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PubMed1994

Mild pregnancy-induced hypertension at term.

It was elected to induce labor in Mrs AB after excluding any evidence of severe preeclampsia. Both the fetus and Mrs AB were evaluated. The history, physical examination, and laboratory results were all within normal limits for Mrs AB. Her fetus was appropriately grown for gestational age with an estimated fetal weight of 3,200 g. There was ample but not excessive amniotic fluid noted clinically and by sonography. An amniocentesis to document fetal lung maturation was not done. Two hours after commencing parenteral magnesium sulfate therapy, an oxytocin induction of labor was begun. Fetal well-being was assessed using continuous external electronic monitoring of the fetal heart rate and uterine contractions. Three hours after the induction was started, the cervix was completely effaced and 3 cm dilated. The fetal head was at O station. At this time, the fetal membranes were ruptured and clear amniotic fluid was noted. An internal uterine pressure catheter was inserted, and a fetal scalp electrode applied. The patient received 75 mg of meperidine and 25 mg of promethazine intramuscularly at this time. Five hours after commencing the induction of labor, both mother and fetus were tolerating the labor well. The cervix was 7 cm dilated, and the fetal head was at +2/+5 station. The oxytocin induction was discontinued and another 75 mg dose of meperidine was administered. Blood pressure readings between 150/100 mm Hg and 140/98 mm Hg were recorded throughout labor. Urine output exceeded 150 mL/h. The patient delivered a 3,070-g male infant approximately 9 hours after the start of the induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

[Effects of oxytocin, misoprostol and nimodipine on expression of L-type voltage dependent calcium channel mRNA of the uterine myometrium and left ventricular myocardial cells in late pregnant rats].

OBJECTIVE: To study the effect of oxytocin, misoprostol and nimodiping on expressions of L-type voltage dependent calcium channel (VDCC-L) alpha(1) and VDCC-L beta(2) mRNA in the myometrium and left ventricular myocardial cells of the late pregnant rats. METHODS: A reverse transcription polymerase chain reaction (RT-PCR) method was used to examine and quantitate VDCC-L alpha(1) and VDCC-L beta(2) mRNA expressions in the uterine myometrium and left ventricular myocardial cells of rats, which were divided into the nature labor group, oxytocin group (oxytocin inducing labor), misoprostol group (misoprostol inducing labor) and nimodipine group (active labor at 48 hours after administering nimodipine). RESULTS: (1) In the uterine myometrium, the levels of VDCC-L alpha(1) mRNA expression in the nature labor, oxytocin, misoprostol and nimodipine group were 0.800 3 +/- 0.165 9, 0.863 1 +/- 0.192 1, 0.812 0 +/- 0.173 4 and 0.742 6 +/- 0.182 6, respectively. No significant difference was found in the four groups (P > 0.05). The levels of VDCC-L beta(2) mRNA expression in the above four groups were 0.646 9 +/- 0.130 4, 0.506 2 +/- 0.147 2, 0.500 5 +/- 0.135 6 and 0.492 9 +/- 0.127 6, respectively. There was no remarkable difference between the nature labor group and the other three administering drugs groups (P > 0.05). (2) In the left ventricular myocardial cells, expressions of VDCC-L alpha(1) in the nature labor, oxytocin, misoprostol and nimodipine group were 0.662 5 +/- 0.180 1, 0.636 5 +/- 0.157 8, 0.591 7 +/- 0.141 3 and 0.542 6 +/- 0.143 6, respectively; the levels of VDCC-L beta(2) mRNA expression were 0.670 2 +/- 0.140 5, 0.606 2 +/- 0.143 9, 0.591 4 +/- 0.121 9 and 0.585 2 +/- 0.131 0, respectively. Although both the levels of VDCC-L alpha(1) and VDCC-L beta(2) mRNA expression in the nature labor group were a little higher than those in the other three experiment groups, the statistic difference was not noted (P > 0.05). CONCLUSIONS: Oxytocin, misoprostol or nimodipine can induce or inhibit labor through regulating expressions of VDCC-L alpha(1) and VDCC-L beta(2) mRNA in the rat uterine myometrium and it may not have an adverse effect on heart function of normal pregnant rats. VDCC-L may be the common channel of labor induced by internal or external factors.

