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Plasmodium falciparum infection of the placenta affects newborn immune responses.

The effects of exposure to placental malaria infection on newborn immunological responses, in particular Th1/Th2 cytokines and antigen-presenting cell (APC) function, were compared between cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placentas of Gambian women. Cells were analysed in vitro for their ability to respond to mitogens [phorbol myristate acetate (PMA)/ionomycin, phytohaemagglutinin (PHA)], a malaria-unrelated test antigen [purified protein derivative of Mycobacterium tuberculin[purified protein derivative (PPD)] and Plasmodium falciparum schizont extracts. Mitogens induced strong proliferation and secretion of high concentrations of both IL-13 and sCD30 in CBMC from both groups. Conversely, significantly lower amounts of IFN-gamma were induced in the parasitized group in response to low doses of PHA. Protein antigens induced very low amounts of all tested cytokines, in particular IFN-gamma. However, a significantly higher release of sCD30 was observed in response to schizont extracts in the parasitized group. Addition of LPS to activate APC to low doses of PHA or schizont extracts increased the IFN-gamma production in both groups but levels remained lower in CBMC from the parasitized group. This result correlates with the lower production of IL-12 found following lipopolysaccharide (LPS) stimulation in this group. Taken together, these data show that placental infection with P. falciparum affects Th1 differentiation and sCD30 priming of neonatal lymphocytes and that the probable mode of action is via APC.

Animals↗

Combination chemotherapy for high-risk gestational trophoblastic tumour.

BACKGROUND: Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT. SEARCH STRATEGY: Electronic searches of MEDLINE, EMB, Cochrane Central Register of Controlled Trials (CENTRAL) and CBM were carried out. Four journals were handsearched and other searching methods were used for identifying more studies. SELECTION CRITERIA: The review included randomized controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review. MAIN RESULTS: One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear. AUTHORS' CONCLUSIONS: The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.

Antineoplastic Combined Chemotherapy Protocols↗

[Course of pregnancies and labors in a department of general surgery. A prospective study of pregnancies during a 1-year period at Hørsholms hospital].

The complications of pregnancy and delivery in a material consisting of 841 women without obstetric risk factors were investigated. The deliveries were planned to take place in a department of general surgery with a specialist obstetrician. Seventy-five women (8.9%) were transferred to a specialized obstetric department before delivery, 14 women (1.7%) because of imminent premature delivery. In addition, 69 women were transferred because of removal or their own wish for transfer. A total of 631 patients (90.5%) were delivered vaginally and 66 (9.5%) were delivered abdominally. In thirty-five of these, caesarean sections were performed during the course of delivery. In 34 deliveries (5.1%) vacuo extraction was used. Among 181 women (27.1%), unexpected complications occurred, 80 of these women (12.0%) requiring emergency treatment. A total of 697 infants were delivered. One infant died before delivery because of placental separation. Twenty-two infants (3.2%) were transferred to a paediatric department during the neonatal period, three because of asphyxia. Three of the liveborn infants (0.4%) had Apgar scores at 1 minute between 0 and 3, 40 infants (5.7%) had scores between 4 and 6. After 5 minutes, no infants had Apgar scores between 0 and 3, but three infants had scores between 4 and 6. It is concluded, that the low perinatal mortality and morbidity might indicate, that deliveries in a department of general surgery are safe, provided a specialist obstetrician is available and the rules of referral strictly observed.

Apgar Score↗

[Biochemical studies on alkaline phosphatase isoenzyme profile in endometrial cancer].

