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PubMed2000

Indications for labor induction. Differences between university and community hospitals.

OBJECTIVE: To compare the rates of and indications for labor induction between a university hospital and two community hospitals and to examine the risk of cesarean delivery among labor induction cases. STUDY DESIGN: Labor induction cases over a six-month period were included (N = 536). Medical records were reviewed by a trained abstractor using a standardized form to determine maternal characteristics, reason for induction and perinatal outcomes. RESULTS: Rates of labor induction were significantly different between the three hospitals: university, 18.2%; community hospital A, 21.4%; community hospital B, 33.7% (P < .001). At the university hospital, 95% of labor inductions were medically indicated using American College of Obstetricians and Gynecologists (ACOG) criteria. Forty-four percent of labor inductions at community hospital A and 57% at community hospital B were for elective reasons. Cesarean rates among induction cases were highest at the university hospital (19%) as compared to community hospital A (15%) and community hospital B (11%), although the difference was not statistically significant. Parity, race and cervical status, but not elective induction, were significantly associated with cesarean delivery. CONCLUSION: Labor induction was more frequent in community hospitals but more likely to meet ACOG-approved indications at the university hospital. The more-frequent inductions at the community hospitals did not result in higher cesarean rates.

Adult↗
PubMed2002

U.S. national trends in labor induction, 1989-1998.

OBJECTIVE: To examine the epidemiology of labor induction in the United States. STUDY DESIGN: We used U.S. natality data from 1989 to 1998 and examined the rate of labor induction by year, geographic region, maternal characteristics and pregnancy complications. RESULTS: Between 1990 and 1998, the rate of labor induction increased from 9.5% to 19.4% of all births nationwide. However, the induction rate varied widely by state. White race, higher education and early initiation of prenatal care were associated with a higher rate of induction. For all gestational ages, a significantly increased induction rate occurred during the study period. The increase for clinically indicated induction was significantly slower than the overall increase, suggesting that elective induction has risen much more rapidly. CONCLUSION: The rate of induction of labor more than doubled in the U.S. nationwide in the decade from 1989 to 1998. The increased use of labor induction may be attributable to both clinically indicated and elective induction.

Adolescent↗
PubMed2001

A comparative study of vaginal misoprostol and intravenous oxytocin for induction of labour in women with intra uterine fetal death in Mulago Hospital, Uganda.

BACKGROUND: Intrauterine fetal death is a major problem in obstetrics particularly in developing countries such as Uganda. Induction of labour in cases of fetal death using the available method of oxytocin is often difficult, expensive and frustrating. OBJECTIVES: To compare the effectiveness of vaginal misoprostol and intravenous oxytocin in induction of labour in women with intrauterine fetal death. METHODS: One hundred and twenty mothers were allocated in a randomised controlled way to one of the two induction groups. Oxytocin infusion was titrated based on patient response. The starting dose was 50 mcg (1/4 tablet) in misoprostol group and the dose was doubled every six hours till effective contractions were achieved. The two groups were compared for induction to delivery intervals, costs of the drugs and their safety during induction. RESULTS: The success rate within 48 hours of induction was 100% in the misoprostol group and 96.7% in oxytocin group. The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group (23.3 versus 12.4 hours; p= 0.004). In the gestational age before 28 weeks, the induction to delivery interval in oxytocin group, was more than twice that used in misoprostol. However beyond 28 weeks, there was no significant difference. Women with intact membranes had induction to delivery interval of 27.9 hours in the oxytocin group and 14.7 hours in the misoprostol group (p=0.002). When the membranes were ruptured, the values were 10.5 and 8.5 hours respectively (p=0.6). The induction to delivery time in cases with Bishop's score < 6 was 29.8 hours in the oxytocin group and 15.9 hours in misoprostol group (p=0.001). The corresponding values for Bishop's scores > 6 were 10 and 7.9 hours respectively (p=0.6). The majority of patients in misoprostol group (62%), required less than one tablet for successful induction. Misoprostol was cheaper (0.65 US dollars than oxytocin (7.86 US dollars) Retained placenta occurred in only 3.3% of the patients in the misoprostol group. There were no cases of ruptured uterus in both groups. CONCLUSION: Intravaginal misoprostol is more effective and cheaper than intravenous oxytocin for inducing labour in patients with intrauterine fetal death.

Abortifacient Agents, Nonsteroidal↗
PubMed2003

[Survey of the practice of cervical ripening and labor induction in France].

