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Effects of maternal diabetes on placental transfer of glucose in rats.

In situ perfusion of the fetal side of the anesthetized rat placenta was used to monitor glucose fluxes in nondiabetic, streptozocin-induced diabetic (STZ-D), acutely hyperglycemic nondiabetic, and acutely normoglycemic STZ-D rats. STZ-D resulted in increased accumulation of glucose in the perfusate during a single passage through the fetal vasculature compared with nondiabetic rats, and this increase was maintained in normoglycemic STZ-D rats, indicating glucose release from placental stores. The fractional clearance of 3-O-[14C]methylglucose, a nonmetabolizable glucose analogue, across the placenta was decreased in both STZ-D groups compared with nondiabetic rats but unchanged in hyperglycemic nondiabetic rats, implying a reduction in glucose transporters in diabetic placentas. The difference between the transfer of D-[3H]glucose and 3-O-[14C]methylglucose indicated that 17% of the glucose was retained while traversing the placenta of nondiabetic rats, whereas a smaller percentage (8%) but a larger absolute amount (9 vs. 6 mumol/h) of glucose was retained by the placentas of the severely STZ-D rats. This retention was markedly enhanced in hyperglycemic nondiabetic rats and STZ-D rats when rendered normoglycemic. The net accumulation of perfusate glucose was less than that predicted from radiolabeled transfer data, indicating that glucose is also back transferred from the perfusate to the mother's placenta. We conclude that maternal diabetes markedly affects placental glucose flux.

Animals↗

Role of metallothionein in human placenta and rats exposed to cadmium.

A strong positive relationship between zinc and copper and metallothionein (MT) in placentas has been found, but a negative one between cadmium and MT. In rats given cadmium i.p. as the chloride, liver cadmium is lower and kidney cadmium higher than in cadmium-treated non-pregnant rats, suggesting that pregnancy enhances mobilization of cadmium from liver to kidney. The cadmium concentration of digested whole fetuses is not significantly increased in offspring of dams given cadmium i.p. as the chloride or CdMT, but the placental levels of cadmium and MT are increased. The placenta therefore acts as a barrier to maternal-fetal cadmium transfer. The way in which cadmium is retained in the placenta but zinc and copper are transferred to the fetus is not understood, since all are bound to MT. Focal renal tubular necrosis and placental necrosis occur at the same level of cadmium exposure, suggesting a similar threshold to cadmium toxicity for the two organs.

Adolescent↗

A randomised evaluation of two techniques of management of the third stage of labour in women at low risk of postpartum haemorrhage.

OBJECTIVE: To determine whether early placental drainage plus cord traction reduces the incidences of manual removal and blood loss, and to determine the risk factors associated with blood loss after delivery. DESIGN: Prospective randomised study. SETTING: University teaching hospital, Montpellier, France. METHODS: A randomised study compared 239 women who had placental cord drainage plus cord traction with 238 women with expectant delivery. The need for manual removal of the placenta and the drop in haemoglobin after delivery were assessed. The duration of the third stage of labour and the time between birth and the beginning of perineal suturing were measured. Statistical analysis used the paired t test for continuous variables, the Kruskal-Wallis test for nonparametric data and chi2 test for categoric variables. Stepwise logistic regression analyses were performed with a drop in haemoglobin as the outcome variable. RESULTS: No significant difference was found in the two groups with regard to the incidence of manual removal of retained complete or incomplete placenta or postpartum haemorrhage. The median values of the duration of the third stage of labour, birth-to-perineal suture time and drop in haemoglobin were significantly lower in the cord drainage group than in the control group. After controlling for confounding variables, parity proved to be the only significant predictor of drop in haemoglobin. CONCLUSION: Cord drainage decreases the duration of the third stage of labour and reduces blood loss but not the incidence of manual removal of the placenta.

Adult↗

The passage of thiamine across the rat placenta and its uptake by the fetal organs. I. The transport of thiamine across the placenta.

