Comparison of Efficiency and Function of Vascular Endothelial Growth Factor Adenovirus Vectors in Endothelial Cells for Gene Therapy of Placental Insufficiency.

Severe fetal growth restriction (FGR) affects 1:500 pregnancies, is untreatable and causes serious neonatal morbidity and death. Reduced uterine blood flow (UBF) and lack of bioavailable VEGF due to placental insufficiency is a major cause. Transduction of uterine arteries in normal or FGR sheep and guinea pigs using an adenovirus (Ad) encoding VEGF isoforms A (Ad.VEGF-A165) and a FLAG-tagged pre-processed short form D (DΔNΔC, Ad.VEGF-DΔNΔC-FLAG) increases endothelial nitric oxide expression, enhances relaxation and reduces constriction of the uterine arteries and their branches. UBF and angiogenesis are increased long term, improving fetal growth in utero. For clinical trial development we compared Ad.VEGF vector transduction efficiency and function in endothelial cells (ECs) derived from different species. We aimed to compare the transduction efficiency and function of the pre-clinical study Ad. constructs (Ad.VEGF-A165, Ad.VEGF-DΔNΔC-FLAG) with the intended clinical trial construct (Ad.VEGF-DΔNΔC) where the FLAG tag is removed. We infected ECs from human umbilical vein, pregnant sheep uterine artery, pregnant guinea pig aorta and non-pregnant rabbit aorta, with increasing multiplicity of infection (MOI) for 24 or 48 hours of three Ad.VEGF vectors, compared to control Ad. containing the LacZ gene (Ad.LacZ). VEGF supernatant expression was analysed by ELISA. Functional assessment used tube formation assay and Erk-Akt phosphorylation by ELISA. VEGF expression was higher after Ad.VEGF-DΔNΔC-FLAG and Ad.VEGF-DΔNΔC transduction compared to Ad.VEGF-A165 in all EC types (*p < 0.001). Tube formation was higher in ECs transduced with Ad.VEGF-DΔNΔC in all species compared to other constructs (***p < 0.001, *p < 0.05 with rabbit aortic ECs). Phospho-Erk and phospho-Akt assays displayed no differences between the three vector constructs, whose effect was, as in other experiments, higher than Ad.LacZ (***p < 0.001). In conclusion, we observed high transduction efficiency and functional effects of Ad.VEGF-DΔNΔC vector with comparability in major pathway activation to constructs used in pre-clinical studies, supporting its use in a clinical trial.

What's new in obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease, the obstetric features of which include recurrent early miscarriage, fetal death at or beyond 10 weeks of gestation, and early delivery for severe preeclampsia or placental insufficiency. Controversies regarding the specificity of these obstetric clinical features, as well as the laboratory diagnostic criteria, are the subject of current debate and reanalysis. Clinical and laboratory features can be used to stratify women with APS in terms of risk of adverse second and third trimester pregnancy outcomes. Numerous "treatments" have been used in high-risk and refractory patients, but rigorously designed clinical trials are needed. APS is a rare disease that requires innovative investigative approaches to provide credible results.

Challenges to improve antenatal and intrapartum care in South Africa.

The major causes of maternal and perinatal deaths have been well described in South Africa. These causes are related to HIV infection, placental insufficiency and intrapartum asphyxia. The health system failures that most commonly lead to preventable mortality are related to managing hypertensive disorders in pregnancy (HDP), detecting fetal growth restriction antenatally and managing labour effectively by providing caesarean delivery to those who need it and avoiding it in those who do not. Improving antenatal and intrapartum care are vital aspects in efforts to improve survival, but to achieve this the following challenges need to be overcome: managing the increased antenatal care contacts needed to detect HDP creating a next level of expertise, and access for women to high-risk care creating the environment for respectful care and companionship in labour managing labour as physiologically as possible detecting and managing placental insufficiency.  This article provides some exciting solutions to these health system barriers.

Update on the diagnosis and prognosis of pre-eclampsia in singleton pregnancies based on the sFlt-1/PlGF ratio / Actualización del diagnóstico y el pronóstico de la preeclampsia en embarazos únicos con la ayuda del cociente sFlt-1/PlGF

Pre-eclampsia belongs to a group of obstetric complications that are closely related through placental insufficiency, which also includes intrauterine growth restriction and placental abruption. Timely and accurate detection and treatment of pre-eclampsia is usually difficult, since diagnostic criteria are still based on nonspecific signs and symptoms and there is no clear association between the usual criteria for severity and unfavorable outcomes for mother and fetus. The discovery of the role of angiogenic factors (sFlt-1 y PlGF) in the pathophysiology of placental insufficiency is a key step toward improving early diagnosis and establishing a prognosis in cases occurring before week 34 of pregnancy. At present, ≤ 38 is widely accepted to be threshold value of the sFlt-1/PlGF ratio that rules out suspected pre-eclampsia. The use of the ratio is considered cost-effective. However, current data on the treatment and prognosis of women with an abnormally high sFlt1/PlGF ratio are more limited. The present article summarizes current knowledge on the clinical application of the sFlt-1/PlGF for the diagnosis and prognosis of pre-eclampsia and highlights those areas that should be addressed with respect to biomarkers, for example, their role as targets in the development and follow-up of new treatments