Animals↗
PubMed1997

Involvement of nitric oxide pathway in prostaglandin F2 alpha-induced preterm labor in rats.

OBJECTIVE: Our purpose was to investigate the roles of nitric oxide and prostaglandins in controlling parturition. STUDY DESIGN: Pregnant rats on day 18 of gestation were injected intraperitoneally with prostaglandin F2 alpha, prostaglandin F2 alpha plus diethylenetriamine-nitric oxide (a donor of nitric oxide), prostaglandin F2 alpha plus diethylenetriamine without nitric oxide, or vehicle. Uterine nitrite production, nitric oxide synthase messenger ribonucleic acid and contractile response in vitro, and serum progesterone levels were measured. The labor and delivery of the rats also were monitored. RESULTS: Exogenously administered prostaglandin F2 alpha significantly inhibited nitric oxide production by the uterus in a time-dependent manner with maximal effects observed 48 hours after prostaglandin F2 alpha treatment. Messenger ribonucleic acid for inducible nitric oxide synthase but not endothelial nitric oxide synthase messenger ribonucleic acid in the uterus was significantly inhibited by prostaglandin F2 alpha with maximal inhibition at 48 hours after prostaglandin F2 alpha injection. The serum progesterone concentration was substantially reduced by prostaglandin F2 alpha, and this reduction was partially reversed by administration of diethylenetriamine-nitric oxide but not diethylenetriamine without nitric oxide. Prostaglandin F2 alpha caused increases in contractile activity of the uterus in a dose-dependent manner. Diethylenetriamine-nitric oxide (10(-4) mol/L) blocked prostaglandin F2 alpha-induced contractions. Premature parturition was induced within 48 hours after prostaglandin F2 alpha injection in 100% of the animals. Coadministration of diethylenetriamine-nitric oxide completely prevented the preterm labor induced by prostaglandin F2 alpha. CONCLUSION: Prostaglandin F2 alpha inhibited inducible nitric oxide synthase messenger ribonucleic acid and subsequent nitric oxide generation in the rat uterus. Nitric oxide can prevent prostaglandin F2 alpha-induced preterm labor, possibly by attenuating the fall in serum progesterone and blocking uterine contractions induced by prostaglandin F2 alpha administration.

Animals↗
PubMed1983

Origin of prostanoids in human amniotic fluid: the fetal kidney as a source of amniotic fluid prostanoids.

The present study was designed to investigate the origin of prostanoids that are present in amniotic fluid. We evaluated the concentration of prostaglandins in fetal urine that was obtained from newborn infants immediately after delivery either before or after the onset of spontaneous labor or after oxytocin-induced labor. We found that the levels of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and 13, 14-dihydro-15-keto-PGF2 alpha in the fetal urine of newborn infants delivered after the spontaneous onset of labor and after oxytocin-induced labor were significantly greater than the levels in the fetal urine of newborn infants delivered before the spontaneous onset of labor. We conclude that one source of the prostanoids present in amniotic fluid is fetal urine, and, thence, fetal kidneys, and that labor, whether spontaneous or induced, caused increased excretion of prostanoids in fetal urine.

Amniotic Fluid↗
PubMed2003

Postdates pregnancy in an indigent population: the financial burden.

