Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non-pregnant women.

Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses. Oral administration of ferrous sulfate, prescribed to cure iron deficiency (ID) and ID anemia (IDA), often fails to increase hematological parameters and causes adverse effects. Recently, we demonstrated safety and efficacy of bovine lactoferrin (bLf) in pregnant women suffering from ID/IDA. Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA. In both trials, women received oral administration of bLf 100 mg/twice/day (Arm A), or ferrous sulfate 520 mg/day (Arm B). Hematological parameters, serum IL-6 and prohepcidin were assayed before and after therapy. Unlike ferrous sulfate, bLf increased hematological parameters (P less than 0.0001). In pregnant women, bLf decreased serum IL-6 (P less than 0.0001), and increased prohepcidin (P=0.0007). In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin (P less than 0.0001). Ferrous sulfate increased IL-6 (P less than 0.0001) and decreased prohepcidin (P=0.093). bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis, whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA.

Microsurgery versus laparoscopy in distal tubal obstruction hysterosalpingographically or laparoscopically investigated.

OBJECTIVE: To compare pregnancy rates after laparotomic microsurgical or laparoscopic distal tuboplasty. DESIGN: Two hundred and twenty-four women with infertility due to distal tubal occlusion were randomized to be treated with either laparotomy or laparoscopy from 1987 to 2001 at the Institute of Gynaecology and Obstetrics, University of Rome, "La Sapienza". RESULTS: The results were evaluated taking into account the type of surgical approach, the severity of tubal damage and of adhesions. After a 24-month follow-up period, the overall pregnancy rate obtained with microsurgery was 43.7%, of which 33.3% were term pregnancies, 5.0% abortions, and 5.0% ectopic pregnancies. After laparoscopy, the overall pregnancy rate was 41.6%, of which 29.1% were term pregnancies, 8.3% abortions and 3.9% ectopic pregnancies. No significant differences was observed between the two groups in terms of fertility rate (chi-square 0.016, p = 0.9003). CONCLUSIONS: Laparotomy plus microsurgery and laparoscopy were equally effective in restoring fertility in women with comparable tubal damage. The severity of the damage is a critical factor for the results.

[Controlled release vaginal dinoprostone for the induction of labour]. / Induzione del travaglio di parto con dinoprostone vaginale a rilascio controllato.

AIM: To study the efficacy and safety of controlled release dinoprostone (PGE2) for the induction of labour. METHODS: From March 2001 to August 2002, a total of 173 patients hospitalized for postdate pregnancy, maternal hypertension, intrauterine delayed growth, reduction of amniotic fluid, were studied. In 33 of these patients, a hydrogel strip containing 10 mg dinoprostone, inserted into the posterior fornix of the vagina and release PGE2 at constant rate of 0.3-0.4 mg/h was used. RESULTS: Indications for induction, mode and time of delivery, maternal, fetal and neonatal parameters anomalies are evaluated. In 23 patients dinoprostone was used for postdate pregnancy, in 4 for maternal hypertension, in 4 for oligohydramnios and in 2 for intrauterine delayed growth. In 2 cases, the vaginal insert was removed for hyperstimulation in 1 case and for abnormal fetal heart rate in the other case. After vaginal delivery, Apgar scores and umbilical artery pH values were evaluated without anomalies. Vaginal delivery within 24 hours occurred in 51.6% of patients and medium time to delivery was 17.5 (nulliparous) and 12.3 (multiparous) hours. Only one case of uterine hyperstimulation to PGE2 was recorded, and the induction was suspended. The cesarean section rate was 12% and vaginal delivery after 24 hours was 38.7%. CONCLUSION: The continuous release of PGE2 from the vaginal insert permits a controlled and safe induction of labour, minimal risk of hyperstimulation, fast and easy removal of drugs in cases of fetal or maternal anomalies, easy accetability for patients, but high cost.

Thrombotic thrombocytopenic purpura and pregnancy: a case report and a review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.

Linoleic acid hydroperoxide-induced peroxidation of endothelial cell phospholipids and cytotoxicity.

