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PubMed2006

Possible role of jasmonic acid in the regulation of floral induction, evocation and floral differentiation in Lemna minor L.

Jasmonic acid (JA) is implicated in a wide variety of developmental and physiological processes in plants. Here, we studied the effects of JA and the combination of JA and ethylenediamine-dio-hydroxyphenyl-acetic acid (EDDHA) on flowering in Lemna minor in axenical cultures. JA (0.475-47.5 nmol l(-1)) enhanced floral induction in L. minor under long-day (LD) conditions. Under the same conditions, at a concentration of 237.5 nmol l(-1), JA inhibited floral induction, and at a concentration of 475 nmol l(-1) it prevented floral induction. Under LD conditions with LD preculture, a combination of EDDHA (20,500 nmol l(-1)) and JA (47.5 nmol l(-1)) had a synergistic effect on the promotion of floral induction. Floral induction was enhanced to the greatest extent in experiments with LD precultures. Microscopic examination of microphotographs of histological sections showed that JA and, to an even greater extent, JA+EDDHA at optimal concentrations promote apical floral induction (evocation). Furthermore, JA, and to an even greater extent JA in combination with EDDHA in an optimal concentration, also promote flower differentiation, especially the development of stamens, as is evident from the microphotographs. The experimental results show that JA promotes floral induction in other species of Lemnaceae from various groups according to their photoperiodic response. The results support our hypothesis that, in addition to previously ascribed functions, JA may regulate floral induction, evocation and floral differentiation. Our hypothesis is supported also by the results obtained by quantitative determination of endogenous JA levels in L. minor at three growth stages. The levels of endogenous JA decreased from 389 ng JA g(-1) (fresh weight) of L. minor during the vegetative stage to 217 ng JA g(-1) during the evocation stage, and to 37.5 ng JA g(-1) during the flowering stage, which proves that JA is used for flowering.

Araceae↗
PubMed1997

Maternal colonization with group B Streptococcus and prelabor rupture of membranes at term: the role of induction of labor. TermPROM Study Group.

OBJECTIVES: Our purpose was to determine the effect of induction of labor on neonatal infection if mothers are group B streptococci positive and have prelabor rupture of membranes at term. STUDY DESIGN: In the TermPROM study 5041 women were randomized to induction with intravenous oxytocin, induction with vaginal prostaglandin E2 gel, or expectant management with induction, if needed. Of these, 4834 women had vaginal or introital swabs for group B streptococci taken at entry. We used logistic regression to test for effects of treatment within group B streptococci subgroups. RESULTS: Group B streptococci were predictive of neonatal infection for the induction with vaginal prostaglandin E2 gel and expectant groups but not for the induction with oxytocin group. For women positive for group B streptococci the rates of neonatal infection were 2.5% for the induction with oxytocin group and > 8% for all other groups. CONCLUSIONS: Induction of labor with intravenous oxytocin may be preferable for group B streptococci-positive women with prelabor rupture of membranes at term.

Administration, Intravaginal↗
PubMed1990

Coinhibition of viral interferon induction by benzo[a]pyrene in association with occupation-related particles.

Benzo[a]pyrene (B[a]P) in combination with coal, asbestos, or metal particles was studied for its inhibitory effects on interferon-alpha/beta induction by influenza virus in rhesus monkey kidney (LLC-MK2) cell monolayers. B[a]P per se had no adverse effect on the induction process. However, when cell cultures were pretreated with B[a]P that was bioactivated by rat liver S9 homogenate, from 52 to 65% inhibition of interferon induction occurred. Significantly greater (P less than 0.05) depression (coinhibition) of viral interferon induction (greater than 83%) resulted when bioactivated B[a]P was incorporated with coal particles representative of coal rank (anthracite, bituminous, lignite, peat). Coinhibition affected by bioactivated B[a]P was coal rank-independent but any interferon inhibitory activity affected by coal particles per se was coal rank-dependent. When metals (aluminum, aluminum oxide, ferric oxide, nickel, or chromium) or asbestos fibers (chrysotile, crocidolite, anthophyllite, or amosite) were individually mixed with bioactivated B[a]P, coinhibition of cellular interferon synthesis also resulted which was significantly greater (P less than 0.05) than that manifested by bioactivated B[a]P or particles per se. Coinhibition of interferon induction by silicates (Min-U-Sil, DQ-12, hypersthene, or wollastonite) and the bioactivated hydrocarbon was not in evidence although some silicates alone partially inhibited the induction process. Viral interferon induction was inhibited in a dose-response manner by B[a]P (+/- S9) in combination with selected particles. The adsorption of B[a]P to all types of particles was no more than 5.98 micrograms B[a]P/mg of particles and, moreover, less than 0.5% by weight. These findings provide further evidence that bioactivated B[a]P and occupation-related particles act together to coinhibit a biological defense mechanism, the interferon induction phase of the interferon system.