Heat-stable ALP has been attracting attention as one of the oncodevelopmental proteins. ALP are now subdivided by biochemical methods into three major groups e.g. tissue-unspecific, intestinal and term placental isoenzymes. Furthermore, term placental ALP in cancer is classified into L-leucine insensitive-Regan and L-leucine sensitive-Nagao isoenzymes. In this paper, we report ALP isoenzyme profiles of normal endometrium and endometrial cancers. 21 cases of normal endometrium and 11 cases of endometrial cancer were examined, and the ALP activity of their butanol extracts was measured by Fishman's method. To identify the ALP isoenzyme pattern, biochemical methods such as 65 degrees C heat-treatment and amino acid inhibition tests were carried out. Most of the ALP in both normal endometrium and endometrial cancers showed biochemical characteristics of tissue-unspecific ALP isoenzyme. A very small amount of term placental isoenzyme was found in normal endometrium. In endometrial cancers, term placental isoenzyme was often found at a higher level than in normal endometrium. Nagao isoenzyme was also found to emerge in a few endometrial cancer cases. From these data it was suggested that the ALP isoenzyme of endometrium underwent a change and "enzyme deviation" occurred during the course of endometrial carcinogenesis and that the ALP isoenzyme deviation might have occurred due to a change in ALP isoenzyme gene expression accompanying cancerous change.

Alkaline Phosphatase↗

Peripheral changes in estrone sulfate concentration during the first trimester of gestation in cattle: comparison with unconjugated estrogens and relationship to fetal number.

Estrone sulfate originates mainly in the conceptus during gestation in cattle. Its concentration in maternal body fluids is a useful indicator of placental function. The objective of this study was to determine the profiles of estrone sulfate during early gestation in singleton and twin bearing cows using a newly developed extraction method. One or two blastocysts produced in vitro were nonsurgically transferred to regularly cycling Holstein cows on Day 7 (Day 0 was defined as the first day of standing estrus). Pregnancy was diagnosed on Days 30, 45 and 60 by transrectal ultrasonography and finally confirmed at parturition. Six cows with singleton and six with twin pregnancies were used in the experiment. Blood was collected every other morning by jugular venipuncture from the day after transfer to Day 100. Harvested plasma was applied to reversed-phase C18 cartridges. Estrone sulfate and unconjugated estrogens (estrone and estradiol-17beta) retained in the cartridge were eluted separately by methanol stepwise gradient and each measured by validated radioimmunoassay. On average, estrone sulfate concentrations fluctuated between 2 and 6 pg/ml until Day 50 in both groups and then gradually increased. However, the levels of estrone and estradiol- 17beta remained low (1-5 pg/ml) until Day 80. The concentration of estrone sulfate after Day 50 was significantly affected by the day of gestation (P < 0.0001) and the number of fetuses (P < 0.01). After Day 80. estrone sulfate increased drastically, followed by increases in estrone and estradiol-17beta concentrations. The rate of increase in estrone sulfate during Days 80-100 was the greatest among all estrogens (P < 0.05). The rates of increase in estrone sulfate during Days 50-80 and 80-100 were 1.7 times greater in twin pregnancies than in cows having one fetus. These results suggest that the concentration of estrone sulfate in bovine peripheral blood plasma during early gestation has potential application in monitoring embryonic growth as well as fetoplacental development.

Animals↗

The factor V Leiden mutation is not a common cause of recurrent miscarriage.

Some investigators suggest that placental thrombosis and infarction can cause recurrent miscarriage. We have shown that the common missense mutation in the factor V gene, the Leiden mutation, which renders factor Va resistant to cleavage inactivation by activated protein C, predisposes to placental thrombosis and spontaneous miscarriage. Our objective was to determine the frequency of the Leiden mutation in a population with well-characterized idiopathic recurrent miscarriage. DNA was extracted from whole blood of 40 couples with a history of idiopathic recurrent miscarriage and 25 couples with a history of proven fertility (seven or more live births). The polymerase chain reaction was used to amplify exon 10 of the factor V gene followed by allele-specific restriction with Mnl1 for mutation detection. Results were analyzed with a chi 2 contingency table. None of the 40 women with idiopathic recurrent miscarriage carried the mutation and only one of their reproductive partners was heterozygous for the mutation. Similarly, none of the control women carried the mutation, and only one of the 25 control male partners was heterozygous for the mutation. In our referral population, the factor V Leiden mutation which predisposes to thrombosis is not a common cause of recurrent miscarriage.