OBJECTIVE: The objective of this study was to determine the comparative financial burden of twice-weekly fetal testing from 41 weeks of gestation until delivery, as compared with early dating ultrasound evaluation in an indigent population. STUDY DESIGN: All women who were seen for antepartum testing for postdating pregnancy at Lyndon Baines Johnson Hospital were enrolled. Patient age, parity, gestational age at initiation of prenatal care, the number of prenatal visits, gestational age at first ultrasound scan, and the number of biophysical profiles that were performed before delivery were recorded. The labor and delivery database was searched for all deliveries at >41 weeks of gestation. The charge for a single ultrasound scan at <20 weeks of gestation was compared with twice-weekly testing in the population as a whole with the use of three strategies (no dating ultrasound scans and biophysical profiles until delivery, routine dating ultrasound scan and routine induction at 41 weeks of gestation, and current practice at our institution). RESULTS: One hundred twenty-seven subjects with postdated pregnancy were enrolled (mean age, 25.2 years; median parity, 0 [range, 0-6]). The mean gestational age at the initiation of prenatal care was 21.2 +/- 10.5 weeks. Forty-seven women (38.0%) initiated care at <20 weeks. The mean number of biophysical profiles performed before delivery was 1.5 +/- 1.34; the mean gestational age at delivery was 42.1 +/- 0.87 weeks (spontaneous labor, 39.6%; induced labor, 40.4%). The charge for a biophysical profile is $492.90 US dollars and $551.00 US dollars for a 20-week ultrasound scan; there is no difference in the charge for induced or spontaneous labor. During the 4-month study period, 1638 patients were delivered at our hospital; 341 patients were delivered at >41 weeks of gestation. The estimated financial burden of antenatal testing of 341 patients from 41 weeks to delivery was calculated to be $252,118 US dollars, compared with $902,538 US dollars for a single ultrasound scan at 20 weeks for the entire population of 1638 patients. The estimated financial burden of current practice (10% of patients with no prenatal care, 38% of patients with examination at <20 weeks who were eligible for dating ultrasound scanning, and 37% of patients with examination for postdate testing) was $402,457 US dollars. CONCLUSION: Patients who were seen for postdate antepartum testing in an indigent population lack early initiation of prenatal care and early ultrasound scans. Because on average only 1.5 biophysical profiles are performed per patient before delivery, routine early ultrasound scanning and routine induction at 41 weeks of gestation would add considerable financial burden to the system.

Adult↗
PubMed1985

Induction of human labor at term: uterine activity, inducibility, duration and neonatal jaundice.

A total of 821 patients, 39-40 weeks pregnant, was obstetrically normal at admission. In 212 of them intra-uterine pressure (IUP) was monitored before and during inducing labor by oxytocin, in 212 patients delivery was also induced by oxytocin but not monitored, in 197 by combining oxytocin and amniotomy, and 200 had spontaneous delivery. Inducibility could be predicted by uterine baseline activity and a 50 mu i.v. shot of oxytocin, together with determination of cervical status and placental location. The duration of labour induction was affected by parity, placental location and cervical status, but was predicted only to a minor degree by baseline activity and uterine oxytocin sensitivity. Amniotomy did not affect caesarean, section rate. The newborn child benefited from IUP monitoring: fewer transfers to pediatrics were necessary, there was less neonatal jaundice and fewer blood exchanges. It is assumed that if labor is not monitored through IUP, oxytocin may cause neonatal hyperbilirubinaemia through episodes of increased uterine resting pressure.

Female↗
PubMedDate not supplied

Inflammatory cytokines in a murine model of infection-induced preterm labor: cause or effect?

OBJECTIVE: To characterize the expression of inflammatory cytokines in a murine model of preterm delivery induced by heat-killed bacteria. METHODS: The right uterine horns of female CD-1 mice on day 14.5 of 19-20 days of gestation were inoculated with either sterile media or killed Escherichia coli bacteria (10(5)-10(10) organisms per mouse). The incidence of preterm delivery was recorded. The concentrations of cytokines (interleukin [IL-] 1 alpha, IL-1 beta, IL-1 receptor antagonist [IL-1ra], IL-6, and tumor necrosis factor alpha [TNF alpha]) within maternal and fetal tissue homogenates were determined by enzyme-linked immunosorbent assay at various times after inoculation. RESULTS: Killed E. coli induced preterm delivery in a dose-dependent fashion. Inoculation with 10(10) bacteria (sufficient to cause delivery in all mice) produced increases in IL-1 alpha, IL-1 beta, IL-6, and TNF alpha within uteri and fetal membranes, but not within placentas, fetal bodies, and maternal serum. Maximum mean uterine levels of IL-1 and IL-6 exceeded those of fetal tissues (membranes, placentas, and fetal bodies) by greater than 15-fold. Maximal uterine IL-1 and TNF alpha levels following inoculation with 10(10) bacteria exceeded those that followed inoculation with 10(7) bacteria (below the threshold for delivery) by 2.5- to 5-fold. The anti-inflammatory cytokine IL-1ra was expressed in higher concentrations in fetal than in maternal tissues and was unaltered by the bacterial inoculum. CONCLUSIONS: E. coli induce labor in mice even in the absence of bacterial viability. Although IL-1 and TNF alpha were upregulated by bacterial inocula causing delivery, peak levels were only 2.5- to 5-fold higher than those that occurred with inocula below the threshold for delivery (1000-fold fewer bacteria). Whether IL-1 and TNF alpha mediate labor during in vivo infection, or whether the upregulation of these cytokines merely represents an epiphenomenon accompanying infection, remains unknown.