Animals↗
PubMedDate not supplied

Differential effects of protein tyrosine kinase inhibitors on interferon-gamma-induction of major histocompatibility complex class II and intercellular adhesion molecule-1 expression in human corneal epithelial cells.

PURPOSE: Interferon (IFN)-gamma induces major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1) expression on human corneal epithelial (HCE) cells. So far, it has not been clarified whether both inductions by IFN-gamma use the same signal transduction pathway. Therefore, in the present study, we tried to determine the significance of the protein tyrosine kinase (PTK)-dependent signaling pathway in the induction of both MHC class II and ICAM-1 expression by IFN-gamma in cultured HCE cells. METHODS: Cultured HCE cells were treated with human recombinant IFN-gamma. The induction of protein tyrosine phosphorylation of proteins including PTKs, janus kinase (JAK)1, and JAK2, was examined by Western blotting and immunoprecipitation. The effects of treatment of HCE cells with specific PTK inhibitors on IFN-gamma-induction of MHC class II and ICAM-1 expression were examined by flow cytometry. RESULTS: IFN 1 (Interferon) induced tyrosine phosphorylation of multiple substrates, particularly that of 75,000; 90,000; 130,000; and 160,000 molecular weight proteins including JAK1 and JAK2 in cultured HCE cells. The PTK inhibitors, herbimycin A and genistein, inhibited tyrosine phosphorylation of those proteins. Also, these PTK inhibitors prevented IFN-gamma-induction of MHC class II synthesis and surface expression. However, neither herbimycin A nor genistein had any effect on IFN-gamma-induction of ICAM-1 expression. CONCLUSIONS: Tyrosine phosphorylation of proteins including JAK1 and JAK2 is essential for IFN-gamma-induction of MHC class II expression, but not critical for that of ICAM-1 expression in cultured HCE cells. In addition, it is suggested that the IFN-gamma-induction of MHC class II requires PTK activities not only in the primary JAK-signal transducers and activators of transcription (STAT) pathway but also in the subsequent pathway mediated by IFN-gamma-induced intermediate proteins.

Benzoquinones↗
PubMed1999

Risk of cesarean delivery with elective induction of labor at term in nulliparous women.

OBJECTIVE: To quantify the risk of cesarean delivery associated with elective induction of labor in nulliparous women at term. METHODS: We performed a cohort study on a major urban obstetric service that serves predominantly private obstetric practices. All term, nulliparous women with vertex, singleton gestations who labored during an 8-month period (n = 1561) were divided into three groups: spontaneous labor, elective induction, and medical induction. The risk of cesarean delivery in the induction groups was determined using stepwise logistic regression to control for potential confounding factors. RESULTS: Women experiencing spontaneous labor had a 7.8% cesarean delivery rate, whereas women undergoing elective labor induction had a 17.5% cesarean delivery rate (adjusted odds ratio [OR] 1.89; 95% confidence interval [CI] 1.12, 3.18) and women undergoing medically indicated labor induction had a 17.7% cesarean delivery rate (OR 1.69; 95% CI 1.13, 2.54). Other variables that remained significant risk factors for cesarean delivery in the model included: epidural placement at less than 4 cm dilatation (OR 4.66; 95% CI 2.25, 9.66), epidural placement after 4 cm dilatation (OR 2.18; 95% CI 1.06, 4.48), chorioamnionitis (OR 4.61; 95% CI 2.89, 7.35), birth weight greater than 4000 g (OR 2.59; 95% CI 1.69, 3.97), maternal body mass index greater than 26 kg/m2 (OR 2.36; 95% CI 1.61, 3.47), Asian race (OR 2.35; 95% CI 1.04, 5.34), and magnesium sulfate use (OR 2.18; 95% CI 1.04, 4.55). CONCLUSION: Elective induction of labor is associated with a significantly increased risk of cesarean delivery in nulliparous women. Avoiding labor induction in settings of unproved benefit may aid efforts to reduce the primary cesarean delivery rate.

