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PubMed2006

Elective induction of labor.

Induction of labor rates have more than doubled nationwide in the past 15 years. The increase in medically induced inductions was slower than the overall increase, suggesting that inductions for marginal or elective reasons rose more rapidly. Elective inductions seem to account for at least half of all inductions and 10% of all deliveries. Whether the experience of an elective induction is satisfactory to the patient, obstetrician, and intrapartum crew warrants more widespread attention. Cesarean rates are high for nulliparas undergoing an induction with an unfavorable cervix. Prospective studies are limited or nonexistent to recommend induction of labor for elective or marginal indications. Until more prospective work is performed, it will be difficult to evaluate the true impact of the elective induction of labor on population-wide cesarean delivery rates. Strategies for increased obstetrician awareness are proposed through practice guidelines and through clinical research trials.

Attitude to Health↗
PubMed1989

Different patterns of donor MHC antigen induction in rat kidney allografts following active and passive enhancement.

We compare the expression of donor class I and class II major histocompatibility complex antigens in DA kidney grafts transplanted to PVG recipients treated by different protocols of donor-specific immunosuppression. MHC expression was evaluated using donor-specific antibodies and assays by immunohistology and quantitative absorption analysis. PVG recipients were either untreated or treated by (A) twice-weekly intravenous injections of 0.5 ml DA blood for 12 weeks; (B) 0.5 ml DA blood intravenously at 7 days pregraft; (C) as for (B), but with the addition or oral cyclosporine at 10 mg/kg/day from the day of grafting; and (D) passive enhancement with DA anti-PVG serum. Grafts were assessed at 3, 5, and 7 days after transplantation. In untreated controls at day 3, there is a periarteriolar leukocyte infiltrate, weak or absent class II induction, but strong class I induction. Class II induction in untreated controls is maximal at day 5. We confirm that active enhancement by blood transfusion, even using the intensive protocol of twice-weekly transfusions for 3 months, results in accelerated leukocyte infiltration and accelerated donor class I and class II MHC induction. At day 3, there is an intense, diffuse leukocyte infiltration and maximal class II induction. Cyclosporine treatment of blood-transfused recipients reduced the leukocyte infiltration and MHC induction to levels seen in untreated controls--i.e., the accelerated MHC induction caused by the transfusion was partially reversible by cyclosporine. In passively enhanced recipients, leukocyte infiltration and class I MHC induction were similar to untreated controls. However, class II induction was much delayed, not being evident until day 7.

Animals↗
PubMed2001

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗
PubMed1973

The interaction of respiration and photosynthesis in induction of nitrate reductase activity.

The respiration and photosynthesis requirement for induction and maintenance of nitrate reductase activity was determined on leaves of Hordeum vulgare L. In this induction, glucose substituted for light in both dark-grown and carbohydrate-depleted green leaves. Oxygen appeared to be required for induction in all cases studied. In light and under N(2), 3-(3,4-dichlorophenyl)-1,1-dimethylurea completely inhibited induction, presumably by inhibiting the production of O(2), Hence, under N(2) the leaves appeared to utilize both the O(2) produced by photosynthesis and the CO(2) produced by respiration. CO(2) fixation can then produce both photosynthate to drive the induction and terminal electron acceptors to allow photosynthetic electron flow. This possibility was further suggested by the observation that CO(2) was an absolute requirement for induction in carbohydrate-depleted barley leaves. Results obtained with respiratory inhibitors also indicated that respiration drove the induction of nitrate reductase.Exogenously supplied glucose also substantially slowed the loss of nitrate reductase that occurred when barley leaves were placed in darkness. It is presumed that glucose allowed the synthetic or activation phase of the induction to proceed more rapidly. Our results support the hypothesis that one of the main effects of light may be to supply photosynthate to support respiration, which then drives the induction process.

Journal Article↗
PubMed1985

Induction and recovery characteristics of isoflurane and halothane anaesthesia for short outpatient operations in children.

