Lipid profile and lipid oxidative modification parameters in the first trimester of high- risk pregnancies - possibilities for preeclampsia prediction.

OBJECTIVES: The goal of this study was to investigate metabolic changes in lipids and oxidative stress parameters in the first trimester of pregnancy with the more specific aim of estimating the significance and strength of researched parameters in the prediction of preeclampsia. DESIGN AND METHODS: The study included 87 high-risk pregnant (HRG) female subjects, 14 with developed preeclampsia (PEC) and 43 healthy pregnant female subjects matched for gestational age (CG). Thiobarbituric acid-reactive substances (TBARS) concentration, lipid hydroperoxides (LOOH), pro-oxidant antioxidant balance (PAB) and total oxidative status (TOS) were measured as oxidative stress markers, while total antioxidant capacity (TAC) was measured as an antioxidative defense parameter. The Atherogenic Index of Plasma (AIP) was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides (TG) to the plasma concentration of high-density lipoprotein cholesterol (HDL-C), with each concentration expressed in mmol/L. RESULTS: The results have shown that lipid indices, especially AIP, were significantly higher in the first trimester of HRG (p < 0.001) and PEC (p < 0.001). Oxidative stress parameters were significantlly higher, while TAC was significantly lower in HRG vs. CG [0.7 ± 0.15 vs 1.1 ± 0.16; (p < 0.001)] and in PEC [0.6 ± 0.12 vs 1.1 ± 0.16; (p < 0.001)] vs. CG. Also, in the HRG, results have shown an independent association of AIP with the preeclampsia development (p < 0.05), while placental growth factor did not show the expected level of significance (p = 0.648). Analysis of the Receiver Operating Characteristics (ROC) curves indicated that certain parameters included in the research model have very good diagnostic accuracy for preeclampsia (AUC = 0.856). CONCLUSIONS: AIP is associated with high-risk pregnancies. Furthermore, our results firmly underscored AIP as a potential marker for preeclampsia prediction.

Hormonal therapy after the operation for catamenial pneumothorax - is it always necessary?

BACKGROUND: Our recent clinical observations put into question the routine hormonal therapy for pneumothorax recurrence prevention, in patients operated for catamenial pneumothorax (CP). METHODS: Retrospective review of the treatment of four women operated for CP in a recent 32-months period. RESULTS: The four presented patients with CP represent 4.8 % of the overall number of patients operated for spontaneous pneumothorax and 19 % of women operated for pneumothorax in the same period. In all patients, typical multiple diaphragm holes existed. The involved part of the diaphragm was removed with diaphragm suture in three patients, whilst in one patient, a diaphragm placation was done. Endometriosis was histologically confirmed in two patients. During the follow-up period of 6-43 months, none of the patients underwent a postoperative hormonal therapy for different reasons, and in none of them the pneumothorax recurrence occurred. CONCLUSION: The clinical course of these patients, with the absence of the pneumothorax recurrence despite the omission of the hormonal treatment, suggests that the appropriateness of the routine hormonal treatment with gonadotrophin-releasing hormone analogues for 6-12 months, should be reconsidered and re-evaluated in further studies.

Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction.

Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding.

Doppler parameters of maternal renal blood flow in normal pregnancy.

UNLABELLED: The purpose of this investigation was to evaluate changes in maternal renal arterial blood flow during pregnancy. MATERIALS AND METHODS: The study included 40 non-pregnant, 200 pregnant, and 30 women after delivery. The authors measured pulsatility index (Pi) and resistance index (Ri) in the right and left renal arteries in the hilus. The authors compared the values between non-pregnant and women during first, second, and third trimester and post-partum period and tested correlation with gestational age. RESULTS: The authors did not find a statistical difference in Pi and Ri between the right and left kidneys. There was no difference in Pi and Ri in pregnancy trimester compared to the non-pregnant state. There was no correlation between the values of Pi and Ri and gestational weeks. CONCLUSION: During pregnancy there are no changes in the values of maternal renal Pi and renal Ri. Unchanged total vascular resistance may result from physiological changes of the glomerular filtration rate.