Animals↗
PubMed2005

The molecular pathophysiology of bacterially induced preterm labor: insights from the murine model.

Premature delivery, the most important problem in obstetrics in developed countries, continues to vex clinicians and researchers. Despite decades of investigation, the pathophysiology of premature labor is incompletely understood, and therapies or preventive strategies tailored to each of the many potential causes do not exist. The present review addresses one cause of prematurity, namely, intrauterine bacterial infection. Given the vastness of the literature for even this single etiology, we focus on the mouse as a model organism from which much can be learned about mammalian parturition. The underpinnings of bacterially induced labor are believed to involve a signaling cascade that begins with recognition of offending pathogens by cell-surface receptors (toll-like receptors). This cascade then operates through multiple branching and redundant pathways to bring about the changes within the gestational compartment that produce cervical ripening, labor, and ultimately delivery. The major challenge facing researchers is to understand the levels of complexity in the host response, so that prevention and treatment strategies may be sufficiently focused to minimize unwanted side effects, yet sufficiently broad to be effective. Given the complexity of the problem, this understanding can be aided by efficient model systems, of which one in vivo example is the mouse, an organism that shares with humans many similarities in the biochemical and molecular aspects of inflammation-induced preterm labor. We propose that tools with the power to assess simultaneously the myriad elements of the hypothesized signaling cascade (ie, genomic and proteomic technologies) are important components of the solution to the puzzle of parturition.

Animals↗
PubMedDate not supplied

Comparative analysis of the effectiveness of misoprostol and prostaglandin E(2) in the preinduction and induction of labor.

BACKGROUND: Amniotomy and oxytocin infusion are the routine methods most frequently applied to induce labor. These methods are not effective when the cervix is unripe. Prostaglandins may accelerate the process of cervical ripening independently of the stimulation of uterine contractions, since they induce the formation of a gap junction (spread of excitation) and release uterine contractions. The purpose of this study is a comparative analysis of the effectiveness and safety of misoprostol and PGE2 in the process of cervical ripening and inducing labor in patients at full term delivery with a live fetus and indications for inducing labor due to an unripe uterine cervix. MATERIAL AND METHODS: The experimental group consisted of 30 patients at 38-41 weeks of gestation who received misoprostol administered into the posterior vaginal fornix (group M). The control group included 26 patients at 39-42 weeks of gestation in whom labor was induced using natural prostaglandin E(2) (group P). RESULTS: There were no statistically significant differences in maternal age, body weight and height, or uterine cervical ripening between the two groups of patients. The average time of gestation was 0.92 weeks shorter in group M. The time from administration of the drug to the onset of regular contraction activity of the uterus and delivery of an infant was shorter in the group of patients receiving misoprostol intravaginally. CONCLUSIONS: Our results would seem to indicate that misoprostol is an effective drug that can be used for elective preinduction and induction of labor. However, the application of this drug to induce labor with a live fetus requires special caution and care, as well as continuous cardiotocographic monitoring to assure the safety of both the mother and the infant.

Cervical Ripening↗
PubMed2001

Risk of uterine rupture during labor among women with a prior cesarean delivery.

BACKGROUND: Each year in the United States, approximately 60 percent of women with a prior cesarean delivery who become pregnant again attempt labor. Concern persists that a trial of labor may increase the risk of uterine rupture, an uncommon but serious obstetrical complication. METHODS: We conducted a population-based, retrospective cohort analysis using data from all primiparous women who gave birth to live singleton infants by cesarean section in civilian hospitals in Washington State from 1987 through 1996 and who delivered a second singleton child during the same period (a total of 20,095 women). We assessed the risk of uterine rupture for deliveries with spontaneous onset of labor, those with labor induced by prostaglandins, and those in which labor was induced by other means; these three groups of deliveries were compared with repeated cesarean delivery without labor. RESULTS: Uterine rupture occurred at a rate of 1.6 per 1000 among women with repeated cesarean delivery without labor (11 women), 5.2 per 1000 among women with spontaneous onset of labor (56 women), 7.7 per 1000 among women whose labor was induced without prostaglandins (15 women), and 24.5 per 1000 among women with prostaglandin-induced labor (9 women). As compared with the risk in women with repeated cesarean delivery without labor, uterine rupture was more likely among women with spontaneous onset of labor (relative risk, 3.3; 95 percent confidence interval, 1.8 to 6.0), induction of labor without prostaglandins (relative risk, 4.9; 95 percent confidence interval, 2.4 to 9.7), and induction with prostaglandins (relative risk, 15.6; 95 percent confidence interval, 8.1 to 30.0). CONCLUSIONS: For women with one prior cesarean delivery, the risk of uterine rupture is higher among those whose labor is induced than among those with repeated cesarean delivery without labor. Labor induced with a prostaglandin confers the highest risk.

