Harpin Hpa1 Interacts with Aquaporin PIP1;4 to Promote the Substrate Transport and Photosynthesis in Arabidopsis.

Science.gov (United States)

Li, Liang; Wang, Hao; Gago, Jorge; Cui, Haiying; Qian, Zhengjiang; Kodama, Naomi; Ji, Hongtao; Tian, Shan; Shen, Dan; Chen, Yanjuan; Sun, Fengli; Xia, Zhonglan; Ye, Qing; Sun, Wei; Flexas, Jaume; Dong, Hansong

2015-11-26

Harpin proteins produced by plant-pathogenic Gram-negative bacteria are the venerable player in regulating bacterial virulence and inducing plant growth and defenses. A major gap in these effects is plant sensing linked to cellular responses, and plant sensor for harpin Hpa1 from rice bacterial blight pathogen points to plasma membrane intrinsic protein (PIP). Here we show that Arabidopsis AtPIP1;4 is a plasma membrane sensor of Hpa1 and plays a dual role in plasma membrane permeability of CO2 and H2O. In particular, AtPIP1;4 mediates CO2 transport with a substantial contribute to photosynthesis and further increases this function upon interacting with Hpa1 at the plasma membrane. As a result, leaf photosynthesis rates are increased and the plant growth is enhanced in contrast to the normal process without Hpa1-AtPIP1;4 interaction. Our findings demonstrate the first case that plant sensing of a bacterial harpin protein is connected with photosynthetic physiology to regulate plant growth.

Maternal lipids in pregnancy are associated with increased offspring cortisol reactivity in childhood.

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Mina, Theresia H; Lahti, Marius; Drake, Amanda J; Forbes, Shareen; Denison, Fiona C; Räikkönen, Katri; Norman, Jane E; Reynolds, Rebecca M

2017-09-01

Prenatal programming of hypothalamic-pituitary-adrenal (HPA) axis activity has long term implications for offspring health. Biological mechanisms underlying programming of the offspring HPA axis are poorly understood. We hypothesised that altered maternal metabolism including higher maternal obesity, glucose and lipids are novel programming factors for altered offspring HPA axis activity. Salivary cortisol levels were measured in 54 children aged 3-5 years under experimental conditions (before and after a delay of self-gratification test). Associations of child cortisol responses with maternal obesity in early pregnancy and with fasting glucose, triglycerides, HDL and total cholesterol measured in each pregnancy trimester were tested. Higher levels of maternal triglycerides and total cholesterol throughout pregnancy were associated with increased offspring cortisol reactivity. The associations were independent of maternal obesity and other confounders, suggesting that exposure to maternal lipids could be a biological mechanism of in utero programming of the offspring's HPA axis. Copyright © 2017. Published by Elsevier Ltd.

Hpa1 harpin needs nitroxyl terminus to promote vegetative growth ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Home; Journals; Journal of Biosciences; Volume 39; Issue 1. Hpa1 harpin needs nitroxyl terminus to ... Hansong Dong1 Chunling Zhang1. State Ministry of Education Key Laboratory of Integrated Management of Crop Pathogens and Insect Pests, Nanjing Agricultural University, Jiangsu, 210095, China ...

Transgenic expression of a functional fragment of harpin protein Hpa1 in wheat induces the phloem-based defence against English grain aphid.

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Fu, Maoqiang; Xu, Manyu; Zhou, Ting; Wang, Defu; Tian, Shan; Han, Liping; Dong, Hansong; Zhang, Chunling

2014-04-01

The harpin protein Hpa1 has multiple beneficial effects in plants, promoting plant growth and development, increasing crop yield, and inducing resistance to pathogens and insect pests. For these effects, the 10-40 residue fragment (Hpa1₁₀₋₄₂) isolated from the Hpa1 sequence is 1.3- to 7.5-fold more effective than the full-length protein. Here it is reported that the expression of Hpa1₁₀₋₄₂ under the direction of an insect-induced promoter induces the phloem-based defence to English grain aphid, a dominant species of wheat aphids. The expression of Hpa1₁₀₋₄₂ was found to compromise the colonization preference of aphids on the plant and further inhibit aphid reproduction in leaf colonies. In Hpa1₁₀₋₄₂-expressing wheat lines, moreover, aphid feeding from the phloem was repressed in correlation with the phloem-based defence. This defensive mechanism was shown as enhanced expression of wheat genes encoding phloem lectin proteins (PP2-A1 and PP2-A2) and β-1,3-glucan synthase-like enzymes (GSL2, GSL10, and GSL12). Both PP2-A and β-1,3-glucan formed high molecular mass polymers to block phloem sieve plate pores and therefore impede aphid feeding from the phloem. However, the phloem-based defence was impaired by treating plants with ethylene signalling inhibitors, suggesting the requirement for the ethylene signalling pathway. In addition, if Hpa1₁₀₋₄₂-expressing plants were subjected to attack by a small number of aphids, they newly acquired agriculturally beneficial characters, such as enhanced vegetative growth and increased tiller numbers and grain output values. These results suggest that the defensive and developmental roles of Hpa1₁₀₋₄₂ can be integrated into the germplasm of this agriculturally significant crop.

Transgenic expression of a functional fragment of harpin protein Hpa1 in wheat induces the phloem-based defence against English grain aphid

Science.gov (United States)

Fu, Maoqiang; Xu, Manyu; Zhang, Chunling

2014-01-01

The harpin protein Hpa1 has multiple beneficial effects in plants, promoting plant growth and development, increasing crop yield, and inducing resistance to pathogens and insect pests. For these effects, the 10–40 residue fragment (Hpa110–42) isolated from the Hpa1 sequence is 1.3- to 7.5-fold more effective than the full-length protein. Here it is reported that the expression of Hpa110–42 under the direction of an insect-induced promoter induces the phloem-based defence to English grain aphid, a dominant species of wheat aphids. The expression of Hpa110–42 was found to compromise the colonization preference of aphids on the plant and further inhibit aphid reproduction in leaf colonies. In Hpa110–42-expressing wheat lines, moreover, aphid feeding from the phloem was repressed in correlation with the phloem-based defence. This defensive mechanism was shown as enhanced expression of wheat genes encoding phloem lectin proteins (PP2-A1 and PP2-A2) and β-1,3-glucan synthase-like enzymes (GSL2, GSL10, and GSL12). Both PP2-A and β-1,3-glucan formed high molecular mass polymers to block phloem sieve plate pores and therefore impede aphid feeding from the phloem. However, the phloem-based defence was impaired by treating plants with ethylene signalling inhibitors, suggesting the requirement for the ethylene signalling pathway. In addition, if Hpa110–42-expressing plants were subjected to attack by a small number of aphids, they newly acquired agriculturally beneficial characters, such as enhanced vegetative growth and increased tiller numbers and grain output values. These results suggest that the defensive and developmental roles of Hpa110–42 can be integrated into the germplasm of this agriculturally significant crop. PMID:24676030

Association of maternal anti-HLA class II antibodies with protection from allergy in offspring.

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Jones, M; Jeal, H; Harris, J M; Smith, J D; Rose, M L; Taylor, A N; Cullinan, P

2013-09-01

Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years. Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age. Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order. This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

International Nuclear Information System (INIS)

Ribes, Diana; Fuentes, Silvia; Torrente, Margarita; Colomina, M. Teresa; Domingo, Jose L.

2010-01-01

Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

HPA e Nitro-HPA em Ambiente Semifechado Impactado por Emissão da Combustão de Diesel/Biodiesel (B5

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Fabio Cal Sabino

2015-09-01

Full Text Available Com o objetivo de verificar a presença de HPA e nitro-HPA associados à fração fina do material particulado (MP1,0 e MP2,5 proveniente da combustão de mistura diesel/biodiesel (B5 foram realizadas amostragens diárias no terminal urbano de ônibus de Londrina. Para a determinação do nitro-HPA foi utilizada a espectroscopia de massa acoplado à cromatografia a líquido com ionização química a pressão atmosférica e detector por aprisionamento de íons. Os HPA foram determinados por cromatografia a líquido com detecções por fluorescência e arranjo de fotodiodos. Foram determinados 9 HPA e 1-nitropireno. As concentrações dos HPA de 4 a 6 anéis (FLUT, PIR, CRI, BBF, BKF e DBA foram mais elevadas em comparação aos HPA mais leves (ACE, FLU e ANT. A ∑HPA associado ao MP1,0 correspondeu a 66% do MP2,5 com concentrações que excedem ao recomendado pela OMS. As razões de diagnóstico para pares de HPA e NHPA foram calculadas e seus valores são indicativos das emissões B5. O uso de bicombustíveis no território brasileiro é estimulado e o acompanhamento das alterações nas emissões decorrentes dos processos de combustão é importante e necessário para inferir sobre a alteração da qualidade do ar e o impacto sobre o ambiente.

Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: effects on the structure of the β3 subunit of the αIIbβ3 integrin.

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Vincent Jallu

Full Text Available The HPA-1 alloimmune system carried by the platelet integrin αIIbβ3 is the primary cause of alloimmune thrombocytopenia in Caucasians and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b alleles are defined by a leucine and a proline, respectively, at position 33 in the β3 subunit. Although the structure of αIIbβ3 is available, little is known about structural effects of the L33P substitution and its consequences on immune response and integrin functions.A complete 3D model of the L33-β3 extracellular domain was built and a P33 model was obtained by in silico mutagenesis. We then performed molecular dynamics simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and confirmed higher exposure of residue 33 in the L33 β3 form. These analyses also showed major structural flexibility of all three domains in both forms, but increased flexibility in the P33 β3 form. The L33P substitution does not alter the local structure (residues 33 to 35 of the PSI domain, but modifies the structural equilibrium of the three domains.These results provide a better understanding of HPA-1 epitopes complexity and alloimmunization prevalence of HPA-1a. P33 gain of structure flexibility in the β3 knee may explain the increased adhesion capacity of HPA-1b platelets and the associated thrombotic risk. Our study provides important new insights into the relationship between HPA-1 variants and β3 structure that suggest possible effects on the alloimmune response and platelet function.

Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

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Schechter, Daniel S.; Moser, Dominik A.; Paoloni-Giacobino, Ariane; Stenz, Ludwig; Gex-Fabry, Marianne; Aue, Tatjana; Adouan, Wafae; Cordero, María I.; Suardi, Francesca; Manini, Aurelia; Sancho Rossignol, Ana; Merminod, Gaëlle; Ansermet, Francois; Dayer, Alexandre G.; Rusconi Serpa, Sandra

2015-01-01

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD

Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

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Daniel Scott Schechter

2015-05-01

Full Text Available Prior research has shown that mothers with Interpersonal Violence-related Posttraumatic Stress Disorder (IPV-PTSD report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis, characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress

Plant growth enhancement and associated physiological responses are coregulated by ethylene and gibberellin in response to harpin protein Hpa1.

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Li, Xiaojie; Han, Bing; Xu, Manyu; Han, Liping; Zhao, Yanying; Liu, Zhilan; Dong, Hansong; Zhang, Chunling

2014-04-01

The harpin protein Hpa1 produced by the bacterial blight pathogen of rice induces several growth-promoting responses in plants, activating the ethylene signaling pathway, increasing photosynthesis rates and EXPANSIN (EXP) gene expression levels, and thereby enhancing the vegetative growth. This study was attempted to analyze any mechanistic connections among the above and the role of gibberellin in these responses. Hpa1-induced growth enhancement was evaluated in Arabidopsis, tomato, and rice. And growth-promoting responses were determined mainly as an increase of chlorophyll a/b ratio, which indicates a potential elevation of photosynthesis rates, and enhancements of photosynthesis and EXP expression in the three plant species. In Arabidopsis, Hpa1-induced growth-promoting responses were partially compromised by a defect in ethylene perception or gibberellin biosynthesis. In tomato and rice, compromises of Hpa1-induced growth-promoting responses were caused by a pharmacological treatment with an ethylene perception inhibitor or a gibberellin biosynthesis inhibitor. In the three plant species, moreover, Hpa1-induced growth-promoting responses were significantly impaired, but not totally eliminated, by abolishing ethylene perception or gibberellin synthesis. However, simultaneous nullifications in both ethylene perception and gibberellin biosynthesis almost canceled the full effects of Hpa1 on plant growth, photosynthesis, and EXP2 expression. Theses results suggest that ethylene and gibberellin coregulate Hpa1-induced plant growth enhancement and associated physiological and molecular responses.

Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response.

Science.gov (United States)

Lee, Joonho; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Xu, Yi; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai

2013-10-01

from white blood cells with a whole-genome DASL assay. Proteomic analysis of fetal serum was conducted by two-dimensional difference gel electrophoresis. Differential gene expression was considered significant when there was a P 1.5. (i) The frequency of placental lesions consistent with maternal anti-fetal rejection was higher in patients with preterm deliveries than in those with term deliveries (56% versus 32%; P rejection than those without such lesions (P blood RNA demonstrated differential expression of 128 genes between fetuses with and without lesions associated with maternal anti-fetal rejection; and (vi) comparison of the fetal serum proteome demonstrated 20 proteins whose abundance differed between fetuses with and without lesions associated with maternal anti-fetal rejection. We describe a systemic inflammatory response in human fetuses born to mothers with evidence of maternal anti-fetal rejection. The transcriptome and proteome of this novel type of fetal inflammatory response were different from that of FIRS type I (which is associated with acute infection/inflammation). Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

Absence of hemolytic disease of fetus and newborn despite maternal high-titer IgG anti-Ku.

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Kakaiya, R M; Whaley, A; Howard-Menk, C; Rami, J; Papari, M; Campbell-Lee, S; Malecki, Z

2010-01-01

Anti-Ku seen in K(o) (Kell-null) individuals has previously been shown to cause severe hemolytic transfusion reactions. Maternal anti-Ku can cause none or moderate to severe hemolytic disease of the fetus and newborn (HDFN). In two of four previously described HDFN cases, intrauterine transfusions were required because of severe anemia. We report a case in which maternal anti-Ku did not cause HDFN. Standard serologic methods were used for RBC antibody screening and identification, adsorption and elution of RBC antibodies, and antigen typing. A gravida 3, para 3 (G3P3) woman was first evaluated in 2006 and was found to have an IgG RBC antibody that reacted against all panel RBCs in the anti-human globulin phase. A panel of RBCs treated with DTT did not react with the antibody. The antibody failed to react with one example of K(o) RBCs. The patient’s RBCs typed negative for the following Kell blood group antigens: KEL1, KEL2, KEL3, KEL4, KEL6, KEL7, KEL11, KEL13, and KEL18. These results established the presence of anti-Ku in maternal serum. The newborn was group A, D+ and required phototherapy for hyperbilirubinemia, but did not require transfusion. The woman was seen again in January 2010 during the third trimester (G4P3). At this time, anti-Ku titer was 256. She delivered a healthy group O, D+ baby boy at 37 weeks' gestation. Cord RBCs were 4+ for IgG by DAT. An eluate reacted with all RBCs tested, but did not react when tested against a panel of DTT-treated RBCs. K(o) phenotype is rare to begin with, and the maternal anti-Ku formation may require more than one pregnancy. Therefore, cases that can be evaluated for anti-Ku–related HDFN are rare. Our case contributes to serologic and clinical aspects of such rare cases.

Few long-term consequences after prolonged maternal separation in female Wistar rats.

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Stina Lundberg

Full Text Available Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to study the long-term effects of different early-life rearing conditions on adult behavior, HPA axis activity and long-term voluntary alcohol intake in female rats. Litters were subjected to 15 min (MS15 or 360 min (MS360 of daily maternal separation during postnatal day 1-21. In adulthood, the behavioral profiles were investigated using the multivariate concentric square field™ (MCSF test or examined for HPA axis reactivity by cat-odor exposure with subsequent characterization of voluntary alcohol intake and associated changes in HPA axis activity. Adult female MS360 offspring showed mostly no, or only minor, effects on behavior, HPA axis reactivity and long-term alcohol intake relative to MS15. Instead, more pronounced effects were found dependent on changes in the natural hormonal cycle or by the choice of animal supplier. However, changes were revealed in corticosterone load after long-term alcohol access, as females subjected to MS360 had higher concentrations of fecal corticosterone. The present findings are in line with and expand on previous studies on the long-term effects of maternal separation in female rats with regard to behavior, HPA axis activity and voluntary alcohol intake. It can also be a window into further studies detailing how early-life experiences interact with other risk and protective factors to impact the adult phenotype and how possible sex differences play a role.

[Foetal/neonatal alloimmune thrombocytopenia. A review and case report].

Science.gov (United States)

Rodríguez Wilhelmi, P; Aranguren, A; Muñiz, E; Aranburu, E; Ezpeleta, I; Ardanaz, M F; Ayape, M L

2008-01-01

Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnancies led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening.

Contemporary management of neonatal alloimmune thrombocytopenia: good outcomes in the intravenous immunoglobulin era: results from the Australian neonatal alloimmune thrombocytopenia registry.

Science.gov (United States)

Crighton, Gemma L; Scarborough, Ri; McQuilten, Zoe K; Phillips, Louise E; Savoia, Helen F; Williams, Bronwyn; Holdsworth, Rhonda; Henry, Amanda; Wood, Erica M; Cole, Stephen A

2017-10-01

To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry. Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected. This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial.

Maternally derived anti-fibroblast growth factor 23 antibody as new tool to reduce phosphorus requirement of chicks.

Science.gov (United States)

Ren, Zhouzheng; Bütz, Daniel E; Sand, Jordan M; Cook, Mark E

2017-04-01

Novel means to reduce phosphate input into poultry feeds and increase its retention would preserve world phosphate reserves and reduce environmental impact of poultry production. Here we show that a maternally derived antibody to a fibroblast growth factor-23 (FGF-23) peptide (GMNPPPYS) alleviated phosphorus deficiency in chicks fed low non-phytate phosphorus (nPP) diets. White Leghorn laying hens were vaccinated with either an adjuvant control or the synthetic FGF-23 peptide, and chicks with control or anti-FGF-23 maternal antibodies were fed a diet containing either 0.13 or 0.45% nPP (experiment 1), and 0.20 or 0.45% nPP (experiment 2) for 14 d. In both experiments, decreasing nPP from 0.45 to 0.13 or 0.20% decreased BW gain, G:F, excreta phosphorus, plasma phosphate, and plasma FGF-23 at all time periods examined (nPP main effect, P posture scores (d 7, 14) and bone lesion scores (d 14) decreased and plasma phosphate (d 14) increased in anti-FGF-23 chicks fed 0.13% nPP, compared to those with control antibody on the same diet (P < 0.05). In experiment 2, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and plasma phosphate (d 14) and 1,25(OH)2D3 (d 14) levels, compared to chicks with control antibody (antibody main effect, P < 0.05). BW gain and G:F were increased in chicks with anti-FGF-23 antibody fed 0.20% nPP, compared to control antibody chicks on the same diet, at all time periods examined (P < 0.05). In conclusion, maternally-derived anti-FGF-23 antibody increased phosphorus retention in chicks fed diets containing either 0.13 or 0.20% nPP and thereby, reduced signs of phosphorus deficiency. © 2016 Poultry Science Association Inc.

Maternal undernutrition and fetal developmental programming of obesity: the glucocorticoid connection.

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Correia-Branco, Ana; Keating, Elisa; Martel, Fátima

2015-02-01

An adequate maternal nutrition during pregnancy is crucial for the health outcome of offspring in adulthood. Maternal undernutrition during critical periods of fetal development can program the fetus for metabolic syndrome (MetS) later in life, especially when postnatally challenged with a hypernutritive diet. Adipogenesis, which begins in utero and accelerates in neonatal life, is a major candidate for developmental programming. During fetal development, the hypothalamic-pituitary-adrenal (HPA) axis is extremely susceptible to programming, and the HPA tone is increased throughout life in undernourished conditions. As a consequence, an alteration in the expression and function of glucocorticoid (GC) receptors and of the major GC regulatory enzymes (11β-hydroxysteroid dehydrogenase 1 and -2) occurs. In this review, we will give insights into the role of maternoplacental adverse interactions under the specific context of maternal undernutrition, for later-in-life MetS development, with a special emphasis on the role of GCs. © The Author(s) 2014.

Maternal intimate partner violence exposure, child cortisol reactivity and child asthma.

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Bair-Merritt, Megan H; Voegtline, Kristin; Ghazarian, Sharon R; Granger, Douglas A; Blair, Clancy; Johnson, Sara B

2015-10-01

Psychosocial stressors like intimate partner violence (IPV) exposure are associated with increased risk of childhood asthma. Longitudinal studies have not investigated the role of hypothalamic-pituitary-adrenal (HPA) axis reactivity (and associated alterations in cortisol release) in the child IPV exposure-asthma association. We sought to investigate this association, and to assess whether this relationship differs by child HPA reactivity. This secondary analysis used longitudinal cohort data from the Family Life Project. Participants included 1,292 low-income children and mothers; maternal interview and child biomarker data, including maternal report of IPV and child asthma, and child salivary cortisol obtained with validated stress reactivity paradigms, were collected when the child was 7, 15, 24, 35, and 48 months. Using structural equation modeling, maternal IPV when the child was 7 months of age predicted subsequent reports of childhood asthma (B=0.18, p=.002). This association differed according to the child's HPA reactivity status, with IPV exposed children who were HPA reactors at 7 and 15 months of age--defined as a ≥10% increase in cortisol level twenty minutes post peak arousal during the challenge tasks and a raw increase of at least .02μg/dl--being significantly at risk for asthma (7 months: B=0.17, p=.02; 15 months: B=0.17, p=.02). Our findings provide support that children who are physiologically reactive are the most vulnerable to adverse health outcomes when faced with environmental stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gestational cortisol and social play shape development of marmosets' HPA functioning and behavioral responses to stressors.

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Mustoe, Aaryn C; Taylor, Jack H; Birnie, Andrew K; Huffman, Michelle C; French, Jeffrey A

2014-09-01

Both gestational cortisol exposure (GCE) and variability in postnatal environments can shape the later-life behavioral and endocrine outcomes of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the influence of GCE and social play on HPA functioning in developing marmosets. Maternal urinary cortisol samples were collected across pregnancy to determine GCE for 28 marmoset offspring (19 litters). We administered a social separation stressor to offspring at 6, 12, and 18 months of age, during which we collected urinary cortisol samples and behavioral observations. Increased GCE was associated with increased basal cortisol levels and cortisol reactivity, but the strength of this relationship decreased across age. Increased social play was associated with decreased basal cortisol levels and a marginally greater reduction in cortisol reactivity as offspring aged, regardless of offspring GCE. Thus, GCE is associated with HPA functioning, but socially enriching postnatal environments can alter the effects associated with increased fetal exposure to glucocorticoids. © 2014 Wiley Periodicals, Inc.

Maternal intraguild predation risk affects offspring anti-predator behavior and learning in mites

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Seiter, Michael; Schausberger, Peter

2015-01-01

Predation risk is a strong selective force shaping prey morphology, life history and behavior. Anti-predator behaviors may be innate, learned or both but little is known about the transgenerational behavioral effects of maternally experienced predation risk. We examined intraguild predation (IGP) risk-induced maternal effects on offspring anti-predator behavior, including learning, in the predatory mite Phytoseiulus persimilis. We exposed predatory mite mothers during egg production to presence or absence of the IG predator Amblyseius andersoni and assessed whether maternal stress affects the anti-predator behavior, including larval learning ability, of their offspring as protonymphs. Protonymphs emerging from stressed or unstressed mothers, and having experienced IGP risk as larvae or not, were subjected to choice situations with and without IG predator traces. Predator-experienced protonymphs from stressed mothers were the least active and acted the boldest in site choice towards predator cues. We argue that the attenuated response of the protonymphs to predator traces alone represents optimized risk management because no immediate risk existed. Such behavioral adjustment could reduce the inherent fitness costs of anti-predator behaviors. Overall, our study suggests that P. persimilis mothers experiencing IGP risk may prime their offspring to behave more optimally in IGP environments. PMID:26449645

硫糖铝在体外对抗幽门螺杆菌HpaA IgY的保护作用评价%Evaluation on Protective Effects of Sucralfate on Anti-H.pylori HpaA IgY in Vitro

Institute of Scientific and Technical Information of China (English)

邓西川; 黄伟; 戴维; 胡晓莉; 沈旭东; 杨致邦

2011-01-01

目的 评价硫糖铝对HpaAIgY的保护作用,为制备IgY口服制剂奠定基础.方法 大量诱导工程菌DH5α-HpaA-pQE30,制备纯化的重组蛋白HpaA.以HpaA为抗原接种洛曼母鸡,制备纯化的IgY.在不同pH值,舍不同浓度胃蛋白酶的HpaAIgY液中加入不同浓度的硫糖铝;将IgY液反复冻融;以ELISA法测定HpaAIgY的剩余抗体活性(AR/AC).结果 在pH1.5条件下,60%硫糖铝可使IgY抗体剩余活性维持65.8%;在pH 2.0条件下,舍30%硫糖铝的IgY可使抗体活性维持85.4%,含50%硫糖铝的IgY可完全维持抗体活性.在pH 3.0条件下,含30%硫糖铝的IgY可使抗体活性维持87.3%,而含40%以上硫糖铝的IgY几乎可完全维持抗体活性.在胃蛋白酶浓度0.02mg/mL条件下,当含10%、30%、50%硫糖铝IgY的剩余活性,在pH值2.0时,分别为62.8%、71.6%、82.5%;在pH值3.0时,分别为75.6%、87.4%、94.5%;反复冻融后,含10%硫糖铝的IgY可使抗体活性提高到70.6%,含30%硫糖铝可使IgY的抗体活性提高到82.7%,50%硫糖铝可提高到89.3%.结论 30%以上的硫糖铝可增强VacAIgY对低pH和胃蛋白酶的耐受能力,抗冻融能力,是较理想的IgY保护剂.

Toddlers' bias to look at average versus obese figures relates to maternal anti-fat prejudice.

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Ruffman, Ted; O'Brien, Kerry S; Taumoepeau, Mele; Latner, Janet D; Hunter, John A

2016-02-01

Anti-fat prejudice (weight bias, obesity stigma) is strong, prevalent, and increasing in adults and is associated with negative outcomes for those with obesity. However, it is unknown how early in life this prejudice forms and the reasons for its development. We examined whether infants and toddlers might display an anti-fat bias and, if so, whether it was influenced by maternal anti-fat attitudes through a process of social learning. Mother-child dyads (N=70) split into four age groups participated in a preferential looking paradigm whereby children were presented with 10 pairs of average and obese human figures in random order, and their viewing times (preferential looking) for the figures were measured. Mothers' anti-fat prejudice and education were measured along with mothers' and fathers' body mass index (BMI) and children's television viewing time. We found that older infants (M=11months) had a bias for looking at the obese figures, whereas older toddlers (M=32months) instead preferred looking at the average-sized figures. Furthermore, older toddlers' preferential looking was correlated significantly with maternal anti-fat attitudes. Parental BMI, education, and children's television viewing time were unrelated to preferential looking. Looking times might signal a precursor to explicit fat prejudice socialized via maternal anti-fat attitudes. Copyright © 2015 Elsevier Inc. All rights reserved.

Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

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Xin eDu

2015-03-01

Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

Simultaneous genotyping of HPA-17w to -21w by PCR-SSP in Chinese Cantonese.

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Zhou, Haojie; Ding, Haoqiang; Chen, Yangkai; Li, Xiaofan; Ye, Xin; Nie, Yongmei

2015-01-01

Studies have reported the polymorphism of human platelet antigen (HPA)-17w, -18w, -19w, -20w, and -21w. However, the distribution of these five antigens in Chinese Cantonese is still unknown. In this study, we designed new sequence-specific primers for HPA-19w to -21w and used published primers for HPA-17w and -18w to develop a polymerase chain reaction with the sequence-specific primers (PCR-SSP) method for simultaneously genotyping HPA-17w to -21w. A total of 820 unrelated Cantonese apheresis platelet donors in Guangzhou were involved in this study. Among the five HPAs, complete a/a homozygosity was observed for HPA-17w to -20w with an allele frequency of 1.0000. For HPA-21w, nine individuals (9/820, 1.10%) were found to be HPA-21a/bw heterozygous and the allele frequencies of HPA-21a and HPA-21bw were 0.9945 (1631/1640) and 0.0055 (9/1640), respectively. The reliability of the PCR-SSP method was determined by comparing with the genotyping results by DNA sequencing, and no inconsistencies were observed between the two methods. This study provides a reliable PCR-SSP method for simultaneously genotyping HPA-17w to -21w and could improve HPA-matched platelet transfusion in Chinese Cantonese.

The Dublin Declaration on Maternal Health Care and Anti-Abortion Activism

Science.gov (United States)

2017-01-01

Abstract The Dublin Declaration on Maternal Healthcare—issued by self-declared pro-life activists in Ireland in 2012—states unequivocally that abortion is never medically necessary, even to save the life of a pregnant woman. This article examines the influence of the Dublin Declaration on abortion politics in Latin America, especially El Salvador and Chile, where it has recently been used in pro-life organizing to cast doubt on the notion that legalizing abortion will reduce maternal mortality. Its framers argue that legalizing abortion will not improve maternal mortality rates, but reproductive rights advocates respond that the Dublin Declaration is junk science designed to preserve the world’s most restrictive abortion laws. Analyzing the strategy and impact of the Dublin Declaration brings to light one of the tactics used in anti-abortion organizing. PMID:28630540

Neonatal pain and reduced maternal care: Early-life stressors interacting to impact brain and behavioral development.