Adolescent↗
PubMed1998

Use of prostaglandin E2 to ripen the cervix of the mare prior to induction of parturition.

Eleven light-breed pregnant mares (335 to 347 d gestaton) were used to evaluate the use of prostaglandin E2 as a cervical ripening agent prior to induction of parturition during the months of April and May. Six hours prior to induction, each mare's cervix was examined per vagina for softness and dilation. Each mare was then assigned to 1 of 2 treatment groups: Group PGE mares (n = 7) received 2.0 to 2.5 mg prostaglandin E2 deposited intracervically; Group SAL mares (n = 4) received 0.5 mL of sterile NaCl deposited intracervically. Six hours later, the mares were readied for parturition by wrapping the tail, scrubbing and rinsing the perineum and udder, and examining the cervix as previously described. Each mare was then administered 15 U, i.v. oxytocin at 15-min intervals until the chorioallantois ruptured. Intervals from initial oxytocin injection until rupture of the chorioallantois, from initial oxytocin injection until delivery of the foal, from delivery of the foal until the foal stood unassisted, and from delivery of the foal until the foal suckled were recorded. Mean cervical dilation immediately prior to induction of parturition tended to be greater in Group PGE mares (3.9 +/- 1.7 cm) than in Group SAL mares (1.9 +/- 1.9 cm; P = 0.10). Mean change in cervical dilation over the 6-h period prior to induction (3.4 +/- 1.9 cm vs 1.5 +/- 2.1 cm), mean number of injections of oxytocin required until the chorioallantois ruptured (1.9 +/- 0.7 vs 2.5 +/- 1.0), and mean intervals from initial injection of oxytocin to rupture of the chorioallantois (20 +/- 10 min vs 28 +/- 19 min) and delivery of the foal (28 +/- 7 min vs 34 +/- 22 min) were not different between Group PGE and SAL mares, respectively (P > 0.10). The proportion of foals that stood within 1 h of birth also did not differ between Group PGE foals (6/7; 86%) and Group SAL foals (3/4; 75%; Chi-square = 0.17; P > 0.10). The proportion of foals that nursed within 2 h of birth was higher in Group PGE foals (6/7; 86%) than in Group SAL foals (1/4; 25%; Chi-square = 4.02; P < 0.05). Premature separation requiring manual rupture of the chorioallantois at the vulvar labia occurred in 1 Group PGE mare (cervical dilation of 1.5 cm at time of induction) and 1 Group SAL mare (cervix closed and firm at time of induction). Foals born from the 2 mares with premature placental separation had the longest intervals from initial oxytocin injection to delivery, delivery to ability to stand unassisted, and delivery to suckling within their respective treatment groups. In summary, it appears that cervical ripening prior to induction of parturition favors shorter deliveries and foal vigor. Intracervical administration of prostaglandin E2 may prove useful for ripening the cervix of the mare prior to induction of parturition. Further studies are indicated to determine optimal dosage and method of administration of prostaglandin E2.

Allantois↗
PubMed2000

Antisense DNA against calcineurin facilitates memory in contextual fear conditioning by lowering the threshold for hippocampal long-term potentiation induction.

