Hypothyroidism during pregnancy: Controversy over screening and intervention

Thyroid hormones are critical for foetal neurological development and maternal health. Maternal hypothyroidism during pregnancy is associated with adverse impact on health of the mother as well as the progeny. Reduced thyroid hormone levels predispose the child to develop mental retardation and cognitive delay in early life. In the mother, hypothyroidism during pregnancy is associated with spontaneous abortion, placental abruption, preterm delivery and hypertensive disorders. Therefore, screening and therapeutic intervention is justified to prevent foetal as well as maternal co-morbidities. In view of impact of such a large-scale screening and intervention program on limited healthcare resources, it is debatable if a targeted rather than universal screening program will result in comparable outcomes. In addition, there is an ongoing debate regarding best evidence-based practice for the management of isolated hypothyroxinaemia, subclinical hypothyroidism and euthyroid women with autoimmune hypothyroidism. We have carried out a review of the literature; firstly, to determine whether universal screening for asymptomatic women in early pregnancy would be cost-effective. Secondly, we have retrospectively reviewed the literature to analyse the evidence regarding the impact of therapeutic intervention in women with subclinical hypothyroidism.

Comprehension of Risk Factors of Malaria during Pregnancy among Pregnant Women Attending Antenatal Care in Malawi

A study was conducted to determine the comprehension of pregnant women on malaria risk factors during pregnancy. Comprehension of Malaria risks is important to ensure compliance to prevention methods and treatment by the pregnant women and hence optimizes the pregnancy outcomes. The study was conducted in 2012 at three health facilities, Queen Elizabeth Central Hospital, Ndirande health Centre and St. Joseph Mission Hospital in Malawi. The study design was descriptive and utilized quantitative data collection and analysis methods on a random sample of 316 antenatal mothers. The study targeted antenatal mothers who were aged between 15 and 49 years, in the gestation period of 28 to 36 weeks and able to converse in English or vernacular language. A structured questionnaire was used to collect data which were analyzed using SPSS version 16.0. Most of the participants (79.4%, n = 251) knew the risk factors of malaria during pregnancy but very few (18.4%, n = 58) knew about intermittent prevention treatment despite taking SP as prescribed. The motivation factors for taking SP were husband support and the desire to protect their babies and themselves from Malaria. Although the comprehension of the intermittent prevention treatment among the women was low, the women were motivated to adhere to the treatment when instructed by the healthcare workers due to the desire for good health for themselves and their unborn babies. Husbands were the most significant other that motivated the pregnant women to adhere to treatment. Results show that there is a need for healthcare workers to facilitate comprehension of intermittent prevention treatment among pregnant mothers.

Advances in understanding and treating liver diseases during pregnancy:A review

Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal survival.It includes pre-eclampsia;eclampsia;haemolysis,elevated liver enzymes,and low platelets syndrome;acute fatty liver of pregnancy;hyperemesis gravidarum;and intrahepatic cholestasis of pregnancy.Recent basic researches have shown the various etiologies involved in this disease entity.With these advances,rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival.The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention.Therefore,correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis.Therefore,here we review and summarized recent advances in understanding the etiologies,clinical courses and management of liver disease in pregnancy.This information will contribute to physicians for diagnosis of disease and optimum management of patients.

Effect of exercise during pregnancy on offspring development through ameliorating high glucose and hypoxia in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose transporter(GLUT)1 plays a role in GDM offspring organ development remains unknown.AIM To determine the effect of exercise during pregnancy on the cardiac,hepatic and renal development of GDM mother’s offspring.METHODS Placenta samples were collected from humans and mice.GDM mouse models were created using streptozotocin along with a GDM with exercise group.The hearts,livers and kidneys of 3-and 8-week-old offspring were collected for body composition analysis and staining.The effects of high glucose levels and hypoxia were investigated using HTR8/SVneo.Transwell and wound-healing assays were performed to assess cell migration.Immunofluorescence accompanied with TUNEL and Ki67 staining was used to explore apoptosis and proliferation.RESULTS Exercise during pregnancy downregulated the GLUT1 and hypoxia inducible factor-1αexpression in placenta from individuals with GDM.Cobalt chloride induced hypoxia and high glucose levels also significantly decreased migration and apoptosis of HTR8/SVneo cells.In addition,exercise reduced inflammatory cell infiltration in the liver and decreased the tubular vacuolar area in the kidneys of offspring.CONCLUSION GDM affects the growth and development of organs in offspring.Exercise during pregnancy can reverse adverse effects of GDM on the development of the heart,liver,and kidney in offspring.