OBJECTIVES: Labor induction is a widespread medical practice in France. The medical or obstetric indications for induction as well as the protocols used probably vary from one maternity to another. The objective of this national survey was to describe current medical practices and procedures in France, regarding labor induction and cervical ripening, eight years after the national consensus on labor induction management. A second objective was to assess mothers' opinion on the induction of their labor/level of satisfaction on their childbirth experience. MATERIALS AND METHODS: The sample of maternities was randomly extracted from a list published by the French Ministry of Health. Sampling was performed according to maternity size, geography, and private vs public. Medical information was collected on consecutive labor induction cases in each maternity. Mother's opinions were estimated through a score based on the validated Labour Agentry Scale. RESULTS: Within the 38 maternities included, 21 (55.3%) were public, and 17 (44.7%) private. 1192 women were included in this study and 1090 (91.4%) answered the questionnaire on level of satisfaction. Global rate of elective induction (no medical or obstetric indication) was 24.8% (n=295). Prostaglandins are almost as widely used as oxytocin (45.8% and 47.7% of total labor inductions, respectively). Mostly used methods of delivering prostaglandin are intravaginal (27.1%), controlled-release pessaries (10.2%) and intracervical (8.1%). Among the elective inductions, an important rate of unfavorable cervix was found (n=81, 27.5%) as well as a quite high level of use of prostaglandins (n=51, 17.3%). The statistically independent criteria linked to a high satisfaction score are an older age (OR=1.58; CI 95% [1.80-3.33]), an elective induction (OR=2.44; IC 95% [1.80-3.33]) and a favorable cervix (OR=1.47; [1.08-1.98]). CONCLUSION: The use of prostaglandins in labor induction and cervical ripening is now widespread in France. This technique is not always used in accordance with available scientific data. These results should lead health professionals to set up an evaluation process for their practices, when these are not based on clear scientific evidence.

Adult↗
PubMed2006

Pretreatment with magnesium sulphate is associated with less succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemodynamic changes than precurarization with vecuronium during rapid sequence induction.

Although it has side effects, succinylcholine is still widely used in rapid sequence induction. The aim of the present study is to evaluate the effects of pretreat ment with magnesium and precurarization of vecuroni um on succinylcholine-induced fasciculation and subse quent tracheal intubation-induced hemodynamic changes during rapid sequence induction. Fifty-five patients were allocated to three groups by a blinded randomization: Group M received saline 100 ml with magnesium 40 mg x kg(-1) for 5 min at 6.5 min before induction and sub sequently administered saline 1-2 ml at 1.5 min before induction; Group V received saline 100 ml for 5 min at 6.5 min before induction and subsequently administered vecuronium 0.02 mg x kg(-1) at 1.5 min before induction; Group C received saline 100 ml for 5 min at 6.5 min before induction and then saline 1-2 ml at 1.5 min before induction. Fasciculation scores and mean percent changes of heart rate, systolic blood pressure and rate pressure product between baseline and after induction were significantly lower in group M than those in group C and group V. Pretreatment with magnesium is more effective to limit succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemody namic changes in rapid sequence induction compared with vecuronium pretreatment, although magnesium does not prevent the elevation of serum potassium con centration after induction.

Adult↗
PubMed1991

Prostaglandin E2 gel for cervical ripening and labour induction: a multicentre placebo-controlled trial.

OBJECTIVE: To determine the effect of a single intracervical dose of prostaglandin E2 (PGE2) gel on cervical ripening and the need for subsequent labour induction with oxytocin. DESIGN: Multicentre randomized, double-blind, placebo-controlled study. SETTING: Tertiary care hospitals. PATIENTS: A total of 397 women met the inclusion criteria: gestational age of at least 36 weeks, parity of 3 or less, a Bishop score of 4 or less, intact membranes, an indication for induction, no contraindication to vaginal delivery, no history of cesarean section or major uterine surgery, no hypersensitivity to prostaglandins, no previous attempt at cervical ripening or induction, no vaginal bleeding and no fetal abnormalities. INTERVENTION: The experimental group (203 women) received a low dose (0.5 mg) of PGE2 in 2.5 mL of gel and the control group (194) 2.5 mL of a placebo gel intracervically. The observation period was 12 hours before further induction (with oxytocin) was attempted. OUTCOME MEASURES: Ripening effect of gel, need for induction with oxytocin, rate of labour induction, time from gel administration to delivery. RESULTS: Seventeen women could not be evaluated because induction was not attempted after the first 12 hours (in nine cases) or the induction attempt was delayed for 24 hours (in six); in the other two cases the gel was in place for only 2 1/2 and 4 hours respectively before cesarean section was required. The Bishop score 12 hours after the gel administration and the difference in the score from the time of admission to the end of the 12-hour observation period were significantly higher in the experimental group than in the control group (p less than 0.001). In all, 91 (46%) of the 196 patients in the experimental group went into labour within the 12-hour observation period, as compared with 21 (11%) of the 184 in the control group (p less than 0.001). When the women who required further induction were included the rate of successful induction was 85% (166 women) and 72% (132) respectively (p less than 0.004). The mean interval from the time of gel administration to delivery was smaller in the experimental group than in the control group (19.8 v. 24.1 hours respectively) (p less than 0.001). CONCLUSIONS: A single, low dose of PGE2 gel administered intracervically is a safe and reliable method of dealing with indicated but potentially difficult inductions.