Abortion, Habitual↗

Cytotoxic effects of cigarette smoke alkaloids inhibit the progesterone production and cell growth of cultured MA-10 Leydig tumor cells.

Inhibition of corpus luteum progesterone synthesis by cigarette smoke alkaloids might, in part, explain the generally poorer outcome of pregnancy in smoking women. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone biosynthesis and cell growth. Studies were based using the MA-10 Leydig tumor cell line. The steroid pathway in MA-10 cells has only two specific enzymatic steps. The cholesterol passes to the cholesterol side-chain cleavage enzyme and then metabolizes the resulting pregnenolone to progesterone and partly to 20alpha-dihydroprogesterone. Incubation of MA-10 cells with nicotine, cotinine, anabasine, all of these alkaloids, or an aqueous extract of cigarette smoke resulted in dose-dependent inhibition of progesterone and 20alpha-dihydroprogesterone synthesis. The number of cells in the treated dishes seemed less than the control. This latter finding prompted experiments evaluating the short-term effects of the alkaloids on cell growth. Growth of MA-10 cells influenced with alkaloids or smoke extract was also inhibited. All of the inhibitory effects of nicotine, cotinine, anabasine and cigarette smoke extract on MA-10 cells were explained by cytotoxicity. The cytotoxic effect could reduce the fertilization, implantation, and early human development. This mechanism entails the consequence of impaired placental growth, disorder in the placental vascular architecture and placental circulation, and small-for-date babies.

20-alpha-Dihydroprogesterone↗

Lower alkaline phosphatase activity and occurrence of an abnormal hybrid intestinal/tissue non-specific isoform in Down's syndrome amniotic fluids.

Quantitative and qualitative analysis of alkaline phosphatases (AP) was performed on amniotic fluid in 59 normal pregnancies and 14 Down's syndrome (DS) pregnancies at 16, 18 and 19 weeks of gestation. In DS cases, intestinal and placental isoenzyme levels were significantly reduced (P<0.001) and the AP electrophoretic pattern was seen to be modified on polyacrylamide gel electrophoresis. A unique component was detected. After extraction and purification of the abnormal isoenzyme, peptide fragments obtained after cyanogen bromide cleavage indicated a hybrid heterodimeric AP composed of intestinal and tissue non-specific subunits, as evaluated by SDS polyacrylamide gel electrophoresis.

Adult↗

Maternal, placental, and neonatal associations with early germinal matrix/intraventricular hemorrhage in infants born before 32 weeks' gestation.