It is well known that thiamine is highly soluble in water. However, if chloroplatinic acid (H2PtCl6) is used during fixation, an insoluble, electron-dense thiamine-PtCl6 precipitate is formed. Using this method we performed electron microscope autoradiography of the placental labyrinth of rats in their 15th day of pregnancy after injection into the maternal bloodstream of 3H-thiamine, and we also measured the radioactivity of the tissues, in order to study the transport of the thiamine across the placenta. Both developed silver grains and radioactivity were found in the largest amounts 30 min after injection; the amounts of both declined after 2 hrs and declined further after 5 hrs. The majority of the developed silver grains were localized in the smooth-surfaced endoplasmic reticulum, which is generally thought to be the vehicle for the transport of materials in the cell, while in the mitochondria, Golgi apparatus, etc. the grains were few. Considering the substantial depletion of the amounts of both sivler grains and radioactivity after the relatively short time of 5 hrs, we conclude that the greater portion of the thiamine passes quickly across the placenta to the fetus, where it is used in the metabolism of the fetal organs, and that only a small part of the thiamine is retained in the placenta for its own metabolism.

Animals↗

Transfer of riboflavin by the perfused human placenta.

The transfer of radioactive riboflavin across the human term placenta has been studied in an in vitro perfusion system. The clearance index (clearance riboflavin:clearance antipyrine) toward the fetus averaged 0.69 and the transfer index (clearance riboflavin:clearance L-glucose) averaged 3.40. The respective indices in the reverse direction were 0.25 and 0.87. Stepwise increases in the concentration of riboflavin in the maternal perfusate were associated with parallel increases in transfer rates, expressed as ng/min, up to concentrations approximating 100 ng/ml. Above that concentration, the transfer rates continued to increase at a slower rate. Concurrently, there was a reduction of the transfer index from 2.7 to 1.1 at 1000 ng/ml. With the fetal circulation closed, the placenta established a gradient toward the fetus over a period of 150 min of 1.7. The transferred radioactivity was identified as riboflavin by high-performance liquid chromatography, whereas that retained within the placenta was metabolized to flavin mononucleotide (33-75%). The observations indicate a very effective active transport system directed toward the fetus which is limited in capacity to low concentrations of riboflavin.

Antipyrine↗

Transfer of 2,4,5,2',4',5'-hexachlorobiphenyl across the in situ perfused guinea pig placenta.

The transplacental crossover of 14C-2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) from the maternal circulation to the fetal side of the placenta was examined in intact fetuses and following the in situ perfusion of the guinea pig placenta. Fetal, late pregnant, and nonpregnant female guinea pig lipoprotein profiles and the association of 6-CB with these plasma constituents were also determined in vivo. Very low density lipoprotein (VLDL) concentrations were 10-fold higher in fetal than in maternal plasma, and the great majority of 6-CB which was transferred to intact fetuses became associated with this plasma fraction. 6-CB was found primarily in association with low density lipoproteins (LDL) in nonpregnant animals. In the late pregnant guinea pig, 6-CB became primarily associated with plasma protein in spite of circulating protein concentrations lower than those seen in the nonpregnant state. No differences in the levels of the three plasma lipoprotein classes were observed between pregnant and nonpregnant animals. It was found that an amount of 6-CB similar to that found in intact litter mates crossed the perfused placenta over the same time period. Despite the much higher VLDL concentrations on the fetal side of the placenta and the association of 6-CB with VLDL in intact fetuses, addition of 1,000 mg/dl VLDL to the 5.4% bovine serum albumin perfusion medium failed to influence the magnitude of 6-CB crossover. 6-CB crossover was influenced by protein concentration in the perfusion media in a concentration-dependent fashion. It is hypothesized that 6-CB and free fatty acids traverse the placenta and are retained by the fetus via similar mechanisms.

Animals↗

[Rat placental barrier permeability for the new antihistaminic preparation, fenkarol].

As established, following a single introduction of phencarol tagged with tritium in a quinuclidine nucleus perorally to rats on the 13th day of gestation its insignificant amounts gain access to the fetus through the placenta. The maximum concentration of the drug in the maternal blood was recorded 3 hours after its introduction, following 6 hours--in the placenta, with the radioactivity continuing to be constant during the first 6 hours in the embryonal tissues. In 48 hours after introduction the radioactive tag is still demonstrable in the study tissues. It is concluded that the drug is largely retained in the placenta, when introduced on the 13th day of pregnancy; on the 21st day of gestation the barrier functions of the placenta declines. The presence of phencarol and its transformation products in the embryonal tissues is confirmed by the method of thin-layer chromotography.

Animals↗

Immunologic memory in the placenta: a lymphocyte recirculation hypothesis.