In the previous study, we demonstrated that the antisense oligodeoxynucleotides against calcineurin Aalpha and Abeta, catalytic subunits of Ca(2+)/calmodulin-dependent protein phosphatase, produce a facilitatory effect on long-term potentiation induction in the hippocampal CA1 region in rats anesthetized with urethane. Here, we have studied how animals, in which the hippocampal long-term potentiation induction is enhanced by antisense oligodeoxynucleotides against calcineurin, perform in learning tasks that depend on hippocampal function. The rats received antisense oligodeoxynucleotides by bilateral ventricular administration via miniosmotic pumps. We tested four groups of rats, three infused with either antisense oligodeoxynucleotides, scramble oligodeoxynucleotides, or saline, and untreated rats, for two types of hippocampus-dependent learning, water maze and contextual fear conditioning. After the behavioral tests, we conducted a long-term potentiation induction test to determine whether long-term potentiation induction was enhanced. In contextual fear conditioning, rats in which long-term potentiation induction was enhanced by antisense oligodeoxynucleotides displayed significantly more conditioned freezing response than control rats. Rats with enhanced long-term potentiation induction showed no differences in shock sensitivity, general activity, or light-dark choice from control rats. In contrast with contextual fear conditioning, rats with enhanced long-term potentiation induction showed no difference in spatial learning performance on the water maze compared with control rats. These results demonstrate that an enhancement in long-term potentiation induction produced by the inhibition of calcineurin leads to an increase in memory strength in specific forms of hippocampus-dependent learning.

Animals↗
PubMed2006

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Adult↗
PubMed2000

Rapid induction of anesthesia with high concentrations of halothane or sevoflurane in children.

STUDY OBJECTIVE: To compare the characteristics of the rapid induction of anesthesia in pediatric patients with high concentrations of sevoflurane or halothane, and to determine the ability of anesthesiologists to correctly identify the anesthetic drug when administered in this fashion. DESIGN: Randomized, prospective, open-label study. SETTING: Academic university hospital. PATIENTS: 78 ASA physical status I and II healthy children scheduled for brief surgical procedures with general anesthesia and medicated with midazolam. INTERVENTIONS: Assessments were made by 5 pediatric anesthesiologists and 18 anesthesiology residents. Sevoflurane or halothane was randomly selected for anesthetic induction. The anesthetic circuit was primed with the drug (8% sevoflurane or 4% halothane) in 50% nitrous oxide and oxygen. The anesthesiologists were blinded as to the anesthetics being administered. After completion of anesthetic induction, the anesthesiologists were asked to identify the anesthetic and to assess the quality and speed of induction. MEASUREMENT AND MAIN RESULTS: The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%). This figure is statistically better than what could be achieved by random guessing (p < 0.001). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing (p = 0.06). Speed of induction was subjectively felt to be faster with sevoflurane than halothane but there were no differences in actual induction time (sevoflurane group, 3.7 +/- 2.7 min; halothane group, 3.7 +/- 2.6 min). There were no differences in the quality of induction or the incidence of airway complications. The perceived incidence of tachycardia was significantly higher with sevoflurane than halothane(sevoflurane group, 74%; halothane group 20%). CONCLUSION: The induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished. Pediatric anesthesiologists can differentiate between halothane and sevoflurane when either drug is given in high initial concentrations. The presence of tachycardia may have served as the primary clue in determining which drug was being used.

Anesthesia↗
PubMed1997

Etomidate and thiopental-based anesthetic induction: comparisons between different titrated levels of electrophysiologic cortical depression and response to laryngoscopy.