Induction and recovery characteristics of isoflurane anaesthesia were compared with halothane anaesthesia during outpatient myringotomy and placement of Sheely ventilation tubes in 101 unpremedicated children. Compared with halothane, isoflurane resulted in prolonged induction times and inferior induction scores due to increased salivation, coughing, breathholding and laryngospasm. However, when modified by halothane induction, isoflurane anaesthesia decreased induction time and improved induction scores. Induction with thiamylal 4 mg/kg did not improve induction scores significantly. Recovery times from halothane plus isoflurane and pure isoflurane anaesthesia were quicker than pure halothane and thiamylal plus isoflurane, although this was not statistically significant. Compared to halothane, anaesthetic induction using isoflurane is associated with an increased incidence of respiratory problems in unpremedicated children.

Adolescent↗
PubMed1997

Comparison of inhalation inductions with xenon and sevoflurane.

BACKGROUND: Xenon is an odorless gas with low blood-gas solubility coefficient and without occupational and environmental hazards. This investigation was performed to evaluate the speed of induction, and respiratory and cardiovascular reactions to inhalation induction with xenon compared to an equianesthetic concentration of sevoflurane. METHOD: Twenty-four adult ASA 1-2 patients premedicated with 0.05 mg/kg of midazolam were instructed to take vital capacity breaths of 1 minimum alveolar concentration (MAC) of either xenon or sevoflurane until they lost consciousness. Induction time, total ventilatory volume, tidal volume, respiratory rate, minute ventilation, end-tidal MAC fraction, cardiovascular parameters and oxygen saturation were recorded. The patients were interviewed on the following day to evaluate their acceptability rating of the inhalation inductions. RESULTS: Compared to equianesthetic sevoflurane, xenon produced a faster induction of anesthesia (147 +/- 59 versus 71 +/- 21 s, respectively) with smaller decreases in respiratory rate, tidal volume and minute ventilation. Both agents showed comparable cardiovascular stability and oxygen saturation during induction. One patient in the sevoflurane group had breath-holding and movements of extremities and another had only breath-holding. No patients in the xenon group experienced any complications. CONCLUSION: Xenon produced a faster induction of anesthesia without any complications than sevoflurane. Xenon had smaller decreases in tidal volume and respiratory rate during induction than sevoflurane. Xenon might offer an alternative to sevoflurane for an inhalation induction.

Adult↗
PubMed2004

Anaesthesia induction in children: a psychological evaluation of the efficiency of parents' presence.

BACKGROUND: The induction of anaesthesia for surgery is a stressful time for both child and parents. To treat preoperative anxiety in children, pharmacological methods (premedication) and behavioural methods (the presence of parents during the induction of anaesthesia) have been used, both independently and in combination. The purpose of this investigation was to study the effect of both premedication and parental presence on preoperative anxiety in a homogeneous population. METHODS: In this study conducted between January and April 2001 in the Meyer Hospital in Florence (Anaesthesia Department and Surgical Department), we studied 39 Italian speaking children aged 2-14 years who were undergoing minor surgery. Before the surgical intervention the State Trait Anxiety Inventory (STAI) questionnaire and a questionnaire for the social-demographic characteristics were given to the parents. The stress of the children was evaluated during induction of anaesthesia. We also studied behavioural areas of both children and parents with two specific questionnaires administered after the surgery. RESULTS: The STAI scores showed that the mothers had a higher level of anxiety compared with the fathers. The induction of anaesthesia for surgery was a stressful time for 23% of children of our sample. The correlation between stress of the child at induction and state (P = 0.034) and trait (P = 0.049) anxiety of parents was statistically significant. The child's loss of consciousness was for the majority of parents (56%) the moment of greatest stress and 97% of parents did feel useful during the induction of anaesthesia. There was a significant difference, P = 0.032, in the presence or absence of stress depending on whether the mother or father accompanied the child to the operating room. There was no significant difference in the presence of stress between children who did and did not receive premedication. CONCLUSIONS: Maternal presence, compared with the father's presence, is fundamental in helping to overcome anxiety in a child receiving anaesthesia. If the parents are present during the induction, the addition of premedication does not offer further benefit. Parents themselves judged their presence during the induction of anaesthesia in their child as a positive event. We also found a statistical significant correlation between anxiety of the parents with the level of the stress of the child during induction of anaesthesia.

Adolescent↗
PubMed1993

Additive induction of Egr-1 (zif/268) mRNA expression in neuroblastoma x glioma hybrid NG108-15 cells via cholinergic muscarinic, alpha 2-adrenergic, and bradykinin receptors.