Cervix Uteri↗
PubMed1982

Case-control analysis of post-term induction of labor.

At Akershus Central Hospital the main indication for induction of labor is post-term pregnancy, and induction is carried out by i.v. oxytocin drip. During 3 years between 1974 and 1977, labor was induced in 11.6% of all births in this hospital. Thirty per cent of first induction attempts were unsuccessful; the success rates, implying labor contractions and delivery consequent upon induction, were slightly higher among mothers of parities 1 + than among those giving birth for the first time. Most of the induced births took place between noon and 8 p.m. In a case-control study of post-term inductions of live single fetuses in cephalic presentation, comprising 721 sets of cases and controls, unreliable term dating was more frequent among induced than among control mothers, significantly so in the para 1 + group. Mothers requiring induction were slightly shorter and slightly heavier than those with spontaneous onset of labor, and pregnancy hypertension was more frequent among the former. Labor was of shorter duration in induced cases than in those with labor of spontaneous onset, and operative intervention during delivery was significantly more frequent in the induction groups. Birth weight and crown-heel length were similar in the two groups, but Apgar scores of the infants born after induction were significantly lower than of those born after spontaneous labor, at both 1 and 5 minutes. While the frequency of diseases and injuries in the newborns were similar, more children born after induction were transferred to the intensive care unit. There was a striking preponderance of boys born after induction, both to para 0 and para 1 + mothers. In spite of matching, the comparability of cases and controls is always an object of criticism in studies like this one. Therefore, although the information obtained is valuable, there is a need for large-scale randomized studies on induction of labor.

Cesarean Section↗
PubMed1999

Adsorption capacity as a key parameter for enzyme induction and pentachlorophenol degradation in Mycobacterium chlorophenolicum PCP-1.

Adsorption of pentachlorophenol (PCP) on induced cells of Mycobacterium chlorophenolicum PCP-1 and its influence on enzyme induction and PCP degradation of this strain were studied. Compared to non-induced cells, induced degrading cells had a lower adsorption capacity (q(ads)), particularly at prolonged induction and low PCP concentration. Unlike the effects of pH and biomass concentration previously reported for non-induced cells, the variation of q(ads) of induced cells was associated with changes of both the capacity and intensity constants of the Freundlich equation which was used to describe PCP adsorption on M. chlorophenolicum PCP-1. This indicated changes of cell surface properties during enzyme induction and PCP degradation. The latter was shown in turn to be affected by several parameters such as PCP concentration, pH value and induction time. Interestingly, irrespective of the pH and PCP concentration, the specific PCP degradation rate (q(t)(PCP)) at a given induction time was found to be solely a function of q(ads), revealing that adsorption capacity is an inherent key parameter for enzyme induction and PCP degradation. Based on this knowledge, a kinetic model was developed for q(t)(PCP) which used only q(ads) and induction time as variables. The model considered inhibition of PCP on both enzyme induction and enzyme activity and described the experimental data at different PCP concentrations and pH values well. q(ads) also turned out to be a useful criterion for choosing optimum induction concentration of PCP. Irrespective of pH and biomass concentration, an initial adsorption capacity of 2-3 micromol PCP/g cells was found to be optimum for enzyme induction in M. chlorophenolicum PCP-1.

Adsorption↗
PubMed1994

Roles for protein kinases in the induction of nitric oxide synthase in astrocytes.