Influence of placental mannose/n-acetyl glucosamine-binding proteins on the interaction of insulin and insulin-like growth factors with their receptors.

Placenta is a source of carbohydrate-binding proteins that function as molecular scavengers, but they could also be involved in interactions that assist in metabolic control. Mannose/N-acetyl-glucosamine (Man/GlcNAc)-binding proteins from placenta were isolated and their reactivity towards placental insulin and insulin-like growth factor receptors (IR and IGF-Rs) was analyzed. The lectins reduced the binding of insulin and IGF-I in a dose-dependent manner, while almost no effect was observed on the binding of IGF-II. The shape of the inhibition curves changed, suggesting altered binding specificity. The presence of sugar could not reverse completely the effect of the lectins, implicating both lectin-sugar and protein-protein conformational recognition. Since biological molecules in our experimental system were those that are in close relation in vivo, placental Man/GlcNAc-specific lectins may be regarded as potential allosteric modulators of ligand-receptor interactions in a system of homologous ligands, selectively affecting only binding to tyrosine kinase type receptors (IR and IGF-1R).

Thrombophilia in women with pregnancy-associated complications: fetal loss and pregnancy-related venous thromboembolism.

BACKGROUND/AIMS: Existing data regarding the prevalence of thrombophilia in women with pregnancy complications are conflicting. METHODS: To investigate the relationship between pregnancy-associated complications and the presence of thrombophilia, we studied the records of 453 women with pregnancy-associated complications. In 55 women, intrauterine fetal death (fetus mortus in utero, FMU) after 20 weeks of gestation was recorded, in 231 two or more consecutive recurrent fetal losses (RFL) were recorded, while 167 had a venous thromboembolism (VTE) during one of their pregnancies. The control group consisted of 128 healthy women, with no previous history of thrombotic events or miscarriages. RESULTS: In the FMU group we found 54.5% of women had thrombophilia, in the RFL group 38%, and in the VTE group 52.7%. The most frequent thrombophilia in the VTE group was the FV Leiden (OR 17.9, 95% CI 4.2-75.9). The most frequent thrombophilia in the FMU group was the FII G20210A (OR 7.09, 95% CI 1.8-27.9). Statistical difference between RFL and the control group was observed only for FV Leiden (OR 6.8, 95% CI 1.6-29.7). CONCLUSION: Thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the women with normal pregnancies, most frequently in patients with VTE or FMU.

Fentanyl analogs: structure-activity-relationship study.

Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.

[Cesarean section combined with splenectomy in severely resistant immune thrombocytopenia]. / Carski rez kombinovan sa splenektomijom u teskoj rezistentnoj imunoj trombocitopeniji.

Immune thrombocytopenic purpura (ITP) associated with pregnancy often involves considerable risk both for mother and child, and usually worsens in the third trimester of gestation. Pregnancy and delivery are especially difficult in patients with severe ITP (platelet count below 20 x 10(9)/L), who are resistant to prednisone and high dose intravenous immunoglobulin (IVIgG). In those cases we applied cesarean section (CS), to prevent intracranial haemorrhage due to fetal/neonatal ITP, and splenectomy at the same time as an effective therapeutic strategy for ITP. We present 5 patients (4 with chronic ITP and 1 with ITP associated with HIV infection), aged 21-35 years, with severe ITP (platelet count 2-10 x 109/L), resistant to prednisone (1-2 mg/kg), and 2/3 were resistant to IVIgG (0.4 g/kg x 5 d). Four patients with severe resistant ITP were supported with 1-2 doses of platelets from cell separator before CS and 1-3 dose during splenectomy. One patient increased platelet count to 55 x 109/L after treatment with IVIgG and splenectomy following CS were done without platelet transfusion. Splenectomy was performed immediately after CS in all patients, and two of them were hysterectomised (one with HIV infection). After splenectomy, platelet count was normalised in all patients, and they had no haemorrhage, wound haematoma formation or any adverse events. But ITP relapsed in 2/5 patients after 1-2 months. Two newborns had severe thrombocytopenia, which solved spontaneously after 3 days in one or after treatment with IVIgG in other. We propose that splenectomy following cesarean section should be considered as approach for delivery and treatment option for mothers with severe resistant ITP.