STUDY OBJECTIVE: To determine whether etomidate-based induction can provide better hemodynamics than a standard thiopental sodium-based anesthetic induction. DESIGN: Prospective, single-blind clinical trial. SETTING: Multicenter university neurosurgical operating room. PATIENTS: 66 ASA physical status II and III inpatients undergoing neurosurgical procedures for intracranial tumor or other pathology. INTERVENTIONS: Patients were divided into two groups for anesthetic induction. The first group (control) was divided into two subgroups, with the first subgroup receiving "low-dose" etomidate (LET) 0.4 to 0.6 mg/kg titrated to an electroencephalographic (EEG) spectral edge frequency (SEF) of 10 to 12 Hz. The second subgroup received thiopental sodium (THIO) 3 to 6 mg/kg titrated to the same EEG endpoint. The study group was given high-dose etomidate (HET) 0.5 to 1.7 mg/kg titrated to an early burst suppression pattern. MEASUREMENTS AND MAIN RESULTS: Baseline (awake) measurements of mean arterial pressure (MAP) heart rate (HR), and SEF were obtained prior to anesthetic induction that was accomplished using a small bolus plus an infusion of the induction drug titrated to the EEG target. MAP, HR, and SEF were recorded just prior to laryngoscopy and intubation (T1), 30 seconds after laryngoscopy and intubation (T2), and 90 seconds after (T3) laryngoscopy and intubation. Times to reach EEG endpoint, along with total dose of anesthetic given, were also recorded. Compared with baseline values, the THIO group had the highest increase in both HR (22.9 +/- 4.4 bpm.) and MAP (16.8 +/- 4.2 mmHg) (P < 0.05) after laryngoscopy and intubation. The LET group also had significant increases compared with the HET group that demonstrated the least hemodynamic variability. No correlations could be made between age and dose of induction drug. CONCLUSIONS: Etomidate-based anesthetic induction, titrated to EEG burst suppression, produced stable hemodynamics during laryngoscopy and intubation as compared with lower dose, more "classic" inductions with etomidate or thiopental.

Adult↗
PubMed1998

Mycophenolate mofetil reduces production of interferon-dependent major histocompatibility complex induction during allograft rejection, probably by limiting clonal expansion.

The immunosuppressive drug mycophenolate mofetil (MMF) acts by releasing mycophenolic acid (MPA), which inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH) and thus inhibits de novo purine synthesis. Unlike cyclosporine (CsA), MMF has no direct effect on cytokine gene expression in vitro. We examined the effect of MMF, in comparison to CsA, on in vivo production of interferon-gamma (IFN-gamma) in mice. Two stimuli for IFN-gamma induction were used: (1) allogeneic P815 mastocytoma ascites tumour cells and (2) bacterial lipopolysaccharide (LPS). The allogeneic response is dependent on clonal expansion of T cells, while the LPS response is polyclonal and T cell independent. Since major histocompatibility complex (MHC) induction in mouse kidney is IFN-gamma dependent, we assessed the in vivo induction of IFN-gamma indirectly by measuring MHC induction in mouse kidneys in three systems: radiolabelled antibody binding assay, immunoperoxidase staining in tissue sections, and Northern blotting for steady-state MHC mRNA levels. IFN-gamma steady-state mRNA levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). In the allogeneic response, MMF (40-160 mg/kg/day) reduced the production of IFN-gamma in a dose-dependent fashion. MHC class I and II induction was reduced by 35% to 74% and 30% to 74%, respectively. However, MMF had less effect on the induction of MHC by a nonimmune stimulus, bacterial LPS, whereas CsA reduced the induction of IFN-gamma in both responses. We conclude that MMF reduces the IFN-dependent induction of MHC in vivo during specific immune responses, probably by limiting clonal expansion, while preserving nonspecific cytokine production in response to LPS.

Animals↗
PubMed2006

Pilot study of labor induction with titrated oral misoprostol.