Lipopolysaccharide (LPS) or a combination of interferon (IFN)-gamma and interleukin (IL)-1 beta can induce a calcium-independent nitric oxide synthase (iNOS) in astrocyte cultures (Simmons and Murphy: J Neurochem 59:897, 1992; Eur J Neurosci 5:825, 1993; Galea et al: Proc Natl Acad Sci USA 89:10945, 1992). This induction can be measured by assaying cyclic GMP levels in the cultures, which correlates with, but is more sensitive than, measurement of nitrite accumulation. To study potential second-messenger systems involved in the induction of iNOS, phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, and various protein kinase inhibitors were employed. PMA induced a time-, dose-, and L-arginine-dependent increase in cyclic GMP, which could be inhibited by dexamethasone or actinomycin D. This induction could be dramatically increased by concurrent treatment with IFN-gamma. The presence of iNOS mRNA could be demonstrated by hybridization with a specific cDNA probe. H7 (a non-specific serine/threonine kinase inhibitor) but not H89 (a more specific PKA inhibitor) prevented induction by all agents. However, downregulation of PKC or pretreatment with the PKC inhibitor calphostin C did not prevent the induction by LPS or cytokines, suggesting that PKC is not necessary for iNOS induction by these mediators. Additionally, genistein (a nonspecific tyrosine kinase inhibitor) could prevent induction by all agents, but the more specific inhibitor, tyrphostin, attenuated only NOS induction by LPS. These results suggest that activation of PKC can lead to, but is not necessary for, the induction of NOS in astrocytes and that there is a potential role for tyrosine kinases in NOS induction by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1997

Effect of cytochrome P450 induction on phosphorus metabolites and proton relaxation times measured by in vivo 31P-magnetic resonance spectroscopy and 1H-magnetic resonance relaxometry in human liver.

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.

Adult↗
PubMed1996

The regulation by gender, strain, dose, and feeding status of the induction of multiple forms of cytochrome P450 isozymes in rat hepatic microsomes by 2,4,5,2',4',5'-hexachlorobiphenyl.

2,4,5,2',4',5'-hexachlorobiphenyl (HCB) induces hepatic microsomal cytochromes P450 with a similar selectivity for responsive genes to phenobarbital (PB). CYP2Bl, CYP2B2, CYP2C6, CYP3Al, and CYP2Al each showed large strain differences in induction by HCB Fisher F344 >> Wistar Furth (WF) that were much more evident in female rats, paralleling previous observations with PB. These five P450s and epoxide hydrolase were, however, induced more effectively by HCB than by PB and strain differences were even larger. With HCB, strain differences in male rats were much more apparent than with PB. This change was not due to the greater HCB induction since a 2-fold lower induction was maintained even with a 10-fold lower dose of HCB. The sex and strain differences were seen both by immunoblot analysis and by form-selective enzyme activity assays. induction of CYP2B1, CYP2B2, and CYP3A1 by HCB was decreased 3-fold when starvation during the final 24 hr was replaced by continuous feeding. This effect was similar in each strain and therefore independent of the regulatory processes associated with the differential suppression of induction in WF rats. This modulation of induction by feeding was also seen with PB which caused only a 30% lowering of induction in continuously fed F344 rats. A 52-kDa microsomal protein (p52) was prominently induced by both HCB and PB after starvation, while minor induction of a 50-kDa microsomal protein (p50) also occurred after the same treatment. Furthermore, a 100-kDa microsomal protein (p100) was induced by HCB but not by PB and only in rats that were continuously fed. These results suggest that the induction of multiple forms of P450 following HCB treatment functions through the same PB-stimulated pathway that shows a strain-dependent endocrine (GH/T3/testosterone)-sensitive suppression mechanism. The induction of p5O, p52, and plOO by HCB suggests the presence of at least two additional hepatic response mechanisms for HCB.

Animal Feed↗
PubMed2006

CYP induction-mediated drug interactions: in vitro assessment and clinical implications.

Cytochrome P450 (CYP) induction-mediated interaction is one of the major concerns in clinical practice and for the pharmaceutical industry. There are two major issues associated with CYP induction: a reduction in therapeutic efficacy of comedications and an induction in reactive metabolite-induced toxicity. Because CYP induction is a metabolic liability in drug therapy, it is highly desirable to develop new drug candidates that are not potent CYP inducer to avoid the potential of CYP induction-mediated drug interactions. For this reason, today, many drug companies routinely include the assessment of CYP induction at the stage of drug discovery as part of the selection processes of new drug candidates for further clinical development. The purpose of this article is to review the molecular mechanisms of CYP induction and the clinical implications, including pharmacokinetic and pharmacodynamic consequences. In addition, factors that affect the degree of CYP induction and extrapolation of in vitro CYP induction data to in vivo situations will also be discussed. Finally, assessment of the potential of CYP induction at the drug discovery and development stage will be discussed.