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Mooney-Leber, Sean M; Brummelte, Susanne

2017-02-07

Advances in neonatal intensive care units (NICUs) have drastically increased the survival chances of preterm infants. However, preterm infants are still exposed to a wide range of stressors during their stay in the NICU, which include painful procedures and reduced maternal contact. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, in response to these stressors during this critical period of brain development, has been associated with many acute and long-term adverse biobehavioral outcomes. Recent research has shown that Kangaroo care, a non-pharmacological analgesic based on increased skin-to-skin contact between the neonate and the mother, negates the adverse outcomes associated with neonatal pain and reduced maternal care, however the biological mechanism remains widely unknown. This review summarizes findings from both human and rodent literature investigating neonatal pain and reduced maternal care independently, primarily focusing on the role of the HPA axis and biobehavioral outcomes. The physiological and positive outcomes of Kangaroo care will also be discussed in terms of how dampening of the HPA axis response to neonatal pain and increased maternal care may account for positive outcomes associated with Kangaroo care. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Fluorescence Imaging of Streptococcus pneumoniae with the Helix pomatia agglutinin (HPA As a Potential, Rapid Diagnostic Tool

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Mirian Domenech

2017-07-01

Full Text Available Streptococcus pneumoniae is a common human pathogen and a major causal agent of life-threatening infections that can either be respiratory or non-respiratory. It is well known that the Helix pomatia (edible snail agglutinin (HPA lectin shows specificity for terminal αGalNAc residues present, among other locations, in the Forssman pentasaccharide (αGalNAc1→3βGalNAc1→3αGal1→4βGal1→4βGlc. Based on experiments involving choline-independent mutants and different growth conditions, we propose here that HPA recognizes the αGalNAc terminal residues of the cell wall teichoic and lipoteichoic acids of S. pneumoniae. In addition, experimental evidence showing that pneumococci can be specifically labeled with HPA when growing as planktonic cultures as well as in mixed biofilms of S. pneumoniae and Haemophilus influenzae has been obtained. It should be underlined that pneumococci were HPA-labeled despite of the presence of a capsule. Although some non-pneumococcal species also bind the agglutinin, HPA-binding combined with fluorescence microscopy constitutes a suitable tool for identifying S. pneumoniae and, if used in conjunction with Gram staining and/or other suitable technique like antigen detection, it may potentially facilitate a fast and accurate diagnosis of pneumococcal infections.

Broadband S-band class E HPA

NARCIS (Netherlands)

Wanum, M.; van Dijk, R.; de Hek, A.P.; van Vliet, Frank Edward

2009-01-01

A broadband class E High Power Amplifier (HPA) is presented. This HPA is designed to operate at S-band (2.75 to 3.75 GHz). A power added efficiency of 50% is obtained for the two stage amplifier with an output power of 35.5 dBm on a chip area of 5.25 times 2.8 mm2.

Plant growth enhancement and associated physiological responses are coregulated by ethylene and gibberellin in response to harpin protein Hpa1

OpenAIRE

Li, Xiaojie; Han, Bing; Xu, Manyu; Han, Liping; Zhao, Yanying; Liu, Zhilan; Dong, Hansong; Zhang, Chunling

2014-01-01

The harpin protein Hpa1 produced by the bacterial blight pathogen of rice induces several growth-promoting responses in plants, activating the ethylene signaling pathway, increasing photosynthesis rates and EXPANSIN (EXP) gene expression levels, and thereby enhancing the vegetative growth. This study was attempted to analyze any mechanistic connections among the above and the role of gibberellin in these responses. Hpa1-induced growth enhancement was evaluated in Arabidopsis, tomato, and rice...

Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in offspring.

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Knaepen, Liesbeth; Pawluski, Jodi L; Patijn, Jacob; van Kleef, Maarten; Tibboel, Dick; Joosten, Elbert A

2014-07-01

It has been estimated that 20% of pregnant women are facing perinatal stress and depression. Perinatal maternal stress has been shown to increase pain sensitivity in offspring. For the treatment of their depressive symptoms, pregnant women are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). Since the descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure has been shown to affect pain sensitivity in offspring. In the present review, we summarize experimental and clinical evidence for the effect of perinatal maternal stress and SSRI exposure on pain sensitivity in offspring. Both experimental and clinical studies show the effect of perinatal maternal stress on regulation of the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory system. Alterations in these two systems likely underlie long-term alterations in the development of pain sensitivity. This review sheds light on the effect of perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity, in relation to the developing HPA system and 5-HT signaling. © 2013 Wiley Periodicals, Inc.

A case report of neonatal alloimmune thrombocytopenic purpura: the importance of correct diagnosis for future pregnancies

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Rita Fontão-Wendel

Full Text Available CONTEXT: Neonatal alloimmune thrombocytopenic purpura (NAITP is a neonatal disorder characterized by maternal alloimmunization against fetal platelet antigens inherited from the father. Intracranial hemorrhage leading to death or permanent neurological disability may occur in the fetus. CASE REPORT: A healthy 30-year-old woman gave birth to her first baby by cesarean after an uneventful 36-week pregnancy. Ten hours after birth, the infant presented severe petechiae, with platelet count of 8 x 10³/µl. The mother’s platelet count was normal (180 x 10³/µl. The infant received intravenous immunoglobulin and was discharged 18 days later, with platelet count of 100 x 10³/µl. The cause of thrombocytopenia was not elucidated at that time. One year later, the infant died of neuroblastoma. Since the parents wanted another child, they were referred for investigation of this thrombocytopenia. Platelet genotyping and platelet antibody screening were performed, showing total HPA-1 system mismatch between mother (HPA-1b1b and father (HPA-1a1a, with anti-HPA-1a antibodies in the mother’s serum. We concluded that the first baby was born with NAITP. Thus, in the second pregnancy, the mother was treated with several infusions of intravenous immunoglobulin. Careful ultrasound monitoring was performed, with normal results for mother and fetus throughout the pregnancy. The second baby was born by cesarean at 39 weeks, presenting 92x10³ platelets/µl six hours after birth. The baby’s platelets were genotyped as HPA-1a1b and the mother’s serum again showed anti-HPA-1a antibodies. No clinical bleeding was observed. Intravenous immunoglobulin therapy was an effective treatment for preventing NAITP in the second baby.

Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

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Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

2017-08-03

Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

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Avent, Neil D

2014-12-01

Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

Impact of maternal undernutrition on the hypothalamic-pituitary-adrenal axis responsiveness in sheep at different ages postnatal.

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Chadio, S E; Kotsampasi, B; Papadomichelakis, G; Deligeorgis, S; Kalogiannis, D; Menegatos, I; Zervas, G

2007-03-01

Epidemiological and experimental data support the hypothesis of 'fetal programming', which proposes that alterations in fetal nutrition and endocrine status lead to permanent adaptations in fetal homeostatic mechanisms, producing long-term changes in physiology and determine susceptibility to later disease. Altered hypothalamic-pituitary-adrenal (HPA) axis function has been proposed to play an important role in programming of disease risk. The aim of the present study was to examine the effects of maternal nutrient restriction imposed during different periods of gestation on the HPA axis function in sheep, at different ages postnatal. Pregnant ewes were fed a 50% nutrient-restricted diet from days 0-30 (group R1, n = 7), or from days 31-100 of gestation (group R2, n = 7) or a control 100% diet throughout pregnancy, (Control, n = 8). Blood samples were collected at 10-day intervals from day 40 of gestation to term. Lambs were born naturally and fed to appetite throughout the study period. At 2, 5.5, and 10 months of age lambs were given an i.v. injection of corticotrophin-releasing hormone (CRH) and blood samples were collected at -15, 0, 15, 30, 60, 120, and 180 min postinjection. Maternal cortisol levels were significantly higher (P < 0.05) in group R1 compared with the other two groups, whereas maternal insulin levels were lower (P < 0.05) in group R2 compared with control. Birth weight of lambs was not affected by the maternal nutritional manipulation. The area under the curve for ACTH and cortisol response to CRH challenge was greater (P < 0.05) in lambs of group R1 at two months of age, whereas no difference was detected at the ages of 5.5 and 10 months. However, significantly higher (P < 0.01) basal cortisol levels were observed in lambs of R1 group at 5.5 months of age. There was no interaction between treatment and sex for both pituitary and adrenal responses to the challenge. A significant sex effect was evident with females responding with higher ACTH and

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

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Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

2016-01-01

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

Successful management of severe hemolytic disease of the fetus due to anti-Jsb using intrauterine transfusions with serial maternal blood donations: a case report and a review of the literature.

Science.gov (United States)

Al Riyami, Arwa Z; Al Salmani, Moza; Al Hashami, Sabria; Al Mahrooqi, Sabah; Al Hinai, Sumaiya; Al Balushi, Halima; Al Riyami, Nihal; Gowri, V; Al Dughaishi, Tamima; Al Hosni, Saif; Al-Khabori, Murtadha; Al-Farsi, Khalil; Al Huneini, Mohammed; Alkindi, Salam

2014-01-01

The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure. © 2013 American Association of Blood Banks.

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

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Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-02-01

Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of maternal separation on dynamics of urocortin 1 and brain-derived neurotrophic factor in the rat non-preganglionic Edinger-Westphal nucleus.

Science.gov (United States)

Gaszner, Balázs; Jensen, Kai-Ole; Farkas, József; Reglodi, Dóra; Csernus, Valér; Roubos, Eric W; Kozicz, Tamás

2009-08-01

Although mood disorders are frequently genetically determined and to some degree gender-dependent, the concept of early life 'programming', implying a relation between perinatal environmental events and adult mood disorders, has recently gained considerable attention. In particular, maternal separation (MS) markedly affects various stress-sensitive brain centers. Therefore, MS is considered as a suitable experimental paradigm to study how early life events affect brain plasticity and, hence, cause psychopathologies like major depression. In adult mammals, the classical hypothalamo-pituitary-adrenal (HPA-) axis and the urocortin 1 (Ucn1)-containing non-preganglionic Edinger-Westphal nucleus (npEW) respond in opposite ways to chronic stressors. This raises the hypothesis that MS, which is known to increase vulnerability for adult mood disorders via the dysregulation of the HPA-axis, will affect npEW dynamics as well. We have tested this hypothesis and, moreover, studied a possible role of brain-derived neurotrophic factor (BDNF) in such npEW plasticity. By triple immunocytochemistry we show that BDNF and Ucn1 coexist in rat npEW-neurons that are c-Fos-positive upon acute stress. Quantitative immunocytochemistry revealed that MS increases the contents of Ucn1 and BDNF in these cells. Furthermore, in males and females, the c-Fos response of npEW-Ucn1 neurons upon restraint stress was blunted in animals with MS history, a phenomenon that was concomitant with dampening of the HPA corticosterone response in females but not in males. Based on these data we suggest that the BDNF-containing npEW-Ucn1 system might be affected by MS in a sex-specific manner. This supports the idea that the npEW would play a role in the appearance of sex differences in the pathogenesis of stress-induced mood disorders.

Association of a variable number of tandem repeats (VNTR) in glycoprotein Ib alpha and HPA-2 alloantigens

NARCIS (Netherlands)

Simsek, S.; Bleeker, P. M.; van der Schoot, C. E.; von dem Borne, A. E.

1994-01-01

The human platelet alloantigen HPA-2(Koa/Kob) system is involved in two clinical syndromes, neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness. We have previously described that the human platelet alloantigens HPA-2a(Kob) and HPA-2b(Koa), are caused by a Thr145Met amino

Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi).

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Birnie, Andrew K; Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A

2013-12-01

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan. Published by Elsevier Ltd.

The signal peptide-like segment of hpaXm is required for its association to the cell wall in transgenic tobacco plants.

Science.gov (United States)

Li, Le; Miao, Weiguo; Liu, Wenbo; Zhang, Shujian

2017-01-01

Harpins, encoded by hrp (hypersensitive response and pathogenicity) genes of Gram-negative plant pathogens, are elicitors of hypersensitive response (HR). HpaXm is a novel harpin-like protein described from cotton leaf blight bacteria, Xanthomonas citri subsp. malvacearum-a synonym of X. campestris pv. malvacearum (Smith 1901-1978). A putative signal peptide (1-MNSLNTQIGANSSFL-15) of hpaXm was predicted in the nitroxyl-terminal (N-terminal)by SignalP (SignalP 3.0 server). Here, we explored the function of the N-terminal leader peptide like segment of hpaXm using transgenic tobacco (Nicotiana tabacum cv. Xanthi nc.). Transgenic tobacco lines expressing the full-length hpaXm and the signal peptide-like segment-deleted mutant hpaXmΔLP were developed using transformation mediated by Agrobacterium tumefaciens. The target genes were confirmed integrated into the tobacco genomes and expressed normally. Using immune colloidal-gold detection technique, hpaXm protein was found to be transferred to the cytoplasm, the cell membrane, and organelles such as chloroplasts, mitochondria, and nucleus, as well as the cell wall. However, the deletion mutant hpaXmΔLP expressed in transgenic tobacco was found unable to cross the membrane to reach the cell wall. Additionally, soluble proteins extracted from plants transformed with hpaXm and hpaXmΔLP were bio-active. Defensive micro-HR induced by the transgene expression of hpaXm and hpaXmΔLP were observed on transgenic tobacco leaves. Disease resistance bioassays to tobacco mosaic virus (TMV) showed that tobacco plants transformed with hpaXm and with hpaXmΔLP exhibited enhanced resistance to TMV. In summary, the N-terminal signal peptide-like segment (1-45 bp) in hpaXm sequence is not necessary for transgene expression, bioactivity of hpaXm and resistance to TMV in transgenic tobacco, but is required for the protein to be translocated to the cell wall.

26 CFR 1.410(a)-9 - Maternity and paternity absence.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Maternity and paternity absence. 1.410(a)-9... Maternity and paternity absence. (a) Elapsed time—(1) Rule. For purposes of applying the rules of § 1.410(a...)(5)(E) and 411(a)(6)(E) (relating to maternity or paternity absence), the severance from service date...

Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

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Wang Jia

2009-11-01

Full Text Available Abstract Background Protein kinase C interacting protein (PKCI/HINT1 is a small protein belonging to the histidine triad (HIT family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Results Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST and the tail suspension (TST tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. Conclusion PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.

Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

DEFF Research Database (Denmark)

Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

2013-01-01

seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

Science.gov (United States)

Jokinen, Jussi; Nordström, Peter

2008-11-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

Optimal beamforming in MIMO systems with HPA nonlinearity

KAUST Repository

Qi, Jian

2010-09-01

In this paper, multiple-input multiple-output (MIMO) transmit beamforming (TB) systems under the consideration of nonlinear high-power amplifiers (HPAs) are investigated. The optimal beamforming scheme, with the optimal beamforming weight vector and combining vector, is proposed for MIMO systems with HPA nonlinearity. The performance of the proposed MIMO beamforming scheme in the presence of HPA nonlinearity is evaluated in terms of average symbol error probability (SEP), outage probability and system capacity, considering transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, namely, parameters of nonlinear HPA, numbers of transmit and receive antennas, and modulation order of phase-shift keying (PSK), on performance. ©2010 IEEE.

Optimal beamforming in MIMO systems with HPA nonlinearity

KAUST Repository

Qi, Jian; Aissa, Sonia

2010-01-01

In this paper, multiple-input multiple-output (MIMO) transmit beamforming (TB) systems under the consideration of nonlinear high-power amplifiers (HPAs) are investigated. The optimal beamforming scheme, with the optimal beamforming weight vector and combining vector, is proposed for MIMO systems with HPA nonlinearity. The performance of the proposed MIMO beamforming scheme in the presence of HPA nonlinearity is evaluated in terms of average symbol error probability (SEP), outage probability and system capacity, considering transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, namely, parameters of nonlinear HPA, numbers of transmit and receive antennas, and modulation order of phase-shift keying (PSK), on performance. ©2010 IEEE.

[Prenatal maternal mnemonic effects on the human neuro-psychic sex: a new proposition from fetus-maternal tolerance-rejection].

Science.gov (United States)

Valenzuela, Carlos Y

2008-12-01

In approximately 15% of homosexual men, their phenotype is associated to the fraternal birth order. Older biological brothers induce in their mothers anti-male factors (antibodies) that interfere the brain maleness development of younger fetuses. This effect is seldom seen in non-right-handed men and is not seen in women. The influence of older siblings is seen in their sex ratio (SR). In contradiction with previous hypothesis, significant heterogeneities of SR have been found among older siblings of males or females, right or non-right-handed and homo or heterosexual individuals. This can only be understood as if the findings among homosexuals were part of a general mechanism of fetus-maternal tolerance-rejection processes of placental mammals. We found, in relation to ABO and Rh systems and sex, that embryos with genes different from those of their mothers, induced better pregnancies and maternal tolerance than embryos similar to their mothers. Assuming that homo or heterosexuality and right or non-right-handedness behave similar to ABO or Rh alleles, the author provides a speculative interpretation of these results. Homosexual women and especially if they are non-right-handed, are preceded by siblings with a high SR (maternal environment with anti-female or pro-male factors); then lesbianism or non-right-handedness may induce tolerance to be a woman in such anti-female environment. Non-right-handedness could induce tolerance for anti-male factors of mothers, thus preventing the production of gays in a pro-male maternal environment, but leading to the production of non-right-handed gays in anti-male maternal environments. Several new hypotheses and interpretations merge from this new proposition. Also, complete sexual orientation could be acquired after birth.

Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

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Jeremy D Coplan

2015-07-01

Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

Science.gov (United States)

Chittiprol, Seetharamaiah; Kumar, Adarsh M; Satishchandra, P; Taranath Shetty, K; Bhimasena Rao, R S; Subbakrishna, D K; Philip, Mariyamma; Satish, K S; Ravi Kumar, H; Kumar, Mahendra

2008-01-01

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls

Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

International Nuclear Information System (INIS)

Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

2009-01-01

Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 μg/kg (females) or 100 or 150 μg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

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Linn S Strandberg

Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

The HPA photon protocol and proposed electron protocol

International Nuclear Information System (INIS)

Pitchford, W.G.

1985-01-01

The Hospital Physicists Association (HPA) photon dosimetry protocol has been produced and was published in 1983. Revised values of some components of Csub(lambda) and refinements introduced into the theory in the last few years have enabled new Csub(lambda) values to be produced. The proposed HPA electron protocol is at present in draft form and will be published shortly. Both protocels are discussed. (Auth.)

EURAMET.M.P-S9: comparison in the negative gauge pressure range -950 to 0 hPa

Science.gov (United States)

Saxholm, S.; Otal, P.; AltintaS, A.; Bermanec, L. G.; Durgut, Y.; Hanrahan, R.; Kocas, I.; Lefkopoulos, A.; Pražák, D.; Sandu, I.; Åetina, J.; Spohr, I.; Steindl, D.; Tammik, K.; Testa, N.

2016-01-01

A comparison in the negative gauge pressure range was arranged in the period 2011 - 2012. A total of 14 laboratories participated in this comparison: BEV (Austria), CMI (Czech Republic), DANIAmet-FORCE (Denmark), EIM (Greece), HMI/FSB-LPM (Croatia), INM (Romania), IPQ (Portugal), LNE (France), MCCAA (Malta), METROSERT (Estonia), MIKES (Finland), MIRS/IMT/LMT (Slovenia), NSAI (Ireland) and UME (Turkey). The project was divided into two loops: Loop1, piloted by MIKES, and Loop2, piloted by LNE. The results of the two loops are reported separately: Loop1 results are presented in this paper. The transfer standard was Beamex MC5 no. 25516865 with internal pressure module INT1C, resolution 0.01 hPa. The nominal pressure range of the INT1C is -1000 hPa to +1000 hPa. The nominal pressure points for the comparison were 0 hPa, -200 hPa, -400 hPa, -600 hPa, -800 hPa and -950 hPa. The reference values and their uncertainties as well as the difference uncertainty between the laboratory results and the reference values were determined from the measurement data by Monte Carlo simulations. Stability uncertainty of the transfer standard was included in the final difference uncertainty. Degrees of equivalences and mutual equivalences between the laboratories were calculated. Each laboratory reported results for all twelve measurement points, which means that there were 168 reported values in total. Some 163 of the 168 values (97 %) agree with the reference values within the expanded uncertainties, with a coverage factor k = 2. Among the laboratories, four different methods were used to determine negative gauge pressure. It is concluded that special attention must be paid to the measurements and methods when measuring negative gauge pressures. There might be a need for a technical guide or a workshop that provides information about details and practices related to the measurements of negative gauge pressure, as well as differences between the different methods. The comparison is

Interlaboratory variation in the detection of HPA-specific alloantibodies and in molecular HPA typing

NARCIS (Netherlands)

Allen, D.; Ouwehand, W. H.; de Haas, M.; Kekomaki, R.; Kaplan, C.; Metcalfe, P.

2007-01-01

Platelet immunology quality assurance exercises have been organized by National Institute for Biological Standards and Control since 1991 and, as of 2006, 35 laboratories participate in the serology section. Molecular human platelet antigen (HPA) typing has been included in the exercises since 1998

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

Science.gov (United States)

Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

2013-01-01

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Glucose-6-phosphate dehydrogenase is required for hpa1xoo (harpin protein fragment)-mediated salt stress tolerance in transgenic arabidopsis thaliana

International Nuclear Information System (INIS)

Sang, S.L.; Xie, L.L.; Cui, X.W.; Wang, Z.Y.

2018-01-01

Harpin induces salicylic acid and abscisic acid signaling in plants under biotic and abiotic stress, respectively. Our previous report showed that the effective harpin fragment Hpa1xoo enhanced H2O2 production and pathogen resistance in a transgenic Arabidopsis mutant. In this study, we examined contents of thiobarbituric acid reactive substance (TBARS), H2O2 and glutathione, and glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and glutathione peroxidase (GPX) enzyme activity in Hpa1xoo-expressing Arabidopsis under salt stress. The results revealed increased amounts of TBARS and H2O2 in wild-type (WT) compared to mutant plants under salt stress conditions. In contrast, increased levels were observed in the mutant under stress-free conditions. Moreover, a higher reduced glutathione (GSH) content and ratio of GSH/oxidized glutathione (GSSG) was observed in mutant compared to WT plants under both stress-free and salt stress conditions. In addition, mutant plants exhibited significantly higher G6PDH, GR and GPX activity than WT plants under salt stress. Suppression of G6PDH activity via 6-aminonicotinamide (6-AN, a specific inhibitor of G6PDH) was partly reversed by L-buthionine-sulfoximine (BSO, a specific inhibitor of GSH regeneration) and aggravated by GSH. Combined with previous reports, these findings suggest that the G6PDH enzyme plays a key role in harpin fragment (Hpa1xoo)-mediated salt stress tolerance in transgenic Arabidopsis. (author)

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Science.gov (United States)

Calis, M; Gökçe, C; Ates, F; Ulker, S; Izgi, H B; Demir, H; Kirnap, M; Sofuoglu, S; Durak, A C; Tutus, A; Kelestimur, F

2004-01-01

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

Science.gov (United States)

Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

2016-08-01

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

Hemolytic disease of the fetus and newborn caused by anti-E

OpenAIRE

Usman, Adiyyatu Sa?idu; Mustaffa, Rapiaah; Ramli, Noraida; Diggi, Sirajo A.

2013-01-01

Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting wit...

Two-way CSI-assisted AF relaying with HPA nonlinearity

KAUST Repository

Qi, Jian

2015-09-11

In this paper, we investigate half-duplex two-way dual-hop channel state information (CSI)-assisted amplify-andforward (AF) relaying in the presence of high-power amplifier (HPA) nonlinearity at relays. The expression for the end-toend signal-to-noise ratio (SNR) is derived as per the modified system model by taking into account the interference caused by relaying scheme and HPA nonlinearity. The system performance of the considered relaying network is evaluated in terms of average symbol error probability (SEP) in Nakagami-m fading channels, by making use of the moment-generating function (MGF) approach. Numerical results are provided and show the effects of several parameters, such as quadrature amplitude modulation (QAM) order, number of relays, HPA parameters, and Nakagami parameter, on performance. © 2015 IEEE.

HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome.

Science.gov (United States)

Martins, Clarissa Silva; Elias, Daniel; Colli, Leandro Machado; Couri, Carlos Eduardo; Souza, Manoel Carlos L A; Moreira, Ayrton C; Foss, Milton C; Elias, Lucila L K; de Castro, Margaret

2017-03-01

Metabolic syndrome (MetS) shares several similarities with hypercortisolism. To evaluate hypothalamic-pituitary-adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls. Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirão Preto Medical School University Hospital. Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In addition, p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα) expression were assessed by quantitative polymerase chain reaction. Plasma and salivary cortisol (nmol/L) after 1-mg DEX were higher in MetS patients compared with controls (PF: 70.2 ± 17.3 vs 37.9 ± 2.6, P = .02, and SF: 4.9 ± 1.7 vs 2.2 ± 0.3, P molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

The relation of maternal job strain and cortisol levels during early pregnancy with body composition later in the 5-year-old child: The ABCD study

NARCIS (Netherlands)

van Dijk, Aimée E.; van Eijsden, Manon; Stronks, Karien; Gemke, Reinoud J. B. J.; Vrijkotte, Tanja G. M.

2012-01-01

Background: Prenatal exposure to maternal stress may program the fetal HPA axis, potentially leading to altered metabolism in later life, associated with adiposity and diabetes. Aims: This association is little studied in humans, and thus we explore whether high maternal job strain during early

The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

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Li-Juan Zhu

Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

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Jokinen, Jussi; Nordström, Peter

2009-07-01

Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

Food availability and maternal immunization affect transfer and persistence of maternal antibodies in nestling pigeons.

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Ahmad Ismail

Full Text Available The ability of mothers to transfer antibodies (Abs to their young and the temporal persistence of maternal Abs in offspring constitute important life-history traits that can impact the evolution of host-parasite interactions. Here, we examined the effects of food availability and parental immunization on the transfer and persistence of maternal antibodies in nestling pigeons (Columba livia. This species can transmit maternal Abs to offspring before hatching through the egg yolk and potentially after hatching through crop milk. However, the role of this postnatal substance in immunity remains elusive. We used a full cross-fostering design to disentangle the effects of food limitation and parental immunization both before and after hatching on the levels and persistence of maternal Abs in chicks. Parents were immunized via injection with keyhole limpet hemocyanin antigens. Using an immunoassay that specifically detected the IgY antibodies that are known to be transmitted via the yolk, we found that the levels of anti-KLH Abs in newly hatched chicks were positively correlated with the levels of anti-KLH Abs in the blood of their biological mothers. However, this correlation was not present between chicks and their foster parents, suggesting limited IgY transfer via crop milk to the chick's bloodstream. Interestingly, biological mothers subjected to food limitation during egg laying transferred significantly fewer specific maternal Abs, which suggests that the transfer of antibodies might be costly for them. In addition, the persistence of maternal Abs in a chick's bloodstream was not affected by food limitation or the foster parents' anti-KLH Ab levels; it was only affected by the initial level of maternal anti-KLH Abs that were present in newly hatched chicks. These results suggest that the maternal transfer of Abs could be costly but that their persistence in an offspring's bloodstream may not necessarily be affected by environmental conditions.

The role of BDNF and HPA axis in the neurobiology of burnout syndrome.

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Onen Sertoz, Ozen; Tolga Binbay, Ibrahim; Koylu, Ersin; Noyan, Aysin; Yildirim, Emre; Elbi Mete, Hayriye

2008-08-01

Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p=0.592; for cortisol level after 1 mg DST, p=0.921), but we did find lowered sBDNF levels in burnout group (88.66+/-18.15 pg/ml) as compared to healthy controls (102.18+/-20.92 pg/ml) and the difference was statistically significant (p=0.005). Logistic Regression Analysis revealed that emotional exhaustion (p=0.05), depersonalization (p=0.005) and depression (p=0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r=-,268, p=0.026), depersonalization (r=-,333, p=0.005) and correlated positively with competence (r=0.293, p=0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r=0.80, p=0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

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G.H. Callejas

2018-03-01

Full Text Available Gastroschisis (GS is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg after the surgical induction of GS (day 18.5 of gestation and compared to controls. Fetuses were divided into 4 groups: 1 control (C; 2 C+CBD (CCBD; 3 gastroschisis (G, and 4 G+CBD (GCBD. On day 21.5 of gestation, the fetuses were harvested and evaluated for: a body weight (BW, intestinal weight (IW, and IW/BW ratio; b histometric analysis of the intestinal wall; c immunohistochemically analysis of inflammation (iNOS and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005, IW and IW/BW ratio: GCBD was smaller than G (P<0.005, GCBD presented lower thickness in all parameters compared to G (P<0.005, iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005. Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

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Ryan, Karen K; Mul, Joram D; Clemmensen, Christoffer

2014-01-01

function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic...... in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were......The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated...

Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

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Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

2012-01-01

Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

Maternal anti-M induced hemolytic disease of newborn followed by prolonged anemia in newborn twins.

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Arora, Satyam; Doda, Veena; Maria, Arti; Kotwal, Urvershi; Goyal, Saurabh

2015-01-01

Allo-anti-M often has an immunoglobulin G (IgG) component but is rarely clinically significant. We report a case of hemolytic disease of the fetus and newborn along with prolonged anemia in newborn twins that persisted for up to 70 days postbirth. The aim was to diagnose and successfully manage hemolytic disease of newborn (HDN) due to maternal alloimmunization. Direct antiglobulin test (DAT), antigen typing, irregular antibody screening and identification were done by polyspecific antihuman globulin cards and standard tube method. At presentation, the newborn twins (T1, T2) had HDN with resultant low reticulocyte count and prolonged anemia, which continued for up to 70 days of life. Blood group of the twins and the mother was O RhD positive. DAT of the both newborns at birth was negative. Anti-M was detected in mothers as well as newborns. Type of antibody in mother was IgG and IgM type whereas in twins it was IgG type only. M antigen negative blood was transfused thrice to twin-1 and twice to twin-2. Recurring reduction of the hematocrit along with low reticulocyte count and normal other cell line indicated a pure red cell aplastic state. Anti-M is capable of causing HDN as well as prolonged anemia (red cell aplasia) due to its ability to destroy the erythroid precursor cells. Newborns with anemia should be evaluated for all the possible causes to establish a diagnosis and its efficient management. Mother should be closely monitored for future pregnancies as well.

Maternal anti-M induced hemolytic disease of newborn followed by prolonged anemia in newborn twins

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Satyam Arora

2015-01-01

Full Text Available Allo-anti-M often has an immunoglobulin G (IgG component but is rarely clinically significant. We report a case of hemolytic disease of the fetus and newborn along with prolonged anemia in newborn twins that persisted for up to 70 days postbirth. The aim was to diagnose and successfully manage hemolytic disease of newborn (HDN due to maternal alloimmunization. Direct antiglobulin test (DAT, antigen typing, irregular antibody screening and identification were done by polyspecific antihuman globulin cards and standard tube method. At presentation, the newborn twins (T1, T2 had HDN with resultant low reticulocyte count and prolonged anemia, which continued for up to 70 days of life. Blood group of the twins and the mother was O RhD positive. DAT of the both newborns at birth was negative. Anti-M was detected in mothers as well as newborns. Type of antibody in mother was IgG and IgM type whereas in twins it was IgG type only. M antigen negative blood was transfused thrice to twin-1 and twice to twin-2. Recurring reduction of the hematocrit along with low reticulocyte count and normal other cell line indicated a pure red cell aplastic state. Anti-M is capable of causing HDN as well as prolonged anemia (red cell aplasia due to its ability to destroy the erythroid precursor cells. Newborns with anemia should be evaluated for all the possible causes to establish a diagnosis and its efficient management. Mother should be closely monitored for future pregnancies as well.

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

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Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

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Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

2013-11-01

Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

Clinically significant hemolytic disease of the newborn secondary to passive transfer of anti-D from maternal RhIG.

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Cohen, Daniel N; Johnson, Mary S; Liang, Wayne H; McDaniel, Heather L; Young, Pampee P

2014-11-01

RhIG is used worldwide to reduce the incidence of alloimmunization to D during pregnancy. We report a case of clinically significant neonatal hemolysis mediated by maternally administered RhIG. A 25-year-old, O-, primigravid mother with a negative antenatal antibody screen delivered a 6-lb 4-oz, blood group A, D+ baby girl at 36.5 weeks' gestation. Prenatal care included a dose of intramuscular RhIG at 28 weeks' gestation. At delivery, the newborn was markedly jaundiced with a total bilirubin of 6.3 mg/dL, which reached more than 20 mg/dL after 6 days. The newborn's lactate dehydrogenase (LDH) was 485 U/L (normal, newborn's direct antiglobulin test (DAT) was positive for immunoglobulin (Ig)G, with an anti-D identified by elution studies. The possibility of hemolytic disease of the newborn (HDN) due to anti-A was considered, but ultimately ruled out by the absence of anti-A1 in the eluate. The newborn's hyperbilirubinemia was adequately managed with phototherapy. Analysis of the mother's plasma 10 days postpartum revealed an anti-D titer of 8. Two months after birth, the child's laboratory studies, DAT, antibody screen, and peripheral smear were unremarkable. In the context of neonatal anemia, elevated LDH, and reticulocytosis, a positive IgG DAT with anti-D identified in the eluate suggests RhIG-mediated HDN. This appears to be a rarely reported event. © 2014 AABB.

Prenatal Maternal Stress and the Risk of Asthma in Children

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Konstantinos Douros

2017-09-01

Full Text Available Emerging evidence indicate that maternal prenatal stress (MPS can result in a range of long-term adverse effects in the offspring. The underlying mechanism of MPS is not fully understood. However, its complexity is emphasized by the number of purportedly involved pathways namely, placental deregulated metabolism of maternal steroids, impaired maturation of fetal HPA axis, imbalanced efflux of commensal bacteria across the placenta, and skewed immune development toward Th2. Fetal programming probably exerts a pivotal role in the end result of the above pathways through the modulation of gene expression. In this review, we highlight the current knowledge from epidemiological and experimental studies regarding the effects of MPS on asthma development in the offspring.

Cerebro-placental ratio and fetal response to maternal extracorporal sFlt-1 removal.

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Weber, Marie L; Schaarschmidt, Wiebke; Thadhani, Ravi; Stepan, Holger

2017-12-11

Preeclampsia (PE) is a serious complication in obstetrics that affects approximately 3-5% of all pregnancies and it constitutes the leading cause of maternal mortality and morbidity worldwide. Although PE appears to be a maternal disease, iatrogenic preterm birth shifts the burden on the neonate after delivery. Impaired throphoblast invasion and differentiation in the first trimester with high placental impedance is considered to be the pathogenetic pathway of early and severe PE. Maternal rise of blood pressure represents the counter-regulation to maintain fetal supply. The excessive release of anti-angiogenics by the preeclamptic placenta creates an angiogenic imbalance leading to endothelial damage and its consequences. This article is protected by copyright. All rights reserved.

Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine.

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Zhiqun Wang

Full Text Available BACKGROUND: Passively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Totally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively. In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10-999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521, respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726, respectively. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B.

HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

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Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

2015-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

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Mello Andrea de Abreu Feijó de

2003-01-01

Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

Associations between HIV, highly active anti-retroviral therapy, and hypertensive disorders of pregnancy among maternal deaths in South Africa 2011-2013.

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Sebitloane, Hannah M; Moodley, Jagidesa; Sartorius, Benn

2017-02-01

To explore potential relationships between HIV and highly active anti-retroviral therapy (HAART), and hypertensive disorders of pregnancy (HDP). A retrospective secondary analysis of maternal-deaths data from the 2011-2013 Saving Mothers Report from South Africa. The incidence of HIV infection amongst individuals who died owing to HDP was determined and comparisons were made based on HIV status and the use of HAART. Among 4452 maternal deaths recorded in the Saving Mothers report, a lower risk of a maternal deaths being due to HDP was observed among women who had HIV infections compared with women who did not have HIV (relative risk [RR] 0.57, 95% confidence interval [CI] 0.51-0.64). Further, reduced odds of death being due to HDP were recorded among women with AIDS not undergoing HAART compared with women with HIV who did not require treatment (RR 0.42, 95% CI 0.3-0.58). Notably, among all women with AIDS, a greater risk of death due to HDP was demonstrated among those who received HAART compared with those who did not (RR 1.15, 95% CI 1.02-1.29). HIV and AIDS were associated with a decreased risk of HDP being the primary cause of death; the use of HAART increased this risk. © 2016 International Federation of Gynecology and Obstetrics.

Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

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Jayanthi eManiam

2014-05-01

Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

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Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

2014-01-01

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

Limited Nesting Stress Alters Maternal Behavior and In Vivo Intestinal Permeability in Male Wistar Pup Rats.

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Nabila Moussaoui

Full Text Available A few studies indicate that limited nesting stress (LNS alters maternal behavior and the hypothalamic pituitary adrenal (HPA axis of dams and offspring in male Sprague Dawley rats. In the present study, we evaluated the impact of LNS on maternal behavior in Wistar rats, and on the HPA axis, glycemia and in vivo intestinal permeability of male and female offspring. Intestinal permeability is known to be elevated during the first week postnatally and influenced by glucocorticoids. Dams and neonatal litters were subjected to LNS or normal nesting conditions (control from days 2 to 10 postnatally. At day 10, blood was collected from pups for determination of glucose and plasma corticosterone by enzyme immunoassay and in vivo intestinal permeability by oral gavage of fluorescein isothiocyanate-dextran 4kDa. Dams exposed to LNS compared to control showed an increase in the percentage of time spent building a nest (118%, self-grooming (69%, and putting the pups back to the nest (167%. LNS male and female pups exhibited a reduction of body weight by 5% and 4%, adrenal weights/100g body weight by 17% and 18%, corticosterone plasma levels by 64% and 62% and blood glucose by 11% and 12% respectively compared to same sex control pups. In male LNS pups, intestinal permeability was increased by 2.7-fold while no change was observed in females compared to same sex control. There was no sex difference in any of the parameters in control pups except the body weight. These data indicate that Wistar dams subjected to LNS during the first postnatal week have an altered repertoire of maternal behaviors which affects the development of the HPA axis in both sexes and intestinal barrier function in male offspring.

Maternal High-Fat Diet Programming of the Neuroendocrine System and Behavior

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Sullivan, Elinor L.; Riper, Kellie M.; Lockard, Rachel; Valleau, Jeanette C.

2015-01-01

Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic pituitary adrenal (HPA) axis. PMID:25913366

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

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Francesca L. Guest

2013-01-01

Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

Preeclampsia and the Anti-Angiogenic State

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Agarwal, Isha; Karumanchi, S. Ananth

2011-01-01

Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide, however, its etiology remains unclear. Abnormal placental angiogenesis during pregnancy resulting from high levels of anti-angiogenic factors, soluble Flt1 (sFlt1) and soluble endoglin (sEng), has been implicated in preeclampsia pathogenesis. Accumulating evidence also points to a role for these anti-angiogenic proteins as serum biomarkers for the clinical diagnosis and prediction of preeclampsia. Uncoverin...

Modulation of HPA axis response to social stress in schizophrenia by childhood trauma.

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Lange, Claudia; Huber, Christian G; Fröhlich, Daniela; Borgwardt, Stefan; Lang, Undine E; Walter, Marc

2017-08-01

HPA axis functioning plays an important role in the etiology of schizophrenia spectrum disorders (SSD). However, only few studies have examined HPA axis responsivity to psychosocial stress in SSD, and results are heterogeneous. Furthermore, childhood trauma is known to influence psychopathology and treatment outcome in SSD, but studies on the influence of childhood trauma on stress related HPA axis activity are missing. The purpose of this study was to investigate cortisol response to a psychosocial stress challenge in SSD patients, and to examine its association with severity of childhood trauma. The present study included 25 subacutely ill patients with a current episode of a chronic SSD and 25 healthy controls. Participants underwent the modified Trier Social Stress Test, and salivary cortisol levels were assessed. The childhood trauma questionnaire was used to assess severity of adverse life events. Overall, cortisol response was blunted in the patient group compared to the control group (pchildhood trauma experience: responders had experienced more emotional abuse in their past (pchildhood trauma might influence stress-related HPA axis activity in SSD. Our data contribute to the hypothesis that severity of childhood trauma may be of pathophysiological relevance in schizophrenia. In addition, it may be an overlooked factor contributing to inconsistent findings regarding HPA axis response to psychosocial stress in SSD. Copyright © 2017. Published by Elsevier Ltd.

Performance analysis of AF cooperative systems with HPA nonlinearity in semi-blind relays

KAUST Repository

Qi, Jian

2012-12-01

In this paper, dual-hop amplify-and-forward (AF) cooperative systems in the presence of high-power amplifier (HPA) nonlinearity at semi-blind relays, are investigated. Based on the modified AF cooperative system model taking into account the HPA nonlinearity, the expression for the output signal-to-noise ratio (SNR) at the destination node is derived, where the interference due to both the AF relaying mechanism and the HPA nonlinearity is characterized. The performance of the AF cooperative system under study is evaluated in terms of average symbol error probability (SEP), which is derived using the moment-generating function (MGF) approach, considering transmissions over Nakagami-m fading channels. Numerical results are provided and show the effects of some system parameters, such as the HPA parameters, numbers of relays, quadrature amplitude modulation (QAM) order, Nakagami parameters, on performance. © 2012 IEEE.

Performance analysis of AF cooperative systems with HPA nonlinearity in semi-blind relays

KAUST Repository

Qi, Jian; Aï ssa, Sonia; Alouini, Mohamed-Slim

2012-01-01

In this paper, dual-hop amplify-and-forward (AF) cooperative systems in the presence of high-power amplifier (HPA) nonlinearity at semi-blind relays, are investigated. Based on the modified AF cooperative system model taking into account the HPA nonlinearity, the expression for the output signal-to-noise ratio (SNR) at the destination node is derived, where the interference due to both the AF relaying mechanism and the HPA nonlinearity is characterized. The performance of the AF cooperative system under study is evaluated in terms of average symbol error probability (SEP), which is derived using the moment-generating function (MGF) approach, considering transmissions over Nakagami-m fading channels. Numerical results are provided and show the effects of some system parameters, such as the HPA parameters, numbers of relays, quadrature amplitude modulation (QAM) order, Nakagami parameters, on performance. © 2012 IEEE.

Constructing a population-based research database from routine maternal screening records: a resource for studying alloimmunization in pregnant women.

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Brian K Lee

Full Text Available BACKGROUND: Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues. STUDY DESIGN AND METHODS: Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies presented as online moving graphical displays. RESULTS: More than one million (1,191,761 births with valid screening information from 1982-2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time. CONCLUSION: This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important

The placental immune milieu is characterized by a Th2- and anti-inflammatory transcription profile, regardless of maternal allergy, and associates with neonatal immunity.

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Abelius, Martina S; Janefjord, Camilla; Ernerudh, Jan; Berg, Göran; Matthiesen, Leif; Duchén, Karel; Nilsson, Lennart J; Jenmalm, Maria C

2015-05-01

How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear. Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring. Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

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Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

2015-01-01

It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hemolytic disease of the fetus and newborn caused by anti-E

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Adiyyatu Sa′idu Usman

2013-01-01

Full Text Available Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

Compensation for HPA nonlinearity and I/Q imbalance in MIMO beamforming systems

KAUST Repository

Qi, Jian; Aissa, Sonia

2010-01-01

In this paper, we investigate the effects of high-power amplifier (HPA) nonlinearity and in-phase and quadrature-phase (I/Q) imbalance on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems. Specifically, we propose a compensation method for HPA nonlinearity and I/Q imbalance together in MIMO TB systems. The performance of the MIMO TB system under study is evaluated in terms of the average symbol error probability (SEP) and system capacity, considering transmission over uncorrelated frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, such as the HPA parameters, image-leakage ratio, numbers of transmit and receive antennas, length of pilot symbols, and modulation order of phase-shift keying (PSK), on performance. © 2010 IEEE.

Compensation for HPA nonlinearity and I/Q imbalance in MIMO beamforming systems

KAUST Repository

Qi, Jian

2010-10-01

In this paper, we investigate the effects of high-power amplifier (HPA) nonlinearity and in-phase and quadrature-phase (I/Q) imbalance on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems. Specifically, we propose a compensation method for HPA nonlinearity and I/Q imbalance together in MIMO TB systems. The performance of the MIMO TB system under study is evaluated in terms of the average symbol error probability (SEP) and system capacity, considering transmission over uncorrelated frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, such as the HPA parameters, image-leakage ratio, numbers of transmit and receive antennas, length of pilot symbols, and modulation order of phase-shift keying (PSK), on performance. © 2010 IEEE.

Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

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Aparna Reddy

Full Text Available Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1, endoglin (sEng and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies.To assess the effects of labour, samples were taken from 10 normal pregnant (NP and 10 pre-eclamptic (PE women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively.The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase.Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report

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Yousuf Rabeya

2012-02-01

Full Text Available Abstract Introduction Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization. Case presentation A one-day-old Chinese baby boy was born to a mother who was group A RhD negative. The baby was jaundiced with hyperbilirubinemia, but with no evidence of infection. His blood group was group A RhD positive, his direct Coombs' test result was positive and red cell elution studies demonstrated the presence of anti-D and anti-S alloantibodies. Investigations performed on the maternal blood during the 22 weeks of gestation showed the presence of anti-S antibodies only. Repeat investigations performed post-natally showed the presence of similar antibodies as in the newborn and an anti-D titer of 1:32 (0.25 IU/mL, which was significant. A diagnosis of hemolytic disease of the fetus and newborn secondary to anti-D and anti-S was made. The baby was treated with phototherapy and close monitoring. He was discharged well after five days of phototherapy. Conclusions This case illustrates the possibility of an anamnestic response of allo-anti-D from previous sensitization in a RhD-negative mother, or the development of anti-D in mid-trimester. Thus, it highlights the importance of thorough antenatal ABO, RhD blood grouping and antibody screening, and if necessary, antibody identification and regular monitoring of antibody screening and antibody levels for prevention or early detection of hemolytic disease of the fetus and newborn, especially in cases of mothers with clinically significant red cell alloantibody.

Maternal obesity alters feto-placental Cytochrome P4501A1 activity

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DuBois, Barent N.; O’Tierney, Perrie; Pearson, Jacob; Friedman, Jacob E.; Thornburg, Kent; Cherala, Ganesh

2012-01-01

Cytochrome P4501A1 (CYP1A1), an important drug metabolizing enzyme, is expressed in human placenta throughout gestation as well as in fetal liver. Obesity, a chronic inflammatory condition, is known to alter CYP enzyme expression in non-placental tissues. In the present study, we test the hypothesis that maternal obesity alters the distribution of CYP1A1 activity in feto-placental unit. Placentas were collected from non-obese (BMI30) women at term. Livers were collected from gestation day 130 fetuses of non-human primates fed either control diet or high-fat diet (HFD). Cytosol and microsomes were collected using differential centrifugation, and incubated with 7-Ethoxyresorufin. The CYP1A1 specific activity (pmoles of resorufin formed/min/mg of protein) was measured at excitation/emission wavelength of 530/590nm. Placentas of obese women had significantly reduced microsomal CYP1A1 activity compared to non-obese women (0.046 vs. 0.082; p<0.05); however no such effect was observed on cytosolic activity. Similarly, fetal liver from HFD fed mothers had significantly reduced microsomal CYP1A1 activity (0.44±0.04 vs. 0.20±0.10; p<0.05), with no significant difference in cytosolic CYP1A1 activity (control, 1.23±0.20; HFD, 0.80±0.40). Interestingly, multiple linear regression analyses of placental efficiency indicates cytosolic CYP1A1 activity is a main effect (5.67±2.32 (β±SEM); p=0.022) along with BMI (−0.57±0.26; p=0.037), fetal gender (1.07±0.26; p<0.001), and maternal age (0.07±0.03; p=0.011). In summary, while maternal obesity affects microsomal CYP1A1 activity alone, cytosolic activity along with maternal BMI is an important determinant of placental efficiency. Together, these data suggest that maternal lifestyle could have a significant impact on CYP1A1 activity, and hints at a possible role for CYP1A1 in feto-placental growth and thereby well-being of fetus. PMID:23046808

Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

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Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

2018-01-01

In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood.

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Davis, Elysia Poggi; Head, Kevin; Buss, Claudia; Sandman, Curt A

2017-01-01

Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6-9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6-9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain. Copyright © 2016. Published by Elsevier Ltd.

Persistent hemolytic disease of the fetus and newborn (HDFN) associated with passive acquisition of anti-D in maternal breast milk.

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Li, Marissa; Blaustein, John C

2017-09-01

Anti-D is a well-documented, significant cause of hemolytic disease of the fetus and newborn (HDFN), but its presence in breast milk is not routinely described. Theoretically, breast milk containing anti-D could have the potential to exacerbate HDFN if ingested by the affected infant. This is a case report of a 28-week premature male neonate with hydrops fetalis born to a 32-year-old woman (gravidity 3/parity 3) with anti-D and anti-G. The male neonate experienced prolonged HDFN due to passive acquisition of anti-D in the mother's breast milk. The mother's breast milk reacted strongly (4+) with the D-positive cells in the antibody screen test. Discontinuation of breast milk feeding and addition of total parenteral nutrition led to the cessation of clinically significant HDFN. Although anti-D is a significant cause of HDFN through placental transfer of antibody, exacerbation of the condition through breast milk antibodies is rarely described. The current case highlights the possibility of this occurring. Discontinuation of maternal breast milk feedings should be considered in infants with HDFN who do not respond to standard treatment. © 2017 AABB.

Oxidized LDL-induced angiogenesis involves sphingosine 1-phosphate: prevention by anti-S1P antibody.

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Camaré, Caroline; Trayssac, Magali; Garmy-Susini, Barbara; Mucher, Elodie; Sabbadini, Roger; Salvayre, Robert; Negre-Salvayre, Anne

2015-01-01

Neovascularization occurring in atherosclerotic lesions may promote plaque expansion, intraplaque haemorrhage and rupture. Oxidized LDL (oxLDL) are atherogenic, but their angiogenic effect is controversial; both angiogenic and anti-angiogenic effects have been reported. The angiogenic mechanism of oxLDL is partly understood, but the role of the angiogenic sphingolipid, sphingosine 1-phosphate (S1P), in this process is not known. Thus, we investigated whether S1P is involved in the oxLDL-induced angiogenesis and whether an anti-S1P monoclonal antibody can prevent this effect. Angiogenesis was assessed by capillary tube formation by human microvascular endothelial cells (HMEC-1) cultured on Matrigel and in vivo by the Matrigel plug assay in C57BL/6 mice. Human oxLDL exhibited a biphasic angiogenic effect on HMEC-1; low concentrations were angiogenic, higher concentrations were cytotoxic. The angiogenic response to oxLDL was blocked by the sphingosine kinase (SPHK) inhibitor, dimethylsphingosine, by SPHK1-siRNA and by an anti-S1P monoclonal antibody. Moreover, inhibition of oxLDL uptake and subsequent redox signalling by anti-CD36 and anti-LOX-1 receptor antibodies and by N-acetylcysteine, respectively, blocked SPHK1 activation and tube formation. In vivo, in the Matrigel plug assay, low concentrations of human oxLDL or murine oxVLDL also triggered angiogenesis, which was prevented by i.p. injection of the anti-S1P antibody. These data highlight the role of S1P in angiogenesis induced by oxLDL both in HMEC-1 cultured on Matrigel and in vivo in the Matrigel plug model in mice, and demonstrate that the anti-S1P antibody effectively blocks the angiogenic effect of oxLDL. © 2014 The British Pharmacological Society.

Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome.

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Javad Barouei

Full Text Available OBJECTIVE: To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS and/or restraint stress in adulthood (AS in Wistar rats. DESIGN: Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3 × 10(9 CFU/mL and Propionibacterium jensenii 702 (8.0 × 10(8 CFU/mL from 10 days before conception until postnatal day (PND 22 (weaning day, or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. RESULTS: Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. CONCLUSION: Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly

Differential sensitization of parenting on early adolescent cortisol: Moderation by profiles of maternal stress.

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Martin, Christina Gamache; Kim, Hyoun K; Fisher, Philip A

2016-05-01

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the body's stress-response neurobiological system, and its development and functioning are shaped by the social environment. Much of our understanding of the effects of the caregiving environment on the HPA axis is based on (a) parenting in young children and (b) individual maternal stressors, such as depression. Yet, less is known about how parenting behaviors and maternal stressors interact to influence child cortisol regulation, particularly in older children. With an ethnically diverse sample of 199 mothers and their early adolescent children (M=11.00years; 54% female), a profile analytic approach was used to investigate how multiple phenotypes of maternal stress co-occur and moderate the relation between parenting behaviors and youths' diurnal cortisol rhythms. Latent profile analysis yielded 4 profiles: current parenting stress, concurrent parenting and childhood stress, childhood stress, and low stress. For mothers with the concurrent parenting and childhood stress profile, inconsistent discipline, poor parental supervision, and harsh caregiving behaviors each were related to flattened diurnal cortisol rhythms in their adolescents. For mothers with the current parenting stress and childhood stress profiles, their use of inconsistent discipline was associated with flattened diurnal cortisol rhythms in their adolescents. For mothers with the low stress profile, none of the parenting behaviors was related to their adolescents' cortisol regulation. Findings suggest that based on mothers' stress profile, parenting behaviors are differentially related to youths' diurnal cortisol rhythms. Implications for parenting interventions are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

OpenAIRE

Lee, Richard; Sawa, Akira

2014-01-01

In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

[Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM].

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Huguet, S; Sghiri, R; Ballot, E; Johanet, C

2004-01-01

The Cyto-Dot 4 HM043 kit commercialised by BMD, has replaced the Cyto-Dot HM010 kit that allowed three auto-antibodies detection (anti-Jo-1, anti-M2 and anti-ribosomal protein). Detection of anti-LKM1 auto-antibody was added. These four auto-antibodies have in common only the intracytoplasmic localisation of their respective antigen. The aim of our study was to evaluate this new kit using 104 sera and to compare our results with reference techniques (indirect immunofluorescence IF for anti-M2, anti-ribosomal protein and anti-LKM1, double immunodiffusion ID for anti-Jo-1 and anti-LKM1, western blotting WB for anti-M2) and with Cyto-Dot HM010. The one hundred and four sera were divided into five groups: Group I (n = 12) with anti-Jo-1 detected by ID; Group II (n = 28) with 26 anti-M2 positive by IF and WB, 2 anti-M2 positive only by WB; Group III (n = 10) with anti-ribosomal protein detected by IF 5 of which precipitated by ID; Group IV (n = 32) with anti-LKM1 by IF and ID divided into 18 AIH2 and 14 HCV; Group V (n = 22) consisting of 14 healthy individuals and 8 patients with hypergammaglobulinemia. Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use. Cyto-Dot 4 is a very good anti-LKM1 confirmation method as it is ID. Copyright John Libbey Eurotext 2003.

Long-term effects of early parental loss due to divorce on the HPA axis.

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Bloch, Miki; Peleg, Ido; Koren, Danny; Aner, Hamotal; Klein, Ehud

2007-04-01

We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (p<0.03). Group by time effect reached a trend level (p<0.06). A correlation was found between psychiatric symptomatology and PBI scores; however, both parameters did not correlate with HPA axis activity. A significant correlation was found between DAS scores and ACTH. A regression model revealed a contributing effect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2012-01-01

Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2015-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2017-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Comparative Genomics Identifies a Novel Conserved Protein, HpaT, in Proteobacterial Type III Secretion Systems that Do Not Possess the Putative Translocon Protein HrpF

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Céline Pesce

2017-06-01

Full Text Available Xanthomonas translucens is the causal agent of bacterial leaf streak, the most common bacterial disease of wheat and barley. To cause disease, most xanthomonads depend on a highly conserved type III secretion system, which translocates type III effectors into host plant cells. Mutagenesis of the conserved type III secretion gene hrcT confirmed that the X. translucens type III secretion system is required to cause disease on the host plant barley and to trigger a non-host hypersensitive response (HR in pepper leaves. Type III effectors are delivered to the host cell by a surface appendage, the Hrp pilus, and a translocon protein complex that inserts into the plant cell plasma membrane. Homologs of the Xanthomonas HrpF protein, including PopF from Ralstonia solanacearum and NolX from rhizobia, are thought to act as a translocon protein. Comparative genomics revealed that X. translucens strains harbor a noncanonical hrp gene cluster, which rather shares features with type III secretion systems from Ralstonia solanacearum, Paraburkholderia andropogonis, Collimonas fungivorans, and Uliginosibacterium gangwonense than other Xanthomonas spp. Surprisingly, none of these bacteria, except R. solanacearum, encode a homolog of the HrpF translocon. Here, we aimed at identifying a candidate translocon from X. translucens. Notably, genomes from strains that lacked hrpF/popF/nolX instead encode another gene, called hpaT, adjacent to and co-regulated with the type III secretion system gene cluster. An insertional mutant in the X. translucens hpaT gene, which is the first gene of a two-gene operon, hpaT-hpaH, was non-pathogenic on barley and did not cause the HR or programmed cell death in non-host pepper similar to the hrcT mutant. The hpaT mutant phenotypes were partially complemented by either hpaT or the downstream gene, hpaH, which has been described as a facilitator of translocation in Xanthomonas oryzae. Interestingly, the hpaT mutant was also complemented

The prevalence of maternal F cells in a pregnant population and potential overestimation of foeto-maternal haemorrhage as a consequence.