OBJECTIVE: To evaluate the safety and efficacy of titrated oral misoprostol for labor induction at term. MATERIALS AND METHODS: Seventy-seven pregnant women (37 nullipara and 40 multipara), with medical or obstetric indications for labor induction after 37 weeks of gestation and unfavorable cervices (Bishop's score < 7), were induced according to the principles of titrated oral doses of misoprostol against uterine response. Our primary outcome measurements were the percentage of patients who had a vaginal delivery within 24 hours of induction and the interval from induction to vaginal delivery. Secondary measurements included oxytocin requirement, total misoprostol dosage, number of cesarean deliveries, induction failure, uterine hyperstimulation rates and neonatal outcomes. RESULTS: Seventy-five women (97.4%) experienced active labor within 24 hours, with 72 (93.5%) completing vaginal delivery within 24 hours. The mean interval from induction to vaginal delivery for all the women was 9.7 hours, with a 2.3-hour active phase. The mean misoprostol dosage was 206 microg, with eight women (10.4%) requiring oxytocin augmentation. There was no uterine hyperstimulation or induction failure, except for seven cases of uterine tachysystole (9.1%). CONCLUSION: Titrated oral misoprostol is a safe and effective method of labor induction because the dosage can be adjusted according to individual response.

Adolescent↗
PubMedDate not supplied

Development of a culture sub-population induction model: signaling pathways synergy and taxanes production by Taxus canadensis.

Cell cultures of Taxus canadensis were subjected to exogenously applied ethylene (ET) hormone and methyl jasmonate (MJ) elicitation in factorial design experiments. Levels of extracellular taxanes, including paclitaxel, were used with principal component analysis for fault detection and real-coded genetic algorithms for parameter optimization to construct a culture sub-population induction model. Culture sub-populations were identified by the model as (1) uninduced, (2) induced to unilateral function of the ET-signaling pathway, and (3) induced to cooperation between jasmonic acid (JA)- and ET-signaling pathways. Comprehensive model results suggested greater rates of cellular induction (resulting in exogenous taxane production) by ET gas as opposed to MJ elicitation. However, cellular induction of ET-signaling pathway genes increased the rate of induction of JA-signaling pathway genes by orders of magnitude. In addition, model results showed that induction of genes leading to extracellular production of the simple taxane 10-deacetylbaccatin III was regulated by the unilateral ET-signaling pathway. However, it was suggested that further processing of this simple taxane to complex taxane structures, such as paclitaxel, required further gene induction by the JA-signaling pathway. Thus, production rate constants of exogenous complex taxanes were predicted to be an order of magnitude lower than that for the simple taxane 10-deacetylbaccatin III. The fraction of the cell culture sub-population displaying unilateral ET-signaling pathway gene induction was found inversely proportional to levels of MJ elicitation. When coupled with simple non-growth product models, levels of all extracellular taxanes were effectively predicted using the culture sub-population induction model.

Acetates↗
PubMed1999

Pore induction in human epidermal membrane during low to moderate voltage iontophoresis: A study using AC iontophoresis.

The present study aimed to investigate new pore induction as a flux-enhancing mechanism in human epidermal membrane (HEM) with low to moderate voltage electric fields. The extent of pore induction and the effective pore sizes of these induced pores were to be assessed using a low frequency (12.5 Hz) low to moderate voltage (2. 0 to 4.0 V) square-wave alternating current (ac) "passive" permeation method (ac iontophoresis). This ac approach was to allow for inducing and sustaining a state of pore induction in HEM while permitting no significant transport enhancement via electroosmosis; thus, transport enhancement entirely due to new pore induction (enhanced passive permeation) was to be assessed without any contributions from electroosmosis. Good proportionality between the increase in HEM permeability and its electrical conductance was found with the "passive" transport data obtained during square-wave ac iontophoresis using urea as the model permeant. Typically, at 3.0 to 4.0 V, HEM conductance increases (and permeability increases) ranged from around 3- to 30-fold. These results appear to be the first direct evidence that new pore induction in HEM is a significant flux enhancing mechanism under moderate voltage conditions. The extents of pore induction in HEM under low frequency moderate voltage (2.0 to 3.0 V) ac, pulsed direct current (dc), and continuous dc were also compared. The extents of pore induction from square-wave ac and pulsed dc were generally of the same order of magnitude but somewhat less than that observed during continuous dc iontophoresis at the same applied voltage and duration, suggesting less extent of pore induction with reversing polarity or when a brief delay is provided between pulses to allow for membrane depolarization. The average effective pore sizes calculated for the induced pores from the experimental data with urea and mannitol as probe permeants and the hindered transport theory were 12 +/- 2 A, which are of the same order of magnitude as those of preexisting pores determined from conventional passive diffusion experiments.