Administration of carbachol, noradrenaline, and bradykinin induced Egr-1 mRNA expression within 1 h in mouse neuroblastoma x rat glioma hybrid NG108-15 cells. With specific receptor antagonists, the Egr-1 inductions by carbachol and noradrenaline were shown to be mediated via cholinergic muscarinic and alpha 2-adrenergic receptors, respectively. At their saturation levels for Egr-1 induction, the two agonists had additive effects when added together, but no prolongation of the effect on Egr-1 induction was observed. Addition of carbachol or noradrenaline 6 h after primary stimulation with carbachol or noradrenaline did not result in secondary Egr-1 induction, probably because of receptor desensitization. On the other hand, bradykinin consistently had an additive effect on Egr-1 induction, irrespective of the time of its addition, suggesting that the signal pathways for Egr-1 induction by carbachol or noradrenaline and by bradykinin are different. Treatment of cells with pertussis toxin or cholera toxin strongly inhibited Egr-1 induction by carbachol or noradrenaline but only partially inhibited the induction by bradykinin. Thus, the signals transduced in NG108-15 cells by different neurotransmitter receptors appear to have different effects on Egr-1 induction, depending on the times of stimulation and the combinations of receptors stimulated.

Animals↗
PubMed2000

Are routine arrhythmia inductions necessary in patients with pectoral implantable cardioverter defibrillators?

INTRODUCTION: The value of ventricular arrhythmia inductions as part of routine implantable cardioverter defibrillator (ICD) follow-up in new-generation pectoral ICDs is unknown. METHODS AND RESULTS: We performed a retrospective analysis of a prospectively collected database analyzing data from 153 patients with pectoral ICDs who had routine arrhythmia inductions at predismissal, and 3 months and 1 year after implantation. Routine predismissal ventricular fibrillation (VF) induction yielded important findings in 8.8% of patients, all in patients with implantation defibrillation threshold (DFT) > or = 15 J or with concomitant pacemaker systems. At 3 months and 1 year, routine VF induction yielded important findings in 5.9% and 3.8% of tested patients, respectively, all in patients who had high DFT on prior testing. Ventricular tachycardia (VT) induction at predismissal, and 3 months and 1 year after implantation resulted in programming change in 37.4%, 28.1%, and 13.8% of tested patients, almost all in patients with inducible VT on baseline electrophysiologic study and clinical episodes since implantation. CONCLUSION: Although helpful in identifying potentially important ICD malfunctions, routine arrhythmia inductions during the first year after ICD implantation may not be necessary in all cases. VF inductions have a low yield in patients with previously low DFTs who lack concomitant pacemakers. VT inductions have a low yield in patients without baseline inducible VT and in the absence of clinical events. Definite recommendations regarding patient selection must await larger prospective studies as well as consensus in the medical community about what comprises an acceptable risk justifying avoidance of the costs and inconveniences of routine arrhythmia inductions.

Adolescent↗
PubMed1984

Induction and disappearance of excitability in the oocyte of Xenopus laevis: a voltage-clamp study.

Electrically excitable, sodium-selective channels are induced in the membrane of the oocytes of Xenopus laevis when it is submitted to prolonged positive potentials (Kado, Marcher & Ozon, 1979; Baud, Kado & Marcher, 1982). Under a long positive voltage-clamp step, the membrane current, initially outward, becomes inward with a sigmoidal time course. The mean time to half-maximal inward current (t 1/2) is about 18 s at 16 degrees C when stepping the membrane potential to +55 mV. The rate of channel induction was very temperature dependent (Q10 about 5). In an Arrhenius plot, the t 1/2 for induction at temperatures between 5 and 22 degrees C showed a single slope. The rate of induction was dependent on the membrane potential, increasing exponentially with positive membrane potential (e-fold for a 20 mV change). When the membrane was maintained at resting potential after induction, the ability to produce inward currents with short depolarizing steps slowly disappeared with a t 1/2 of 4 min at 16 degrees C. The temperature dependence for disappearance was larger than that found for induction (Q10 about 7). The rate of disappearance was not dependent on holding the membrane potential in the range -30 to -100 mV. Induction proceeded in calcium-free medium. Cycloheximide, a potent protein synthesis inhibitor had no effect (100 micrograms/ml) on the induction rate. Isobutylmethylxanthine (IBMX) or theophyllin (phosphodiesterase inhibitors) applied externally (10(-4) M) did not affect the induction or disappearance rates. From the present results, mechanisms such as protein synthesis or a second messenger (such as calcium or cyclic AMP) do not appear to be involved. During the depolarization necessary to obtain induction, another conductance was also activated. It was more slowly established, appeared to be non-saturable and had a reversal potential between zero and -10 mV. It was found to be very much reduced at temperatures below about 16 degrees C.