LENUS (Irish Health Repository)

Corcoran, Deirdre

2014-06-12

Acid elution (AE) is used to estimate foeto-maternal haemorrhage (FMH). However AE cannot differentiate between cells containing foetal or adult haemoglobin F (F cells), potentially leading to false positive results or an overestimate of the amount of FMH. The prevalence of F cells in pregnant populations remains poorly characterised. The purpose of this study was to ascertain the incidence of HbF-containing red cells in our pregnant population using anti-HbF-fluorescein isothiocyanate flow cytometry (anti-HbF FC) and to assess whether its presence leads to a significant overestimate of FMH.

Maternal Mortality in Women with Epilepsy

LENUS (Irish Health Repository)

Holohan, M

2016-10-01

It is estimated that, in Ireland, there are 10,000 women with epilepsy of childbearing potential1. In this paper the maternal mortality rate for women with epilepsy attending the Rotunda Hospital Epilepsy Clinic 2004 - 2013 was determined. There were 3 maternal deaths in women with epilepsy during this time, which represents a mortality rate of 0.8%. In those women who died, there were concerns in relation to risks to the foetus by taking Anti-Epileptic Drugs (AED) and also issues with access to neurology services before pregnancy, acceptance of specialist support and lack of consistency in advice from health care professionals outside of Ireland. Implementing the nationally agreed care plan for women with epilepsy will improve the quality of care given and potentially we will see a reduction in maternal mortality in these women.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

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Schwandt, Melanie L; Cortes, Carlos R; Kwako, Laura E; George, David T; Momenan, Reza; Sinha, Rajita; Grigoriadis, Dimitri E; Pich, Emilio Merlo; Leggio, Lorenzo; Heilig, Markus

2016-01-01

Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21–65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse. PMID:27109623

Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat

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Huang Yuejun

2012-02-01

Full Text Available Abstract Background Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. Results We used the behavioural tests to assess the model of chronic unpredictable stress (CUS in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. Conclusions Our data demonstrate that pre-gestational stress alters HPA

Postpartum depression: Etiology, treatment and consequences for maternal care.

Science.gov (United States)

Brummelte, Susanne; Galea, Liisa A M

2016-01-01

This article is part of a Special Issue "Parental Care". Pregnancy and postpartum are associated with dramatic alterations in steroid and peptide hormones which alter the mothers' hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes. Dysregulations in these endocrine axes are related to mood disorders and as such it should not come as a major surprise that pregnancy and the postpartum period can have profound effects on maternal mood. Indeed, pregnancy and postpartum are associated with an increased risk for developing depressive symptoms in women. Postpartum depression affects approximately 10-15% of women and impairs mother-infant interactions that in turn are important for child development. Maternal attachment, sensitivity and parenting style are essential for a healthy maturation of an infant's social, cognitive and behavioral skills and depressed mothers often display less attachment, sensitivity and more harsh or disrupted parenting behaviors, which may contribute to reports of adverse child outcomes in children of depressed mothers. Here we review, in honor of the "father of motherhood", Jay Rosenblatt, the literature on postnatal depression in the mother and its effect on mother-infant interactions. We will cover clinical and pre-clinical findings highlighting putative neurobiological mechanisms underlying postpartum depression and how they relate to maternal behaviors and infant outcome. We also review animal models that investigate the neurobiology of maternal mood and disrupted maternal care. In particular, we discuss the implications of endogenous and exogenous manipulations of glucocorticoids on maternal care and mood. Lastly we discuss interventions during gestation and postpartum that may improve maternal symptoms and behavior and thus may alter developmental outcome of the offspring. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal body condition influences magnitude of anti-predator response in offspring.

Science.gov (United States)

Bennett, Amanda M; Murray, Dennis L

2014-11-07

Organisms exhibit plasticity in response to their environment, but there is large variation even within populations in the expression and magnitude of response. Maternal influence alters offspring survival through size advantages in growth and development. However, the relationship between maternal influence and variation in plasticity in response to predation risk is unknown. We hypothesized that variation in the magnitude of plastic responses between families is at least partly due to maternal provisioning and examined the relationship between maternal condition, egg provisioning and magnitude of plastic response to perceived predation risk (by dragonfly larvae: Aeshna spp.) in northern leopard frogs (Lithobates pipiens). Females in better body condition tended to lay more (clutch size) larger (egg diameter) eggs. Tadpoles responded to predation risk by increasing relative tail depth (morphology) and decreasing activity (behaviour). We found a positive relationship between morphological effect size and maternal condition, but no relationship between behavioural effect size and maternal condition. These novel findings suggest that limitations imposed by maternal condition can constrain phenotypic variation, ultimately influencing the capacity of populations to respond to environmental change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Two-way CSI-assisted AF relaying with HPA nonlinearity

KAUST Repository

Qi, Jian; Aissa, Sonia; Alouiniz, Mohamed-Slim

2015-01-01

In this paper, we investigate half-duplex two-way dual-hop channel state information (CSI)-assisted amplify-andforward (AF) relaying in the presence of high-power amplifier (HPA) nonlinearity at relays. The expression for the end-toend signal

From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants

NARCIS (Netherlands)

Pecoraro, Norman; Dallman, Mary F.; Warne, James P.; Ginsberg, Abigail B.; Laugero, Kevin D.; la Fleur, Susanne E.; Houshyar, Hani; Gomez, Francisca; Bhargava, Aditi; Akana, Susan F.

2006-01-01

The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly

Hemolytic disease of the newborn caused by anti-Wright (anti-Wra): case report and review of literature.

Science.gov (United States)

Squires, Amanda; Nasef, Nehad; Lin, Yulia; Callum, Jeannie; Khadawardi, Emad M; Drolet, Christine; Core, David; Simmons, Brian

2012-01-01

Antibodies to red cell antigens that are found at low frequency in the general population are rare causes of hemolytic disease of the newborn. To understand how to detect these cases, we provide a basic review of routine antenatal maternal antibody testing and report a case of a neonate with severe HDN caused by anti-Wright (anti-Wra), successfully managed with transfusion, phototherapy, and high-dose intravenous immunoglobulin. When hemolysis in a newborn is suspected in the absence of major blood group incompatibility or commonly detected maternal red cell antibodies, a direct antiglobulin test should be performed. A positive DAT should alert the clinician to the presence of maternal antibodies against low-incidence antigens. Antibodies to the Wra antigen are one such rare cause of HDN.

HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

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Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

2017-06-01

It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125 , p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with Aging: A Meta-Analysis of Clinical Studies.

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Judit Tenk

Full Text Available Obesity is one of the major public health challenges worldwide. It involves numerous endocrine disorders as etiological factors or as complications. Previous studies strongly suggested the involvement of the hypothalamic-pituitary-adrenal (HPA axis activity in obesity, however, to date, no consistent trend in obesity-associated alterations of the HPA axis has been identified. Aging has been demonstrated to aggravate obesity and to induce abnormalities of the HPA axis. Thus, the question arises whether obesity is correlated with peripheral indicators of HPA function in adult populations.We aimed to meta-analyze literature data on peripheral cortisol levels as indicators of HPA activity in obesity during aging, in order to identify possible explanations for previous contradictory findings and to suggest new approaches for future clinical studies.3,596 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 26 articles were suitable for analyses.Empirical research papers were eligible provided that they reported data of healthy adult individuals, included body mass index (BMI and measured at least one relevant peripheral cortisol parameter (i.e., either morning blood cortisol or 24-h urinary free cortisol.We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. Meta-regression was applied to explore the effect of BMI and age on morning blood and urinary free cortisol levels. To assess publication bias Egger's test was used.Obesity did not show any correlation with the studied peripheral cortisol values. On the other hand, peripheral cortisol levels declined with aging within the obese, but not in the non-obese groups.Our analysis demonstrated that obesity or healthy aging does not lead to enhanced HPA axis activity, peripheral cortisol levels rather decline with aging.

In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with Aging: A Meta-Analysis of Clinical Studies.

Science.gov (United States)

Tenk, Judit; Mátrai, Péter; Hegyi, Péter; Rostás, Ildikó; Garami, András; Szabó, Imre; Solymár, Margit; Pétervári, Erika; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Füredi, Nóra; Párniczky, Andrea; Zsiborás, Csaba; Balaskó, Márta

2016-01-01

Obesity is one of the major public health challenges worldwide. It involves numerous endocrine disorders as etiological factors or as complications. Previous studies strongly suggested the involvement of the hypothalamic-pituitary-adrenal (HPA) axis activity in obesity, however, to date, no consistent trend in obesity-associated alterations of the HPA axis has been identified. Aging has been demonstrated to aggravate obesity and to induce abnormalities of the HPA axis. Thus, the question arises whether obesity is correlated with peripheral indicators of HPA function in adult populations. We aimed to meta-analyze literature data on peripheral cortisol levels as indicators of HPA activity in obesity during aging, in order to identify possible explanations for previous contradictory findings and to suggest new approaches for future clinical studies. 3,596 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 26 articles were suitable for analyses. Empirical research papers were eligible provided that they reported data of healthy adult individuals, included body mass index (BMI) and measured at least one relevant peripheral cortisol parameter (i.e., either morning blood cortisol or 24-h urinary free cortisol). We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. Meta-regression was applied to explore the effect of BMI and age on morning blood and urinary free cortisol levels. To assess publication bias Egger's test was used. Obesity did not show any correlation with the studied peripheral cortisol values. On the other hand, peripheral cortisol levels declined with aging within the obese, but not in the non-obese groups. Our analysis demonstrated that obesity or healthy aging does not lead to enhanced HPA axis activity, peripheral cortisol levels rather decline with aging.

Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

Directory of Open Access Journals (Sweden)

Marieke J van der Werf-Eldering

Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

The Anti-Inflammatory Effects of Acupuncture and Their Relevance to Allergic Rhinitis: A Narrative Review and Proposed Model

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John L. McDonald

2013-01-01

Full Text Available Classical literature indicates that acupuncture has been used for millennia to treat numerous inflammatory conditions, including allergic rhinitis. Recent research has examined some of the mechanisms underpinning acupuncture's anti-inflammatory effects which include mediation by sympathetic and parasympathetic pathways. The hypothalamus-pituitary-adrenal (HPA axis has been reported to mediate the antioedema effects of acupuncture, but not antihyperalgesic actions during inflammation. Other reported anti-inflammatory effects of acupuncture include an antihistamine action and downregulation of proinflammatory cytokines (such as TNF-α, IL-1β, IL-6, and IL-10, proinflammatory neuropeptides (such as SP, CGRP, and VIP, and neurotrophins (such as NGF and BDNF which can enhance and prolong inflammatory response. Acupuncture has been reported to suppress the expression of COX-1, COX-2, and iNOS during experimentally induced inflammation. Downregulation of the expression and sensitivity of the transient receptor potential vallinoid 1 (TRPV1 after acupuncture has been reported. In summary, acupuncture may exert anti-inflammatory effects through a complex neuro-endocrino-immunological network of actions. Many of these generic anti-inflammatory effects of acupuncture are of direct relevance to allergic rhinitis; however, more research is needed to elucidate specifically how immune mechanisms might be modulated by acupuncture in allergic rhinitis, and to this end a proposed model is offered to guide further research.

Adaptive maternal immune deviations as a ground for autism spectrum disorders development in children.

Science.gov (United States)

Poletaev, Alexander B; Poletaeva, Alina A; Pukhalenko, Alexander I; Zamaleeva, Roza S; Cherepanova, Natalia A; Frizin, Dmitry V

2014-01-01

Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 - 1:150) with late diagnosed autism spectrum disorders (ASD) and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet. One of the most likely mechanisms inducing ASD may be a maternal immune imprinting. This phenomenon is based on transplacental translocation of maternal antibodies of IgG class and, as a consequence, on the epigenetic "tuning" of immune system of the fetus and child. This mechanism provides development of child's anti-infection resistance before meeting with microorganisms, but it can be also a cause of inborn pathology including the ASD appearance. The quantitative changes in maternal blood serum autoantibodies depend on a specific microbial population, or are induced by environmental chemical pollutants in association with some individual features of the maternal metabolism. These immune changes are adaptive in most cases for the maternal organism, but can be pathogenic for the fetus in some cases. We discuss in the present paper the possibilities to predict the risk from abnormal development of nervous system in fetus and early diagnosis of ASD in high-risk group of children.

Xenohormesis in early life: New avenues of research to explore anti-aging strategies through the maternal diet.

Science.gov (United States)

de Medina, Philippe

2017-11-01

Aging is a progressive internal physiological deterioration of the organism, leading to the occurrence of age-related lethal diseases. It has become a major societal challenge to understand the processes that drive aging and to develop rational pharmacological agents and dietary approaches to fight against age-related deterioration and diseases. Interestingly, several lines of evidence highlight an influence of the developmental period on the risk of age-related diseases later in life. This field is known as the developmental origins of health and disease. Following this logic, studying the modification of maternal diet during early life may provide innovative new anti-aging approaches. Nutritional and psychological stresses during gestation are associated with poorer offspring health conditions in late life, and must be avoided during pregnancy. Besides these recommendations, very little has been published about the possible use of maternal diet to program offspring for healthy aging and an extended lifespan. Such health benefits may be provided by different foreign molecules, and particularly the phytochemicals produced by stressed plants, or xenohormetins. The xenohormesis hypothesis proposes that xenohormetins are signals of environmental change and trigger a beneficial adaptive response in individuals who consume them. No studies to date have investigated whether the consumption of stressed plants during pregnancy and lactation could provide chemical cues that impact early life programming and thus influence the future health and lifespan of offspring. Investigating the effect of xenohormesis in early life will involve adding edible plants exposed to different stressors (i.e. UV light, heat, ozone, etc.) to maternal diet and the exposure of offspring to this xenohormetin-enriched maternal diet at different periods of their prenatal life. The hypothesis proposed in this article is a potential tool to decipher the possible impact of xenohormesis during early

Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice.

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Martín-Sánchez, Ana; Valera-Marín, Guillermo; Hernández-Martínez, Adoración; Lanuza, Enrique; Martínez-García, Fernando; Agustín-Pavón, Carmen

2015-01-01

Virgin adult female mice display nearly spontaneous maternal care towards foster pups after a short period of sensitization. This indicates that maternal care is triggered by sensory stimulation provided by the pups and that its onset is largely independent on the physiological events related to gestation, parturition and lactation. Conversely, the factors influencing maternal aggression are poorly understood. In this study, we sought to characterize two models of maternal sensitization in the outbred CD1 strain. To do so, a group of virgin females (godmothers) were exposed to continuous cohabitation with a lactating dam and their pups from the moment of parturition, whereas a second group (pup-sensitized females), were exposed 2 h daily to foster pups. Both groups were tested for maternal behavior on postnatal days 2-4. Godmothers expressed full maternal care from the first test. Also, they expressed higher levels of crouching than dams. Pup-sensitized females differed from dams in all measures of pup-directed behavior in the first test, and expressed full maternal care after two sessions of contact with pups. However, both protocols failed to induce maternal aggression toward a male intruder after full onset of pup-directed maternal behavior, even in the presence of pups. Our study confirms that adult female mice need a short sensitization period before the onset of maternal care. Further, it shows that pup-oriented and non-pup-oriented components of maternal behavior are under different physiological control. We conclude that the godmother model might be useful to study the physiological and neural bases of the maternal behavior repertoire.

Apolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner.

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Packard, Amy E B; Zhang, Jintao; Myers, Brent; Ko, Chih-Wei; Wang, Fei; Tso, Patrick; Ulrich-Lai, Yvonne M

2017-12-01

There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus. Given that both peripheral and central metabolic processes are important modulators of hypothalamic-pituitary-adrenocortical (HPA) axis activity, the present work tests the hypothesis that apoA-IV activity affects stress responses. As emerging data suggests that apoA-IV actions can vary with background strain, we also explore the strain-dependence of apoA-IV stress regulation. These studies assess HPA axis, metabolic (hyperglycemia), and anxiety-related behavioral responses to psychogenic stress in control (wildtype) and apoA-IV-deficient (KO) mice on either the C57Bl/6J (C57) or 129×1/SvJ (129) background strain. The results indicate that apoA-IV KO increases post-stress corticosterone and anxiety-related behavior specifically in the 129 strain, and increases stress-induced hyperglycemia exclusively in the C57 strain. These data support the hypothesis that apoA-IV is a novel factor that limits stress reactivity in a manner that depends on genetic background. An improved understanding of the complex relationship among lipid homeostasis, stress sensitivity, and genetics is needed to optimize the development of personalized treatments for stress- and metabolism-related diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of resistance exercise on the HPA axis response to psychological stress during short-term smoking abstinence in men.

Science.gov (United States)

Ho, Jen-Yu; Kraemer, William J; Volek, Jeff S; Vingren, Jakob L; Fragala, Maren S; Flanagan, Shawn D; Maladouangdock, Jesse; Szivak, Tunde K; Hatfield, Disa L; Comstock, Brett A; Dunn-Lewis, Courtenay; Ciccolo, Joseph T; Maresh, Carl M

2014-03-01

The purpose of this study was to examine the effects of resistance exercise on the hypothalamic-pituitary-adrenal axis (HPA) response to mental challenge, withdrawal symptoms, urge to smoke, and cognitive stress during 24-hour smoking abstinence. 8 sedentary smokers (mean±SD age: 20.1±1.7y; height: 171.6±10.8cm; body mass: 70.4±12.0kg; smoking history: 2.9±0.8y) completed a 24-hour ad libitum smoking trial (SMO) followed by two 24-hour smoking abstinence trials. During abstinence trials, participants performed six whole body resistance exercises (EX) or a control condition (CON) in the morning, followed by mental challenge tasks in the afternoon. Plasma adrenocorticotropin hormone (ACTH), and salivary and serum cortisol were measured during each visit at rest (REST), and then before (PRE-EX), immediately after (IP-EX), and 30min after exercise (30-EX); and before (PRE-MC), immediately after (IP-MC), and 30min after mental challenge (30-MC). Resistance exercise significantly (p≤0.05) elevated plasma ACTH and serum cortisol at IP-EX during EX compared with SMO and CON trials. Resting ACTH, salivary and serum cortisol concentrations at Pre-MC did not differ between EX and CON trials. The HPA axis response to mental challenge was similar after EX and CON trials. Finally, resistance exercise did not reduce withdrawal symptoms, urge to smoke, or stress. Resistance exercise did not substantially alter resting HPA hormones or the HPA response to mental challenge tasks during 24h of smoking abstinence. © 2013.

Detection of anti-liver cytosol antibody type 1 (anti-LC1) by immunodiffusion, counterimmunoelectrophoresis and immunoblotting: comparison of different techniques.

Science.gov (United States)

Muratori, L; Cataleta, M; Muratori, P; Manotti, P; Lenzi, M; Cassani, F; Bianchi, F B

1995-12-01

Liver cytosol specific antibody type 1 (anti-LC1) was first described in a proportion of patients with liver/kidney microsomal antibody type 1 (anti-LKM1)-positive autoimmune hepatitis (AIH) and is routinely evaluated by immunodiffusion (ID). Using human liver cytosol as the source of antigen, we have used ID, counterimmunoelectrophoresis (CIE) and immunoblotting (IB), to test sera from 167 patients with documented chronic liver diseases of different etiology. 15 patients had antinuclear antibody (ANA) and/or smooth muscle antibody (SMA)-positive AIH, 13 had anti-LKM1-positive AIH, four had ANA/SMA/anti-LKM1-negative AIH, 76 had anti-LKM1-positive hepatitis C (recently renamed unclassified chronic hepatitis-UCH), 40 had chronic hepatitis C, 15 had chronic hepatitis B, and 4 had chronic hepatitis D. A precipitin line of identity with an anti-LC1 reference serum was detected both by ID and CIE in 16 patients: six with anti-LKM1-positive 'definite' AIH, four with ANA/SMA/anti-LKM1-negative 'definite' AIH, and six with anti-LKM1-positive UCH. By IB, 14 out of the 16 anti-LC1-positive sera (87.5%) reacted with a 58 kDa human liver cytosolic polypeptide, whereas three out of 16 (19%) recognised an additional 60 kDa band. Compared to ID, CIE is more economical in terms of both time and reagents and provides more clear-cut results. The 58 kDa reactivity by IB was detectable in nearly all CIE/ID anti-LC1-positive patients, was not found among CIE/ID anti-LC1-negative patients. In conclusion, CIE is the ideal screening test for the detection of anti-LC1, an autoantibody that can be regarded as an additional serological marker of AIH and is especially useful in ANA/SMA/anti-LKM1 negative cases.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

Science.gov (United States)

Hida, Ayumi; Yamashita, Takenari; Hosono, Yuji; Inoue, Manami; Kaida, Kenichi; Kadoya, Masato; Miwa, Yusuke; Yajima, Nobuyuki; Maezawa, Reika; Arai, Satoko; Kurasawa, Kazuhiro; Ito, Kazuhiro; Shimada, Hiroyuki; Iwanami, Tomoko; Sonoo, Masahiro; Hatanaka, Yuki; Murayama, Shigeo; Uchibori, Ayumi; Chiba, Atsuro; Aizawa, Hitoshi; Momoo, Takayuki; Nakae, Yoshiharu; Sakurai, Yasuhisa; Shiio, Yasushi; Hashida, Hideji; Yoshizawa, Toshihiro; Sakiyama, Yoshio; Oda, Aya; Inoue, Kiyoharu; Takeuchi, Sousuke; Iwata, Nobue K; Date, Hidetoshi; Masuda, Naoki; Mikata, Takashi; Motoyoshi, Yasufumi; Uesaka, Yoshikazu; Maeda, Meiko Hashimoto; Nakashima, Ran; Tsuji, Shoji; Kwak, Shin; Mimori, Tsuneyo; Shimizu, Jun

2016-07-19

We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM. © 2016 American Academy of Neurology.

How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

Science.gov (United States)

Frodl, Thomas; O'Keane, Veronica

2013-04-01

There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

Interaction between the SLC19A1 gene and maternal first trimester fever on offspring neural tube defects.

Science.gov (United States)

Pei, Lijun; Zhu, Huiping; Ye, Rongwei; Wu, Jilei; Liu, Jianmeng; Ren, Aiguo; Li, Zhiwen; Zheng, Xiaoying

2015-01-01

Many studies have indicated that the reduced folate carrier gene (SLC19A1) is associated with an increased risk of neural tube defects (NTDs). However, the interaction between the SLC19A1 gene variant and maternal fever exposure and NTD risk remains unknown. The aim of this study was to investigate whether the risk for NTDs was influenced by the interactions between the SLC19A1 (rs1051266) variant and maternal first trimester fever. We investigated the potential interaction between maternal first trimester fever and maternal or offspring SLC19A1 polymorphism through a population-based case-control study. One hundred and four nuclear families with NTDs and 100 control families with nonmal newborns were included in the study. SLC19A1 polymorphism was determined using polymerase chain reaction-restricted fragment length polymorphism. Mothers who had the GG/GA genotype and first trimester fever had an elevated risk of NTDs (adjusted odds ratio, 11.73; 95% confidence interval, 3.02-45.58) as compared to absence of maternal first trimester fever and AA genotype after adjusting for maternal education, paternal education, and age, and had a significant interactive coefficient (γ = 3.17) between maternal GG/GA genotype and first trimester fever. However, there was no interaction between offspring's GG/GA genotype and maternal first trimester fever (the interactive coefficient γ = 0.97) after adjusting for confounding factors. Our findings suggested that the risk of NTDs was potentially influenced by a gene-environment interaction between maternal SLC19A1 rs1051266 GG/GA genotype and first trimester fever. Maternal GG/GA genotype may strengthen the effect of maternal fever exposure on NTD risk in this Chinese population. © 2014 Wiley Periodicals, Inc.

Maternal salivary cortisol levels during pregnancy are positively associated with overweight children.

Science.gov (United States)

Hohwü, Lena; Henriksen, Tine B; Grønborg, Therese K; Hedegaard, Morten; Sørensen, Thorkild I A; Obel, Carsten

2015-02-01

Animal and human studies suggest that programing of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the development of obesity, but human studies of biological indicators of HPA axis activity are lacking. We studied the association between levels of the stress hormone cortisol during pregnancy and overweight offspring during childhood into adolescence. Salivary samples from 655 Danish pregnant women with singleton pregnancies (1989-1991) were collected once in the morning and once in the evening in their second and third trimester. We followed the offspring from two to 16 years of age with at least one measurement of height and weight, and classified their body mass index into overweight and normal weight. The adjusted relative difference in median salivary cortisol (with 95% confidence interval (CI)) during pregnancy (the four samples), in second and third trimester (morning and evening samples) between overweight and normal weight offspring was estimated. Furthermore, the adjusted median ratio between morning and evening maternal salivary cortisol level was estimated for normal weight and overweight children. All the analyses were stratified into the equal age groups: 2-6, 7-11, and 12-16 years. We found non-significant higher maternal cortisol levels during pregnancy in offspring that were overweight at the age of 2-6, 7-11 and 12-16 years than in normal weight peers; adjusted relative difference in median salivary cortisol 11% (95% CI: -2; 25), 6% (95% CI: -7; 20), and 9% (95% CI: -4; 24), respectively. A statistically significantly higher level of maternal cortisol was found in the second trimester in 2-6-year-old and 12-16-year-old overweight offspring; relative difference 19% (95% CI: 3; 37), and 20% (95% CI: 3; 41), respectively. The median ratio between morning and evening maternal salivary cortisol level was similar for overweight and normal weight children; e.g. at age 2-6 years in third trimester 4.31 (95% CI: 4.05; 4.60)nmol/l and 4

Tetanus and diphtheria immunity among term and preterm infant-mother pairs in Turkey, a country where maternal and neonatal tetanus have recently been eliminated.

Science.gov (United States)

Erener-Ercan, Tugba; Aslan, Mustafa; Vural, Mehmet; Erginoz, Ethem; Kocazeybek, Bekir; Ercan, Gokmen; Turkgeldi, Lale Wetherilt; Perk, Yildiz

2015-03-01

The aim of our study was to investigate the anti-tetanus and anti-diphtheria antibody titres and the placental transfer of these antibodies in a group of vaccinated and unvaccinated mothers and their term or preterm offsprings. Anti-tetanus and anti-diphtheria toxoid IgG antibodies were measured quantitatively by ELISA in 91 infant-mother pairs. Protective concentrations of anti-tetanus and anti-diphtheria were found in 58.3 and 50% of mothers in the unvaccinated group and 94.5 and 85.5% of the mothers in the vaccinated group. Protective concentrations were found in 63.9 and 50% of cord samples, respectively, in the unvaccinated group and in 96.4 and 85.5% of cord samples, respectively, in the vaccinated group (p = 0.0001). There were no differences in the maternal and cord geometric mean concentrations (GMCs) of anti-toxoid antibodies between those who received two doses or one dose of Td. The GMCs of maternal and cord anti-tetanus and anti-diphtheria were statistically similar between preterm and term groups. Placental transfer ratios (TR) for anti-tetanus and anti-diphtheria were 175 and 150%, respectively, in the preterm group and 213 and 178%, respectively, in the term group. There was a strong correlation between maternal and cord anti-toxoid antibody levels. Maternal vaccination was the only predictor of having protective concentrations of anti-toxoid antibodies in cord blood. Vaccinating pregnant women with at least one dose of Td would confer protection for both the term and preterm infant-mother pairs. Therefore, health personnel caring for pregnant women have the responsibility to emphasize the importance of Td vaccination to avoid missed immunization opportunities.

Síndrome antissintetase anti-Jo-1 Anti-Jo-1 antisynthetase syndrome

Directory of Open Access Journals (Sweden)

Samuel Katsuyuki Shinjo

2010-10-01

Full Text Available OBJETIVO: Devido à escassez de estudos populacionais, apresentamos um estudo epidemiológico em síndrome antissintetase anti-Jo-1 (SAS. PACIENTES E MÉTODOS: Estudo coorte retrospectivo realizado em um centro de 1980 a 2010. Dados clínico-laboratoriais e demográficos foram obtidos dos prontuários médicos. Todos os pacientes preenchiam critério de Bohan e Peter (1975 e apresentavam anti-Jo-1, além de envolvimento articular, muscular e pulmonar. Dezoito pacientes com SAS anti-Jo-1 foram analisados. RESULTADOS: A média de idade ao início da doença foi de 39,9 ± 15,7 anos, e a média da duração da doença, 9,7 ± 7,0 anos. Todos os pacientes eram brancos, e 94,4% eram mulheres. Sintomas constitucionais ocorreram em metade dos casos. Envolvimento cutâneo e do trato gastrointestinal ocorreram, respectivamente, em 66,6% e 55,6% dos casos. Não houve casos de envolvimento neurológico ou cardíaco. Metade dos pacientes apresentava pneumopatia incipiente, opacidade em vidro-fosco e fibrose pulmonar basal. Houve um caso de tuberculose, três de herpes zoster e um linfoma não Hodgkin. Um óbito ocorreu devido ao choque séptico (broncopneumonia hospitalar. Todos os pacientes receberam prednisona (1mg/kg/dia e 12 (66,7% receberam pulsoterapia com metil prednisolona (1 g/dia, 3 dias. Diferentes imunossupressores foram utilizados como poupadores de corticosteroide, dependendo da tolerância, efeitos colaterais e/ou refratariedade da doença. Embora a recidiva da doença (clínica e/ou laboratorial tenha ocorrido em 87,5% dos casos, 12 dos 16 pacientes (75% estavam com a remissão da doença no desfecho do presente estudo. CONCLUSÃO: A maioria dos pacientes eram mulheres brancas e com alta taxa de recidiva da doença.OBJECTIVE: Given a lack of population-based studies, we report an epidemiological-clinic study of anti-Jo-1 antisynthetase syndrome (ASS. PATIENTS AND METHODS: To study a retrospective cohort of a single-center from 1980 to 2010

Non(anti)commutative N = (1,1/2) supersymmetric U(1) gauge theory

International Nuclear Information System (INIS)

Araki, Takeo; Ito, Katsushi; Ohtsuka, Akihisa

2005-01-01

We study a reduction of deformation parameters in non(anti)commutative N = 2 harmonic superspace to those in non(anti)commutative N = 1 superspace. By this reduction we obtain the exact gauge and supersymmetry transformations in the Wess-Zumino gauge of non(anti)commutative N = 2 supersymmetric U(1) gauge theory defined in the deformed harmonic superspace. We also find that the action with the first order correction in the deformation parameter reduces to the one in the N = 1 superspace by some field redefinition. We construct deformed N = (1,1/2) supersymmetry in N = 2 supersymmetric U(1) gauge theory in non(anti)commutative N = 1 superspace

Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

NARCIS (Netherlands)

Kallen, V. L.; Tulen, J. H. M.; Utens, E. M. W. J.; Treffers, P. D. A.; de Jong, F. H.; Ferdinand, R. F.