Algorithms↗
PubMed2000

Involvement of c-Fos in signaling grp78 induction following ER calcium release.

Release of calcium from the endoplasmic reticulum (ER) signals an increase in transcription of both the early response gene, c-fos, and the late response gene, grp78. We have used thapsigargin (TG), an ER calcium-ATPase pump inhibitor that induces calcium release from the ER, to investigate the possible involvement of c-Fos, a component of the AP-1 transcription factor, in grp78 induction. Two cell lines with markedly different responses to TG treatment were employed: the WEHI7.2 mouse lymphoma line in which TG fails to induce grp78, and the MDA-MB-468 mammary epithelial line in which TG induces grp78. In WEHI7.2 cells, TG-induced calcium release triggers a rapid increase in c-fos mRNA, but the level of c-Fos protein decreases due to degradation by the multicatalytic proteasome. C-FosdeltaC, a proteasome resistant c-Fos mutant with AP-1 activity similar to that of wild type c-Fos, restores grp78 induction in WEHI7.2 cells, detected by both Northern hybridization and a grp78 promoter-luciferase reporter assay. In MDA-MB-468 cells, TG-mediated calcium release induces a sustained elevation of c-Fos protein that precedes grp78 induction. A region of the grp78 promoter containing both ERSE and CORE regions, but missing TRE and CRE regions, is sufficient to mediate induction of reporter luciferase activity. Induction of this reporter was blocked by A-Fos, a dominant negative inhibitor of c-Fos. Also, the induction of grp78-luciferase reporter activity was inhibited by c-fos antisense mRNA. In summary, the findings indicate that c-Fos is involved in signaling grp78 induction following TG treatment, and that grp78 induction is inhibited by proteasome-mediated c-Fos degradation.

Breast↗
PubMed1991

Induction of acyl-CoA oxidase and cytochrome P450IVA1 RNA in rat primary hepatocyte culture by peroxisome proliferators.

We have characterized the induction of acyl-CoA oxidase and cytochrome P450IVA1 RNAs in a primary hepatocyte culture system in vitro, using a sensitive and specific RNAse protection assay. Hepatocytes were cultured with a maximal inducing dose of the peroxisome proliferator clofibric acid (1 mM), or vehicle control, for 4 days, and the level of RNAs compared with the level in rats which had been treated with corn oil or clofibric acid (300 mg/kg) for 4 days. The level of acyl-CoA oxidase and P450IVA1 RNAs in 4-day-old control hepatocytes was less than 2% of that in control liver. However, the level of these RNAs in RNA from treated hepatocytes was 61% of that in liver RNA from treated rats. Hepatocytes were treated with the potent peroxisome proliferator methylclofenapate (100 microM), and the induction of RNAs determined at various times after exposure. P450IVA1 RNA was significantly induced 1 h after dosing, rising to 34-fold above control after 8 h, whereas acyl-CoA oxidase RNA was not significantly induced until 4 h, increasing to 5.2-fold above control after 8 h. A similar time course of induction was seen after treatment of hepatocytes with 100 microM-nafenopin, 100 microM-methylclofenapate, 1 mM-clofibric acid or 1 mM-mono(ethylhexyl) phthalate, suggesting that the differential time course of induction of P450IVA1 and acyl-CoA oxidase RNAs is not related to the esterification, structure or potency of the peroxisome proliferator, but is intrinsic to the process of peroxisome proliferation. Hepatocytes were treated with methylclofenapate in the presence and absence of cycloheximide. P450IVA1 RNA was significantly induced by methylclofenapate in the presence of cycloheximide, rising to 17-fold above control after 8 h. However, no induction of acyl-CoA oxidase RNA was detected in the presence of cycloheximide. Therefore we characterize the induction of acyl-CoA oxidase and P450IVA1 RNAs in primary hepatocyte culture in vitro as a faithful model of the induction response in rat liver, and suggest that induction of P450IVA1 RNA is a primary event in the process of peroxisome proliferation.