Adolescent↗
PubMed1976

[Prenatal weight loss in the infant (author's transl)].

Hillemanns and coworkers established, that infants born after induced labor were heavier, on the average, than those from a control group; who were born after spontaneous labor. Since it was postulated, that a weight loss preceded the onset of spontaneous labor, the birth weight and length of 444 infants born after induced labor and 70 infants born via a primary cesarean section was compared with a control group of 1,028 uncomplicated births via spontaneous labor. Thirty seven post term infants were also included in the study. The birth weight and length of infants after induced labor or delivered by primary cesarean section significantly higher than those in the control group. The post term infants were also significantly longer, but their weight was not significantly lower, than that in the control group. The major differences could not be accounted for by varying periods of gestation nor could they be accounted for by the special conditions of induced labor or cesarean section. Therefore, the only possibility remaining is that a weight loss precedes spontaneous labor. This may possibly be explained by the reduction in the relative water content which begins before birth and continues through the newborn period or by a relative placenta insufficiency. The infant weight loss and loss of amniotic fluid after the thirtyeighth week of pregnancy refutes the theory, that birth is induced by a stretching of the uterine wall. The possibility is discussed, that the onset of labor is influenced by a corresponding relief from tension such as that, which occurs following a premature rupture of the fetal membranes.

Birth Weight↗
PubMed1999

Severe preeclampsia and the very low birth weight infant: is induction of labor harmful?

OBJECTIVE: To compare the effects of labor induction with the effects of cesarean delivery without labor on neonatal outcome in pregnancies complicated by severe preeclampsia and delivery of very low birth weight infants. METHODS: This was a retrospective study of 278 singleton, live-born infants who weighed 750-1500 g and were delivered because of severe preeclampsia between 1988 and 1997. Outcomes of infants delivered by cesarean without labor were compared with those of infants exposed to labor induction. Statistical analysis was performed using Student t test, Mann-Whitney U test, chi2 analysis, and Fisher exact test, where appropriate. Multiple logistic regression analysis was used to adjust for outcomes of interest. RESULTS: One hundred forty-five (52%) of the 278 women with severe preeclampsia who delivered infants weighing between 750 and 1500 g had labor induced and 133 (48%) delivered by cesarean without labor. Vaginal delivery was accomplished by 50 (34%) women in the induced group. Apgar scores of 3 or less at 5 minutes were more likely in the induced-labor group (6 versus 2%, P = .04), but other neonatal outcomes, including respiratory distress syndrome, grade 3 or 4 intraventricular hemorrhage, sepsis, seizures, and neonatal death, were similar in the two groups. Adjustment for birth weight and gestational age did not affect those results. Analysis of data from the induced-labor group did not reveal an effect by route of delivery on neonatal outcome. CONCLUSION: Induction of labor in cases of severe preeclampsia is not harmful to very low birth weight infants.

Adult↗
PubMed1983

The use of obstetrical procedures in the care of low-risk women.

Data from birth certificates were used to examine the pattern of obstetrical procedures used in the care of a sample of low-risk women. The data suggests that hospitals with greater technological capabilities and more specialized medical manpower have a greater tendency to use the obstetrical procedures of cesarean section, forceps delivery and drug induced labor. However, the utilization rates of these procedures also varied considerably between hospitals with comparable technology and medical staffs.

Adult↗
PubMed1987

[Current use of prostaglandins E2].