[Lupus anticoagulant in pregnancy--first experiences in detection and therapy]. / Lupusni antikoagulans u trudnoci--prva iskustva u dijagnostici i terapiji.

We examined 62 women with three or more recurrent adverse pregnancy outcomes where we excluded the other well known causes of this state. We detected lupus anticoagulant (LAC) in three (5%), with the use of set of coagulation tests: activated partial thromboplastin time (APTT), APTT ratio, kaolin clotting time ratio (KCT), APTT of the 50:50 mixture of the patients and control plasmas, APTT ratio of the 50:50 mixture, phospholipid correction test and heat stability test. We excluded connective tissue disorders. Therapy was started between 12th and 14th gestational week. Efficacy was monitored in intervals of 2-6 weeks with following tests: APTT ratio, KCT and plateled count. Patient A, with strong LAC activity and thrombocytophenia, reacted weakly to therapy with Pronison 40 mg/day and Aspirin 80 mg/day. The activity of LAC was slightly diminished but was present all the time. Patient expressed hypertension and gestational diabetes mellitus. The outcome of pregnancy was adverse and placenta had typical pathological changes. Patient B, with moderate LAC activity, reacted quickly and completly on therapy with Pronison 20-40 mg/day and Aspirin 80 mg/day. The course of pregnancy was regular. The outcome was successful and placenta had no pathological changes. Patient C, with mild LAC activity, was treated only with Aspirin 80 mg/day. LAC activity rapidly disappeared, the course of pregnancy was regular and outcome was successful. On the basis of the first results we concluded that applied set of tests was sensitive for LAC of different intensity and that dissapeparance of LAC activity with the use of therapy anticipates successful pregnancy outcome.

[Lyme disease and pregnancy]. / Lajmska bolest i trudnoca.

The authors have investigated Borrelia infection in pregnant women with two or more spontaneous abortions, but with no clinical manifestations of Lyme disease. In 42 such cases the results were negative. On the other hand, in two cases with positive epidemiologic data, but without clinical manifestations of Lyme disease, serologic findings were positive. No complications during pregnancy or after childbirth were recorded.

[Growth of the fetal cerebellum in normal pregnancy]. / Rast cerebeluma ploda u normalnoj trudnoci.

An ultrasonographic study was carried out in 203 physiological pregnancies whose menstrual gestational age (MGA) was between 20 and 40 weeks. The following biometric parameters were determined: transversal cerebellar diameter (TCD), biparietal diameter (BPD), occipito-frontal diameter (OFD) and head circumference (HC). The data analysis gave the optimal mathematical models with the following relations: 1) TCD/MGA (R2 = 0.904; SD = 2.6 mm); 2) MGA/TCD (R2 = 0.924; SD = 1.7 wks); 3) BPD/TCD (R2 = 0.914; SD = 4.3 mm); 4) HC/TCD (R2 = 0.919; SD = 14.3 mm), which are graphically and tabularly presented. Also the variability in the determination of MGA from TCD is calculated before 26 weeks (2 SD = 2.6 wks) and after 26 weeks (2 SD = 3.5 wks). TCD can be practically applied in cases where it is difficult or impossible to measure BPD, or in cases where it is unsuitable because of the expressed moulding of the head, since the cerebellum is not liable to changes in forms and its size is in correlation with MGA and BPD. The use of TCD is also important in the detection of congenital malformations which are manifested in the posterior cranial fossa. The potential importance of TCD in the diagnosis of the fetal intrauterine growth retardation is based on the assumption that the cerebellum is not liable, or at least not considerably liable, for growth retardation.