Animals↗
PubMed1995

Differential effect of cytokines on the phenobarbital or 3-methylcholanthrene induction of P450 mediated monooxygenase activity in cultured rat hepatocytes.

Cultured rat hepatocytes have been used to compare the relative activities of cytokines to inhibit the phenobarbital (PB) or 3-methylcholanthrene (MC) induction of cytochrome P4502B1 and 2B2 (P4502B1/2) or P4501A1 and 1A2 (P4501A1/2), respectively. Recombinant cytokines tested were human interleukin-6 (IL-6), interleukin-1 alpha and -beta (IL-1 alpha and IL-1 beta, respectively), and rat gamma-interferon (INF gamma). Hepatocytes were cultured in the presence of 2 mM PB or 1 microgram MC/mL culture medium for 24 hr with or without the cytokines. Benzyloxyresorufin and ethoxyresorufin O-dealkylase (BROD and EROD, respectively) activities were determined as indices of P4502B1/2 and P4501A1/2, respectively. All cytokines produced a concentration-dependent inhibition of the PB induction of BROD activity. IL-1 beta and IL-6 were approximately equipotent with IC50 values of 1-2 U/mL, causing greater than 90% inhibition of PB induction of BROD activity at a concentration of 50 U/mL culture medium. IL-1 alpha tended to be less active. PB induction of BROD activity was also inhibited by INF gamma, but higher concentrations (62.5 to 500 U/mL culture medium) were required. All cytokines were less effective in inhibiting the MC induction of EROD activity than the PB induction of BROD activity. IL-1 beta and IL-6, at 50 U/mL culture medium, inhibited EROD induction by only 35% compared with the greater than 90% inhibitory effect on the PB induction of BROD activity. INF gamma was ineffective in inhibiting EROD activity at the concentrations studied. Western immunoblot analysis indicated that the cytokines prevented the ability of the inducers to increase the expression of P4502B1/2 and P4501A1/2 immunoreactive proteins, and this effect correlated with their inhibitory effect on induction of enzyme activity. The results suggest that inducible isoforms of cytochrome P450 differ in their susceptibility to regulation by the cytokines, and that cytokines possess differential activity to inhibit the induction of P450 isoforms, with IL-1 beta and IL-6 being the most effective.

Animals↗
PubMed2005

Hepatocytes cultured in alginate microspheres: an optimized technique to study enzyme induction.

An important application of hepatocyte cultures is identification of drugs acting as inducers of biotransformation enzymes that alter metabolic clearance of other therapeutic agents. In the present study we optimized an in vitro system with hepatocytes cultured in alginate microspheres that allow studies of enzyme induction with excellent sensitivity. Induction factors obtained with standard inducers, such as 3-methylcholanthrene or phenobarbital, were higher compared to those with conventional hepatocyte co-cultures on collagen coated dishes. This is illustrated by activities of 7-ethoxyresorufin-O-deethylase (EROD) after incubation with 5 microM 3-methylcholanthrene (3-MC), a standard inducer for cytochrome P4501A1 and 1A2. Mean activities for solvent controls and 3-MC exposed cells were 2.99 and 449 pmol/min/mg protein (induction factor: 150) for hepatocytes cultured in microspheres compared to 2.72 and 80.6 pmol/min/mg (induction factor: 29.6) for hepatocytes on collagen coated dishes. To compare these in vitro data to the in vivo situation male Sprague Dawley rats, the same strain that was used also for the in vitro studies, were exposed to 3-MC in vivo using a protocol that guarantees maximal induction. Activities were 29.2 and 1656 pmol/min/mg in liver homogenate of solvent and 3-MC treated animals (induction factor: 56.7). Thus, the absolute activities of 3-MC exposed hepatocytes in microspheres are lower compared to the in vivo situation. However, the induction factor in vitro was even higher compared to the in vivo situation (150-fold versus 56.7-fold). A similar scenario was observed using phenobarbital (0.75 mM) for induction of CYP2B and 3A isoenzymes: induction factors for testosterone hydroxylation in position 16beta were 127.5- and 50.4-fold for hepatocytes in microspheres and conventionally cultured hepatocytes, respectively. The new in vitro system with hepatocytes embedded in solid alginate microspheres offers several technical advantages: (i) the solid alginate microspheres can be liquefied within 60s, allowing a fast and complete harvest of hepatocytes; (ii) alginate capsules are stable allowing transport and mechanical stress; (iii) high numbers of hepatocytes can be encapsulated in short periods; (iv) defined cell numbers between 600 hepatocytes, the approximate number of cells in one capsule, and 18 x 10(6) hepatocytes, the number of hepatocytes in 6 ml alginate, can be transferred to a culture dish or flask. Thus, encapsulated hepatocytes allow a flexible organization of experiments with respect to cell number. In conclusion, we optimized a technique for encapsulation of hepatocytes in alginate microspheres that allows identification of enzyme induction with an improved sensitivity compared to existing systems.