This study tests the hypothesis that histologic placental lesions were significantly related to incidence of early or late germinal matrix/intraventricular hemorrhage (GM/IVH) in infants of less than 32 weeks' gestation independent of maternal or neonatal factors. Maternal and neonatal charts of 406 singleton liveborn nonanomalous infants born at less than 32 weeks' gestation were studied retrospectively for principal indication for delivery, delivery mode, timing of antenatal steroid treatment, diagnosis of labor and augmentation, tocolysis, fetal presentation, and umbilical arterial and venous blood gas values. Extracted from neonatal charts were gestational age, growth measurements, initial hematocrit and white blood cell count, administration of surfactant, and in the first 3 days of life, the use of pressor agents and volume expansion, lowest blood pressure, and data pertinent to respiratory function. Placental histologic examination was reviewed for various lesions, including histologic acute inflammation (graded on a scale of 0 to 4). GM/IVH (grades 1 to 4) diagnosed ultrasonographically less than 72 hours after birth was "early." GM/IVH diagnosed after 72 hours of life was defined as "late." Of the 406 patients, 44 (10.8%) had early GM/IVH; 21 (4.9%) had late GM/IVH. Stepwise logistic regression selected five factors independently related to increased early GM/IVH risk: Histologic acute inflammation (p < 0.002); gestational age in days (p = 0.053); antenatal steroid treatment less than 48 hours before birth (p < 0.035); volume expansion in the neonate (p < 0.30), and magnesium sulfate tocolysis (p < 0.025). Stepwise regression analysis considering the grade of GM/IVH changed the order of variables, with gestational age and use of pressor therapy being more strongly related to higher grade of GM/IVH than amnion inflammation. Delivery mode, presentation, principal indication for delivery, presence/augmentation of labor, mean biophysical profile scores, mean umbilical arterial and venous blood gas values, and surfactant therapy were not related to early GM/IVH in univariate or multivariate analyses. Neonatal factors associated (p < 0.05) with amnion inflammation were volume expansion at delivery and in the first 3 days of life, low mean systolic pressure, low mean oxygen pressure, low initial hematocrit and cord pH, and increased initial WBC and toxic granulations of neutrophils. Only gestational age, and no maternal or placental factors, was significantly related to late GM/IVH. Infants who have placentas with acute amnion inflammation and receive volume expansion, born to mothers who receive less than 48 hour's exposure to antenatal steroids and are selected to receive magnesium sulfate tocolysis, have increased incidence of early but not late GM/IVH. Amnion inflammation is significantly related to early GM/IVH and with early neonatal abnormalities in oxygenation, perfusion, and effective blood volume. Intra-amniotic infection leads to advanced preterm labor, which is unresponsive to tocolysis because of the inflammation. Intra-amniotic inflammation may sensitize the fetus to postpartum stresses or initiate early GM/IVH in utero via cytokine effects on cardiovascular instability.

Cerebral Hemorrhage↗

Effects of passive immunization of growing guinea-pigs with an insulin-like growth factor-I monoclonal antibody.

The physiological importance of circulating as opposed to locally produced insulin-like growth factor-I (IGF-I) has not been determined. By using a passive immunoneutralization technique, our objectives were to evaluate the role of circulating IGF-I in the regulation of animal growth and pituitary GH content. A monoclonal antibody (MAb) to IGF-I, generated in our laboratory, has an affinity (Ka) of 0.13 litres/pmol for recombinant human IGF-I (rhIGF-I). Cross-reactivities of recombinant des-tripeptide IGF-I and recombinant bovine IGF-II were approximately 40 and 8% respectively. This MAb inhibited binding of purified hIGF-I to human placental membranes. In a radioimmunoassay based on displacement of 125I-labelled rhIGF-I from the MAb, displacement curves generated with dilutions of acid-gel chromatography extracts of guinea-pig serum and rhIGF-I standards were parallel. Twenty-four, 3-week-old male guinea-pigs were treated with the IGF-I MAb, a bovine herpes virus-I (BHV-I) MAb (control MAb) or vehicle (phosphate-buffered saline) (n = 8 per group). Treatments were administered i.p. every 3 days for 24 days at a dose of 20 mg/kg body weight. Blood was obtained on day 23 (48 h after treatment) and on day 25 (24 h after treatment). In a liquid-phase assay, serum from the IGF-I MAb-treated group bound 38 +/- 8% (mean +/- S.E.M.) (day 23) and 56 +/- 7% (day 25) of an 125I-labelled rhIGF-I trace at a final dilution of 1:10,000. Because of the development of an anti-mouse immune response in the guinea-pigs, these parameters would probably have been much greater during the first 2 weeks of the trial. Of the total IGF-I in serum, 50 +/- 5% and 61 +/- 4% could be immunoprecipitated with an excess of rabbit anti-mouse immunoglobulin in samples from days 23 and 25 respectively. Comparisons between the groups treated with IGF-I MAb and BHV-I MAb revealed no significant differences in whole animal growth rate, growth of individual tissues, or pituitary GH content. Mean serum concentrations of IGF-I were 69 and 99% greater in the IGF-I MAb-treated group than in the BHV-I MAb-treated group on days 23 and 25 respectively. These differences probably resulted from an extension of the half-life of IGF-I in serum of animals treated with the IGF-I MAb.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Glucocorticoid-prolactin interactions in Nb2 lymphoma cells: antiproliferative versus anticytolytic effects.