2008-01-01

The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were

Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

Science.gov (United States)

Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2018-01-01

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger

A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health

Directory of Open Access Journals (Sweden)

Kendall-Tackett Kathleen

2007-03-01

Full Text Available Abstract Background Research in the field of psychoneuroimmunology (PNI has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines. Discussion The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation. These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular. Puerperal women are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain, and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise. Breastfeeding has a protective effect on maternal mental health because it attenuates stress and modulates the inflammatory response. However, breastfeeding difficulties, such as nipple pain, can increase the risk of depression and must be addressed promptly. Conclusion PNI research suggests two goals for the prevention and treatment of postpartum depression: reducing maternal stress and reducing inflammation. Breastfeeding and exercise reduce maternal stress and are protective of maternal mood. In addition, most current treatments for depression are anti-inflammatory. These include long-chain omega-3 fatty acids, cognitive therapy, St. John's wort, and conventional antidepressants.

X-ray investigation of the interface structure of free standing InAs nanowires grown on GaAs[ anti 1 anti 1 anti 1]{sub B}

Energy Technology Data Exchange (ETDEWEB)

Bauer, Jens; Gottschalch, Volker; Wagner, Gerald [Universitaet Leipzig, Halbleiterchemie, Leipzig (Germany); Pietsch, Ullrich; Davydok, Anton; Biermanns, Andreas [Universitaet Siegen, Festkoerperphysik, Siegen (Germany); Grenzer, Joerg [Forschungszentrum Rossendorf, Institut fuer Ionenstrahlphysik und Materialforschung, Dresden (Germany)

2009-09-15

The heteroepitaxial growth process of InAs nanowires (NW) on GaAs[ anti 1 anti 1 anti 1]{sub B} substrate was investigated by X-ray grazing-incidence diffraction using synchrotron radiation. For crystal growth we applied the vapor-liquid-solid (VLS) growth mechanism via gold seeds. The general sample structure was extracted from various electron microscopic and X-ray diffraction experiments. We found a closed Ga{sub x}In{sub 1-x} As graduated alloy layer at the substrate to NW interface which was formed in the initial stage of VLS growth with a Au-Ga-In liquid alloy. With ongoing growth time a transition from this VLS layer growth to the conventional VLS NW growth was observed. The structural properties of both VLS grown crystal types were examined. Furthermore, we discuss the VLS layer growth process. (orig.)

Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

Science.gov (United States)

Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

2015-01-01

The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant.

HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

Science.gov (United States)

Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

2009-12-01

Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

Directory of Open Access Journals (Sweden)

Magdalena M Przybycien-Szymanska

2011-04-01

Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences.

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Laurent, Heidemarie K; Leve, Leslie D; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Harold, Gordon T; Reiss, David

2013-05-01

This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents' symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk.

Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis.

Science.gov (United States)

Mescam-Mancini, Lénaig; Allenbach, Yves; Hervier, Baptiste; Devilliers, Hervé; Mariampillay, Kuberaka; Dubourg, Odile; Maisonobe, Thierry; Gherardi, Romain; Mezin, Paulette; Preusse, Corinna; Stenzel, Werner; Benveniste, Olivier

2015-09-01

Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1 antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies. In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed. Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflammation was mainly located in the perimysium and around vessels in 90.6%. Perimysial fragmentation was observed in 90% of cases. Major histocompatibility complex class I staining was diffusely positive, with a perifascicular reinforcement. Multivariate analysis showed that criteria defining perifascicular pathology: perifascicular necrosis, atrophy, and perimysial fragmentation allow the distinction of anti-Jo-1 antibody-positive patients, among patients suffering from other idiopathic inflammatory myopathies. Anti-Jo-1 antibody-positive patients displayed perifascicular necrosis, whereas dermatomyositis patients exhibited perifascicular atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anti-beta2 glycoprotein 1 and the anti-phospholipid syndrome.

LENUS (Irish Health Repository)

Keane, Pearse A

2012-02-03

PURPOSE: To describe a patient who presented with bilateral retinal vascular occlusion and the use of anti-beta2 glycoprotein 1 (GPI) antibody testing in the diagnosis of antiphospholipid syndrome. DESIGN: Observational case report. METHODS: Hematological investigations were performed on a 49-year-old man who presented with rapid onset of bilateral severe central retinal vein occlusion. RESULTS: Lupus anticoagulant and anticardiolipin antibody testing was negative. Markedly raised titers of anti-beta2 GPI antibodies were detected on two separate occasions. CONCLUSIONS: The raised titers of anti-beta2 GPI antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome.

The association between perceived emotional support, maternal mood, salivary cortisol, salivary cortisone, and the ratio between the two compounds in response to acute stress in second trimester pregnant women.

Science.gov (United States)

La Marca-Ghaemmaghami, Pearl; La Marca, Roberto; Dainese, Sara M; Haller, Marina; Zimmermann, Roland; Ehlert, Ulrike

2013-10-01

Little is known about the effect of social support on the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy. Moreover, when investigating the HPA axis most studies do not consider the activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme within the salivary glands that inactivates cortisol to cortisone. This study explores the association between perceived emotional support and the maternal psychobiological stress response to a standardized naturalistic stressor by assessing maternal mood and the reactivity of salivary cortisol (SalF), salivary cortisone (SalE), and the SalE/(E+F) ratio as a marker of 11β-HSD2 activity. Repeated saliva samples and measures of maternal mood were obtained from 34 healthy second trimester pregnant women undergoing amniocentesis which served as a psychological stressor. The pregnant women additionally responded to a questionnaire of perceived emotional support and provided sociodemographic (e.g., maternal educational degree) and pregnancy-specific data (e.g., planned versus unplanned pregnancy). Perceived emotional support neither showed a significant effect on mood nor on the SalF or SalE response to stress. However, a moderately strong positive association was found between perceived emotional support and SalE/(E+F) (r=.49). Additionally, the final regression analysis revealed a significant negative relationship between educational degree, planned/unplanned pregnancy and SalE/(E+F). Findings suggest a higher metabolization of cortisol to cortisone in pregnant women with higher emotional support. In contrast, higher maternal education and unplanned pregnancy appear to be associated with decreased salivary 11β-HSD2 activity. The current study emphasizes the importance of taking the activity of 11β-HSD2 into account when examining SalF. © 2013.

Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis

NARCIS (Netherlands)

Gardner, M.P.; Lightman, S.; Sayer, A.A.; Cooper, C.; Cooper, R.; Deeg, D.J.H.; Ebrahim, S.; Gallacher, J.; Kivimaki, M.; Kumari, M.; Kuh, D; Martin, R.M.; Peeters, G.; Ben-Shlomoa, Y.

2013-01-01

The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is

The maternal-effect, selfish genetic element Medea is associated with a composite Tc1 transposon.

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Lorenzen, Marcé D; Gnirke, Andreas; Margolis, Jonathan; Garnes, Jeffrey; Campbell, Margie; Stuart, Jeffrey J; Aggarwal, Rajat; Richards, Stephen; Park, Yoonseong; Beeman, Richard W

2008-07-22

Maternal-Effect Dominant Embryonic Arrest ("Medea") factors are selfish nuclear elements that combine maternal-lethal and zygotic-rescue activities to gain a postzygotic survival advantage. We show that Medea(1) activity in Tribolium castaneum is associated with a composite Tc1 transposon inserted just downstream of the neurotransmitter reuptake symporter bloated tubules (blot), whose Drosophila ortholog has both maternal and zygotic functions. The 21.5-kb insertion contains defective copies of elongation initiation factor-3, ATP synthase subunit C, and an RNaseD-related gene, as well as a potentially intact copy of a prokaryotic DUF1703 gene. Sequence comparisons suggest that the current distribution of Medea(1) reflects global emanation after a single transpositional event in recent evolutionary time. The Medea system in Tribolium represents an unusual type of intragenomic conflict and could provide a useful vehicle for driving desirable genes into populations.

An example of auto-anti-A1 agglutinins.

Science.gov (United States)

Wright, J; Lim, F C; Freedman, J

1980-10-01

The serum of an elderly man, group A, Le(a+b-), contained an IgM antibody that agglutinated his own cells and the cells of random group A1 donors. Over a period of 5 months, the titre of these auto-anti-A1 agglutinins was 4 at 22 degrees C.

The influence of maternal islet beta-cell autoantibodies in conjunction with gestational hyperglycemia on neonatal outcomes.

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Zhe Li

Full Text Available To determine the predictive value of the presence of maternal islet beta-cell autoantibodies with respect to neonatal outcomes.A total of 311 pregnant women with abnormal 75 g oral glucose tolerance test (OGTT results were enrolled in this study. Maternal glutamic acid decarboxylase autoantibodies (GADA, islet cell autoantibodies (ICA and insulin autoantibodies (IAA were tested in fasting blood both on the day following the routine OGTT and before delivery. The birth weight, Apgar score, blood glucose and outcomes of each neonate were later evaluated and recorded.1. In this study, 33.9% of the pregnant women with gestational hyperglycemia had detectable levels of one or more types of anti-islet cell antibodies in the third trimester. The proportion of women who produced GADA and/or ICA was significantly higher in the group of women with gestational hyperglycemia than in the control group (P<0.05. The groups similarly differed in the proportion of women who tested positive for any anti-islet cell antibody (P<0.05. 2. Of the patients in our study, those who produced GADA exhibited an increase in uterine and umbilical arterial pulsatility indexes (PIs during the third trimesters compared with the control group (P˂0.05. Additionally, an increased frequency of fetal growth restriction (FGR was observed in the infants of women who produced IAA during pregnancy compared with those without autoantibodies (P˂0.05. 3. The rate of newborn admission to the neonatal intensive care unit (NICU was significantly associated with the presence of maternal ICA during the third trimester (OR, 6.36; 95% CI, 1.22-33.26. 4. The incidence of neonatal asphyxia was associated with the presence of maternal GADA in both the second (OR, 10.44; 95% CI, 1.46-74.92 and the third (OR, 8.33; 95% CI, 1.45-47.82 trimesters.Approximately one-third of the women with gestational hyperglycemia produced anti-islet cell antibodies. The incidence of FGR was higher in women with

Co-ordinate expression of Th1/Th2 phenotypes in maternal and fetal blood: evidence for a transplacental nexus.

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Tse, Doris B; Young, Bruce K

2012-01-06

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE ordinate IFN-γ production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-γ. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system.

Hair cortisol concentration (HCC) as a measure for prenatal psychological distress - A systematic review.

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Mustonen, Paula; Karlsson, Linnea; Scheinin, Noora M; Kortesluoma, Susanna; Coimbra, Bárbara; Rodrigues, Ana João; Karlsson, Hasse

2018-06-01

Prenatal environment reportedly affects the programming of developmental trajectories in offspring and the modification of risks for later morbidity. Among the increasingly studied prenatal exposures are maternal psychological distress (PD) and altered maternal hypothalamus-pituitary-adrenal (HPA) axis functioning. Both prenatal PD and maternal short-term cortisol concentrations as markers for HPA axis activity have been linked to adverse child outcomes and it has been assumed that maternal PD affects the offspring partially via altered cortisol secretion patterns. Yet, the existing literature on the interrelations between these two measures is conflicting. The assessment of cortisol levels by using hair cortisol concentration (HCC) has gained interest, as it offers a way to assess long-term cortisol levels with a single non-invasive sampling. According to our review, 6 studies assessing the associations between maternal HCC during pregnancy and various types of maternal PD have been published so far. Measures of prenatal PD range from maternal symptoms of depression or anxiety to stress related to person's life situation or pregnancy. The aim of this systematic review is to critically evaluate the potential of HCC as a biomarker for maternal PD during pregnancy. We conclude that HCC appears to be inconsistently associated with self-reported symptoms of prenatal PD, especially in the range of mild to moderate symptom levels. Self-reports on PD usually cover short time periods and they seem to depict partly different phenomena than HCC. Thus, methodological aspects are in a key role in future studies evaluating the interconnections across different types of prenatal PD and maternal HPA axis functioning. Further, studies including repetitive measurements of both HCC and PD during the prenatal period are needed, as timing of the assessments is one important source of variation among current studies. The significance of prenatal HCC in the context of offspring outcomes

Maternal and perinatal outcomes in 143 Danish women with gestational diabetes mellitus and 143 controls with a similar risk profile

DEFF Research Database (Denmark)

Jensen, Dorte Møller; Sørensen, B; Feilberg-Jørgensen, N

2000-01-01

To assess maternal and fetal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM) compared to non-diabetic pregnancies with an otherwise similar risk profile and to study the association between different anti-diabetic treatments and fetal outcomes.......To assess maternal and fetal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM) compared to non-diabetic pregnancies with an otherwise similar risk profile and to study the association between different anti-diabetic treatments and fetal outcomes....

Efficacy of the anti-VZV (anti-HSV3 vaccine in HSV1 and HSV2 recurrent herpes simplex disease: a prospective study

Directory of Open Access Journals (Sweden)

Le Goaster J

2012-07-01

Full Text Available Jacqueline Le Goaster,1 Sylvie Gonzalo,2 Patrice Bourée,1 Frederic Tangy,3 Anne-Lise Haenni41Department of Tropical Diseases, Centre Hospitalo-Universitaire (CHU, University of Paris XI, Le Kremlin Bicêtre, 2Biomnis Laboratory, Ivry-sur-Seine, 3Retro-Virology, Centre National de Recherche Scientifique (CNRS, Pasteur Institute, Paris; 4Jacques Monod Institute, Centre National de Recherche Scientifique (CNRS, University of Paris VII, Paris, FranceBackground: The aim of this study was to evaluate the possibility of using the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3 vaccine against orobuccal herpes simplex virus type 1 (HSV1 and genital herpes simplex virus type 2 (HSV2. This was suggested by study of the phylogenetic tree of members of the herpes virus family, which showed a close relationship between VZV (HSV3 and the HSV1 and HSV2 herpes viruses.Methods: The present prospective study was conducted from January 2005 through January 2011. Twenty-four patients afflicted with HSV1 and HSV2 herpes recurrences over a period of years, numbering 6–8 and more recurrences per year, agreed to receive the anti-VZV vaccine. They were compared with 26 nonvaccinated patients presenting with herpes simplex diseases 2–5 times a year. All 50 patients were documented with anti-HSV1, anti-HSV2, and anti-VZV antibody serological testing.Results: From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 nonvaccinated herpes patients.Conclusion: Data for the anti-VZV serological antibody levels tested before and after anti-VZV vaccination showed a significant (P < 0.001 increase among vaccinated patients. This suggests defective anti-VZV immune power in these patients. After 6 years of positive results for anti-VZV vaccine, this is a logical and

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

Science.gov (United States)

Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

2017-04-01

Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal obesity, caesarean delivery and caesarean delivery on maternal request: a cohort analysis from China.

Science.gov (United States)

Zhou, Yubo; Blustein, Jan; Li, Hongtian; Ye, Rongwei; Zhu, Liping; Liu, Jianmeng

2015-05-01

To quantify the association between maternal obesity and caesarean delivery, particularly caesarean delivery on maternal request (CDMR), a fast-growing component of caesarean delivery in many nations. We followed 1,019,576 nulliparous women registered in the Perinatal Healthcare Surveillance System during 1993-2010. Maternal body mass index (BMI, kg/m(2) ), before pregnancy or during early pregnancy, was classified as underweight (obese (≥27.5), consistent with World Health Organization guidelines for Asian people. The association between maternal obesity and overall caesarean and its subtypes was modelled using log-binomial regression. During the 18-year period, 404,971 (39.7%) caesareans and 93,927 (9.2%) CDMRs were identified. Maternal obesity was positively associated with overall caesarean and CDMR. Adjusted risk ratios for overall caesarean in the four ascending BMI categories were 0.96 [95% confidence interval (CI) 0.94, 0.97], 1.00 (Reference), 1.16 [95% CI 1.14, 1.18], 1.39 [95% CI 1.43, 1.54], and for CDMR were 0.95 [95% CI 0.94, 0.96], 1.00 (Reference), 1.20 [95% CI 1.18, 1.22], 1.48 [95% CI 1.433, 1.54]. Positive associations were consistently found in women residing in southern and northern provinces and in subgroups stratified by year of delivery, urban or rural residence, maternal age, education, level of delivering hospital, and birthweight. In a large Chinese cohort study, maternal obesity was associated with an increased risk of caesarean delivery and its subtypes, including CDMR. Given the rising global prevalence of obesity, and in view of the growth of CDMR, it seems likely that caesarean births will increase, unless there are changes in obstetrical practice. © 2015 John Wiley & Sons Ltd.

Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection.

Science.gov (United States)

Salovin, Amy; Glanzman, Jason; Roslin, Kylie; Armangue, Thais; Lynch, David R; Panzer, Jessica A

2018-07-01

To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE). Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort "Philadelphia" included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort "Barcelona" contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined. In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3-17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7-7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3-7.7, p = 0.007). Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE.

Neurological Complications Associated With Anti-Programmed Death 1 (PD-1) Antibodies.

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Kao, Justin C; Liao, Bing; Markovic, Svetomir N; Klein, Christopher J; Naddaf, Elie; Staff, Nathan P; Liewluck, Teerin; Hammack, Julie E; Sandroni, Paola; Finnes, Heidi; Mauermann, Michelle L

2017-10-01

Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016. All patients receiving anti-PD-1 monoclonal antibodies were identified using the Mayo Cancer Pharmacy Database. Patients with development of neurological symptoms within 12 months of anti-PD-1 therapy were included. Patients with neurological complications directly attributable to metastatic disease or other concurrent cancer-related treatments were excluded. Clinical and pathological characteristics, time to development of neurological symptoms, and modified Rankin Scale (mRS) score. Among 347 patients treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab), 10 (2.9%) developed subacute onset of neurological complications. Seven patients were receiving pembrolizumab, and 3 patients were receiving nivolumab. The patients included 8 men and 2 women. Their median age was 71 years (age range, 31-78 years). Neurological complications occurred after a median of 5.5 (range, 1-20) cycles of anti-PD-1 inhibitors. Complications included myopathy (n = 2), varied neuropathies (n = 4), cerebellar ataxia (n = 1), autoimmune retinopathy (n = 1), bilateral internuclear ophthalmoplegia (n = 1), and headache (n = 1). Peripheral neuropathies included axonal and demyelinating polyradiculoneuropathies (n = 2), length-dependent neuropathies (n = 1), and asymmetric vasculitic neuropathy (n = 1). The time to maximum

Change in parent-child conflict and the HPA-axis: Where should we be looking and for how long?

Science.gov (United States)

Kuhlman, Kate R.; Repetti, Rena L.; Reynolds, Bridget M.; Robles, Theodore F.

2017-01-01

Objective Salivary cortisol is increasingly used as a longitudinal indicator of change in neuroendocrine regulation and as a predictor of health outcomes in youth. The purpose of this study was to describe which indices of HPA-axis functioning are sensitive to changes in parent-child conflict over a three week period and to explore the time course under which these changes can be measured. Methods Youth (n = 47; ages 8–13) completed daily diaries of their conflict with parents for 56 days. On days 17–18 and 38–39, youth contributed saliva samples upon waking, 30-minutes post-waking, afternoon, and bedtime. We assessed change in average diurnal HPA-axis functioning between day 17–18 and day 38–39 as a function of the slopes of change in parent-child conflict over 3 weeks. Results Increasing parent-child conflict was positively associated with concurrent increases in total cortisol output (AUCg), flattening of the diurnal slope, and increases in cortisol at bedtime, but not with change in the cortisol awakening response (CAR). Further, associations between parent-child conflict and both AUCg and bedtime cortisol were observed with at least 14 days of daily diary reporting, whereas any additional ratings of conflict beyond 3 days of daily diaries did not improve model fit for changes in diurnal slope. Conclusions This study demonstrates the within-subject up-regulation of the HPA-axis across three weeks in a healthy sample of youth exposed to natural increases in family conflict. In particular, cortisol at bedtime may be the HPA-axis index that is most sensitive to change over time in parent-child conflict, above and beyond conflict occurring that day. Further, when testing associations between family stressors and diurnal cortisol, the optimal schedule for assessing parent-child conflict varies for different indices of HPA-axis functioning. PMID:26963373

Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

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Wieke de Vente

2015-01-01

Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

In Search of HPA Axis Dysregulation in Child and Adolescent Depression

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Guerry, John D.; Hastings, Paul D.

2011-01-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

Swine as a model for the study of maternal neonatal immunoregulation

International Nuclear Information System (INIS)

Butler, J.E.; Cambier, J.C.; Klobasa, F.; Werhahn, E.

1986-01-01

Swine provide a useful model for evaluating maternal antibody influences on the immune system of developing neonates. Unlike rodents and humans, no antibodies are transferred passively in utero so that newborn piglets, unlike mice pups and babies, enter the world having had no previous exposure to antibodies of their mothers. If maternal antibodies transmitted in utero are immunoregulatory and are in part the basis for neonatal unresponsiveness in neonatal mice and infants, swine offer a model with which to study this regulation. Neonatal piglets can be obtained at birth before suckling and reared in ''artificial sows'' without maternal antibodies which may be administered to neonates in metered amounts with regard to specificity, isotype and idiotype. Fetal piglets can be manipulated surgically in utero; their blood vascular system can be cannulated permitting in utero immunization and continuous sampling. Maternal immunoglobulins play an immunoregulatory role in both conventional and artificial feeding experiments. Data are presented which illustrate the magnitude of this phenomenon and which show that such an effect occurs naturally when piglets suckling first gestation and multilitter sows are compared. Finally, data are reviewed on the characterization of an idiotype anti-idiotype system developed to probe the mechanism of maternal neonatal immunoregulation

Glucocorticoids and fetal programming part 1: Outcomes.

Science.gov (United States)

Moisiadis, Vasilis G; Matthews, Stephen G

2014-07-01

Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.

Positive and negative social support and HPA-axis hyperactivity: Evidence from glucocorticoids in human hair.

Science.gov (United States)

Iob, Eleonora; Kirschbaum, Clemens; Steptoe, Andrew

2018-06-12

While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health. Hair glucocorticoids such as cortisol and cortisone are emerging as promising biomarkers of long-term retrospective HPA activation. Therefore, the aim of this investigation was to examine the effects of positive and negative experiences of social support within key relationships (i.e. spouse/partner, children, other family members, and friends) on cortisol and cortisone. These associations were tested in a sample of 2520 older adults (mean age 68.1) from the English Longitudinal Study of Ageing. Hair samples were collected in wave 6 (2012/13). To understand the impact of cumulative exposure to poor social support, the analysis used self-reported data from waves 4 (2008/09) and 6. Covariates included demographic, socioeconomic, lifestyle, and hair characteristics. In cross sectional analyses, lower positive support from all sources and specifically from children were associated with higher cortisol. Additionally, lower positive support from children was positively associated with cortisone. Similarly, higher overall negative support was related to higher cortisol, and greater negative support from children was also positively associated with cortisone. In longitudinal analyses, there was evidence for positive associations between hair glucocorticoids and cumulative exposure to poorer social support. Experiences of low positive and high negative social support, particularly from children, were both related to higher hair glucocorticoids. Hence, social relationships of

Maternal vitamin D status in type 1 diabetic pregnancy: impact on neonatal vitamin D status and association with maternal glycaemic control.

Directory of Open Access Journals (Sweden)

Sarah E Bennett

Full Text Available The first aim of this study was to assess 25-hydroxy vitamin D (25OHD concentrations in women with type 1 diabetes (T1DM during pregnancy, post-delivery and also foetal (cord blood 25OHD concentrations and to examine relationships between these. The second aim of the study was to investigate potential interactions between maternal body mass index (BMI and foetal vitamin D status. A further study aim was to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c throughout pregnancy.This was an observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS.Vitamin D deficiency (25OHD 30 kg/m(2 (nmol/L ± SD; 19.93 ± 11.15 vs. 13.73 ± 4.74, p=0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p=0.004; p=0.001; p=0.05.In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese women than in their normal weight counterparts. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control.

A production in anti p - d interactions below 1 GeV/c

International Nuclear Information System (INIS)

Smith, D.W.; Billiris, B.; Mandelkern, L.R.; Price, L.R.; Schultz, J.

1979-01-01

382 Λ events have been measured and analyzed in an anti p - d bubble chamber experiment at 552, 740, and 905 MeV/c. We compare our data with two other anti p - d experiments at beam momenta from 1 to 3 GeV/c. Some features of the double scattering mechanism are calculated using an anti K and anti Λ as the exchanged particles. The anti K exchange appears to be a more likely candidate for the production mechanism. (auth)

Undiagnosed phenylketonuria in parents of phenylketonuric patients, is it worthwhile to be checked?

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Wiedemann, A; Leheup, B; Battaglia-Hsu, S-F; Jonveaux, P; Jeannesson, E; Feillet, F

2013-01-01

In our phenylketonuria (PKU) cohort of 120 patients, we uncovered a couple of cases of undiagnosed mild phenylketonuria (mPKU)/hyperphenylalaninemia (mHPA) in maternal parents of the PKU cohort. This finding prompted us to evaluate the risk of either mild phenylketonuria or mild hyperphenylalaninemia in the parent population whose children were diagnosed with hyperphenylalaninemia (HPA). Taking into account the phenylalanine hydroxylase (PAH) mutation carrier frequency and the PAH mild mutation rate, we estimated that the prevalence of the parental mPKU/mHPA varied widely, from 1/74 in Turkey to 1/708 in Lithuania. The benefits of the parental detection procedure described here are the prevention of further maternal PKU syndrome, the follow-up of the newly detected patients and the accuracy of the genetic counseling provided to these families. This very simple procedure should be incorporated into neonatal PKU management of the hospitals in countries where a routine systematic neonatal screening is operational. © 2013.

Severe acute maternal morbidity and maternal death audit - a rapid ...

African Journals Online (AJOL)

Severe acute maternal morbidity and maternal death audit - a rapid diagnostic tool for evaluating maternal care. L Cochet, R.C. Pattinson, A.P. Macdonald. Abstract. Objective. To analyse severe acute maternal morbidity (SAMM) and maternal mortality in the Pretoria region over a 2-year period (2000 - 2001). Setting.

The Moderating Role of Sensory Overresponsivity in HPA Activity: A Pilot Study with Children Diagnosed with ADHD

Science.gov (United States)

Reynolds, Stacey; Lane, Shelly J.; Gennings, Chris

2010-01-01

Objective: To determine if sensory overresponsivity (SOR) is a moderating condition impacting the activity of the Hypothalamic Pituitary Adrenal (HPA) Axis in children with ADHD. Method: Participants were children with (n = 24) and without ADHD (n = 24). Children in the ADHD group were divided into SOR (ADHDs) and non-SOR (ADHDt) groups using the…

Maternal Mortality – A Challenge?