The placenta is an immunologically unique organ where a balance between maternal immunity and fetoplacental well-being must be maintained for successful pregnancy to occur. The intervillous blood is important in this context, yet little is known about local immunologic processes, particularly how placenta-specific memory immune responses are maintained. Using malaria as an illustrative case, we describe an hypothetical model in which recirculation of memory T lymphocytes from the intervillous blood to local lymphoid tissue facilitates maintenance of local memory immunity. This explains how memory cells might be retained when the placenta is expelled at parturition and thus remain available for rapid recall from the local lymphoid tissue to the intervillous space when exposure to the same antigenic stimulus occurs in subsequent pregnancies. Study of cell-mediated immunity to infections like malaria in the intervillous blood and the use of animal models will be necessary to provide proof for this hypothesis.

Female↗

Prostaglandin mediates premature delivery in pregnant sheep induced by estradiol at 121 days of gestational age.

The experiments reported here were designed for both in vivo and in vitro approaches in the same animals to obtain a better picture of the role of estrogen in the control of parturition. Chronically catheterized pregnant ewes were treated with vehicle (n = 5) or estradiol (n = 6), 5 mg twice a day, im for 2 d starting at d 119 of gestation. Maternal and fetal plasma estradiol, progesterone, and cortisol were measured by RIA and maternal plasma prostaglandin (PG) F2alpha was measured by enzyme immunoassay. Intrauterine PG H synthase 2 mRNA and protein and placental P450(c17)alpha hydroxylase mRNA were determined by Northern, in situ hybridization, Western blot analysis, and immunocytochemistry. Data were analyzed by ANOVA. Five of six estradiol-treated ewes delivered their fetuses within 48 h; however, the placenta was still retained 5-6 h after fetal delivery. Both maternal plasma estradiol and PGF2 alpha increased significantly in the estradiol-treated group. Maternal and fetal plasma progesterone and cortisol were not altered in either group. There were significant increases of PGH synthase 2 mRNA and protein in myometrium, endometrium, and maternal placenta but not in fetal placenta in estradiol-treated ewes. Placental P450(c17)alpha hydroxylase mRNA was not detectable in vehicle or estradiol-treated groups. Estradiol can, in the absence of increase in plasma cortisol, stimulate uterine PG production and induce labor, resulting in fetal delivery in the sheep. Failure of placental delivery after estradiol treatment suggests that estradiol alone is insufficient to stimulate some of the key changes required to complete delivery at the stage of gestation studied.

Animals↗

Clara's birth.

Advocacy for homebirth is based on the strong assumption that birthing is a physiological process and does not require medical interventions unless things turn "wrong." Let us assume that something might always go wrong, for instance during Clara's birth when the placenta was still retained after three hours. What needs to be done? The moment the midwife entered the house she was endowed with a responsibility for any problem caused by her failure to give proper guidance. With this weight on her shoulder, and according to her training and experience, there was no other way for her than to suggest an intervention regarding the placenta. The two midwives, B, and C., might not agree on risk estimations, the nature of the intervention, whether it should be performed at home or in a hospital. The estimation of abnormalities, evaluation of risks and the procedures with which to handle them are the main practical difference between classic obstetrics and non-interventionist midwifery--by analogy, between allopathy and naturopathy. The rest (positive thinking) is basically literature. A delivery will not remain normal just because we decide it "must" be physiological. Dr. Barua, a professor of obstetrics in Pondicherry, pointed out that normal deliveries are rare--fewer than 10 percent in South India. What we have instead is either pathological or "natural" deliveries in which regenerative processes take care of abnormal situations. Unless she has developed sensitive hands, a birth assistant or midwife must rely on monitoring procedures to evaluate deviations from the normal process. Even with the greatest care, these procedures are intrusive in that they disconnect the parturient from her own sensations. While successful unattended homebirth stories emphasise the extraordinary power and sensitivity of a birthing woman, the whole dream seems to collapse in abnormal or pathological cases. It would have collapsed for Sonia as well, had she not discarded negative suggestions. Dependency on medical experts is an alienation by which the patient is forced to tolerate what is not tolerable to her at a precise moment. The trauma of medicalized birth is not surprisingly associated with rape. It remains that the leitmotif in homebirth literature is more "empowerment," self assertion, militancy for the freedom of choice and ownership of her own body, than "self reliance" which involves a long-term sensitisation. Even outstanding essays a advocating non-medicalized birth may contain a sentence with implicit fear talk defusing the argument. For instance: "And if need be, [the midwife] can transport you to the hospital if you truly need the help that only modern obstetrics can provide...."] The sentence may be countereffective to a reader who is insecure about homebirth. The problem lies in the proximity of "truly" and "only." It was indeed the writer's intention to emphasise "truly" with an interrogative connotation: "Are you sure you need it?" However, the effect is overruled by the assertive strength of "only." The reader's unconscious reading may be that, truly, she needs the help that only modern obstetrics can provide. This is an example of negative suggestions conveyed by confidence building talk about health and pregnancy. Another example was Denis and Sonia's obsession with the placenta retention problem that had been causally exposed by midwife B. Why should her empowerment end suddenly when there is a life threatening complication during the delivery? If the pregnant woman claims a fundamental right to choose her way of birthing in uncomplicated cases, she needs even more self determination when she is in real danger. This paradox is striking evidence that the common sense attitude toward danger is affected by the "allopathic mind." It sets up an insurmountable barrier between the physiological and the pathological, whereby symptoms are failures of the normal regenerative processes. Hence, testimonies of women feeling that their bodies "b