La preeclampsia pertenece a un grupo de complicaciones obstétricas estrechamente relacionadas entre ellas por la existencia de una insuficiencia placentaria, que incluye también la restricción del crecimiento intrauterino y el desprendimiento placentario. El reconocimiento y tratamiento oportuno y preciso de la preeclampsia suele ser difícil, ya que los criterios diagnósticos aún se basan en signos y síntomas inespecíficos y no existe una relación clara entre los criterios habituales de gravedad y los resultados desfavorables para la madre o el feto. El descubrimiento del papel que juegan los factores relacionados con la angiogénesis (sFlt-1 y PlGF) en la fisiopatología subyacente de la insuficiencia placentaria ha constituido un paso importante a la hora de mejorar el diagnóstico precoz y establecer un pronóstico en los casos que se presentan antes de la semana 34 de gestación. En la actualidad está ampliamente aceptado que el valor límite del cociente sFlt-1/PlGF que permite excluir la existencia de preeclampsia en pacientes en las que se sospecha esta enfermedad es de 38 o menos, y que el uso de este cociente resulta costo-eficiente. Sin embargo, los datos disponibles relativos al tratamiento y al pronóstico de las mujeres con niveles anormalmente altos del cociente sFlt1/PlGF son más limitados. Este artículo resume los conocimientos actuales relativos a la aplicación clínica del cociente sFlt-1/PlGF para diagnosticar y pronosticar el curso de la preeclampsia, y señala las próximas tareas que serán necesarias abordar en relación con estos biomarcadores, como por ejemplo el papel que pueden jugar como dianas para el desarrollo y el seguimiento de nuevos tratamientos

Hyperbaric oxygenation and glucose/amino acids substitution in human severe placental insufficiency.

In the first case, the AA and glucose were infused through a perinatal port system into the umbilical vein at 30 weeks' gestation due to severe IUGR. The patient received daily hyperbaric oxygenation (HBO, 100% O2 ) with 1.4 atmospheres absolute for 50 min for 7 days. At 31+4  weeks' gestation, the patient gave birth spontaneously to a newborn weighing 1378 g, pH 7.33, APGAR score 4/6/intubation. In follow-up examinations at 5 years of age, the boy was doing well without any neurological disturbance or developmental delay. In the second case, the patient presented at 25/5  weeks' gestation suffering from severe IUGR received HBO and maternal AA infusions. The cardiotocography was monitored continuously during HBO treatment. The short-time variations improved during HBO from 2.9 to 9 msec. The patient developed pathologic CTG and uterine contractions 1 day later and gave birth to a hypotrophic newborn weighing 420 g. After initial adequate stabilization, the extremely preterm newborn unfortunately died 6 days later. Fetal nutrition combined with HBO is technically possible and may allow the prolongation of the pregnancy. Fetal-specific amino-acid composition would facilitate the treatment options of IUGR fetuses and extremely preterm newborn.

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery.

INTRODUCTION: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. METHODS: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. RESULTS: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. DISCUSSION: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

A placenta clinic approach to the diagnosis and management of fetal growth restriction.

Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening programs for placental complications. However, placental ultrasound can be diagnostic in the context of fetal growth restriction, for example in Breus' mole and triploidy, which in turn may enhance diagnosis and management. Several examples are illustrated in our figures and supplementary videos. Recent advances in the ability of multiparameter screening and intervention programs to reduce the risk of severe preeclampsia will likely increase efforts to deliver similar improvements for women at risk of fetal growth restriction. Placental pathology is important because the underlying pathologies associated with fetal growth restriction have a wide range of recurrence risks. Rare conditions such as massive perivillous fibrinoid deposition or chronic histolytic intervillositis may recur in >50% of subsequent pregnancies. Postpartum care in a placenta-focused program can provide effective counseling for modifiable maternal risk factors, and can assist in planning future pregnancy care based on the pathologic basis of fetal growth restriction.

Screening for fetal growth restriction and placental insufficiency.