Alginates↗
PubMed2002

Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study.

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

Adolescent↗
PubMed1987

Induction of aromatase activity in porcine granulosa cells by FSH and cyclic AMP.

This paper examines the involvement of mRNA and protein synthesis in the induction of aromatase activity by FSH and also the site of action of androgens on FSH induction of aromatase activity in porcine granulosa cells. Treatment of cells with FSH or dbcAMP for an initial 48 h (induction period) resulted in an induction of aromatase activity, as measured by the production of estradiol during a subsequent 6h test period. Addition of testosterone to cells cultured with dbcAMP during the induction period enhanced the aromatase activity during both the induction and test periods. However, while DHT has no effect during the induction period, it significantly inhibited the aromatase activity during the test period. Culturing the granulosa cells with actinomycin D or cycloheximide during the induction period resulted in a dose-dependent inhibition of FSH induction of aromatase activity, suggestive of the synthesis of new protein(s). These results indicate clearly that FSH induction of aromatase activity involves the synthesis of mRNA and proteins.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Staurosporine, a potent protein kinase C inhibitor, augments phorbol ester-caused ornithine decarboxylase induction in mouse epidermis.

A single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin caused an induction of epidermal ornithine decarboxylase (ODC) activity. When mice were topically pretreated with staurosporine, a most potent protein kinase C inhibitor, 6-84 h prior to TPA treatment, TPA-caused ODC induction was markedly enhanced. The enhancement of TPA-caused ODC induction by staurosporine was most pronounced when the time interval between staurosporine and TPA treatment was 36 h. Staurosporine elicited this enhancing effect in a dose-related manner. Staurosporine by itself also induced epidermal ODC activity. But the activity induced was very slight and would not directly contribute to the enhancing effect of this compound. Although staurosporine markedly augmented TPA-caused ODC induction, staurosporine-caused ODC induction was not augmented by this compound. Other protein kinase C inhibitors, such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, sphingosine and palmitoylcarnitine did not mimic the enhancing effect of staurosporine. These results indicate that the enhancement of ODC induction by staurosporine is specific for the induction caused by TPA and that this enhancing effect is not related to the protein kinase C inhibitory action of staurosporine. TPA-caused epidermal ODC induction was inhibited by indomethacin, and this inhibition was reversed by prostaglandin E2 (PGE2). Staurosporine-caused ODC induction was also inhibited by indomethacin but the inhibition was not reversed by PGE2, indicating that the mechanism of staurosporine-caused ODC induction is different from that of TPA.

Administration, Topical↗
PubMed1996

Calcium and calmodulin are involved in blue light induction of the gsa gene for an early chlorophyll biosynthetic step in Chlamydomonas.

The Chlamydomonas reinhardtii nuclear gene gsa, which encodes the early chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase (GSAT), is specifically induced by blue light in cells synchronized in a 12-hr-light and 12-hr-dark regime. Light induction required the presence of a nitrogen source in the incubation medium. Maximal induction also required acetate. However, in the absence of acetate, partial induction occurred when Ca2+ was present in the medium at concentrations of > or = 1 microM. The Ca2+ channel-blocking agents Nd3+ and nifedipine partially inhibited the external Ca(2+)-supported induction of GSAT mRNA but did not inhibit acetate-supported induction. The calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited both external Ca(2+)-supported and acetate-supported induction. The Ca2+ ionophore A23187 caused a transient induction in the dark. These results suggest that Ca2+ and calmodulin are involved in the signal transduction pathway linking blue light perception to the induction of GSAT mRNA. The electron transport uncoupler carbonyl cyanide m-chlorophenylhydrazone inhibited acetate-supported induction of GSAT mRNA but did not inhibit external Ca(2+)-supported induction. It is proposed that in the presence of acetate, an internal pool of Ca2+ can be mobilized as a second message, whereas in the absence of acetate, internal Ca2+ is not available but the requirement for Ca2+ can be partially met by an external Ca2+ source. The mobilization of internal Ca2+ may require energy derived from metabolism of acetate.

Acetates↗