Female↗

[Teratogenic studies on stannous chloride in rats].

This paper describes teratogenic studies of stannous chloride in rats. The compound was administered to pregnant rats on gestational days 7 through 12 orally by a stomach tube at dose levels of 0 mg, 20 mg, 100 mg, 500 mg/kg of stannous chloride and fish liver oil for the positive control group. The experimental results showed that the placenta not only retains some stannous chloride but also diverts parts of the stannous chloride is the fetus. Stannous chloride showed teratogenic effects on the early growing embryos and protruding tongue of fetus.

Abnormalities, Drug-Induced↗

Immunolocalization of alpha and beta chains of human chorionic gonadotropin, placental lactogen and pregnancy-specific beta-glycoprotein in term placenta by a touch preparation method.

Touch preparations of human placenta yield cells retaining antigenic reactivity to immunoperoxidase stains for alpha and beta chains of human chorionic gonadotropin, placental lactogen, and pregnancy-specific beta glycoprotein. This method is a rapid and simple alternative to conventional frozen and paraffin-embedded sections for detection of placental peptides.

Chorionic Gonadotropin↗

Maternal, fetal and placental distribution of lidocaine-epinephrine and bupivacaine after epidural administration for cesarean section.

Bupivacaine and lidocaine are both lipophilic drugs, bupivacaine being more lipophilic and protein-bound. Our earlier studies, using human placenta perfused in vitro, showed that increased placental binding of bupivacaine restricts fetal transfer compared to the higher fetal transfer of lidocaine. However, placental tissue concentrations of local anesthetics have not been determined in the clinical context. Term parturients were randomized to receive either 2% lidocaine-epinephrine (n = 10) or 0.5% bupivacaine (n = 10) through a lumbar epidural catheter for elective cesarean section. Total drug concentrations of lidocaine and bupivacaine in maternal and umbilical plasma and placental tissue were determined. There was a higher incidence of maternal hypotension in the lidocaine-epinephrine group than in the bupivacaine group ( vs , P < 0.05). At delivery, fetal/maternal ratios for total concentrations of lidocaine and bupivacaine were similar (0.49 vs 0.42). The mean placental tissue/maternal plasma concentration ratio of lidocaine was higher than that of bupivacaine (1.45 vs 1.01, P < 0.05). The mean amount of the drug retained in the placenta per unit of dose (mg/kg) was also higher in the lidocaine-epinephrine group, although this difference did not reach statistical significance (0.46 mg/unit dose vs 0.40 mg/unit dose). Values for area under the concentration-time curves per unit of dose were similar. In conclusion, maternal plasma concentrations, fetal/maternal concentration ratios and placental tissue binding of lidocaine resembled those of bupivacaine after epidural administration. These findings are probably explainable by the effect of maternal hypotension on the distribution of lidocaine.

Clinical Trial↗

Main routes of plasma lactate carbon disposal in the midgestation fetal lamb.

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4% was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.

Amino Acids↗

The availability of life-saving obstetric services in developing countries: an in-depth look at the signal functions for emergency obstetric care.