Peroxidation of endothelial cell phospholipids was examined following treatments with linoleic acid hydroperoxide. The treatment effects were analyzed over a range of toxicities and exposure intervals as determined by cell plating efficiencies and survival. Over the concentration ranges where lipid peroxidation was evident (20-40 microM treatments in complete medium), significant cytotoxicity was apparent after 1 h of exposure. The extent of toxicity was dependent on the time interval between the end of peroxide treatment and replating of cells. Maximum toxicity was found when cells were replated 1-3 h after treatment. When cells were replated 4 h after treatment a linear increase in cell survival was found as a function of replating time following peroxide exposure. Analysis of cell phospholipids by HPLC after 1 h of exposure to linoleic acid hydroperoxide revealed that peroxidation (evidenced by conjugated diene content) had taken place among a number of phospholipid species with the most marked increases in phosphatidylcholine. Analysis of the fatty acyl composition of phospholipids also showed that the proportions of polyunsaturated fatty acids were reduced relative to saturated fatty acids, indicating peroxidative damage to phospholipids. Pretreatment of cells with vitamin E prevented the peroxidation of all phospholipids and blocked the cytotoxic action of linoleic acid hydroperoxide. These findings indicate that an immediate cytotoxic action of lipid hydroperoxide is associated with peroxidation of membrane phospholipids. This cytotoxicity is a transient effect, and cells surviving the acute injury display a time-dependent increase in plating efficiency representing a period of repair.

Lipid hydroperoxide-induced peroxidation and turnover of endothelial cell phospholipids.

The effects of lipid peroxidation on rabbit aortic endothelial cell phospholipid turnover was studied using linoleic acid hydroperoxide (LOOH). Following treatments with 20-40 microM LOOH, cells prelabeled with either arachidonic acid (20:4) or oleic acid (18:1) showed a movement of these fatty acids out of the phospholipids and into neutral lipid and free fatty acid pools. There was also a release of radioactive free fatty acids and phospholipids into the media, which was significantly increased as compared to cells maintained under standard culture conditions. Fatty acid uptake and distribution among phospholipid pools was also affected by LOOH treatment where incorporation of 20:4 and 18:1 into phosphatidylcholine (PC) decreased, while uptake into phosphatidylinositol (PI) increased after 1 h of incubation with 40 microM LOOH. These effects were also inhibited by vitamin E. In cells prelabeled with 20:4 or 18:1 under conditions where approximately 99% of the fatty acids were incorporated into neutral and phospholipid pools, LOOH treatment produced a decrease in radioactivity associated with PC, while the specific activity of PI increased. The extent of these changes was greater for 20:4 than 18:1, but in each case the effects were inhibited by vitamin E. The temporal pattern of uptake for labeled choline and inositol after LOOH treatments paralleled those found for fatty acid incorporation. These cell responses indicate that induction of lipid peroxidation produces rapid fatty acid release and phospholipid turnover involving repair as well as de novo synthesis. The implications of these effects on turnover of specific phospholipids and cell responses to oxidative stress are discussed.

Phospholipase A2 stimulation by methyl mercury in neuron culture.

In primary prelabeled cultures of cerebellar granule cells, methyl mercury (MeHg) induced a concentration- and time-dependent release of [3H]arachidonic acid. MeHg-induced [3H]arachidonate release was partially dependent on the extracellular Ca2+ concentration. MeHg at 10-20 microM also stimulated basal 45Ca2+ uptake after 20 min of incubation at 37 degrees C, and at 10 microM inhibited K+ depolarization-stimulated uptake. MeHg stimulated [3H]arachidonate uptake, but had no effect on the rate of phospholipid reacylation. Phospholipase A2 (PLA2) activation preceded cytotoxicity, but at higher concentrations of MeHg such dissociation was not evident. Inhibition of MeHg-induced PLA2 activation by 100 microM mepacrine failed to modify cytotoxicity. MeHg-induced lipoperoxidation, measured as the production of thiobarbituric acid-reacting products, was inhibited by alpha-tocopherol without inhibition of [3H]arachidonate release. The absence of alpha-tocopherol inhibition of MeHg-induced arachidonate release precludes a causal role for lipoperoxide-induced PLA2 activation in this system. Moreover, MeHg induced an increased susceptibility of unilamellar vesicles to exogenous PLA2 in the presence of low Ca2+ concentrations without evidence of lipid peroxidation. [3H]Arachidonate incorporation into granule neuron phospholipids was analyzed by isocratic HPLC analysis. Relatively high proportional incorporation was found in the combined phosphatidylcholine fractions and phosphatidylinositol. With MeHg, an increase in the relative specific activity of incorporation was found in the phosphatidylinositol fraction, indicating a preferential turnover in this phospholipid species in the presence of MeHg.