Fetal growth restriction (FGR) continues to be a leading cause of preventable stillbirth and poor neurodevelopmental outcomes in offspring, and furthermore is strongly associated with the obstetrical complications of iatrogenic preterm birth and pre-eclampsia. The terms small for gestational age (SGA) and FGR have, for too long, been considered equivalent and therefore used interchangeably. However, the delivery of improved clinical outcomes requires that clinicians effectively distinguish fetuses that are pathologically growth-restricted from those that are constitutively small. A greater understanding of the multifactorial pathogenesis of both early- and late-onset FGR, especially the role of underlying placental pathologies, may offer insight into targeted treatment strategies that preserve placental function. The new maternal blood biomarker placenta growth factor offers much potential in this context. This review highlights new approaches to effective screening for FGR based on a comprehensive review of: etiology, diagnosis, antenatal surveillance and management. Recent advances in novel imaging methods provide the basis for stepwise multi-parametric testing that may deliver cost-effective screening within existing antenatal care systems.

[The new directions in the physiotherapeutic applications of the natural potassium salts of the Western Ural]. / Novye napravleniya fizioterapevticheskogo primeneniya prirodnykh kaliinykh solei Zapadnogo Urala.

Salt therapy (halotherapy) as a non-traditional method for the treatment of various pathological conditions has become an increasingly popular therapeutic modality in Russia and abroad. The Perm region houses one of the largest sylvinite-bearing potash deposits in the world. These salts are possessed of special physical and chemical properties of great value for the treatment of different diseases. The objective of the present work was to develop novel approaches to the application of sylvinite for the treatment and prevention of various diseases. MATERIAL AND METHODS: The subjects of investigations were the modern sylvinite constructions of different types. The study included a total of 195 patients who were randomly divided into two groups. The main group consisted of 50 patients presenting with allergic respiratory diseases, 20 ones with atopic dermatitis, and 21 with vulgar psoriasis. 31 patients had undergone aortocoronary bypass surgery in the preceding period. 49 pregnant women presented with a complicated course of pregnancy. 24 patients suffered from chronic generalized catarrhal gingivitis. The control group was comprised of 188 persons presenting with the same diseases (46, 30, 18, 20, 49, 25 patients in each of the above groups respectively) who received only the traditional pharmacotherapeutic treatment. All the patients underwent evaluation of the respiratory and cardiovascular functions. The clinical manifestations and the skin damage areas were estimated in the patients with atopic dermatitis and vulgar psoriasis. Blood circulation in placenta, the state of the periodontal tissues, and local immunity in the oral cavity mucosa, as well as the subjective psychological status were evaluated. The physical and chemical characteristics of the internal environment of the salt constructions (microclimatic factors, radiation, air ionization, salt aerosol content) were estimated. RESULTS AND DISCUSSION: The data obtained provided a basis for the development and patenting of the methods for the treatment of atopic dermatitis, vulgar psoriasis, placental insufficiency, and chronic generalized catarrhal gingivitis based on the halotherapeutic modalities. CONCLUSION: The results of the long-term hygienic, physical and clinical investigations made it possible to identify the complex of curative factors inherent in the natural mineral sylvinite constructions. These factors are believed to create the optimal conditions for the efficient management of the patients presenting with dermatological, cardiological, obstetrical, and stomatological problems.

Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. RESULTS: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR) contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA) complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1). Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro.

Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor-11 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined amino acid transporter expression and localization in both a mouse model of placental Insufficiency (PI) and a model of human trophoblast, the BeWo Choriocarcinoma cell line. For in vitro human studies, BeWo Choriocarcinoma cells were maintained in F12 complete medium + 10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 h. MOIs of 10:1 and 100:1 were utilized. In BeWo, transfection efficiency was 100% at an MOI of 100:1 and Ad-IGF-1 significantly increased IGF-1 secretion, proliferation and invasion but reduced apoptosis compared to controls. In vitro, amino acid uptake was increased following Ad-IGF-1 treatment and associated with significantly increased RNA expression of SNAT1, 2, LAT1 and 4F2hc. Only SNAT2 protein expression was increased but LAT1 showed relocalization from a perinuclear location to the cytoplasm and cell membrane. For in vivo studies, timed-pregnant animals were divided into four groups on day 18; sham-operated controls, uterine artery branch ligation (UABL), UABL + Ad-hIGF-1 (10(8) PFU), UABL + Ad-LacZ (10(8) PFU). At gestational day 20, pups and placentas were harvested by C-section. Only LAT1 mRNA expression changed, showing that a reduced expression of the transporter levels in the PI model could be partially rectified with Ad-hIGF1 treatment. At the protein level, System L was reduced in PI but remained at control levels following Ad-hIGF1. The System A isoforms were differentially regulated with SNAT2 expression diminished but SNAT1 increased in PI and Ad-hIGF1 groups. Enhanced amino acid isoform transporter expression and relocalization to the membrane may be an important mechanism contributing to Ad-hIGF-1 mediated correction of placental insufficiency.

Maternal floor infarction: management of an underrecognized pathology.