The interaction between the immunosuppressive effects of glucocorticoids and the mitogenic effects of prolactin (PRL) were examined in Nb2 lymphoma cells, a pre-T cell line. The synthetic glucocorticoid, dexamethasone (Dex), caused a concentration-dependent (6.25-200 nM) inhibition of basal and ovine PRL (oPRL)-stimulated Nb2 cell proliferation. Although Dex was antiproliferative, the steroid had no effect on cell viability in the presence of PRL. However, when PRL was omitted from the medium, Dex increased the proportion of dead Nb2 cells by 24 hr in a concentration (25-200 nM)-dependent fashion without affecting total cell number. The antiproliferative and cytolytic effects of Dex were mimicked by other corticosteroids (cortisol, corticosterone, aldosterone, and deoxycorticosterone) in the expected order of glucocorticoid potency, but not by other steroids (17-beta-estradiol, progesterone, testosterone, 5-alpha-dihydrotestosterone, and dehydroepiandrosterone) or triiodothyronine. In addition, the antiproliferative and cytolytic effects of glucocorticoids were antagonized by the glucocorticoid receptor antagonist RU 486. Since corticosteroid-induced cytolysis was apparent only in the absence of mitogen, the anticytolytic effects of oPRL were tested. In the presence of Dex (100 nM), oPRL (25-1600 pg/ml) caused a concentration-dependent inhibition of cytolysis without changing cell number. Other lactogenic hormones (human growth hormone, human placental lactogen, rat PRL), but not trophic nonlactogenic hormones (rat growth hormone, human chorionic gonadotropin, ACTH), also inhibited Dex (100 nM)-induced cytolysis. Agarose gel electrophoresis of DNA extracted from Nb2 cells revealed that within 12 hr, 100 nM Dex induced DNA fragmentation, indicative of programmed cell death or apoptosis. Coincubation of cells with Dex and oPRL (1 ng/ml) inhibited Dex-induced fragmentation of Nb2 cell genomic DNA. These studies reveal a complex interaction between glucocorticoids and PRL in Nb2 cells. Although a glucocorticoid receptor-mediated antiproliferative effect is evident, PRL (at concentrations that usually stimulate cell proliferation) has the capacity to protect the cell against glucocorticoid-receptor-mediated induction of apoptosis.

Analysis of Variance↗

Complications of pregnancy and foetal outcomes in pregnant diabetic patients managed in a tertiary hospital in Saudi Arabia.

OBJECTIVE: To compare the pregnancy complications and fetal outcomes in pregnancies complicated by diabetes mellitus. DESIGN: A retrospective cohort study. Setting- Abha Maternity Hospital, Abha, Saudi Arabia. MATERIALS AND METHODS: One hundred and eighty five diabetic pregnant patients who delivered at the Abha Maternity Hospital during the 3-year-period from April 2000-March 2003 formed the subjects of this study. There were 27(14.6%) (type 1) - insulin dependent diabetics, group 1, 19 (10.2%)(type 2), non insulin dependent diabetic patients who constituted group 2 and 139(75.2%) gestational diabetic patients who made up group 3. Data extracted from the case files included maternal age, gravidity, parity, number of abortions, gestational age at booking, time of diagnosis of diabetes mellitus, complications during pregnancy, birth weight, placental weight. RESULTS: There were no statistically significant differences in the three groups regarding the mean gravidity, parity, birth weight and placental weight (p > 0.05). However, statistically significant differences were found with respect to the mean maternal age, gestation at booking, fasting blood sugar, and gestation at delivery (p < 0.05). Out of 139 gestational diabetics, 23(16.5%) were diagnosed by the 141 week of pregnancy while 24(17.2%) were diagnosed between the 15- 27 weeks of gestation. The control of blood sugar was adjudged to be poor in 32% of gestational diabetics, 50% of type 2 diabetics and 69% of type l diabetics, with statistically significant difference between the groups, (p < 0.05). Although there was statistically significant difference between the groups regarding one of the pregnancy complications (polyhydramnios) (p < 0.05), none were found in other complications (p > 0.05). The overall caesarean section rate was 48%. The overall perinatal mortality was 5.7%, all the deaths occurred in babies born to patients with gestational diabetes. CONCLUSION: Gestational diabetes accounted for all the fetal losses in this study, while polyhydramnios was the most common antenatal complication which was significantly higher in type 1 diabetics.