Acyl-CoA Oxidase↗
PubMed2001

Randomized study of vaginal misoprostol (PGE(1)) and dinoprostone gel (PGE(2)) for induction of labor at term.

OBJECTIVES: To investigate the efficacy and safety of misoprostol in the induction of labor at term by comparing this agent with the commonly used dinoprostone gel. PATIENTS AND METHODS: A randomized clinical trial of vaginal misoprostol, 50 microg 6-hourly, and dinoprostone gel, 1-2 mg 6-hourly, in 435 women undergoing induction of labor at term. The women, 210 in the misoprostol group and 225 in the dinoprostone group, were compared to determine whether there was a significant difference in achieving vaginal delivery within 24 h, the incidence of hyperstimulation syndrome, Cesarean section rate and adverse neonatal outcome. They were also offered the option of preinduction sonographic cervical assessment. RESULTS: Misoprostol, compared to dinoprostone gel, was associated with a significantly shorter median induction-to-delivery interval (14.6 h vs. 19.0 h; P = 0.0014), a higher incidence of vaginal delivery within 24 h of induction (65.7% vs. 54.2%; P = 0.019) and a reduced need for oxytocin augmentation during labor (20.5% vs. 29.8%; P = 0.034). The groups did not differ significantly in the rates of Cesarean section (18.1% vs. 19.1%; P = 0.88) and hyperstimulation syndrome (2.4% vs. 0.9%; P = 0.27). None of the cases of hyperstimulation required treatment with tocolysis. All nine cases of excessive uterine contractility occurred after the first dose of the drug. There were no significant differences in maternal and neonatal morbidity between the two groups. There was a significant association between preinduction cervical length and the induction-to-delivery interval in both those receiving misoprostol and those treated with dinoprostone. CONCLUSIONS: The use of misoprostol is associated with a shorter duration of labor and a higher rate of vaginal delivery within 24 h from induction without an increase in maternal and neonatal morbidity. Transvaginal sonographic measurement of cervical length is useful in the prediction of the likelihood of vaginal delivery within 24 h of induction and of the induction-to-delivery interval and may be useful in the stratification of patients participating in randomized studies that examine the effectiveness of inducing agents.

Administration, Intravaginal↗
PubMed1999

Comparison of sevoflurane and propofol with rocuronium for modified rapid-sequence induction of anaesthesia.

We compared the use of sevoflurane and propofol with three different doses of rocuronium for modified rapid-sequence induction of anaesthesia. One hundred and forty adult patients were randomly allocated to have a rapid-sequence intravenous induction with propofol 2-3 mg.kg-1 (group P) or an inhalational induction with sevoflurane 8% in oxygen, using a vital capacity technique (group S). Following loss of the eyelash reflex, cricoid pressure was applied and 20 patients in each group were administered rocuronium 0.3 (groups P/0.3 and S/0.3), 0.45 (groups P/0.45 and S/0.45) or 0.6 (groups P/0.6 and S/0.6) mg.kg-1. An additional 10 patients in each group received only saline placebo in place of the muscle relaxant (groups P/Saline and S/Saline). Laryngoscopy was started 60 s later and intubating conditions evaluated by a blinded anaesthetist according to a standard scoring system. Intubating conditions were acceptable in one patient and no patient, respectively, following induction with sevoflurane and propofol without the muscle relaxant. The conditions were acceptable in 30, 55 and 90% of subjects with sevoflurane induction, and in 45, 80 and 90% of subjects with propofol induction following 0.3, 0.45 and 0.6 mg.kg-1 of rocuronium, respectively (no significant difference for each dose of rocuronium). The present study shows that intubating conditions during a rapid-sequence induction using rocuronium 0.6 mg.kg-1 following induction of anaesthesia with sevoflurane or propofol are similar.

Adolescent↗