the O2 demand of high velocity running (Medb? et al. 1988). Recently, an alternative method to determine O2 deficit was proposed (Hill 1996) using only results of supramaximal cycle ergometer tests. The purpose of this study was to evaluate this alternative method with data from treadmill tests. Twenty-six runners ran at 95%, 100%, 105%, and 110% of their velocity at VO2max. Times to exhaustion, velocity, and accumulated oxygen uptake (VO2) from each individual's four tests were fit to the following equation using iterative nonlinear regression: accumulated VO2 = (O2 demand x velocity x time)-O2 deficit. The mean value s derived for O2 demand and O2 deficit were 0.198+/-0.031 ml x kg(-1) x m(-1) and 42+/-22 ml x kg(-1). SEE for the parameters were 0.007+/-0.007 ml x kg(-1) x m(-1) and 8+/-10 ml x kg(-1), respectively. Mean R2 was 0.998+/-0.003. It was concluded that O2 deficit can be determined from all-out treadmill tests without the need to perform submaximal tests.     

Hookworms in the Americas: An alternative to trans-Pacific contact

Recent New World archaeoparasitological discoveries of hookworm in pre-European contexts have revived a long-standing debate about the origin of hookworms in the Americas. Historically, the climatic conditions of Beringia encountered by migrating people have been considered too harsh for tropical hookworms to survive, suggesting that hookworms must have been introduced into South America by 'storm-tossed' fisherman or explorers from Asia. Here, John Hawdon and Susan Johnston review the history of hookworms in the Americas, and propose an alternative to their trans-Pacific introduction based on the unique natural history of one of the human hookworms.     

Clinical effects and cervical tissue changes after treatment with 16,16 dimethyl-trans delta 2 PGE1 methylester in the first trimester

Cervagem pessaries, containing 1 mg of 16,16-dimethyl-trans delta 2-PGE1 methylester, was administered in the posterior vaginal fornix 4 h before vacuum aspiration in the 1st trimester. The effects of cervical dilatation, cervical collagen metabolism and cervical smooth muscle activity were investigated. In treated women the mean cervical dilatation was 7.9 mm as compared with 3.9 mm in controls. The in vitro incorporation of 14C proline in cervical tissue as well as the hydrolytic activity against a synthetic "collagen-like" polypeptide was increased after treatment with cervagem. The cervical smooth muscle sensitivity to prostaglandins, as revealed by inhibition of muscle activity, was higher in treated women than in controls. It is concluded that cervical dilatation, as induced by cervagem, involves an adaptation of both connective tissue and smooth muscle components.     

An alternative to conventional insect marking procedures: detection of a protein mark on pink bollworm by ELISA*

Four experiments were conducted to examine the feasibility of marking pink bollworm, Pectinophora gossypiella (Saunders) with rabbit immunoglobulin G (IgG) protein for mark-release-recapture studies. Pink bollworm were internally marked by feeding larvae an enriched rabbit IgG diet or externally marked by submerging pupae and spraying adults. Individuals were then assayed for the presence of rabbit IgG by sandwich enzyme-linked immunosorbent assay (ELISA) using anti-rabbit IgG. The internal marker was retained in larvae and retained in prepupae and pupae, but not in adults. A second experiment showed that rabbit IgG was retained on adults that were externally marked as pupae. A third series of tests examined the feasibility of externally marking adults with rabbit IgG. Rabbit IgG was retained on externally marked adults for six days in the field. Protein was retained on marked moths in the laboratory after they were captured on and removed from sticky traps. Finally, laboratory tests showed that large groups of externally marked moths transferred rabbit IgG to unmarked moths, but individual males do not readily transfer the protein to unmarked females in small vials.     

In vitro embryo production in the cow: an effective alternative to the conventional embryo production approach

Development of new technology related to in vitro embryo production has allowed for the commercial use of this method of reproduction. In the present work, we evaluate the efficiency of this technology compared with conventional embryo production based on results obtained with a standard procedure, including the sexing of embryos. The donor animals were mature nonlactating dairy cows (n = 92) kept under a constant environment and feeding program in an ET center. Ultrasound guided transvaginal ovum pick-up following 48 h pre-treatment with FSH has been used for the IVF-IVC protocol. A total of 437 oocyte recovery sessions performed on 92 cows yielded 4145 oocytes, which were used in an IVF-IVC protocol. Using the conventional approach, 156 embryo collections on 49 cows yielded 1652 ova and embryos. All Quality 1 and 2 embryos were sexed by a PCR procedure, and embryos of the desired sex were transferred to synchronized recipients located at the center. The results obtained in the IVF protocol showed that 4 oocyte collections per cow performed within 60 d, yielded 38 oocytes, which resulted in 18.8 viable embryos, of which 7.05 were female. After transfer of the female embryos, an average of 3.8 recipients were pregnant at 60 d. One embryo collection under the conventional approach yielded an average of 1.2 female pregnancies, which was confirmed during the same 60-d time period. These results indicate that IVF procedures can effectively replace conventional embryo production methods when a predetermined number of pregnancies of known sex are needed within a short period of time.