Diabetes Mellitus, Type 1↗

Verapamil: placental transfer and effects on maternal and fetal hemodynamics and atrioventricular conduction in the pregnant ewe.

Verapamil may have application in the field of obstetrics for treatment of maternal and fetal tachyarrhythmias. This study was performed to assess the maternal and fetal hemodynamic effects of this drug, as well as to determine its placental transfer and effects on maternal and fetal atrioventricular conduction in the pregnant ewe. Verapamil, 0.2 mg/kg, administered intravenously over 3 min, resulted in a transient decrease in maternal mean and diastolic blood pressures. There was, however, no significant change in fetal systolic, diastolic, and mean blood pressures. Maternal and fetal heart rates also were unchanged throughout the experiment. Atrioventricular conduction, assessed by measurement of PR intervals, was prolonged in both the ewe (41%) and the fetus (78%). Placental transfer of verapamil was limited, as shown by the umbilical vein to uterine artery drug concentration ratios of 0.35-0.45 throughout most of the experiment. Fetal hepatic extraction of the drug appeared to be substantial, since the drug concentration in the fetal carotid artery was less than that of the umbilical vein at 1, 3, and 5 min after drug injection.

Animals↗

Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Abnormalities, Drug-Induced↗

Expression of Fas ligand by human cytotrophoblasts: implications in placentation and fetal survival.

Recent data indicated that local production of Fas ligand (FasL) by cells of the eye and testis may confer immune tolerance at these sites. In the present study, we examined the in vivo and in vitro patterns of expression of FasL in the human placenta to provide a potential mechanism through which the fetus is afforded protection against the cytolytic actions of lymphocytes present within maternal decidua across gestation. Immunohistochemical staining of first trimester human placental tissue sections revealed the presence of FasL in cytotrophoblasts in free floating villi, anchoring villi, and cytotrophoblastic islands. FasL staining was also pronounced in syncytiotrophoblasts of term placenta indicating that FasL expression is maintained across gestation. Multiple molecular forms of FasL, suggestive of altered patterns of glycosylation, were detected in extracts of term placenta, amnion and chorion by Western blotting. In addition, in vitro expression of FasL was demonstrated to increase 2 to 3-fold during differentiation of primary cultures of cytotrophoblasts isolated from human term placentas. Local production of FasL by human cytotrophoblasts provides a mechanism through which cytotrophoblasts may induce immune tolerance and self-regulate survival during invasion and subsequent placentation.

Antigens, Surface↗

[Delivery in multiple pregnancies].

BACKGROUND: A knowledge of clinical physiognomy in pathologies related to multiple births is indispensable for improving maternal and feto-neonatal prognosis. This study is a contribution to the solution of this problem. METHODS: A meta-analysis of data for multiple births at Department B of the Gynecology and Obstetrics Clinic at the University of Turi during the decade 1989-1998 was carried out, focusing on the arrangement and presentation of fetuses, the various types of birth, the gestational age at which birth occurred, the weight of neonates, neonatal mortality and maternal morbidity. RESULTS: Out of 11,523 births, there were a total of 194 (1.68%) multiple births, including 190 sets of twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred <32(nd) week (10.29%). There was a high incidence of podalic presentation (26.30%) and shoulder presentation (5.61%) among twins; 202 were delivered using a cesarian section (51.53%) and 190 by vaginal birth (48.47%), of which 172 (90.52%) spontaneously. Surgical birth was an important means of extracting fetuses rapidly from a pathological environment. two hundred and sixty-two neonates (66.84%) were LBW (<2500 g), including 28 (7.14%) VLBW (>1500 g). The perinatal mortality rate was 3.82%. Maternal complications mainly occurred during the placental state, in the immediate postpartum and in puerperio. CONCLUSIONS: The authors feel that a more careful medical and social assistance, preventive hospitalisation, early recognition of the risk, constant monitoring for the optimal timing of birth, and lastly, qualified medical assistance during labour (expert gynecologist, trained obstetric staff) with other medical personnel (anesthetist, neonatal specialist) represent winning strategies to solve the problems arising during multiple pregnancies.