Prostaglandins E2 have been used since 1959 and introduced in France since 1966. Their main indication is to pre-induce labor in order to mature a cervix barely open (below 6) and induce labor. For the pre-inducement, the extra-amniotic route seems most interesting in a gel form at a dose of 0.500 microgram (Gelovect): the gain on the cervical opening is 1 to 2 points and labor is induced in 50 to 60 p. cent of the cases, without any other treatment, by artificial rupture of the membranes. For inducing labor, the venous route may be interesting when the condition of the cervix is less than optimum, especially in premature rupture of the membranes. The effectiveness is comparable to that of pitocin, but 10 times more potent resulting in a much more strict control of its prescription by intravenous route. The doses used are 0.15 to 0.25 microgram per minute to a maximum of 2 micrograms per minute. Intravenous prostaglandins E2 should not be used concomitantly with pitocin. Other local administration routes are less used in France. In the immediate post-partum, prostaglandins E2 are interesting parenterally (2 to 4 micrograms per minute) or in the myometrium in case of severe haemorrhages. In 2nd trimester miscarriages, maturation of the cervix may be used but prostaglandin-like substances, either PGE (Geneprost) or prostaglandins E2-like products are preferred, intramuscularly.

Abortion, Induced↗
PubMed1991

Effect of maternal carbon dioxide inhalation on human fetal breathing movements in term and preterm labor.

Induced maternal hypercapnia is a potent stimulus to fetal breathing movements in nonlaboring pregnant women. To determine the effect of maternal CO2 administration on fetal breathing movements during spontaneous labor, 14 healthy pregnant volunteers at term and 34 in preterm labor were recruited. If fetal breathing movements were markedly decreased or absent, the subjects were administered a prepared gas mixture of 3% CO2 in air. In term labor and in true preterm labor, fetal breathing movements were markedly decreased and could not be induced by maternal hypercapnia. Among women with suspected preterm labor, initial absence of fetal breathing movements and failure to evoke this response by maternal hypercapnia predicted delivery within 48 hours with a sensitivity of 80% and specificity of 95.5%. Induced maternal hypercapnia fails to stimulate fetal breathing movements in true term and preterm labor and may assist in distinguishing between true and false preterm labor.

Administration, Inhalation↗
PubMed1997

Induction of labor in the nineties: conquering the unfavorable cervix.

OBJECTIVE: To determine the efficacy, safety, and duration of induced labor using an integrative approach (prostaglandin, amniotomy, oxytocin) and to depict these findings graphically. METHODS: Five hundred ninety-seven pregnancies requiring induction of labor between October 1993 and May 1995 were analyzed prospectively. Patients were categorized by Bishop score at entry and by parity for comparison of success of induction, maternal and fetal complications, and duration of labor. RESULTS: The women who had a Bishop score at entry of 3 or less had significantly higher rates of failed induction (9.4 versus 0.7%, P < .01) and of cesarean delivery (29 versus 15.4%, P < .01) than those with a Bishop score above 3. Compared with spontaneous labor, the rates of cesarean delivery in induced labor remained significantly elevated. Complications of induction were infrequent, regardless of Bishop score. The time from initiation of induction to achievement of active phase was significantly longer in women with lower Bishop scores. CONCLUSION: Regardless of cervical status and parity, vaginal delivery can be anticipated in the majority of patients undergoing labor induction. The induction characteristics described may assist in the management of induced labor.

Adult↗
PubMed1975

The coagulation mechanism in labor at term induced with prostaglandin F2 alpha.

The prostaglandins, especially the PGE series, produce profound effects on platelet function in vitro. It has been reported that PGF2alpha and the PGE series do not affect the clotting mechanism when used to induce midterm abortion, in contrast to that induced with hypertonic saline but the effect of these drugs on the clotting mechanism when used to induce term labor has not been reported. Labor was induced with intravenous PGF2alpha in eight patients, at 32 to 41 weeks' gestation, with premature rupture of the membranes. Three samples were obtained: (1) anteceding the administration of the drug, (2) during the peak drug effect during active labor, and (3) approximately 12 hours post partum. No significant changes were seen in the prothrombin or partial thromboplastin times, platelet numbers or aggregation with ADP, fibrinogen levels, euglobulin lysis times, and circulating fibrin split products. The circulation of thrombin as shown by a specific test for fibrin monomer was not demonstrated.

Adenosine Diphosphate↗