Expression of casein kinase genes in glioma cell line U87: Effect of hypoxia and glucose or glutamine deprivation

The endoplasmic reticulum-nuclei-1 (ERN1) sensing and signaling enzyme mediates a set of complex intracellular signaling events known as the unfolded protein response. We have studied the effect of hypoxia and ischemic conditions (glucose or glutamine deprivation) on the expression of several casein kinase-1 and -2 genes in glioma U87 cells and its subline with suppressed function of ERN1. It was shown that blockade of ERN1, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of casein kinase-1G2, -1E, -2B and NUCKS1 mRNA, but suppresses casein kinase-1A1, -1D and -2A1. Moreover, the expression levels of casein kinase-1A1, -1D and 1G3 as well as casein kinase-2A1 and -2A2 mRNAs are significantly increased under glutamine dep- rivation conditions both in control and ERN1- deficient glioma cells. At the same time, casein kinase-1E, -2B and NUCKS1 mRNA expression levels are also increased under this condition, but only in cells with suppressed function of ERN1. The expression level of NUCKS1 mRNA, however, is decreased both in control glioma cells and in genetically modified cells, but casein kinase-1G2—only in control U87 cells. Cell exposure to glucose deprivation conditions enhances the expression levels of casein kinase- 1D, 1G3, -1E and -2A1 in both types of glioma cells used, but casein kinase-2B expression levels increase only in cells with suppressed function of ERN1. Hypoxia induces or suppresses the expression of most of the studied genes mainly in ERN1-knockdown cells only. Results of this study show that hypoxia as well as glutamine and glucose deprivation conditions change the expression level most of casein kinase genes and that these effects are dependent on ERN1 signaling enzyme function.

Use of metformin during pregnancy for women with polycystic ovary syndrome

Objective: The purpose of this article is to review the literature assessing foetal and maternal pregnancy outcomes in women with PCOS who used metformin during pregnancy. Study Design: A literature search was conducted using MEDLINE, with analysis of 25 studies that recorded neonatal and maternal outcomes in women who used metformin during pregnancy. The outcomes assessed in this review include congenital deformities, miscarriages, preterm labour, gestational diabetes (GDM) and pregnancy induced hypertension (PIH). Results: We found that the use of metformin throughout pregnancy correlated with decreased rates of preterm labour, GDM and PIH. Conflicting evidence exists over whether metformin use during pregnancy reduced miscarriage rates. The use of metformin during pregnancy did not increase teratogenicity risks. Conclusion: The use of metformin throughout pregnancy is associated with decreased rates of preterm labour, GDM, and PIH. However, more randomised controls involving larger numbers of participants are required for more definitive results.

Women's willingness to be tested for human immunodeficiency virus during pregnancy: A review

Mother-to-child-transmission of human immunodeficiency virus(HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who didnot receive prevention services. HIV testing of pregnant women is considered to be one of the key strategies for preventing mother-to-child-transmission of HIV, but HIV testing rates among pregnant women in various countries remain suboptimal. Understanding the factors relating to women's willingness to be tested for HIV during pregnancy is critical for developing strategies to increase HIV testing rates among pregnant women. Extensive research points to various factors relating to women's willingness to be tested for HIV during pregnancy, and various recommendations aimed at improving testing rates among pregnant women have been suggested based on the research. In light of the goals set by the United Nations to reduce the rate of infants infected with HIV, it is necessary to summarize what is currently known regarding factors related to women's willingness to be tested for HIV during pregnancy. The purpose of this review is therefore to examine factors related to women's willingness to be tested for HIV during pregnancy, and to summarize recommendations for practice and further research.