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

UNLABELLED: Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line. METHODS: At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL), UABL+Ad-hIGF-1 (10(8) PFU), UABL+Ad-LacZ (10(8) PFU). At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry. RESULTS: In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization. CONCLUSION: Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

Transcutaneous electrical nerve stimulation and placental vascularization in cases of uterine blood flow restriction.

Studies report transcutaneous electrical nerve stimulation (TENS) as a treatment for placental insufficiency. To induce utero-placental insufficiency in rats, the uterine artery was ligated. Transcutaneous electrical nerve stimulation was applied with a frequency of 80 Hz, pulse duration of 200 µs, and low intensity. Placental blood vessels were analyzed after immunohistochemistry. The number, caliber and area occupied by placental vessels, fetal weight and length, and placental volume were lower in cases stimulated by TENS. The interaction between ligation and stimulation by TENS was associated with reduction of all these measurements, suggesting that TENS use during pregnancy may have harmful effects on intra-uterine development.

Selective intrauterine growth restriction in monochorionic twins: pathophysiology, diagnostic approach and management dilemmas.

Selective intrauterine growth restriction (sIUGR) in monochorionic twins is associated with a substantial increase in perinatal mortality and morbidity for both twins. Clinical evolution depends on the combination of the effects of placental insufficiency in the IUGR twin with inter-twin blood transfer through placental anastomoses. Classification of sIUGR into types according to the characteristics of umbilical artery diastolic flow in the IUGR twin permits the differentiation of clinical and prognostic groups. sIUGR type I has normal diastolic flow and relatively good outcome. Type II is defined by persistently absent/reverse end-diastolic flow and is associated with a high risk of intrauterine demise of the IUGR twin and/or very preterm delivery. Type III is defined by the presence of intermittent absent/reverse end-diastolic flow (iAREDF), and is associated with 10-20% risk of unexpected fetal demise of the smaller twin and 10-20% risk of neurological injury in the larger twin. The management strategy for sIUGR with abnormal umbilical artery Doppler (types II and III) remains a challenge, and may include elective fetal therapy or close surveillance with fetal therapy or elective delivery in the presence of severe fetal deterioration. Small clinical series reporting the use of cord occlusion or laser therapy in severe cases suggest that the outcome of the larger twin might be improved. There is probably no single optimal strategy, since decisions will ultimately be influenced by the severity of IUGR, gestational age, parents' wishes and technical issues.

Programação pré-natal de hipertensão arterial na vida adulta / Prenatal programming of adult arterial hypertension

Na busca da melhor compreensão da origem das doenças cardiovasculares, uma importante linha de investigação surgiu a partir da demonstração da associação entre o baixo peso ao nascer e o desenvolvimento de hipertensão foi a base para a formulação da hipótese de que doenças cardiovasculares manifestadas na idade adulta podem ser programadas a partir de insultos ocorridos no período pré natal.Diversos modelos experimentais apóiam esta teoria. Em animais de laboratório, estudos com desnutrição induzida durante a gestação resultaram em animais adultos com níveis mais elevados de pressão arterial do que os controles...

[Corrective action of the microwave electromagnetic field on progeny development in rats with impared uteroplacental circulation]. / Eksperimental'noe issledovanie korrigirueshchego deistviia élektromagnitnykh polei detsimetrovogo diapazona voln na razvitie potomstva krys pri narushenii matochno-platsentarnogo krovoobrashcheniia.

The experiment on 71 non-inbred white pregnant rats, 316 fetuses and placentas, 323 first progeny in experimental chronic impairment of uteroplacental circulation in females with pregnancy in the ploid period has found that decimetric waves (DW) in a weak heat dose (40 mW/cm2) prevents hypotrophy and disorders of fetal and placental development. Also, DW accelerate formation of motorsensory reflexes in the progeny in an early neonatal period and normalize their behavioral reactions at a mature age. The findings may serve experimental-theoretical grounds for application of weak heat DW radiation in obstetric practice in various general and regional hemocirculation.

[Prognosis, prophylaxis, and early therapy of fetoplacental insufficiency]. / Prohnozuvannia, profilaktyka ta rannia terapiia fetoplatsentarnoï nedostatnosti.

Parameters characterizing the bloodflow, system of hemostasis, were determined together with the level of the key hormones (estriol and placental lactogen) in 70 pregnant women running a risk for development of placental insufficiency as well as in those pregnant women presenting with clinical manifestations of placental insufficiency at week 6 to 40. The parameters have been noted to get worse during the period of placentation. Augmentation of resistance of the uterine arteries and umbilical artery, ultrasonic signs, decline in the hormonal activity of the placental complex, changes in the hemostasiogram--all these events come to be seen before the appearance of the first clinical signs of placental insufficiency. The studied parameters have been shown to get improved by early complex treatments of administration.