Directory of Open Access Journals (Sweden)

Shital G. Sonone

2013-01-01

Full Text Available Background : The current maternal mortality rate (MMR in Maharashtra is 104/100000 live births, ranking 3rd in India. There is scope for reducing it as majority of the causes of MMR are preventable and curable. Aims and Objectives: To study the sociodemographic profile and causes of maternal deaths at Dr. V. M. Govt. Medical College, Solapur. Material and Methods: The study population included all deliveries i.e. women admitted in the hospital during pregnancy, child-birth or within 42 days of termination of pregnancy from any cause related to or aggravated due to pregnancy during the period of 2 years from 1st August 2009 to 31st July 2011. IPD case records and autopsy reports of all maternal deaths were taken and various variables were studied. The present study is prospective study of maternal mortality conducted in Dept. of Obstetrics and Gynaecology, Dr. V. M. Medical College Solapur. Cases were distributed ac-cording to their age, literacy rate, residence,socioeconomic status, ante-natal care, gestational age, gravida/parity, place of referral, pregnancy outcome, and place of delivery, perinatal outcome and etiological factors. This study also suggests the measures to reduce maternal mortality. Results: The total number of live births during the study period were 13,188 and total number of maternal deaths were 63 and MMR was 477 per 1, 00,000 live births. In the maternal deaths studied, 1/3rd of the women were illiterate, half of the women belonged to urban slum areas and of lower socioeconomic class.1/3rd of the deaths occurred in primigravida,within 24 hrs from admission, 58.73% of the patients were referred from outside. Out of that 86.49% of women were sent from private hospital and died in post partum period, having poor perinatal outcome. Haemorrhage (28.57% and hypertension (12.69% are two direct causes and severe anemia (33.33% is most common in direct cause of maternal death in our study.

Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

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Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

2017-02-01

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis.

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Zaretsky, Dmitry V; Zaretskaia, Maria V; Sarkar, Sumit; Rusyniak, Daniel E; DiMicco, Joseph A

2017-07-13

The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH 1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105±13 to 278±51pg/ml after 20mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration. Copyright © 2017 Elsevier B.V. All rights reserved.

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

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Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

2014-09-01

Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

ANTI-HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1 (ANTI-RA33 ANTIBODIES IN RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS

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P. A. Kuznetsova

2017-01-01

Full Text Available Anti-heterogeneous nuclear ribonucleoprotein (RNP autoantibodies (AAbs are encountered in many autoimmune rheumatic diseases (ARDs. The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA, ankylosing spondylitis (AS, systemic lupus erythematosus (SLE, systemic sclerosis (SSc, and Sjö gren's syndrome (SS and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6% and 8/53 (13% patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144 of the patients with RA; 40.3% (23/57 of those with AS, in 67.5% (27/40 of those with SSc, in 36.4% (16/44 of those with SLE, and in 13.3% (2/15 of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml, but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.

Anomalías de circulación atmosférica en 500 y 1000 hpa asociada a la sequía producida en la Argentina durante enero de 2003 a marzo de 2004 Anomalies of the atmospheric circulation at 500 and 1000 hpa associated with the dry period in Argentina from january 2003 to march 2004

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Adelia Perla Alessandro

2008-03-01

Full Text Available Neste trabalho se analisa e descreve a situação sinótica associada à precipitação e temperatura do território argentino durante o ano de 2003 e o primeiro trimestre de 2004. A escolha deste período obedece à falta de precipitações em pelo menos dez províncias argentinas, o que ocasionou grandes prejuízos econômicos no setor agropecuário. Com o intuito de determinar as causas deste déficit de precipitações foram analisados os campos médios de altura geopotencial nos níveis de 500 e 1000 hPa e suas anomalias. Em 2003, o déficit de precipitação se associa principalmente às anomalias de geopotencial no nível de 500 hPa, que mostram um fluxo dominante de SO que atravessa o país diagonalmente entre 45°S e 30°S. Em 1000 hPa o anticiclone subtropical do Atlântico se encontra enfraquecido, deslocado para o norte e afastado do continente, enquanto que o anticiclone subrtopical do Pacífico está mais intenso e deslocado para leste respeito da sua posição normal. No primeiro trimestre de 2004 a seca se deve principalmente à presença de uma crista no nível de 500 hPa posicionada no centro do país. As anomalias médias de temperatura do período considerado resultam positivas sobre toda a Argentina. Em 2003, essas anomalias se devem à contribuição do fluxo do N-NE desde o norte do país, à subsidência ocasionada pelo anticiclone do Pacífico mais deslocado para o interior do continente e a orografia. No primeiro trimestre de 2004 as anomalias se originam devido ao fluxo do norte e à freqüente circulação anticiclônica no Atlântico ao sul de 35°S.This paper analyzes and describes the synoptic situation associated with precipitation and temperature in Argentina during 2003 and the first quarter of 2004. The period was selected as during that time drought affected at least ten Argentine provinces, causing great agricultural and ranching losses. In order to find the causes of such rainfall deficit the mean and

Maternal Mortality in a Nigerian Maternity Hospital | Olopade ...

African Journals Online (AJOL)

Despite recent focus on maternal mortality in Nigeria, its rates remain unacceptably high in Nigeria. A retrospective case-control study was carried out at Adeoyo Maternity Hospital, Ibadan between January 2003 and December 2004. This was to determine the maternal mortality ratio in a secondary health facility, to identify ...

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy.

LENUS (Irish Health Repository)

Cooley, Sharon M

2012-02-01

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET.

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

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While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

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While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

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Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2007-01-01

Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

Hemolytic disease of the newborn due to anti-U Doença hemolítica do recém-nascido devido a anti-U

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Marcia Cristina Zago Novaretti

2003-01-01

Full Text Available Anti-U is a rare red blood cell alloantibody that has been found exclusively in blacks. It can cause hemolytic disease of the newborn and hemolytic transfusion reactions. We describe the case of a female newborn presenting a strongly positive direct antiglobulin test due to an IgG antibody in cord blood. Anti-U was recovered from cord blood using acid eluate technique. Her mother presented positive screening of antibodies with anti-U identified at delivery. It was of IgG1 and IgG3 subclasses and showed a titer of 32. Monocyte monolayer assay showed moderate interaction of Fc receptors with maternal serum with a positive result (3.1%. The newborn was treated only with 48 hours of phototherapy for mild hemolytic disease. She recovered well and was discharged on the 4th day of life. We conclude that whenever an antibody against a high frequency erythrocyte antigen is identified in brown and black pregnant women, anti-U must be investigated.Anti-U é um aloanticorpo eritrocitário raro detectado exclusivamente em negros, que pode causar doença hemolítica do recém-nascido e reações transfusionais hemolíticas. Relatamos o caso de um recém-nascido, de sexo feminino, que apresentou teste de antiglobulina direto fortemente positivo, dirigido a um anticorpo IgG em sangue de cordão umbilical. Anti-U foi identificado por técnica de eluição ácida. A mãe apresentava pesquisa de anticorpos irregulares positiva com anticorpo anti-U, de subclasses IgG1 e IgG3, título 32, identificado ao nascimento. O ensaio de monocamada de monócitos apresentou resultado positivo (3.1%, mostrando uma interação moderada de receptores Fc com soro materno. O recém-nascido foi tratado somente por fototerapia durante 48 horas para uma doença hemolítica leve. A criança recuperou-se bem e teve alta médica no quarto dia de vida. Concluímos que quando um anticorpo contra um antígeno eritrocitário de alta freqüência for identificado em gestantes negras e pardas

Inflammation Is an Important Covariate for the Crosstalk of Sleep and the HPA Axis in Rheumatoid Arthritis.

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Straub, Rainer H; Detert, Jaqueline; Dziurla, René; Fietze, Ingo; Loeschmann, Peter-Andreas; Burmester, Gerd R; Buttgereit, Frank

2017-01-01

Rheumatoid arthritis (RA) patients have sleep problems, and inflammation influences sleep. We demonstrated that sleep quality improves during intensified treatment with methotrexate (MTX) or etanercept (ETA). Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in sleep regulation, this study investigated the interrelation between sleep parameters, inflammation as objectified by C-reactive protein (CRP), and serum cortisol and adrenocorticotropic hormone (ACTH) levels. Thirty-one eligible patients (disease activity score, DAS28CRP ≥3.2) participated in a 16-week, open, prospective study of HPA axis outcomes. MTX was initiated in 15 patients (female-to-male ratio 9/6) and ETA in 16 patients (14/2). Clinical, laboratory (after polysomnography [PSG] between 8 and 9 a.m.), sleep (PSG), and HPA axis outcome parameters (after PSG between 8 and 9 a.m.) were recorded at baseline and week 16. Clinical characteristics of patients markedly improved throughout the study (e.g., DAS28CRP: p Sleep efficiency and wake time after sleep onset markedly improved in the ETA group. Serum cortisol and ACTH did not change during observation. At baseline, serum cortisol levels were negatively correlated to sleep efficiency; this may depend on inflammation, because controlling for CRP eliminated this negative correlation. After ETA treatment, serum cortisol had a high positive correlation with total sleep time, sleep efficiency, and a negative correlation with wake time before and after sleep onset, which was not eliminated by controlling for CRP. In RA patients, the data indicate that inflammation is an important covariate for the crosstalk of sleep and the HPA axis. © 2017 S. Karger AG, Basel.

Do different data analytic approaches generate discrepant findings when measuring mother-infant HPA axis attunement?

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Bernard, Nicola K; Kashy, Deborah A; Levendosky, Alytia A; Bogat, G Anne; Lonstein, Joseph S

2017-03-01

Attunement between mothers and infants in their hypothalamic-pituitary-adrenal (HPA) axis responsiveness to acute stressors is thought to benefit the child's emerging physiological and behavioral self-regulation, as well as their socioemotional development. However, there is no universally accepted definition of attunement in the literature, which appears to have resulted in inconsistent statistical analyses for determining its presence or absence, and contributed to discrepant results. We used a series of data analytic approaches, some previously used in the attunement literature and others not, to evaluate the attunement between 182 women and their 1-year-old infants in their HPA axis responsivity to acute stress. Cortisol was measured in saliva samples taken from mothers and infants before and twice after a naturalistic laboratory stressor (infant arm restraint). The results of the data analytic approaches were mixed, with some analyses suggesting attunement while others did not. The strengths and weaknesses of each statistical approach are discussed, and an analysis using a cross-lagged model that considered both time and interactions between mother and infant appeared the most appropriate. Greater consensus in the field about the conceptualization and analysis of physiological attunement would be valuable in order to advance our understanding of this phenomenon. © 2016 Wiley Periodicals, Inc.

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.

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Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

2017-01-01

Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori ( H. pylori ) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA 27-53 , UreA 183-203 , HpaA 132-141 , and HSP60 189-203 ), and also the epitope-rich regions of urease B subunit (UreB 158-251 and UreB 321-385 ) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB 158-172 , UreB 181-195 , UreB 211-225 , UreB 349-363 , HpaA 132-141 , and HSP60 189-203 ). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4 + T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori . These results indic ate

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils

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Le Guo

2017-08-01

Full Text Available Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP, heat shock protein 60 (HSP60 and H. pylori adhesin A (HpaA was constructed based on mucosal adjuvant cholera toxin B subunit (CTB, Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203, and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385 predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203. In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell response, IgG, and secretory IgA (sIgA antibodies to H. pylori. These results indic

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

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Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

2017-06-01

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives

DEFF Research Database (Denmark)

Hertel, Johannes; König, Johanna; Homuth, Georg

2017-01-01

Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased...

UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation.

Science.gov (United States)

Han, Mira; Ban, Jae-Jun; Bae, Jung-Soo; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-11-14

The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.

Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep

Science.gov (United States)

Chiang, Jessica J.; Tsai, Kim M.; Park, Heejung; Bower, Julienne E.; Almeida, David M.; Dahl, Ronald E.; Irwin, Michael R.; Seeman, Teresa E.; Fuligni, Andrew J.

2017-01-01

The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n = 316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency. PMID:27235639

Paternal and maternal obesity but not gestational weight gain is associated with type 1 diabetes

DEFF Research Database (Denmark)

Magnus, Maria C; Olsen, Sjurdur F; Granstrom, Charlotta

2018-01-01

100 000 person-years in MoBa and 28.5 per 100 000 person-years in DNBC. Both maternal pre-pregnancy obesity, adjusted hazard ratio (HR) 1.41 [95% confidence interval (CI): 1.06, 1.89] and paternal obesity, adjusted HR 1.51 (95% CI: 1.11, 2.04), were associated with childhood-onset type 1 diabetes......Background: Our objective was to examine the associations of parental body mass index (BMI) and maternal gestational weight gain with childhood-onset type 1 diabetes. Comparing the associations of maternal and paternal BMI with type 1 diabetes in the offspring will provide further insight...... included parental BMI and maternal gestational weight gain obtained by maternal report. We used Cox-proportional hazards regression to examine the risk of type 1 diabetes (n=499 cases), which was ascertained by national childhood diabetes registers. Results: The incidence of type 1 diabetes was 32.7 per...

Predicting developmental changes in internalizing symptoms: examining the interplay between parenting and neuroendocrine stress reactivity.

Science.gov (United States)

Kuhlman, Kate R; Olson, Sheryl L; Lopez-Duran, Nestor L

2014-07-01

In this study, we examined whether parenting and HPA-axis reactivity during middle childhood predicted increases in internalizing symptoms during the transition to adolescence, and whether HPA-axis reactivity mediated the impact of parenting on internalizing symptoms. The study included 65 children (35 boys) who were assessed at age 5, 7, and 11. Parenting behaviors were assessed via parent report at age 5 and 11. The child's HPA-axis reactivity was measured at age 7 via a stress task. Internalizing symptoms were measured via teacher reports at age 5 and 11. High maternal warmth at age 5 predicted lower internalizing symptoms at age 11. Also, high reported maternal warmth and induction predicted lower HPA-axis reactivity. Additionally, greater HPA-axis reactivity at age 7 was associated with greater increases in internalizing symptoms from age 5 to 11. Finally, the association between age 5 maternal warmth and age 11 internalizing symptoms was partially mediated by lower cortisol in response to the stress task. Thus, parenting behaviors in early development may influence the physiological stress response system and therefore buffer the development of internalizing symptoms during preadolescence when risk for disorder onset is high. © 2013 Wiley Periodicals, Inc.

Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

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Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

2016-10-01

Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects

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Sukhanov, Sergiy; Higashi, Yusuke; Shai, Shaw-Yung; Blackstock, Christopher; Galvez, Sarah; Vaughn, Charlotte; Titterington, Jane; Delafontaine, Patrick

2011-01-01

We have shown previously that insulin like-growth factor I (IGF-1) suppressed atherosclerosis in Apoe−/− mice and activated endothelial nitric oxide (NO) synthase. To determine whether IGF-1-induced atheroprotection depends on NO, IGF-1- or saline-infused mice were treated with L-NAME, the pan-NO synthase inhibitor or with D-NAME (control). IGF-1 reduced atherosclerosis in both the D-NAME and L-NAME groups suggesting that IGF-1’s anti-atherogenic effect was NO-independent. IGF-1 increased plaque smooth muscle cells, suppressed cell apoptosis and downregulated lipoprotein lipase and these effects were also NO-independent. On the contrary, IGF-1 decreased oxidative stress and suppressed TNF-α levels and these effects were blocked by L-NAME. Thus IGF-1’s anti-oxidant effect is dependent on its ability to increase NO but is distinct from its anti-atherosclerotic effect which is NO-independent. PMID:21872589

Maternal gestational cortisol and testosterone are associated with trade-offs in offspring sex and number in a free-living rodent (Urocitellus richardsonii.

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Calen P Ryan

Full Text Available The adaptive manipulation of offspring sex and number has been of considerable interest to ecologists and evolutionary biologists. The physiological mechanisms that translate maternal condition and environmental cues into adaptive responses in offspring sex and number, however, remain obscure. In mammals, research into the mechanisms responsible for adaptive sex allocation has focused on two major endocrine axes: the hypothalamic pituitary adrenal (HPA axis and glucocorticoids, and the hypothalamic pituitary gonadal (HPG axis and sex steroids, particularly testosterone. While stress-induced activation of the HPA axis provides an intuitive model for sex ratio and litter size adjustment, plasma glucocorticoids exist in both bound and free fractions, and may be acting indirectly, for example by affecting plasma glucose levels. Furthermore, in female mammals, activation of the HPA axis stimulates the secretion of adrenal testosterone in addition to glucocorticoids (GCs. To begin to untangle these physiological mechanisms influencing offspring sex and number, we simultaneously examined fecal glucocorticoid metabolites, free and bound plasma cortisol, free testosterone, and plasma glucose concentration during both gestation and lactation in a free-living rodent (Urocitellus richardsonii. We also collected data on offspring sex and litter size from focal females and from a larger study population. Consistent with previous work in this population, we found evidence for a trade-off between offspring sex and number, as well as positive and negative correlations between glucocorticoids and sex ratio and litter size, respectively, during gestation (but not lactation. We also observed a negative relationship between testosterone and litter size during gestation (but not lactation, but no effect of glucose on either sex ratio or litter size. Our findings highlight the importance of binding proteins, cross-talk between endocrine systems, and temporal windows

Relation among HPA and HPG neuroendocrine systems, transmissible risk and neighborhood quality on development of substance use disorder: results of a 10-year prospective study.

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Tarter, Ralph E; Kirisci, Levent; Kirillova, Galina; Reynolds, Maureen; Gavaler, Judy; Ridenour, Ty; Horner, Michelle; Clark, Duncan; Vanyukov, Michael

2013-01-01

Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine systems and behaviors associated with SUD liability. Accordingly, it was hypothesized that (1) parental SUD severity and neighborhood quality correlate with activity of the HPG axis (testosterone level) and HPA axis (cortisol stability), and (2) transmissible risk during childhood mediates these hormone variables on development of SUD measured in adulthood. Transmissible risk for SUD measured by the transmissible liability index (TLI; Vanyukov et al., 2009) along with saliva cortisol and plasma testosterone were prospectively measured in boys at ages 10-12 and 16. Neighborhood quality was measured using a composite score encompassing indicators of residential instability and economic disadvantage. SUD was assessed at age 22. Neither hormone variable cross-sectionally correlated with transmissible risk measured at ages 10-12 and 16. However, the TLI at age 10-12 predicted testosterone level and cortisol stability at age 16. Moreover, testosterone level, correlated with cortisol stability at age 16, predicted SUD at age 22. HPA and HPG axes activity do not underlie variation in TLI, however, high transmissible risk in childhood predicts neuroendocrine system activity presaging development of SUD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

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Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R

2006-01-01

Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport...... in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration....... These results suggest that maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta and that optimal metabolic control reduces these effects....

Is there a correlation between maternal serum TGF-β1 levels and fetal hydronephrosis?

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Seven, Ali; Savran, Bircan; Koçak, Emel; Tok, Sermin; Yüksel, Kadriye Beril; Gözükara, İlay; Kabil Kucur, Suna

2016-01-01

We aimed to identify a noninvasive marker for clinically significant fetal uropathies. To achieve this aim, we detected TGF (transforming growth factor)-β1 serum level which rises in neonatal hydronephrosis, in pregnant patients with fetal hydronephrosis. We evaluated 44 patients, all of whom were pregnant and had a gestational age between 20 and 30 weeks. Twenty-two patients had normal maternal renal ultrasound imaging and had a fetus with fetal hydronephrosis (Group A). The remaining twenty-two patients had normal maternal and fetal renal ultrasound imaging (Group B). The maternal serum levels of TGF-β1 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. The median value for the study group was 55.90 pg/mL (9.67 ± 574.45) and for the control group was 59.49 pg/mL (12.49 ± 402.04). There was no statistical difference in serum TGF-β1 levels between the groups (p = 0.769 - Mann-Whitney U test). In the study group, the diameter of the right renal pelvis was 5.7 mm (5.1-8.9 mm), while the diameter of left renal pelvis was 5.75 mm (5.3-10.04 mm). In our study, the circulating TGF-β1 levels were not statistically different in the fetal hydronephrosis group when compared to the controls. According to our study, TGF-β1 is not useful in the detection and follow-up of fetal hydronephrosis. We therefore require further studies involving larger groups with moderate or severe fetal hydronephrosis to detect the usefulness of the serum levels of TGF-β1 in pregnant women with fetal hydronephrosis.

Maternal sensitivity: a concept analysis.

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Shin, Hyunjeong; Park, Young-Joo; Ryu, Hosihn; Seomun, Gyeong-Ae

2008-11-01

The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions.

Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

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Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

2017-10-01

Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis

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Junko Inagaki

2004-01-01

Full Text Available Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, α1, β1 and γ1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-α1, -β1 and -γ1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-α1, -β1 and -γ1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of α1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with –mouse— laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

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Sudipta Tripathi

2015-02-01

Full Text Available Tolerance of the fetus by the maternal immune system is regulated through various mechanisms involving the different immune cells, both in the periphery and locally at the feto-maternal interface. The maternal T lymphocytes are aware of the paternal fetal antigens and a state of dynamic T cell homeostasis is maintained in the uterus during gestation, which involves increase in antigen-specific regulatory T cell (Treg proliferation, increase in apoptosis of antigen-specific effector T cells, and inhibition of excessive inflammation post successful implantation to ensure tolerance to the fetus. The Tregs play an important role in the maintenance of tolerance during gestation. Recently, the inflammatory T helper type 17 (Th17 cells are reported to have a role in loss of tolerance to the fetus. The interaction between costimulatory molecule programmed death 1 (PD1 and its ligand PDL1 is known to play a role in regulating both the Tregs and Th17 cells. Here we discuss how the PD1/PDL1 pathway affects these two T cell populations and its role in feto-maternal tolerance.

Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

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Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

2011-07-01

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

HPA-axis hyperactivity and mortality in psychotic depressive disorder: preliminary findings.

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Coryell, William; Fiedorowicz, Jess; Zimmerman, Mark; Young, Elizabeth

2008-06-01

The excess mortality associated with depressive disorders has been most often attributed to risks for suicide but diverse findings indicate that depressive disorders also increase risks for cardiovascular (CV) mortality. Among the possible mediators is the hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity that characterizes many cases of relatively severe depressive disorder and severity is characteristic of psychotic depressive disorder. The following describes a 17-year mortality follow-up of 54 patients with Research Diagnostic Criteria (RDC) psychotic major depression or schizoaffective, mainly affective, depression. All had baseline assessments that included a 1mg dexamethasone suppression test with post-dexamethasone samples at 8 a.m., 4 p.m. and 11 p.m. Regression analyses showed that both greater age and higher maximum post-dexamethasone cortisol concentrations predicted deaths due to CV causes (t=4.01, pdepressive disorder to CV mortality.

HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an Autistic Disorder.

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Bitsika, Vicki; Sharpley, Christopher F; Sweeney, John A; McFarlane, James R

2014-03-29

Anxiety and Autistic Disorder (AD) are both neurological conditions and both disorders share some features that make it difficult to precisely allocate specific symptoms to each disorder. HPA and SAM axis activities have been conclusively associated with anxiety, and may provide a method of validating anxiety rating scale assessments given by parents and their children with AD about those children. Data from HPA axis (salivary cortisol) and SAM axis (salivary alpha amylase) responses were collected from a sample of 32 high-functioning boys (M age=11yr) with an Autistic Disorder (AD) and were compared with the boys' and their mothers' ratings of the boys' anxiety. There was a significant difference between the self-ratings given by the boys and ratings given about them by their mothers. Further, only the boys' self-ratings of their anxiety significantly predicted the HPA axis responses and neither were significantly related to SAM axis responses. Some boys showed cortisol responses which were similar to that previously reported in children who had suffered chronic and severe anxiety arising from stressful social interactions. As well as suggesting that some boys with an AD can provide valid self-assessments of their anxiety, these data also point to the presence of very high levels of chronic HPA-axis arousal and consequent chronic anxiety in these boys. Copyright © 2014 Elsevier Inc. All rights reserved.

Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies.

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Kryštůfková, Olga; Barbasso Helmers, Sevim; Venalis, Paulius; Malmström, Vivianne; Lindroos, Eva; Vencovský, Jiří; Lundberg, Ingrid E

2014-10-10

Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers. Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1). BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08). The expression

Anti-Anxiety Effect of (-)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

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Liu, Jie; Lv, Yue-Wei; Shi, Jin-Li; Ma, Xiao-Jie; Chen, Yi; Zheng, Zhi-Quan; Wang, Sheng-Nan; Guo, Jian-You

2017-08-11

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4- O -β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

Maternal correlates of maternal child feeding practices: a systematic review.

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McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena

2014-01-01

Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation. © 2012 John Wiley & Sons Ltd.

A Fatal Case of Severe Hemolytic Disease of Newborn Associated with Anti-Jkb

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Kim, Won Duck

2006-01-01

The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jkb incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jkb with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive boodtype was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jkb was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jkb, and they should be ready to treat this disease with active therapeutic interventions. PMID:16479082

Expanding the Annual Irrigation Maps (AIM) Product to the entire High Plains Aquifer (HPA): Addressing the Challenges of Cotton and Deficit-Irrigated Fields

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Rapp, J. R.; Deines, J. M.; Kendall, A. D.; Hyndman, D. W.

2017-12-01

The High Plains Aquifer (HPA) is the most extensively irrigated aquifer in the continental United States and is the largest major aquifer in North America with an area of 500,000 km2. Increased demand for agricultural products has led to expanded irrigation extent, but brought with it declining groundwater levels that have made irrigation unsustainable in some locations. Understanding these irrigation dynamics and mapping irrigated areas through time are essential for future sustainable agricultural practices and hydrological modeling. Map products using remote sensing have only recently been able to track annual dynamics at relatively high spatial resolution (30 m) for a large portion of the northern HPA. However follow-on efforts to expand these maps to the entire HPA have met with difficulty due to the challenge of distinguishing irrigation in crop types that are commonly deficit- or partially-irrigated. Expanding these maps to the full HPA requires addressing unique features of partially irrigated fields and irrigated cotton, a major water user in the southern HPA. Working in Google Earth Engine, we used all available Landsat imagery to generate annual time series of vegetation indices. We combined this information with climate covariables, planting dates, and crop specific training data to algorithmically separate fully irrigated, partially irrigated, and non-irrigated field locations. The classification scheme was then applied to produce annual maps of irrigation across the entire HPA. The extensive use of ancillary data and the "greenness" time series for the algorithmic classification generally increased accuracy relative to previous efforts. High-accuracy, representative map products of irrigation extent capable of detecting crop type and irrigation intensity within aquifers will be an essential tool to monitor the sustainability of global aquifers and to provide a scientific bases for political and economic decisions affecting those aquifers.

Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection.

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Béland, Kathie; Lapierre, Pascal; Marceau, Gabriel; Alvarez, Fernando

2004-03-01

Various autoantibodies have been reported in patients chronically infected by hepatitis C virus. 2% to 10% of theses patients have anti-liver-kidney microsome type 1 (anti-LKM1) autoantibodies. In type 2 autoimmune hepatitis, anti-LKM1 autoantibodies are frequently associated with anti-liver-cytosol type 1 (anti-LC1) autoantibodies. To determine the prevalence of anti-LC1 autoantibodies in a hepatitis C-positive population and characterize their reactivity. 146 patients suffering from liver diseases, of which 99 were chronically infected by hepatitis C virus, were tested by Western blotting and immunoprecipitation to detect and characterize anti-LC1 autoantibodies. 12% of this hepatitis C population had anti-LC1 autoantibodies. LC1 positivity by Western blotting was 30% of LC1+ sera. Epitopes were found throughout the protein but linear epitopes were situated in the 395-541 amino acid region of formiminotransferase cyclodeaminase. Three putative conformational epitopes were identified by phage display. Anti-LC1 autoantibodies are as prevalent as anti-LKM1 autoantibodies in patients infected with hepatitis C virus and their production is not dependent of anti-LKM1 autoantibodies formation. Autoantibody reactivity against the anti-LC1 antigen is different in hepatitis C than in type 2 autoimmune hepatitis. Anti-LC1 autoantibodies can now be regarded as a serological marker of autoimmunity in chronic hepatitis C infection.

Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea.

Science.gov (United States)

Schaller, M; Gonser, L; Belge, K; Braunsdorf, C; Nordin, R; Scheu, A; Borelli, C

2017-11-01

Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm 2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra ® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1. Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin. © 2017 European Academy of Dermatology and Venereology.

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, Joan; Chicot, Rebecca; Shouldice, Anne; Hinde, Camilla A.

2016-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, J.; Chicot, R.; Schouldice, A.; Hinde, C.A.

2013-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety levels

[The shades of anti-Jo1 positive antisynthetase syndrome in a Hungarian cohort].

Science.gov (United States)

Szabó, Katalin; Nagy-Vincze, Melinda; Bodoki, Levente; Hodosi, Katalin; Dankó, Katalin; Griger, Zoltán

2016-04-10

In idiopathic inflammatory myopathies, the presence of anti-Jo-1 antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial lung disease, Raynaud's phenomenon fever, mechanic's hands), called antisynthetase syndrome. To determine the demographic data as well as clinical, laboratory and terapeutical features of anti-Jo1 positive patients, followed by the department of the authors. The medical records of 49 consecutive anti-Jo1 patients were reviewed. Demographic and clinical results were very similar to those published by other centers. Significant correlation was found between the anti-Jo-1 titer and the creatine kinase and C-reactive protein levels. Distinct laboratory results measured at the time of diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's syndrome, positive rheumatoid factor), and the presence of certain clinical symptoms (fever, vasculitic skin) may indicate a worse prognosis within the antisyntetase positive patient group. In the cases above more agressive immunosuppressive therapy may be required.

Impact of HIV-1 infection on the feto-maternal crosstalk and consequences for pregnancy outcome and infant health.