Regulation of the cell fate by DNA damage and hypoxia

In order to provide the means for the design of novel rational anti-cancer drug therapies research efforts are concentrated on unravelling the molecular circuits which induce programmed cell death and block proliferation of cancer cells.Modern therapeutic strategies are based on the understanding of the complexity of physiological functions such as differentiation,development,immune responses,cell-cycle arrest,DNA damage repair,apoptosis,autophagy,energy metabolism,and senescence.It has become evident that this knowledge will provide the means to target the components of the pathways involved in these processes in a specific and selective manner thus paving the way for the development of effective and personalised anti-cancer therapies.Transcription is a crucial cellular process that regulates a multitude of physiological functions,which are essential in disease progression and cellular response to therapy.Transcription factors such as the p53 tumor suppressor and the hypoxia-inducible factor-α(HIF-α) are key players in carcinogenesis and cellular response to cancer therapies.Both of these transcription factors regulate gene expression of genes involved in cell death and proliferation,in some cases cooperating towards producing the same outcome and in some others mediating opposing effects.It is thus apparent that fine tuning of the activity of these transcription factors is essential to determine the cellular response to therapeutic regimens,in other words whether tumor cells will commit to apoptosis or evade engagement with the anti-proliferative effects of drugs leading to drug resistance.Our observations support the notion that the functional crosstalk between HIF-1α and p53 pathways and thus the fine tuning of their transcriptional activity is mediated by cofactors shared between the two transcription factors such as components of the p300 co-activator multiprotein complex.In particular,there is evidence to suggest that differential composition of the co-modulatory protein complexes associated with p53 and HIF-la under diverse types of stress conditions differentially regulate the expression of distinct subsets of p53 and HIF-la target genes involved in processes such as cell cycle arrest,apoptosis,chronic inflammation,and cellular energy metabolism thereby determining the cellular fate under particular types of microenvironmental stress.

Fuzzy Logic for Solving an Optimal Control Problem of Hypoxemic Hypoxia Tissue Blood Carbon Dioxide Exchange during Physical Activity

This paper aims at using of an approach integrating the fuzzy logic strategy for hypoxemic hypoxia tissue blood carbon dioxide human optimal control problem. To test the efficiency of this strategy, the authors propose a numerical comparison with the direct method by taking the values of determinant parameters of cardiovascular-respiratory system for a 30 years old woman in jogging as her regular physical activity. The results are in good agreement with experimental data.

Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.

First Trimester Pregnancy Loss May Temporary Reduce the Ovarian Response during the Subsequent IVF Cycle

The aim of this study was to compare the in vitro fertilization (IVF) cycles ended by miscarriage with subsequent IVF cycles in relation to various IVF cycle parameters and pregnancy termination modalities. Comparison of pre-miscarriage to post-miscarriage IVF cycles parameters demonstrated that lower peak E2 levels (1087 ± 593 versus 1237 ± 676 pg/ml, respectively;p p p p p p < 0.05), and an increase in the conception rate (34.7% versus 42.2%, respectively) at the second post-miscarriage IVF cycle.

Retinal Vessels Diameter Changes during Pregnancy in Type 1 Diabetes

Objective: Investigate how pregnancy-induced hormonal and hemodynamic changes affect retinal vessels caliber dynamic and the course of diabetic retinopathy. Methods: Retinopathy grading and vessel diameter measurement using digital fundus photographs in women with diabetes type 1 taken no more than one year before conception, during week 10 and/or 22, week 34, and within one year after delivery. Calibers were measured using a custom-developed semi-automated computer algorithm which identified the six largest arteries and six largest veins and calculated the central retinal artery equivalent (CRAE) and central vein equivalent (CRVE) diameters. Glycemic control was assessed quarterly by HbA1c. Systolic and diastolic blood pressure was assessed at week 10, 22 and 34. Results: Photographs at baseline, weeks 10, 22, 34 and after delivery were available in 28 patients, of whom 24 did not progress in retinopathy. For those whose level of retinopathy remained stable CRAE constricted from 138.80 ± 21.27 μm at baseline to 129.88 ± 13.97 μm at week 10 (p = 0.0379) CRVE constricted from 195.16 ± 24.98 μm at baseline to 185.97 ± 21.96 μm at week 10 (p = 0.0400). The patients with retinopathy progression had a CRAE of 131.67 ± 13.37 μm at baseline and 132.08 ± 11.07 μm at week 10 (p = 0.34) while CRVE was 195.33 ± 24.92 μm at baseline and 204.27 ± 10.18 μm at week 10 (p = 0.16). Progressors had higher blood pressures at week 10. Conclusion: Retinal vessels constricted between prepregnancy and first trimester in women who did not experience diabetic retinopathy progression. The study suggests that the vessels constriction seen in early pregnancy contributes to reduce the risk of gestational microvascular complications and progression of diabetes in the eye.

Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats

Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

Systematic review of safety and efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography during pregnancy including studies of radiation-free therapeutic endoscopic-retrograde-cholangiopancreatography

AIM To systematically review safety/efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography(ERCP) performed during pregnancy, considering fetal viability, fetal teratogenicity, premature delivery, and future postpartum development of the infant.METHODS Systematic computerized literature search performed using PubMed with the key words "ERCP" and "pregnancy". Two clinicians independently reviewed the literature, and decided on which articles to incorporate in this review based on consensus and preassigned priorities. Large clinical trials, meta-analyses, systematic reviews, and controlled trials were assigned higher priority than review articles or small clinical series, and individual case reports were assigned lowest priority. Dr. Cappell has formal training and considerable experience in conducting systematic reviews, with 4 published systematic reviews in peer-reviewed journals indexed in PubM ed during the last 2 years, and with a PhD in neurophysiology that involved 5 years of training and research in biomedical statistics.RESULTS Advances in imaging modalities, including abdominal ultrasound, MRCP, and endoscopic ultrasound, have generally obviated the need for diagnostic ERCP in nonpregnant and pregnant patients. Clinical experience with performing ERCP during pregnancy is burgeoning, with > 500 cases of therapeutic ERCP reported in the literature, aside from a national registry study of 58 patients. These studies show that therapeutic ERCP has a very high rate of technical success in clearing the bile duct of gallstones, and has a relatively low and acceptable rate of maternal and fetal complications. The great majority of births after therapeutic ERCP are full-term, have normal birth weights, and are healthy. A recent trend is performing ERCP without radiation to eliminate radiation teratogenicity. Systematic literature review reveals 147 cases of ERCP without fluoroscopy in 8 clinical series. These studies demonstrate extremely high technical success in endoscopically removing choledocholithiasis, favorable maternal outcomes with rare maternal ERCP complications, and excellent fetal outcomes. ERCP without fluoroscopy generally confirms proper biliary cannulation by aspiration of yellow bile per sphincterotome or leakage of yellow bile around an inserted guide-wire.CONCLUSION This systematic literature review reveals ERCP is relatively safe and efficacious during pregnancy, with relatively favorable maternal and fetal outcomes after ERCP. Recommendations are provided about ERCP indications, special ERCP techniques during pregnancy, and prospects for future research.

Mechanism of the decreased food consumption and weight gain in rats following consumption of aqueous extract of the calyx of Hibiscus sabdariffa during pregnancy

Objective:To investigate the possible mechanisms of the decreasing fluid and food consumption following Hibiscus sabdariffa(HS) consumption.Methods:On the 1st day of pregnancy,rats were randomly divided into three groups with six animals per each group.One group was given tap water,one was given with extract at 0.6 g/100 mL while the third group was given with extract at 1.8 g/100 mL as their drinking solution.All groups received normal rat chow and drinking solution ad libitum.Fluid& food intake and weight were measured daily throughout pregnancy and Na^+ concentration in plasma was determined on the 18th day of pregnancy.Results:Results showed decreased fluid and food consumption,decreased weight gain and increased sodium ion concentration in plasma of rats with HS extract compared with the control group.Conclusions: Consumption of aqueous extract of the calyx of HS during pregnancy decreases food consumption and weight gain through mechanisms that may depend on Na^+ in HS content and elevating Na^+ concentration.