OBJECTIVE: This paper examines the frequency with which a set of life-saving interventions or signal functions was performed to treat major obstetric complications. METHODS AND RESULTS: The basic signal functions include parenteral antibiotics, anticonvulsants and oxytocics, and the procedures of manual removal of the placenta, removal of retained uterine products, and assisted vaginal delivery. Comprehensive functions include the six basic functions, cesarean delivery, and blood transfusions. Data from 1906 health facilities in 13 countries indicate that the most likely functions to be reported are oxytocics and antibiotics. The basic function least likely to be reported is assisted vaginal delivery. Many of the facilities surveyed did not have the infrastructure to perform operations or provide blood transfusions. CONCLUSIONS: These data can help governments allocate their budgets appropriately, help policy makers and planners identify systemic bottlenecks and prioritize solutions. Monitoring the performance of the functions informs us of the capacity of the health system to provide key interventions when obstetric emergencies occur.

Anti-Bacterial Agents↗

Prostaglandin F2 alpha and prostacyclin imbalance in cows with placental retention: new findings.

The aim of this work was to investigate possible differences in peripheral blood concentrations of 13, 14 dihydro 15 keto PGF alpha (PGFM) and 6 keto PGF1 alpha (PGIM), between dairy cows retaining (RP) and not retaining (NRP) their placenta. Blood samples were collected 5, 30, and 60 minutes postpartum from 8 RP and 17 NRP cows. PGFM concentrations were significantly lower in RP cows than in NRP cows 60 minutes after birth (8156 pg/ml vs 12016 pg/ml; P less than or equal to 0.05). There was a significant rise of PGFM levels between 30 and 60 minutes in NRP cows (6225 pg/ml vs 12016 pg/ml; P less than or equal to 0.01), while in RP cows PGFM levels remained fairly constant along the period studied. No significant differences were found between RP and NRP cows regarding PGIM levels during this period although absolute values were slightly higher in RP cows. The PGFM/PGIM ratio was significantly higher 60 minutes postpartum in NRP cows than in RP cows (15.5 vs 8.8; P less than or equal to 0.01). This ratio increased significantly in NRP cows between 30 and 60 minutes (7.2 vs 15.5; P less than or equal to 0.01), a pattern not observed in RP cows. There was no correlation between PGIM and PGFM levels during the first 60 minutes postpartum in the NRP cows. However, the same correlation was significantly positive in the RP cows (r = 0.75; P less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

[Value of surgical hysteroscopy in the treatment of myomas and intracavitary fibrous polyps. Evaluation of 26 operations].

Out of a total of 121 hysteroscopies carried out in this unit between December 1981 and June 1984, 26 were operative hysteroscopies. Each of these procedures consisted in removing intra-uterine structures (that could not be removed with a curette) under visual control. All cases had a normal sized or slightly enlarged uterus. There were 7 patients aged 41 years or younger and 19 older than 41. The endoscope used was the "bayonet" Wolf apparatus which is 7 mm in diameter and has two separate canals; one for insufflation and the other for introducing the 3 mm biopsy forceps. This small punch makes it possible to cut the implantation on uterine wall without needing coagulation. The tissue is then removed using a soft curette or a polyp forceps after the cervix has been further dilated. There was no case in which heavy bleeding occurred during or after the operation. Using this technique we were able to remove 18 fibroid polyps, 13 submucous fibroids (8 smaller than 2 cm in diameter and 5 between 2 and 4 cm), 3 old retained portions of placenta; removal was complete in 21 cases and only partial in 5 cases. Out of these 2 had to have hysterectomy. On the other hand abdominal myomectomy or hysterectomy could be avoided in 11 cases. This series shows how often fibrous polyps and small sub-mucous fibroids can be removed under hysteroscopic control when using this kind of apparatus and a relatively simple technique.

Adult↗

Isolation and characterization of human placenta fibronectin.

Fibronectin was isolated from human placenta tissues and compared with human plasma fibronectin. Placenta and plasma fibronectins had similar amino acid compositions, immunological properties, and cell attachment-promoting activities, but differed in apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which could be accounted for at least partly by the difference in carbohydrate composition. Unlike plasma fibronectin, placenta fibronectin failed to form a precipitin line with concanavalin A in a double diffusion system. The non- or low-reactivity of placenta fibronectin with this lectin was also demonstrated by affinity chromatography with concanavalin A-agarose, in which more than 90% of the radiolabeled glycopeptides derived from placenta fibronectin was not retained on the gel. The two fibronectins also differed in the reactivity with Lens culinaris agglutinin of their glycopeptide fractions. These data indicate that placenta and plasma fibronectins are different in their carbohydrate structures and, therefore, suggest the presence of a tissue- or cell-specific mechanism for processing the carbohydrates of this glycoprotein.

Amino Acids↗