Animals↗
PubMed1965

Biochemical changes in lysogenic Bacillus stearothermophilus after bacteriophage induction.

Welker, N. E. (University of Illinois, Urbana), and L. Leon Campbell. Biochemical changes in lysogenic Bacillus stearothermophilus after bacteriophage induction. J. Bacteriol. 90:1129-1137. 1965.-Cultures of Bacillus stearothermophilus 1503-4R (TP-1) continued to grow at an unaltered rate after induction with mitomycin C (MC). MC-induced cultures exhibited a 2.5-fold increase in cell number before lysis occurred. Prior to lysis, cells were observed to elongate and to contain areas of lesser density. Protein synthesis was slightly inhibited in MC- or ultraviolet light (UV)-induced cultures for a period of 5 to 10 min, and then proceeded at a rate identical to that in the noninduced culture. Ribonucleic acid (RNA) synthesis was not affected by MC induction. UV induction caused RNA synthesis to occur in two stages: in the first stage, the rate of RNA synthesis was one-third that observed in the noninduced culture and lasted for a period of 15 min; the second stage of RNA synthesis then proceeded at a rate identical to that in the noninduced culture. The synthesis of deoxyribonucleic acid (DNA) in an MC- or UV-induced culture occurred in two stages. In the first stage, DNA synthesis in induced cultures occurred at a rate of one-half (MC) and one-third (UV) of that observed in the noninduced culture. The first stage of DNA synthesis in MC- or UV-induced cultures lasted for 25 to 30 min and 15 to 20 min, respectively. In the second stage, the rate of DNA synthesis in MC- or UV-induced cultures occurred at a rate three times that of the noninduced culture. UV induction appeared to have a greater inhibitory effect than MC induction on protein, RNA, and DNA synthesis as well as phage yield. The differential rate (K) of inducible and constitutive alpha-amylase synthesis was inhibited by 75 and 100%, respectively, for a period of 20 min after MC induction. After 20 min, the K values for alpha-amylase synthesis were identical to those obtained in the absence of MC induction. The synthesis of TP-1 phage DNA occurred rapidly and was complete 25 min after MC induction, whereas bacterial DNA was degraded or its rate of synthesis was decreased. During the second stage of DNA synthesis, only bacterial DNA was synthesized, but at a rate greater than that found in the noninduced culture.

Amylases↗
PubMed2001

Matrix protein and another viral component contribute to induction of apoptosis in cells infected with vesicular stomatitis virus.

The induction of apoptosis in host cells is a prominent cytopathic effect of vesicular stomatitis virus (VSV) infection. The viral matrix (M) protein is responsible for several important cytopathic effects, including the inhibition of host gene expression and the induction of cell rounding in VSV-infected cells. This raises the question of whether M protein is also involved in the induction of apoptosis. HeLa or BHK cells were transfected with M mRNA to determine whether M protein induces apoptosis when expressed in the absence of other viral components. Expression of M protein induced apoptotic morphological changes and activated caspase-3 in both cell types, indicating that M protein induces apoptosis in the absence of other viral components. An M protein containing a point mutation that renders it defective in the inhibition of host gene expression (M51R mutation) activated little, if any, caspase-3, while a deletion mutant lacking amino acids 4 to 21 that is defective in the virus assembly function but fully functional in the inhibition of host gene expression was as effective as wild-type (wt) M protein in activating caspase-3. To determine whether M protein influences the induction of apoptosis in the context of a virus infection, the M51R M protein mutation was incorporated onto a wt background by using a recombinant infectious cDNA clone (rM51R-M virus). The timing of the induction of apoptosis by rM51R-M virus was compared to that by the corresponding recombinant wt (rwt) virus and to that by tsO82 virus, the mutant virus in which the M51R mutation was originally identified. In HeLa cells, rwt virus induced apoptosis faster than did rM51R-M virus, demonstrating a role for M protein in the induction of apoptosis. In contrast to the results obtained with HeLa cells, rwt virus induced apoptosis more slowly than did rM51R-M virus in BHK cells. This indicates that a viral component other than M protein contributes to induction of apoptosis in BHK cells and that wt M protein acts to delay induction of apoptosis by the other viral component. tsO82 virus induced apoptosis more rapidly than did rM51R-M virus in both HeLa and BHK cells. These two viruses contain the same point mutation in their M proteins, suggesting that sequence differences in genes other than that for M protein affect their rates of induction of apoptosis.