Successful repair of acute type A aortic dissection during pregnancy at 16th gestational week with maternal and fetal survival: A case report and review of the literature

BACKGROUND Aortic dissection during pregnancy is a rare but life-threatening event for mothers and fetuses. It often occurs in the third trimester of pregnancy and the postpartum period. Most patients have connective tissue diseases such as Marfan syndrome. Thus, the successful repair of a sporadic aortic dissection with maternal and fetal survival in the early second trimester is extremely rare. CASE SUMMARY A 28-year-old woman without Marfan syndrome presented with chest pain at the 16th gestational week. Aortic computed tomographic angiography confirmed an acute type A aortic dissection (TAAD) with aortic arch and descending aorta involvement. Preoperative fetal ultrasound confirmed that the fetus was stable in the uterus. The patient underwent total arch replacement with a frozen elephant trunk using moderate hypothermic circulatory arrest with the fetus in situ. The patient recovered uneventfully and continued to be pregnant after discharge. At the 38^th gestational week, she delivered a healthy female infant by cesarean section. After 2.5 years of follow-up, the patient is uneventful and the child’s development is normal. CONCLUSION A fetus in the second trimester may have a high possibility of survival and healthy growth after aortic arch surgery.

Effects of estrogen on CD4^+ CD25^+ regulatory T cell in peripheral blood during pregnancy

Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.

Hydrogen Peroxide Alleviates Hypoxia during Imbibition and Germination of Bean Seeds (<i>Phaseolus vulgaris</i>L.)

Bean seeds (Phaseolus vulgaris L. cv. Tendergreen) were imbibed in water to examine the effects of hypoxia during imbibition and subsequent germination. Hypoxic conditions occurred when seeds were imbibed in water for 24 h or longer and resulted in severe reduction of hypocotyl elongation and stem growth during subsequent germination under non-limiting oxygen conditions. Under continued hypoxic conditions, bean seeds failed to germinate, however, this was reversed in the presence of hydrogen peroxide (20 mM) in the medium. Furthermore, imbibition of seeds in the presence of hydrogen peroxide overcame the adverse hypoxic effects on hypocotyl elongation and stem growth. Exogenous hydrogen peroxide increased the dissolved oxygen levels in the germinating medium, and catalase and transition metal ions such as Fe2+, Cu2+ and Mn2 helped to facilitate the production of oxygen from hydrogen peroxide. In these catalysts, catalase played a major role in the decomposition of hydrogen peroxide as demonstrated by the use of a catalase inhibitor, 3-amino-1, 2, 4-triazole, which reversed the positive effects produced by hydrogen peroxide on germination of seeds under hypoxic conditions. The results show that imbibition is sensitive to oxygen deficits which affect subsequent hypocotyl growth and seedling performance. The adverse effects of hypoxia on germination of bean seeds can be overcome by exogenous hydrogen peroxide.

Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line

The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1—in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Moreover, it is possible that the induction of the expression of retinoblastoma and most retinoblastoma-related genes after knockdown of ERN1 plays an important role in suppression of glioma proliferation.

氨茶碱对慢性低氧所致大鼠肺损伤的抑制作用

目的探讨慢性低氧致气道炎症的作用及氨茶碱抑制气道炎症和肺血管损伤的作用。方法成年雄性Wistar大鼠34只,分为对照组(n=10)、低氧组(n=12,每日低氧7h,共21d)、氨茶碱干预组(n=12,每日低氧前灌胃氨茶碱,100mg/kg),用ELISA法检测血清及BALF中TNFα、IL10、IL13含量。取右下肺行HE染色,行定性分析并测量肺小动脉管径。结果低氧组大鼠血清及BALF中TNFα、IL10、IL13含量显著高于对照组(P<0.01),氨茶碱的干预可显著缓解血清及BALF中TNFα的升高(P<0.01),并使血清IL10、BALF中IL10、IL13含量进一步增加(P<0.05,P<0.01和P<0.01);低氧组大鼠FEV0.3/FVC明显低于对照组(P<0.01),与血清TNFα负相关(P<0.01);氨茶碱干预对低氧大鼠肺小动脉壁厚度和面积的增加有减轻趋势。结论慢性低氧可介导气道炎症,氨茶碱对其有拮抗作用并有改善肺血管重塑的趋势。