Science.gov (United States)

Altfeld, Marcus; Bunders, Madeleine J

2016-11-01

Adaptation of the maternal immune system to establish maternal/fetal equilibrium is required for a successful pregnancy. Viral infections, including HIV-1 infection, can alter this maternal/fetal equilibrium, with significant consequences for pregnancy outcome, including miscarriages, impaired fetal growth, and premature delivery. Furthermore, maternal HIV-1 infection has been shown to have a long-term impact on the developing fetal immune system also when the infant is not infected with the virus. In this review, we discuss the consequences of maternal HIV-1 infection and antiretroviral therapy on pregnancy outcome and the health of the uninfected HIV-1-exposed infant.

Anti-C1q antibodies in systemic lupus erythematosus

DEFF Research Database (Denmark)

Orbai, A-M; Truedsson, L; Sturfelt, G

2015-01-01

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

Maternal Obesity, Inflammation, and Developmental Programming

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Stephanie A. Segovia

2014-01-01

Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

NARCIS (Netherlands)

Dieleman, G.C.; Huizink, A.C.; Tulen, J.H.M.; Utens, E.M.W.J.; Creemers, H.E.; van der Ende, J.; Verhulst, F.C.

2015-01-01

Background: It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

NARCIS (Netherlands)

Dieleman, Gwendolyn C.; Huizink, Anja C.; Tulen, Joke H. M.; Utens, Elisabeth M. W. J.; Creemers, Hanneke E.; van der Ende, Jan; Verhulst, Frank C.

2015-01-01

It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary

Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.

Science.gov (United States)

Zhao, Chen; Tella, Sri Harsha; Del Rivero, Jaydira; Kommalapati, Anuhya; Ebenuwa, Ifechukwude; Gulley, James; Strauss, Julius; Brownell, Isaac

2018-02-01

Immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient's symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. To our knowledge, this is the first report of central DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality. Copyright © 2017 Endocrine Society

The relationship between maternal fear of hypoglycaemia and adherence in children with type-1 diabetes.

Science.gov (United States)

Freckleton, Evril; Sharpe, Louise; Mullan, Barbara

2014-01-01

Regular blood glucose monitoring is important for children with type-1 diabetes; however, the relationship between maternal fear of hypoglycaemia and glycaemic control is not well understood. The relationship between maternal beliefs about diabetes, concerns about glycaemic control and adherence to recommended blood glucose levels in young children with type-1 diabetes were examined in this study. Seventy-one mothers with children under 13 were recruited, and a prospective design was used. Demographics, maternal self-reported hypoglycaemic fear and illness perceptions were measured at baseline. Self-report daily blood sugar levels were recorded over 1 week, and glycosylated haemoglobin (HbA1c) blood glucose levels were collected at baseline and 3 months later. High maternal fears of hypoglycaemia were predictive of suboptimal daily glycaemic control (elevated blood glucose levels), irrespective of illness duration or age at diagnosis. The results suggest that mothers who worry most about hypoglycaemia compensate by maintaining their child's blood glucose levels above recommended levels. Elevated blood glucose levels have important consequences for long-term health, and further research could explore ways to target maternal fear of hypoglycaemia.

Parental Curse as Invisible Violence: Anti-maternity in the Traditional Culture of the XIX Century

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Lidija Radulović

2016-03-01

Full Text Available Curse is an appellative genre, a clichéd verbal proverb that is uttered in belief, that with the assistance of supernatural forces, God or demon, through the magical properties of words, evil will come upon an individual. It is examined through the context of the ideal motherhood discourse in the tradition culture of the XIX and the first half of the XX century, in view that it was perceived to be an idiosyncrasy of female demeanor. Maternity as a cultural construct in the traditional culture of Serbia is based upon the ideal motherhood discourses as a gift from god, as an innate role for women, an inherent instinct for caring towards others, as an unconditional motherly love. In practice, normative regulations and the concrete actions of a mother are not in complete concurrence, mothers love is not an objective fact, it can be present or not, vary in intensity, it can be selective, but it will depend on the personal history and cultural construct. Through such a focal point, motherly curse is perceived as a form of behavior that can be signified as anti-maternity. In the conceptualization of a parental curse, from one viewpoint, the manner of usual behavior of women that has no real implications on the life of the child is legitimized, and on the other hand, it is believed that a mothers curse has the most potent magical effect and is delivered up to the ninth generation. Parental curse and the ritual of "cursing" do not include a black magic connotation, and were considered a legitimate social mechanism through which evil was countered with evil i.e. the transgressor was being punished in cases where there existed no formal mechanism of punishment. Through such actions, the community, or family are re-imposing order in the social relations, synchronously sending a message that reaffirms the correct matrix of behavior and moral values of the community.

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

Science.gov (United States)

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor.

Directory of Open Access Journals (Sweden)

An Ye

Full Text Available The expression of two adjacent imprinted genes, Peg3 and Zim1, is inversely correlated: down-regulation of Peg3 coinciding with up-regulation of Zim1. The current study characterized this inverse correlation using a mutant allele targeting Peg3. According to the results, the mutation on the paternal allele of Peg3 resulted in a dramatic increase in the transcription levels of the maternal allele of Zim1, suggesting the involvement of unknown trans factors in this trans-allelic event. Subsequent ChIP experiments revealed that the protein encoded by Peg3 itself binds to the zinc finger exon of Zim1, which is modified with the repression mark H3K9me3. Interestingly, the levels of H3K9me3 on Zim1 are also reduced in the mutant cells lacking the protein PEG3, suggesting potential roles for PEG3 in establishing H3K9me3 on Zim1. Reintroducing PEG3 into the mutant cell restored down-regulation of Zim1, confirming the predicted repressor role for Peg3 on Zim1. Overall, these results demonstrated that paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor. The current study also provides the first case for the trans-allelic interaction of two oppositely imprinted genes through their gene products.

Maternal obesity and infant mortality: a meta-analysis.

Science.gov (United States)

Meehan, Sean; Beck, Charles R; Mair-Jenkins, John; Leonardi-Bee, Jo; Puleston, Richard

2014-05-01

Despite numerous studies reporting an elevated risk of infant mortality among women who are obese, the magnitude of the association is unclear. A systematic review and meta-analysis was undertaken to assess the association between maternal overweight or obesity and infant mortality. Four health care databases and gray literature sources were searched and screened against the protocol eligibility criteria. Observational studies reporting on the relationship between maternal overweight and obesity and infant mortality were included. Data extraction and risk of bias assessments were performed. Twenty-four records were included from 783 screened. Obese mothers (BMI ≥30) had greater odds of having an infant death (odds ratio 1.42; 95% confidence interval, 1.24-1.63; P obese (BMI >35) (odds ratio 2.03; 95% confidence interval, 1.61-2.56; P obese mothers and that this risk may increase with greater maternal BMI or weight; however, residual confounding may explain these findings. Given the rising prevalence of maternal obesity, additional high-quality epidemiologic studies to elucidate the actual influence of elevated maternal mass or weight on infant mortality are needed. If a causal link is determined and the biological basis explained, public health strategies to address the issue of maternal obesity will be needed. Copyright © 2014 by the American Academy of Pediatrics.

Taking Stress Response out of the Box: Stability, Discontinuity, and Temperament Effects on HPA and SNS across Social Stressors in Mother-Infant Dyads

Science.gov (United States)

Laurent, Heidemarie K.; Ablow, Jennifer C.; Measelle, Jeffrey

2012-01-01

This study investigated continuity and stability of hypothalamic-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) response measures in mother-infant dyads across 2 different types of social stress sessions. Synchrony of response trajectories across systems (SNS-HPA coordination) and partners (mother-infant attunement) was addressed, as…

First report of anti-TIF1γ dermatomyositis in a patient with myelodysplastic syndrome

Directory of Open Access Journals (Sweden)

B. Palterer

2017-08-01

Full Text Available Inflammatory myopathies as para-neoplastic phenomena were first described by Sterz in 1916. Recently, myositis specific autoantibodies were described in cancer-associated myositis. Anti-transcription intermediary factor 1 gamma (anti-TIF1γ antibodies have been found in both young adults affected by juvenile dermatomyositis and in elderly patients with cancer-associated myositis. In this regard, we report herein the first case of anti-TIF1γ dermatomyositis secondary to a myelodysplastic syndrome.

In vitro assessment of recombinant, mutant immunoglobulin G anti-D devoid of hemolytic activity for treatment of ongoing hemolytic disease of the fetus and newborn

DEFF Research Database (Denmark)

Nielsen, Leif K; Green, Trine H; Sandlie, Inger

2008-01-01

A specific treatment for ongoing hemolytic disease of the fetus and newborn (HDFN) due to anti-D would be very attractive. One approach could be administration to the mother of nonhemolytic anti-D, which by crossing the placenta can block the binding of hemolytic maternal anti-D.......A specific treatment for ongoing hemolytic disease of the fetus and newborn (HDFN) due to anti-D would be very attractive. One approach could be administration to the mother of nonhemolytic anti-D, which by crossing the placenta can block the binding of hemolytic maternal anti-D....

Anti-idiotypic antibodies to poliovirus antibodies in commercial immunoglubulin preparations, human serum and milk.

NARCIS (Netherlands)

M. Hahn-Zoric; B. Carlsson; S. Jeansson; H.P. Ekre; A.D.M.E. Osterhaus (Albert); D. Roberton; L.A. Hanson

1993-01-01

textabstractOur previous studies have suggested that fetal antibody production can be induced by maternal antiidiotypic antibodies transferred to the fetus via the placenta. We tested commercial Ig, sera, and milk for the presence of anti-idiotypic antibodies to poliovirus type 1, using affinity

Severe maternal morbidity for 2004-2005 in the three Dublin maternity hospitals.

LENUS (Irish Health Repository)

Murphy, Cliona M

2012-02-01

OBJECTIVE: To assess the prevalence and causes of severe maternal morbidity in Dublin over a two year period from 2004 to 2005. STUDY DESIGN: A prospective cohort study from January 2004 to December 2005 was undertaken in the three large maternity hospitals in Dublin, which serve a population of 1.5 million people. All are tertiary referral centres for obstetrics and neonatology and have an annual combined delivery rate of circa 23,000 births. Cases of severe maternal morbidity were identified. A systems based classification was used. The primary cause of maternal morbidity and the number of events experienced per patient was recorded. RESULTS: We identified 158 women who fulfilled the definition for severe maternal morbidity, giving a rate of 3.2 per 1000 maternities. There were two maternal deaths during the time period giving mortality to morbidity ratio of 1:79. The commonest cause of severe morbidity was vascular dysfunction related to obstetric haemorrhage. Eclampsia comprised 15.4% of cases. Intensive care or coronary care admission occurred in 12% of cases. CONCLUSION: The prevalence of severe maternal morbidity in this population is 3.2\\/1000 maternities. Obstetric haemorrhage was the main cause of severe maternal morbidity.

Perinatal fluoxetine effects on social play, the HPA system, and hippocampal plasticity in pre-adolescent male and female rats: Interactions with pre-gestational maternal stress.

Science.gov (United States)

Gemmel, Mary; Hazlett, Mariah; Bögi, Eszter; De Lacalle, Sonsoles; Hill, Lesley A; Kokras, Nikolaos; Hammond, Geoffrey L; Dalla, Christina; Charlier, Thierry D; Pawluski, Jodi L

2017-10-01

Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the

[Autoimmune hepatitis in a girl with presence of anti-LKM1 antibodies].

Science.gov (United States)

Larraín, F; Miquel, J F; González, S

1997-06-01

Autoimmune hepatitis is an inflammatory liver disease characterized by dense mononuclear cell infiltrate in the portal tract, and serologically by the presence of non-organ and liver-specific autoantibodies and increased levels of gammaglobulins in the absence of a known etiology. Three subgroups of autoimmune hepatitis have been recognized, depending on the nature of the autoantibody present in the serum: Type 1 autoimmune hepatitis, associated with smooth-muscle (SMA) or antinuclear antibody (ANA) seropositivity; type 2, with anti-liver/kidney microsome antibody (anti-LKM1), and type 3, with the absence of ANA, SMA and anti-LKM1 and presence of other autoantibodies such as anti-soluble liver antigen (SLA). Subtypes of chronic autoimmune hepatitis have clinically different features and prognoses. An 8 year old female patient presented mild jaundice of insidious onset. The liver was tender and enlarged. Serologic markers for A, B, C, E, Epstein Barr and cytomegalovirus were negative. The liver biopsy showed a histological picture consistent with chronic active hepatitis. High titers of anti-liver/kidney-microsome antibody were found by indirect immunofluorescence test, and this finding was confirmed by Western blot against specific liver microsome antigens. Therapy with prednisolone induced a clinical and biochemical remission after four weeks. The suspension of therapy under strict medical control produced a rapid relapse of clinical and biochemical features. The reinitiation of prednisolone was successful, and an alternate-day program was started and maintained until 8 months follow-up.

{sup 111}In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages

Energy Technology Data Exchange (ETDEWEB)

Terry, Samantha Y.A. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, London (United Kingdom); Boerman, Otto C.; Gerrits, Danny; Franssen, Gerben M.; Oyen, Wim J.G. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Metselaar, Josbert M. [University of Twente, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, Enschede (Netherlands); Lehmann, Steffi; Gerdes, Christian A. [Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development (pRED), Zurich (Switzerland); Abiraj, Keelara [Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development (pRED), Basel (Switzerland)

2015-08-15

Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. The immunoreactive fraction and IC{sub 50} of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with {sup 111}In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with {sup 111}In-anti-F4/80-A3-1 and isotype-matched control antibody {sup 111}In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. In vitro binding assays showed that {sup 111}In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC{sub 50} was 0.58 nM. In vivo, injection of 10 or 100 μg {sup 111}In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg {sup 111}In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced {sup 111}In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of {sup 111}In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of {sup 111}In-rat IgG2b was lower in the spleen, liver and femur when compared to {sup 111}In-anti-F4/80-A3-1. Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen

Maternal depression and low maternal intelligence as risk factors for malnutrition in children: a community based case-control study from South India.

Science.gov (United States)

Anoop, S; Saravanan, B; Joseph, A; Cherian, A; Jacob, K S

2004-04-01

To determine whether current and postpartum maternal depression and low maternal intelligence are risk factors for malnutrition in children. In rural South India 72 children with malnutrition were identified from a central register; 72 controls were matched for age, gender, and residence. Major depression in the postpartum period (OR 5.0, 95% CI 1.0 to 24.0), current major depression (OR 3.2, 95% CI 1.1 to 9.5), and low maternal intelligence (OR 3.8, 95% CI 1.3 to 11.1) were associated with malnutrition in the child. Low birth weight (OR 2.9, 95% CI 1.2 to 6.8) was also significantly associated with infant malnutrition. Conditional logistic regression adjusting for all other determinants yielded the following results: major depression during the postpartum period (OR 7.8; 95% CI 1.6 to 38.51), current major depression (OR 3.1; 95% CI 0.9 to 9.7), low maternal intelligence (OR 4.6; 95% CI 1.5 to 14.1), and low birth weight (OR 2.7; 95% CI 2.5 to 6.8). The interactions between current maternal depression and low birth weight and between postpartum depression and low maternal intelligence were statistically significant. The level of maternal intelligence was associated with nutritional status. The severity of malnutrition was also significantly associated with major depression during the postpartum period and low maternal intelligence. There is evidence for an association between postpartum maternal depression, low maternal intelligence, and low birth weight with malnutrition in children aged 6-12 months.

Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

LENUS (Irish Health Repository)

Bergin, David A

2012-04-01

Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

Science.gov (United States)

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

2016-02-11

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

DEFF Research Database (Denmark)

Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R

2006-01-01

Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport...... in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration......RNA expression of lipoprotein lipase and lysosomal lipase were similar in women with diabetes and the control group. Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes...

CXCR1 regulates pulmonary anti-Pseudomonas host defense

Science.gov (United States)

Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.

2016-01-01

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta

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Hari Krishna Thulluru

2013-08-01

Full Text Available Nodal, a secreted signaling protein from the TGFβ-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR and preterm birth. As the chromosomal location of NODAL is in the same linkage area as the susceptibility gene STOX1, associated with the familial form of early-onset, IUGR-complicated pre-eclampsia, their potential maternal-fetal interaction was investigated. Pre-eclamptic mothers with children who carried the STOX1 susceptibility allele themselves all carried the NODAL H165R SNP, which causes a 50% reduced activity. Surprisingly, in decidua Nodal knockout mice the fetal placenta showed up-regulation of STOX1 and NODAL expression. Conditioned media of human first trimester decidua and a human endometrial stromal cell line (T-HESC treated with siRNAs against NODAL or carrying the H165R SNP were also able to induce NODAL and STOX1 expression when added to SGHPL-5 first trimester extravillous trophoblast cells. Finally, a human TGFß-BMP-Signaling-Pathway PCR-Array on decidua and the T-HESC cell line with Nodal knockdown revealed upregulation of Activin-A, which was confirmed in conditioned media by ELISA. We show that maternal decidua Nodal knockdown gives upregulation of NODAL and STOX1 mRNA expression in fetal extravillous trophoblast cells, potentially via upregulation of Activin-A in the maternal decidua. As both Activin-A and Nodal have been implicated in pre-eclampsia, being increased in serum of pre-eclamptic women and upregulated in pre-eclamptic placentas respectively, this interaction at the maternal-fetal interface might play a substantial role in the development of pre-eclampsia.

The maternal health outcomes of paid maternity leave: a systematic review.

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Aitken, Zoe; Garrett, Cameryn C; Hewitt, Belinda; Keogh, Louise; Hocking, Jane S; Kavanagh, Anne M

2015-04-01

Paid maternity leave has become a standard benefit in many countries throughout the world. Although maternal health has been central to the rationale for paid maternity leave, no review has specifically examined the effect of paid maternity leave on maternal health. The aim of this paper is to provide a systematic review of studies that examine the association between paid maternity leave and maternal health. We conducted a comprehensive search of electronic databases (Medline, Embase, CINAHL, PsycINFO, Web of Science, Sociological Abstracts) and Google Scholar. We searched websites of relevant organisations, reference lists of key papers and journals, and citation indices for additional studies including those not in refereed journals. There were no language restrictions. Studies were included if they compared paid maternity leave versus no paid maternity leave, or different lengths of paid leave. Data were extracted and an assessment of bias was performed independently by authors. Seven studies were identified, with participants from Australia, Sweden, Norway, USA, Canada, and Lebanon. All studies used quantitative methodologies, including cohort, cross-sectional, and repeated cross-sectional designs. Outcomes included mental health and wellbeing, general health, physical wellbeing, and intimate partner violence. The four studies that examined leave at an individual level showed evidence of maternal health benefits, whereas the three studies conducting policy-level comparisons reported either no association or evidence of a negative association. The synthesis of the results suggested that paid maternity leave provided maternal health benefits, although this varied depending on the length of leave. This has important implications for public health and social policy. However, all studies were subject to confounding bias and many to reverse causation. Given the small number of studies and the methodological limitations of the evidence, longitudinal studies are

Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

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St-Cyr, Sophie; McGowan, Patrick O.

2015-01-01

Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

LENUS (Irish Health Repository)

Cooley, Sharon M

2012-02-01

AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

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Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

Climate Prediction Center (CPC)Area-averaged 850-hPa Western Pacific Trade Wind Anomalies

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National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 135oE-180o (western equatorial...

Climate Prediction Center (CPC)Area-averaged 850-hPa Eastern Pacific Trade Wind Anomalies

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National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 135oW-120oW (eastern...

Climate Prediction Center (CPC)Area-averaged 850-hPa Central Pacific Trade Wind Anomalies

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National Oceanic and Atmospheric Administration, Department of Commerce — This is one of the CPC?s Monthly Atmospheric and SST Indices. It is the 850-hPa trade wind anomalies averaged over the area 5oN ? 5oS, 175oW-140oW (central...

Inflammation-Specific T1 Imaging Using Anti-Intercellular Adhesion Molecule 1 Antibody-Conjugated Gadolinium Diethylenetriaminepentaacetic Acid

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Kyu-Sil Choi

2007-03-01

Full Text Available To examine inflammatory tissue, an initial and common symptom of various types of pathogenesis, we designed inflammation-targeted T1 contrast agents prepared by bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA with anti-intercellular adhesion molecule 1 (ICAM-1 antibody. The anti-ICAM-1 antibody was coupled with DTPA and was then conjugated with Gd. The specific binding of the Gd-DTPA-anti-ICAM-1 antibody complex to the ICAM-1-expressing cells was examined in the cultured endothelial cells where ICAM-1 expression was stimulated. Inflammation-specific T1 imaging was then assessed using a mouse abscess model with the 1.5-Tesla module. The Gd-DTPA-anti-ICAM-1 antibody displayed increased r1, which was two times higher than that of Gd-DTPA and showed predominant binding to cultured endothelial cells, which expressed a high level of ICAM-1. Moreover, the inflammation-specific T1 enhancement was imaged with the Gd-DTPA-anti-ICAM-1 antibody in the mouse acute inflammation model. The Gd-DTPA-anti-ICAM-1 antibody showed significantly increased vascular circulation time, which thereby offered a greater chance for its binding to the target cells. The Gd-DTPA-anti-ICAM-1 antibody displays a potential targeted T1 contrast agent specific to the inflammatory tissue that expresses ICAM-1.

Investigations of HPA Function and the Enduring Consequences of Stressors in Adolescence in Animal Models

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McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, Catherine; Waters, Patti

2010-01-01

Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system.…

Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats.

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Yang, Shui-Jin; Yu, Hai-Yang; Kang, Dan-Yu; Ma, Zhan-Qiang; Qu, Rong; Fu, Qiang; Ma, Shi-Ping

2014-09-01

Salidroside (SA) is the primary bioactive marker compound in the standardized extracts from Rhodiola rosea. Although it has potential antidepressant activity in a rat behavioral despair model, the mechanisms of antidepressant effect for SA remain unclear. The objective of this study was to evaluate the antidepressant effects of SA and to discuss the potential mechanisms in olfactory bulbectomized (OBX) rats. SA of 20, 40 mg/kg (p.o.) for 2 weeks notably alleviated OBX-induced hyperactivity in open field test, decreased immobility time in TST and FST. Chronic treatment with SA could remarkably reduce TNF-α and IL-1β levels in hippocampus. Western blot showed that SA could markedly increase glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Besides, SA could also attenuate corticotropin-releasing hormone (CRH) expression in hypothalamus, as well as reducing significantly the levels of serum corticosterone. In conclusion, this study demonstrated that OBX rats treated with SA could significantly improve the depressive-like behaviors. The antidepressant mechanisms of SA might be associated with its anti-inflammatory effects and the regulation of HPA axis activity. Reversal of abnormalities of GR may be partly responsible for those effects. These findings suggested that SA might become a beneficial agent to prevent and treat the depression. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal serum anti-Müllerian hormone in Sudanese women with preeclampsia.

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Agabain, Eiman; Mohamed, Hameed; Elsheikh, Anas E; Hamdan, Hamdan Z; Adam, Ishag

2017-06-24

A case-control study was conducted at Omdurman Maternity Tertiary Hospital, Sudan, during the period from May to August 2014 to investigate AMH level in women with preeclampsia compared to healthy controls. The cases were women with preeclampsia and healthy pregnant women were the controls. The obstetrics and medical history was gathered using a questionnaire. AMH level was measured using ELISA. There was no significant difference between the two groups (40 in each arm of the study) in the age, parity and gestational age. Thirty-three of the 40 cases were patients with severe preeclampsia. There was no significant difference in median inter-quartile of the AMH level between the women with preeclampsia and the controls [0.700 (0.225-1.500) vs. 0.700 (0.400-1.275) ng/ml, P = 0.967]. In a linear regression model there was no association between the log of AMH and age, parity, gestational age, BMI, hemoglobin level and preeclampsia.

Performance evaluation of working standard NE2581 in comparison with reference standard NE2561 in the determination of absorbed dose to water using IAEA, HPA, NACP, AAPM, NCRP and ICRU protocols

International Nuclear Information System (INIS)

Dolah, M.T.; Supian Samat; Taiman Kadni

2001-01-01

The aim of this study was to evaluate the performance of NE 2581 in comparison with NE 2561 in the determination of the absorbed dose to water in a γ-ray beam using IAEA, HPA, NACP, AAPM, NCRP and ICRU protocols. 13 exposures of the γ-ray beams were used. This number of exposures yielded 26 chamber rate readings for NE 2581 (N=13) and for NE 2561 (N=13). From the 13 NE 2581 readings, 78 absorbed dose to water values were calculated for the IAEA (N=13), HPA (N=13), NACP (N=13), AAPM (N=13), NCRP (N=13) and ICRU (N=13) protocols. Similarly, from the 13 NE 2561 readings, 78 absorbed dose to water values were calculated for IAEA (N=13), HPA (N=13), NACP (N=13), AAPM (N=13), NCRP (N=13) and ICRU (N=13) protocols. From these 156 (=78 x 2) absorbed dose to water values, 78 percentage deviations between the NE 2581 and NE 2561 results were calculated for IAEA (N=13), HPA (N=13), NACP (N=13), AAPM (N=13), NCRP (N=13) and ICRU (N=13) protocols. For a single protocol, the mean μ and standard error σ+s+e of the percentage deviations (N=13) were calculated. results obtained in terms of [protocol, μ ± σ se ] were [IAEA,1.55 ± 0.12], [HPA, 0.98 ± 0.12], [NACP, 1.93 ± 0.12], [AAPM, -0.06 ± 0.12], [NCRP, 0.97 ± 0.12], [ICRU, 0.97 ± 0.12]. It can be seen that the range of percentage deviations is from -0.06 to 1.93. As the quoted IAEA acceptable limit of deviation is ± 3.0%, it was concluded that the working standard NE 2581 chamber has shown acceptable performance. In addition, the use of the AAPM protocol has enable NE 2581 to show a performance that is very similar like NE 2561. (Author)

Anti-Chol-1 antigen, GQ1bα, antibodies are associated with Alzheimer's disease.

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Toshio Ariga

Full Text Available The interaction of amyloid β-proteins (Aβ with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer's disease (AD. Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA and high-performance thin-layer chromatography (HPTLC immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD, and 11 non-demented age-matched pathological controls were examined in order to detect anti-glycosphingolipid (GSL antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides. However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases and VD (100%, respectively. Most surprisingly, anti-GQ1bα antibodies (IgM were found in 90% (9/10 and 100% (6/6 in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.

Maternal Depression and Youth Internalizing and Externalizing Symptomatology: Severity and Chronicity of Past Maternal Depression and Current Maternal Depressive Symptoms

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O’Connor, Erin E.; Langer, David A.; Tompson, Martha C.

2017-01-01

Maternal depression is a well-documented risk factor for youth depression, and taking into account its severity and chronicity may provide important insight into the degree of risk conferred. This study explored the degree to which the severity/chronicity of maternal depression history explained variance in youth internalizing and externalizing symptoms above and beyond current maternal depressive symptoms among 171 youth (58% male) ages 8 to 12 over a span of three years. Severity and chronicity of past maternal depression and current maternal depressive symptoms were examined as predictors of parent-reported youth internalizing and externalizing symptomatology, as well as youth self-reported depressive symptoms. Severity and chronicity of past maternal depression did not account for additional variance in youth internalizing and externalizing symptoms at Time 1 beyond what was accounted for by maternal depressive symptoms at Time 1. Longitudinal growth curve modeling indicated that prior severity/chronicity of maternal depression predicted levels of youth internalizing and externalizing symptoms at each time point when controlling for current maternal depressive symptoms at each time point. Chronicity of maternal depression, apart from severity, also predicted rate of change in youth externalizing symptoms over time. These findings highlight the importance of screening and assessing for current maternal depressive symptoms, as well as the nature of past depressive episodes. Possible mechanisms underlying the association between severity/chronicity of maternal depression and youth outcomes, such as residual effects from depressive history on mother–child interactions, are discussed. PMID:27401880

HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

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Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

2015-01-01

Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

Vinclozolin--no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route.

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Schneider, Steffen; Marxfeld, Heike; Gröters, Sibylle; Buesen, Roland; van Ravenzwaay, Bennard

2013-06-01

The goal of this study was to examine the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti-androgenicity at 100mg/kg bw/d. However, F1-F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity.

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Roberts, Christine L; Ford, Jane B; Algert, Charles S; Bell, Jane C; Simpson, Judy M; Morris, Jonathan M

2009-02-25

Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3-5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising

Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity

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Algert Charles S

2009-02-01

Full Text Available Abstract Background Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH. Methods We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Results Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000 suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3–5.3%. This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Conclusion Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was

What's happening? The expanding role of apheresis platelet support in neonatal alloimmune thrombocytopenia: current status and future trends.