Animals↗
PubMed1997

Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation.

The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II alpha-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC gamma, GAP, and Syp abolished the induction of type II alpha-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.

Animals↗
PubMed1999

Induction for senior house officers. Part II: The departmental programme.

This study was designed to examine the content and usefulness of departmental induction programmes to senior house officers (SHOs) and to explore perceptions of the usefulness of a range of topics to these trainees. A total of 64 SHOs, in five hospitals in the Anglia region, participated in semi-structured interviews up to 3 months after starting their post. The interviews investigated the content of any induction received and also examined what the trainees would have liked to have received. Almost half (29) of the SHOs also completed a questionnaire which examined the perceived usefulness of various induction topics for a trainee starting a new post. The results showed that, although a departmental induction programme is considered important and highly valued, a substantial minority of SHOs had not received one. Of this minority, 75% would have welcomed an induction. Where an induction had taken place, the focus was primarily upon timetables, tours and meeting people, however, a quarter of the questionnaire sample had not received a service timetable, a third had not met any consultants, two-thirds had received no introduction to clinical management, and two-thirds had received no information about how their consultants manage their patients. Thus, although many trainees receive an induction, important information may not be covered. A staged approach to departmental induction is recommended, using a short, high-quality, and comprehensive induction programme. Flexible and timely programmes, supported by comprehensive written information, will contribute to meeting the needs of trainees in an efficient and effective way.

Education, Medical, Graduate↗
PubMed2003

Roles of CaMKII, PKA, and PKC in the induction and maintenance of LTP of C-fiber-evoked field potentials in rat spinal dorsal horn.

Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to hyperalgesia, an increased response to noxious stimulation. The mechanism underlying this form of synaptic plasticity is, however, still unclear. Considerable evidence has shown that calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC) are important for LTP in hippocampus. In this study, the roles of these three protein kinases in the induction and maintenance of LTP of C-fiber-evoked field potentials were evaluated by application of specific inhibitors of CaMKII (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Gö 6983) at the recording segments before and after LTP induction in urethane-anesthetized Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30 min prior to tetanic stimulation, completely blocked LTP induction. At 30 min after LTP induction, KN-93 and AIP reversed LTP completely, and at 60 min after LTP induction, they depressed spinal LTP in most rats tested. Three hours after LTP induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS, chelerythrine, and Gö 6983 blocked the spinal LTP when applied at 30 min before tetanic stimulation and reversed LTP completely at 15 min after LTP induction. In contrast, at 30 min after LTP induction, the drugs never affected the spinal LTP. These results suggest that activation of CaMKII, PKA, and PKC may be crucial for the induction and the early-phase but not for the late-phase maintenance of the spinal LTP.

Animals↗
PubMed2006

IMOP: randomised placebo controlled trial of outpatient cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour - clinical trial with analyses of efficacy, cost effectiveness and acceptability.

BACKGROUND: There is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis. However, there are concerns about the use of prostaglandins, the agents commonly used in hospital settings for this indication, because prostaglandins induce uterine contractions that may lead to fetal hypoxia. Indeed, in a recent study we demonstrated abnormalities in 9% of fetal heart rate tracings performed following prostaglandin induced cervical ripening at term. In contrast, we confirmed in the same study that isosorbide mononitrate (IMN) (administered on an inpatient basis) was both effective in inducing cervical ripening at term, and was associated with no associated fetal heart rate abnormalities. METHODS/DESIGN: The aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour. Specifically, we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery, decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour, compared with placebo treatment. In the study described here (the "IMOP" study), women scheduled for induction of labour at term, and who require pre-induction cervical ripening will be randomised to self-administer at home either IMN 40 mg, or a placebo, each vaginally, at 48 hours, 32 hours and 16 hours before scheduled hospital admission. After admission to hospital, treatment will revert to the usual induction of labour protocol. We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery, the costs to the health service of induction of labour, and women's experience of induction of labour in the two groups. DISCUSSION: This trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term. We will study a formulation of IMN which is cheap and widely available. If the treatment is effective, acceptable to women, and cost effective, it could be implemented into obstetric practice worldwide. TRIAL REGISTRATION: The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRTN39772441.