Adult↗

Alkaline phosphatase isoenzymes in intestinal metaplasia and carcinoma of the stomach.

The enzymological and immunological properties of alkaline phosphatase (ALP) isoenzymes in intestinal metaplasia and gastric carcinoma tissues were compared with those of purified human intestinal, placental, and hepatic ALP's to speculate the gene expression of gastric cancer cells. The results were as follows: Intestinal metaplasia was found in 21 of 23 cases (91%) of gastric cancer, whereas normal gastric mucosa had no ALP activity. ALP extracted from the mucosa of intestinal metaplasia was identical with intestinal ALP as to enzymological and immunological properties. ALP obtained from gastric carcinoma tissues of 23 patients was separated into 3 bands (ALPa, ALPb, and ALPc) by polyacrylamide-gel disc electrophoresis. Ten cases showed ALPa only, 4 cases showed ALPa and ALPb, 5 cases showed ALPa and ALPc, and the other 4 cases showed ALPa, ALPb, ALPc, respectively. It was concluded that ALPa was similar in its enzymological and immunological properties to hepatic-type ALP, ALPb was similar to placental-type ALP, and ALPc was similar to intestinal-type ALP, ALPb probably originates from the cancer cell itself. As for the other enzymes, ALPa and ALPc, further investigation should be made to determine whether they come from the cancer cell itself or not.

Alkaline Phosphatase↗

Effect of experimental conditions on the appearance of distinct forms of placental glucosylceramidase: use of gel filtration analysis as a means of ascertaining their occurrence.

We have found that, under some experimental conditions, the placental glucosylceramidase shows an anomalous behaviour on gel filtration chromatography. At pH 5.6, the optimal pH of the enzymatic assay, the purified enzyme remains bound to either Superose 6 or TSK-40-XL HPLC columns, while the interaction of the crude glucosylceramidase contained in the water extract of the lysosome-mitochondrial fraction of placenta with the two HPLC gel matrices is much weaker. The quite different behaviour of the crude compared to the purified enzyme may be explained by the formation in the crude preparation of associated form(s) of glucosylceramidase with suitable endogenous compound(s), which compete with the gel matrices for the binding to the enzyme. The most likely one component of the enzyme complex is the placental activating factor, previously reported by us (Vaccaro et al. (1985) Biochim. Biophys. Acta 836, 157-166), as indicated by the negligible stimulation of the crude enzyme activity on addition of the factor, either before or after passage through the HPLC columns. On the assumption that the behaviour of crude glucosylceramidase on gel filtration becomes similar to that of the purified enzyme when its interaction with endogenous substance(s) is impaired, we have identified some conditions which prevent the formation of the enzyme associated form(s): (a) the addition of guanidine chloride (0.2 M), a cahotropic agent, to the crude preparation; and (b) the increase of pH up to 8. In conclusion, taking advantage of the anomalous behaviour of glucosylceramidase on gel filtration chromatography, evidence has been obtained that placental glucosylceramidase may occur under several forms which had not been previously reported; a difference in experimental conditions can promote the formation of one or another form, by possibly affecting the composition and/or the stoichiometry and/or the stability of the enzyme complex.

Chromatography, Gel↗