Journal Article↗
PubMed2006

The role of inducible repressor proteins in the adrenergic induction of arylalkylamine-N-acetyltransferase and mitogen-activated protein kinase phosphatase-1 in rat pinealocytes.

In this study, we investigated the role of two inducible repressor proteins, inducible cAMP early repressor (ICER) and Fos-related antigen 2 (Fra-2) in the adrenergic induction of MAPK phosphatase-1 (MKP-1) as compared with their roles in the induction of arylalkylamine-N-acetyltransferase (AA-NAT) in rat pinealocytes. Treatment of pinealocytes with norepinephrine (NE) caused an increase in the mRNA and protein levels of MKP-1 and AA-NAT, as well as in the AA-NAT activity and melatonin production. NE stimulation also caused a simultaneous increase in the mRNA and protein levels of ICER and Fra-2. Transient knockdown of icer using adenovirus expressing small interfering RNA (siRNA) abolished the NE induction of icer expression but had little effect on the NE induction of mkp-1 or aa-nat expression. In contrast, pretreatment with adenovirus overexpressing icer was effective in reducing the NE induction of mkp-1 and aa-nat. The inhibitory effect of overexpressing icer was reversed by cotreatment with siRNA against icer. siRNA against fra-2 also abolished the NE-stimulated expression of fra-2 but had little effect on the NE induction of mkp-1 and aa-nat expression. Proteasomal inhibition, which reduced the NE-stimulated induction of aa-nat, caused a reduction of ICER and Fra-2. Together, these results indicate that whereas overexpression of ICER can suppress the NE induction of aa-nat and mkp-1, the amount of the repressors, ICER and Fra-2, present during NE induction appears insufficient to exert a significant effect in controlling the expression of these genes.

Adrenergic alpha-Agonists↗
PubMed2004

3',5'-cyclic adenosine monophosphate response element-binding protein and CCAAT enhancer-binding protein are dispensable for insulin inhibition of phosphoenolpyruvate carboxykinase transcription and for its synergistic induction by protein kinase A and glucocorticoids.

Phosphoenolpyruvate carboxykinase (PEPCK) transcription is induced by cAMP/protein kinase A (PKA) and glucocorticoids [dexamethasone (Dex)] and is inhibited by insulin to regulate blood glucose. Recent reports suggested that CCAAT enhancer binding protein (C/EBP) binding to the PEPCK cAMP response element (CRE) plays a role in Dex induction and that insulin-induces inhibitory forms of C/EBPbeta to inhibit transcription. Here, we assessed the roles of CRE-binding protein (CREB) and C/EBP factors in mediating hormone-regulated transcription. Neither cAMP nor insulin regulated the phosphorylation of C/EBP. Cycloheximide did not block insulin inhibition, indicating that alternate translation of C/EBPbeta is not required. Dominant-negative CREB or C/EBP blocked induction by PKA, but neither affected regulation by Dex or insulin. Tethering the activation domains of CREB or C/EBP to a CRE-->Gal4 (G4) site mediated varying extents of basal and PKA-inducible activity, but neither activation domain affected induction by Dex or inhibition by insulin. Surprisingly, synergistic induction by PKA and Dex did not require the CRE and was unaffected by dominant-negative CREB or C/EBP. PKA and Dex also synergistically induced a minimal 3 x glucocorticoid response element promoter, but inhibited Dex induction of the mouse mammary tumor virus and IGF-binding protein 1 promoters, even though PKA alone did not regulate these promoters. These results suggest that PKA modifies the activity of other factors involved in Dex induction to mediate synergistic induction or inhibition in a promoter-specific manner. Our data indicate that the roles of CREB and C/EBP are restricted to mediating PEPCK induction by PKA, and that other factors mediate PEPCK induction by Dex, synergism between PKA and Dex, and inhibition by insulin.

Animals↗