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Bessos, Hagop; Seghatchian, Jerard

2005-10-01

Despite some unresolved problems that may be associated with platelet transfusion, such as alloimmunisation, refractoriness, bacterial contamination, and the potential side effects related to the development of some biological response modifiers during storage, platelet therapy remains the most effective treatment for the management and prevention of severe thrombocytopenia and hemorrhage [Seghatchian J, Snyder EL, Krailadsiri P, editors. Platelet therapy: current status and future trends. Amsterdam, The Netherlands: Elsevier; 2000]. This appears to be particularly the case in neonatal alloimmune thrombocytopenia (NAIT), which arises due to an incompatibility of the platelet specific antigens between the pregnant mother and her baby. Over 80% of severe NAIT cases in the Caucasian population occur when the mother and baby differ in their HPA-1 epitope (HPA-1a negative and positive respectively) leading, in 10% of cases, to the production of anti-HPA-1a which can cross the placenta and cause NAIT in utero or post-partum. Anti-HPA-5b is the second most cause of NAIT, although severe cases occur only after the first pregnancy. Clinical manifestations of NAIT vary from mild (petechia and bruises) to severe (intracranial haemorrhage with possible death or life long morbidity). A recent study in Scotland indicated that the cost per case of severe NAIT detected during screening of pregnant women, where anti-HPA-1a is detected for the first time, would amount to $98,771 [Turner M, Bessos H, et al. Prospective epidemiological study of the outcome and cost effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia (NAIT) due to anti-HPA-1a. Transfusion, in press. Yet, unlike the case with Rhesus hemolytic disease of the new born, the cost-effectiveness of HPA-1 screening in NAIT remains unresolved, as does the most optimal mode of treatment. Therefore, in the absence of a consensus on the screening and optimal management of NAIT, the availability and

Comparison of maternal omentin-1 levels and genetic variability between spontaneous term and preterm births.

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Šplíchal, Zbyněk; Zlámal, Filip; Máchal, Jan; Lipková, Jolana; Pavlová, Tereza; Hodická, Zuzana; Ventruba, Pavel; Vašků, Anna; Bienertová-Vašků, Julie

2018-07-01

To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs). Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n = 16) and without (n = 14) preterm premature rupture of membranes (PPROM). Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p = .015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established. High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.

Agricultural losses related to frost events: use of the 850 hPa level temperature as an explanatory variable of the damage cost

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Papagiannaki, K.; Lagouvardos, K.; Kotroni, V.; Papagiannakis, G.

2014-09-01

The objective of this study is the analysis of damaging frost events in agriculture, by examining the relationship between the daily minimum temperature in the lower atmosphere (at an isobaric level of 850 hPa) and crop production losses. Furthermore, the study suggests a methodological approach for estimating agriculture risk due to frost events, with the aim of estimating the short-term probability and magnitude of frost-related financial losses for different levels of 850 hPa temperature. Compared with near-surface temperature forecasts, temperature forecasts at the level of 850 hPa are less influenced by varying weather conditions or by local topographical features; thus, they constitute a more consistent indicator of the forthcoming weather conditions. The analysis of the daily monetary compensations for insured crop losses caused by weather events in Greece shows that, during the period 1999-2011, frost caused more damage to crop production than any other meteorological phenomenon. Two regions of different geographical latitudes are examined further, to account for the differences in the temperature ranges developed within their ecological environment. Using a series of linear and logistic regressions, we found that minimum temperature (at an 850 hPa level), grouped into three categories according to its magnitude, and seasonality, are significant variables when trying to explain crop damage costs, as well as to predict and quantify the likelihood and magnitude of damaging frost events.

Obstetric near-miss and maternal mortality in maternity university hospital, Damascus, Syria: a retrospective study

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Al Chamat Ahmad

2010-10-01

Full Text Available Abstract Background Investigating severe maternal morbidity (near-miss is a newly recognised tool that identifies women at highest risk of maternal death and helps allocate resources especially in low income countries. This study aims to i. document the frequency and nature of maternal near-miss at hospital level in Damascus, Capital of Syria, ii. evaluate the level of care at maternal life-saving emergency services by comparatively analysing near-misses and maternal mortalities. Methods Retrospective facility-based review of cases of near-miss and maternal mortality that took place in the years 2006-2007 at Damascus Maternity University Hospital, Syria. Near-miss cases were defined based on disease-specific criteria (Filippi 2005 including: haemorrhage, hypertensive disorders in pregnancy, dystocia, infection and anaemia. Main outcomes included maternal mortality ratio (MMR, maternal near miss ratio (MNMR, mortality indices and proportion of near-miss cases and mortality cases to hospital admissions. Results There were 28 025 deliveries, 15 maternal deaths and 901 near-miss cases. The study showed a MNMR of 32.9/1000 live births, a MMR of 54.8/100 000 live births and a relatively low mortality index of 1.7%. Hypertensive disorders (52% and haemorrhage (34% were the top causes of near-misses. Late pregnancy haemorrhage was the leading cause of maternal mortality (60% while sepsis had the highest mortality index (7.4%. Most cases (93% were referred in critical conditions from other facilities; namely traditional birth attendants homes (67%, primary (5% and secondary (10% healthcare unites and private practices (11%. 26% of near-miss cases were admitted to Intensive Care Unit (ICU. Conclusion Near-miss analyses provide valuable information on obstetric care. The study highlights the need to improve antenatal care which would help early identification of high risk pregnancies. It also emphasises the importance of both: developing protocols to

Obstetric near-miss and maternal mortality in maternity university hospital, Damascus, Syria: a retrospective study.

Science.gov (United States)

Almerie, Yara; Almerie, Muhammad Q; Matar, Hosam E; Shahrour, Yasser; Al Chamat, Ahmad Abo; Abdulsalam, Asmaa

2010-10-19

Investigating severe maternal morbidity (near-miss) is a newly recognised tool that identifies women at highest risk of maternal death and helps allocate resources especially in low income countries. This study aims to i. document the frequency and nature of maternal near-miss at hospital level in Damascus, Capital of Syria, ii. evaluate the level of care at maternal life-saving emergency services by comparatively analysing near-misses and maternal mortalities. Retrospective facility-based review of cases of near-miss and maternal mortality that took place in the years 2006-2007 at Damascus Maternity University Hospital, Syria. Near-miss cases were defined based on disease-specific criteria (Filippi 2005) including: haemorrhage, hypertensive disorders in pregnancy, dystocia, infection and anaemia. Main outcomes included maternal mortality ratio (MMR), maternal near miss ratio (MNMR), mortality indices and proportion of near-miss cases and mortality cases to hospital admissions. There were 28,025 deliveries, 15 maternal deaths and 901 near-miss cases. The study showed a MNMR of 32.9/1000 live births, a MMR of 54.8/100,000 live births and a relatively low mortality index of 1.7%. Hypertensive disorders (52%) and haemorrhage (34%) were the top causes of near-misses. Late pregnancy haemorrhage was the leading cause of maternal mortality (60%) while sepsis had the highest mortality index (7.4%). Most cases (93%) were referred in critical conditions from other facilities; namely traditional birth attendants homes (67%), primary (5%) and secondary (10%) healthcare unites and private practices (11%). 26% of near-miss cases were admitted to Intensive Care Unit (ICU). Near-miss analyses provide valuable information on obstetric care. The study highlights the need to improve antenatal care which would help early identification of high risk pregnancies. It also emphasises the importance of both: developing protocols to prevent/manage post-partum haemorrhage and training health

A Comparison of Medical Birth Register Outcomes between Maternity Health Clinics and Integrated Maternity and Child Health Clinics in Southwest Finland.

Science.gov (United States)

Tuominen, Miia; Kaljonen, Anne; Ahonen, Pia; Mäkinen, Juha; Rautava, Päivi

2016-07-08

Primary maternity care services are globally provided according to various organisational models. Two models are common in Finland: a maternity health clinic and an integrated maternity and child health clinic. The aim of this study was to clarify whether there is a relation between the organisational model of the maternity health clinics and the utilisation of maternity care services, and certain maternal and perinatal health outcomes. A comparative, register-based cross-sectional design was used. The data of women (N = 2741) who had given birth in the Turku University Hospital area between 1 January 2009 and 31 December 2009 were collected from the Finnish Medical Birth Register. Comparisons were made between the women who were clients of the maternity health clinics and integrated maternity and child health clinics. There were no clinically significant differences between the clients of maternity health clinics and integrated maternity and child health clinics regarding the utilisation of maternity care services or the explored health outcomes. The organisational model of the maternity health clinic does not impact the utilisation of maternity care services or maternal and perinatal health outcomes. Primary maternity care could be provided effectively when integrated with child health services.

Tumor-targeted Nanobullets: Anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment.

Science.gov (United States)

van der Meel, Roy; Oliveira, Sabrina; Altintas, Isil; Haselberg, Rob; van der Veeken, Joris; Roovers, Rob C; van Bergen en Henegouwen, Paul M P; Storm, Gert; Hennink, Wim E; Schiffelers, Raymond M; Kok, Robbert J

2012-04-30

The epidermal growth factor receptor (EGFR) is a validated target for anti-cancer therapy and several EGFR inhibitors are used in the clinic. Over the years, an increasing number of studies have reported on the crosstalk between EGFR and other receptors that can contribute to accelerated cancer development or even acquisition of resistance to anti-EGFR therapies. Combined targeting of EGFR and insulin-like growth factor 1 receptor (IGF-1R) is a rational strategy to potentiate anti-cancer treatment and possibly retard resistance development. In the present study, we have pursued this by encapsulating the kinase inhibitor AG538 in anti-EGFR nanobody-liposomes. The thus developed dual-active nanobody-liposomes associated with EGFR-(over)expressing cells in an EGFR-specific manner and blocked both EGFR and IGF-1R activation, due to the presence of the EGFR-blocking nanobody EGa1 and the anti-IGF-1R kinase inhibitor AG538 respectively. AG538-loaded nanobody-liposomes induced a strong inhibition of tumor cell proliferation even upon short-term exposure followed by a drug-free wash-out period. Therefore, AG538-loaded nanobody-liposomes are a promising anti-cancer formulation due to efficient intracellular delivery of AG538 in combination with antagonistic and downregulating properties of the EGa1 nanobody-liposomes. Copyright © 2011 Elsevier B.V. All rights reserved.

Paid Maternity Leave in the United States: Associations with Maternal and Infant Health.

Science.gov (United States)

Jou, Judy; Kozhimannil, Katy B; Abraham, Jean M; Blewett, Lynn A; McGovern, Patricia M

2018-02-01

Objectives The United States is one of only three countries worldwide with no national policy guaranteeing paid leave to employed women who give birth. While maternity leave has been linked to improved maternal and child outcomes in international contexts, up-to-date research evidence in the U.S. context is needed to inform current policy debates on paid family leave. Methods Using data from Listening to Mothers III, a national survey of women ages 18-45 who gave birth in 2011-2012, we conducted multivariate logistic regression to predict the likelihood of outcomes related to infant health, maternal physical and mental health, and maternal health behaviors by the use and duration of paid maternity leave. Results Use of paid and unpaid leave varied significantly by race/ethnicity and household income. Women who took paid maternity leave experienced a 47% decrease in the odds of re-hospitalizing their infants (95% CI 0.3, 1.0) and a 51% decrease in the odds of being re-hospitalized themselves (95% CI 0.3, 0.9) at 21 months postpartum, compared to women taking unpaid or no leave. They also had 1.8 times the odds of doing well with exercise (95% CI 1.1, 3.0) and stress management (95% CI 1.1, 2.8), compared to women taking only unpaid leave. Conclusions for Practice Paid maternity leave significantly predicts lower odds of maternal and infant re-hospitalization and higher odds of doing well with exercise and stress management. Policies aimed at expanding access to paid maternity and family leave may contribute toward reducing socio-demographic disparities in paid leave use and its associated health benefits.

[Maternal and fetal outcome in Mexican women with rheumatoid arthritis].

Science.gov (United States)

Saavedra, Miguel A; Sánchez, Antonio; Bustamante, Reyna; Miranda-Hernández, Dafhne; Soliz-Antezana, Jimena; Cruz-Domínguez, Pilar; Morales, Sara; Jara, Luis J

2015-01-01

To report our experience in maternal-fetal outcome in women with RA in a national medical referral center. A retrospective analysis of the records of pregnant women with rheumatoid arthritis attending at a Pregnancy and Autoimmune Rheumatic Diseases Clinic was performed. Maternal-fetal outcomes such as disease activity, preclampsia/eclampsia, rate of live births, abortions, stillbirths, preterm birth, weeks of gestation, birth weight, congenital malformations and use of anti-rheumatic drugs were studied. We included 73 pregnancies in 72 patients. Disease activity was documented in 47.2% of patients during pregnancy and/or postpartum and 87.7% of patients received some antirheumatic drug. Preclampsia developed in 8.2% of cases. The live birth rate was 98.6%, with preterm delivery in 15.9% and low weight at term in 17.6% of cases. Cesarean section was performed in 77.1% of cases. The disease activity was not associated with a higher percentage of maternal-fetal complications. Our study showed that most patients do not experience significant activity of RA during pregnancy, fetal outcome is satisfactory and disease activity did not appear to influence significantly the obstetric outcome.

The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

NARCIS (Netherlands)

P.C. Guest (Paul); D. Martins-de-Souza (Daniel); H. Rahmoune (Hassan); S. Bahn (Sabine); P.C. Guest (Paul)

2013-01-01

textabstractOver the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in

Mechanisms underlying the comorbidity between depressive and addictive disorders in adolescents: interactions between stress and HPA activity.

Science.gov (United States)

Rao, Uma; Hammen, Constance L; Poland, Russell E

2009-03-01

Depression may be a precursor to substance use disorder in some youngsters, and substance abuse might complicate the subsequent course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to the development of substance use disorder in depressed and nondepressed adolescents, and whether substance use disorder predicts a worsening course of depression. Urinary-free cortisol was measured for 3 nights in 151 adolescents with no prior history of substance use disorder (55 depressed, 48 at high risk for depression, and 48 normal subjects). Information was obtained on recent stressful life experiences. The participants were followed for up to 5 years to assess the onset of substance use disorder, course of depression, and stressful experiences. The relationships among depression, cortisol as a measure of HPA activity, stressful experiences, and substance use disorder were examined. Elevated cortisol was associated with onset of substance use disorder. Stressful life experiences moderated this relationship. Cortisol and stress accounted for the effects of a history or risk of depression on the development of substance use disorder. Substance use disorder was associated with higher frequency of subsequent depressive episodes. Higher cortisol prior to the onset of substance use disorder may indicate vulnerability to substance use disorder. Stressful experiences increase the risk for substance use disorder in such vulnerable youth. The high prevalence of substance use disorders in depressed individuals may be explained, in part, by high levels of stress and increased HPA activity.

Evidence consistent with human L1 retrotransposition in maternal meiosis I

NARCIS (Netherlands)

Brouha, Brook; Meischl, Christof; Ostertag, Eric; de Boer, Martin; Zhang, Yue; Neijens, Herman; Roos, Dirk; Kazazian, Haig H.

2002-01-01

We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 ((l) under bar ong (i) under bar nterspersed (n) under bar ucleotide (e) under bar lement-1), retrotransposition event most likely occurred in the maternal primary oocyte during meiosis I. We characterized a

Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

DEFF Research Database (Denmark)

Forslind, K; Svensson, Birte; Svenson, M

2001-01-01

To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

The relation between hypothalamic-pituitary-adrenal (HPA) axis activity and age of onset of alcohol use

NARCIS (Netherlands)

Evans, B.E.; Greaves-Lord, K.; Euser, A.S.; Franken, I.H.A.; Huizink, A.C.

2012-01-01

Aims: Hypothalamic-pituitary-adrenal (HPA) axis activity may prove a viable biomarker for identifying those susceptible to alcohol use disorders. The purpose of this study was to examine the relation of the age at which adolescents begin drinking with diurnal and stress cortisol. Design:

¹¹¹In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages.

Science.gov (United States)

Terry, Samantha Y A; Boerman, Otto C; Gerrits, Danny; Franssen, Gerben M; Metselaar, Josbert M; Lehmann, Steffi; Oyen, Wim J G; Gerdes, Christian A; Abiraj, Keelara

2015-08-01

Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with (111)In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with (111)In-anti-F4/80-A3-1 and isotype-matched control antibody (111)In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. In vitro binding assays showed that (111)In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg (111)In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg (111)In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced (111)In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of (111)In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of (111)In-rat IgG2b was lower in the spleen, liver and femur when compared to (111)In-anti-F4/80-A3-1. Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.

Absorbed dose to water comparison between NE 2561 and NE 2671 chambers using IAEA, HPA and NACP protocols for gamma ray beam

International Nuclear Information System (INIS)

Mohd Taufik Dolah; Noriah Mod Ali; Taiman Kadni

2002-01-01

The aim of this study to evaluate the performance of NE 2571 chamber in comparison with NE 2561 chamber in determination of the absorbed dose to water in gamma ray beam. In this study NE 2561 is taking as a reference standard chamber while NE 2571 as a working standard. Irradiation of chamber (alternately) was performed at a reference depth, 5 cm, inside the IAEA water phantom. Both chambers were exposed to 13 difference exposures of gamma rays. The values of absorbed dose to water were then determined using IAEA, HPA and NACP protocols. Deviations of absorbed dose determined by NE 2561 and NE 2571 were calculated for each protocol. result obtained in terms of [protocol, μ (mean deviation) ± σ s e (standard error)] were (IAEA, 1.12 ± 0.04], [HPA, 0.09 ± 0.04], and [NCP, 0.09 ± 0.04]. It can be concluded that NE 2571 shown acceptable performance as it is within acceptable limit ± 3%. (Author)

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

Science.gov (United States)

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis.

Science.gov (United States)

Overeem, S; Dalmau, J; Bataller, L; Nishino, S; Mignot, E; Verschuuren, J; Lammers, G J

2004-01-13

Idiopathic narcolepsy is associated with deficient hypocretin transmission. Narcoleptic symptoms have recently been described in paraneoplastic encephalitis with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in patients with idiopathic narcolepsy. Anti-Ma autoantibodies were not detected in patients with idiopathic narcolepsy. Four patients with anti-Ma2 encephalitis had excessive daytime sleepiness; hypocretin-1 was not detectable in their cerebrospinal fluid, suggesting an immune-mediated hypocretin dysfunction.

Repetitive stress leads to impaired cognitive function that is associated with DNA hypomethylation, reduced BDNF and a dysregulated HPA axis.

Science.gov (United States)

Makhathini, Khayelihle B; Abboussi, Oualid; Stein, Dan J; Mabandla, Musa V; Daniels, William M U

2017-08-01

Exposure to repetitive stress has a negative influence on cognitive-affective functioning, with growing evidence that these effects may be mediated by a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, abnormal neurotrophic factor levels and its subsequent impact on hippocampal function. However, there are few data about the effect of repetitive stressors on epigenetic changes in the hippocampus. In the present study, we examine how repetitive restrain stress (RRS) affects cognitive-affective functioning, HPA axis regulation, brain-derived neurotrophic factor (BDNF) levels, and global hippocampal DNA methylation. RRS was induced in rats by restraining the animals for 6h per day for 28 days. The novel object recognition test (NORT) was used to assess cognitive functioning and the open field test (OFT) was performed to assess anxiety-like behavior during the last week of stress. Hippocampal BDNF levels, glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA were assessed using real-time PCR and confirmed with Western blot, while ELISAs were used to determine plasma corticosterone levels and the global methylation status of the hippocampus. Animals exposed to repetitive stress demonstrated significant alterations in the NORT and OFT, had significantly increased plasma corticosterone and significantly decreased hippocampal BDNF concentrations. The expression levels of GR and MR mRNA and protein levels of these genes were significantly decreased in the stressed group compared to control animals. The global DNA methylation of the hippocampal genome of stressed animals was also significantly decreased compared to controls. The data here are consistent with previous work emphasizing the role of the HPA axis and neurotrophic factors in mediating cognitive-affective changes after exposure to repetitive stressors. Our findings, however, extend the literature by indicating that epigenetic alterations in the hippocampal genome may also play an important role in the

Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS.

Science.gov (United States)

Xie, Weidong; Zhang, Yaou; Bu, Cunya; Sun, Shijing; Hu, Shaoliang; Cai, Guoping

2011-01-01

Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. Copyright © 2010 Elsevier B.V. All rights reserved.

Case report: Severe hemolytic disease of the fetus and newborn due to anti-C+G.

Science.gov (United States)

Jernman, Riina; Stefanovic, Vedran; Korhonen, Anu; Haimila, Katri; Sareneva, Inna; Sulin, Kati; Kuosmanen, Malla; Sainio, Susanna

2015-01-01

Anti-G is commonly present with anti-D and/or anti-C and can confuse serological investigations. in general, anti-G is not considered a likely cause of severe hemolytic disease of the fetus and newborn (HDFN), but it is important to differentiate it from anti-D in women who should be administered anti-D immunoglobulin prophylaxis. We report one woman with three pregnancies severely affected by anti-C+G requiring intrauterine treatment and a review of the literature. In our case, the identification of the correct antibody was delayed because the differentiation of anti-C+G and anti-D+C was not considered important during pregnancy since the father was D-. In addition, anti-C+G and anti-G titer levels were not found to be reliable as is generally considered in Rh immunization. Severe HDFN occurred at a maternal anti-C+G antibody titer of S and anti-G titer of 1 in comparison with the critical titer level of 16 or more in our laboratory. close collaboration between the immunohematology laboratory and the obstetric unit is essential. In previously affected families, early assessment for fetal anemia is required even when titers are low.

Maternal Concern for Child Undereating.

Science.gov (United States)

Brown, Callie L; Pesch, Megan H; Perrin, Eliana M; Appugliese, Danielle P; Miller, Alison L; Rosenblum, Katherine; Lumeng, Julie C

To describe features of maternal concern for her child undereating; examine maternal and child correlates of maternal concern for undereating; and determine whether maternal concern for undereating is associated with feeding practices. This was a cross-sectional analysis of an observational study with 286 mother-child dyads (mean child age, 71 months). Maternal concern for undereating was assessed using a semistructured interview. Mothers completed questionnaires to assess picky eating, food neophobia, and feeding practices. Feeding practices were further assessed using videotaped mealtime observations. Logistic regression was used to assess the association of maternal and child characteristics with maternal concern for undereating. Regression was used to assess the association of maternal concern for undereating with feeding practices, controlling for covariates. Over a third of mothers (36.5%) expressed concern that their child does not eat enough. Correlates of concern for undereating included child body mass index z-score (BMIz; odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.43-0.77) and picky eating (OR = 2.41; 95% CI, 1.26-4.59). Maternal concern for undereating was associated with greater reported pressure to eat (relative risk [RR] = 1.97; 95% CI, 1.55-2.50), greater observed bribery (OR = 2.63; 95% CI, 1.50-4.60), and higher observed pressure (OR = 1.90; 95% CI, 1.08-3.36) during mealtimes. Mothers of children who are picky eaters and have a lower BMIz are more likely to be concerned that their children do not eat enough, and maternal concern for undereating is associated with pressuring and bribing children to eat. Pediatricians might address maternal concern for undereating by advising feeding practices that do not involve pressure and bribery, particularly among healthy weight children. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Hee-Sook Kim

2015-08-01

Full Text Available BackgroundThe purpose of this study was to evaluate maternal and neonatal outcomes in Korean women with type 1 diabetes and type 2 diabetes.MethodsWe performed a retrospective survey of 163 pregnancies in women with type 1 diabetes (n=13 and type 2 diabetes (n=150 treated from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups.ResultsDifferences in glycosylated hemoglobin between type 1 and type 2 diabetes were not significant. Birth weight (3,501±689.6 g vs. 3,366±531.4 g and rate of major congenital malformations (7.7% vs. 5.6% were not significantly different. However, women with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006, large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004, macrosomia (38.5% vs. 13.4%, P=0.032, and admission for neonatal care (41.7% vs. 14.8%, P=0.03 than women with type 2 diabetes.ConclusionMaternal and neonatal outcomes for women with type 1 diabetes were poorer than for women with type 2 diabetes, especially preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.

Relative IGF-1 and IGF-2 gene expression in maternal and fetal tissues from diabetic swine

International Nuclear Information System (INIS)

Wolverton, C.K.; Leaman, D.W.; White, M.E.; Ramsay, T.G.

1990-01-01

Fourteen pregnant, crossbred gilts were utilized in this study. Seven gilts were injected with alloxan (50 mg/kg) at day 75 of gestation to induce diabetes. Gilts underwent caesarean section on day 105 of gestation. Samples were collected from maternal skeletal muscle, adipose tissue, uterus and endometrium; and from fetal skeletal muscle, adipose tissue, placenta, liver, lung, kidney, heart, brain and spleen. Tissues were frozen in liquid nitrogen for later analysis of IGF-1 and IGF-2 gene expression. Samples were pooled and total RNA was isolated using the guanidine isothiocynate method. Total mRNA was analyzed by dot blot hybridization. Blots were probed with 32 P-cDNA for porcine IGF-1 and rat IGF-2. IGF-1 gene expression in maternal tissues was unaffected by diabetes. Maternal diabetes increased IGF-2 mRNA in maternal adipose tissue but exhibited no effect in muscle or uterus. Expression of IGF-2 by maternal endometrium was decreased by diabetes. Maternal diabetes induced an increase in IGF-1 gene expression in muscle and placenta while causing an increase in IGF-2 expression in fetal liver and placenta. IGF-2 mRNA was lower in lung from fetuses of diabetic mothers than in controls. These results suggest that maternal diabetes alters IGF-1 and IGF-2 gene expression in specific tissues and differential regulation of these genes appears to exist in the mother and developing fetus

Evaluation of commercial antiglobulin sera over a two-year period. Part I. Anti-beta 1A, anti-alpha 2D, and anti-beta 1E levels.

Science.gov (United States)

Issitt, P D; Issitt, C H; Wilkinson, S L

1974-01-01

Antiglobulin sera from nine different manufacturers have been tested, over a two-year period, for their ability to detect the complement components beta 1A, alpha 2D, and beta 1E. The results demontrate considerable variation in the abilities of sera from different manufacturers to detect these components and indicate that not all sera on the market are suitable reagents for diagnostic use and compatibility tests. The results also show that there is considerable variation between different lots of serum from some of the manufacturers. In general, the anti-complement levels of these reagents have increased during the two-year period of study but not all companies produce suitable reagents for routine use.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

Science.gov (United States)

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Effects of lactose as an inducer on expression of Helicobacter pylori rUreB and rHpaA,and Escherichia colirLTKA63 and rLTB

Institute of Scientific and Technical Information of China (English)

Jie Yan; Shou-Feng Zhao; Ya-Fei Mao; Yi-Hui Luo

2004-01-01

AIM: To demonstrate the effect of lactose as an inducer on expression of the recombinant proteins encoded by Helicobacter pylori ureB and hpaA, and Escherichia coli LTB and LTKA63 genes and to determine the optimal expression parameters.METHODS: By using SDS-PAGE and BIO-RAD gel image analysis system, the outputs of the target recombinant proteins expressed by pET32a-ureB-E. coliBL21, pET32ahpaA-E. coliBL21, pET32a-L TKA63-E. coliBL21 and pET32aLTB-E.coliBL21 were measured when using lactose as inducer at different dosages, original bacterial concentrations,various inducing temperatures and times. The results of the target protein expression induced by lactose were compared to those by isopropyl-β-D-thiogalactoside (IPTG).The proteins were expressed in E.coli.RESULTS: Lactose showed higher efficiency of inducing the expression of rHpaA, rUreB, rLTB and rLTKA63 than IPTG. The expression outputs of the target recombinant proteins induced at 37 ℃ were remarkably higher than those at 28 ℃. Other optimal expression parameters for the original bacterial concentrations, dosages of lactose and inducing time were 0.8, 50 g/L and 4 h for rHpaA; 0.8, 100 g/L and 4 h for rLTKA63; 1.2, 100 g/Land 5 h for both rUreB and rLTB, respectively.CONCLUSION: Lactose, a sugar with non-toxicity and low cost, is able to induce the recombinant genes to express the target proteins with higher efficiency than IPTG. The results in this study establish a beneficial foundation for industrial production of H pylori genetic engineering vaccine.

Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid

International Nuclear Information System (INIS)

Nye, Jonathon A.; Jarkas, Nashwa; Schuster, David M.; Savir-Baruch, Bital; Voll, Ronald J.; Camp, Vernon M.; Goodman, Mark M.

2011-01-01

Introduction: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[ 18 F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[ 18 F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans. Methods: A DU145 xenograft rodent model was used to measure anti-2-[ 18 F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[ 18 F]FACPC-1 toxicity was assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247±61 MBq bolus injection of anti-2-[ 18 F]FACPC-1. Estimates of radiation dose from anti-2-[ 18 F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software. Results: High anti-2-[ 18 F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[ 18 F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq. Conclusion: Anti-2-[ 18 F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting malignant tissues in these regions.

Analysis and compensation for the joint effects of HPA nonlinearity, I/Q imbalance and crosstalk in MIMO beamforming systems

KAUST Repository

Qi, Jian

2011-03-01

In this paper, we investigate the joint effects of high-power amplifier (HPA) nonlinearity, in-phase/quadrature-phase (I/Q) imbalance and crosstalk, on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems, and propose a compensation method for the three impairments together. The performance of the MIMO TB system equipped with the proposed compensation scheme is evaluated in terms of average symbol error probability and capacity when transmissions are performed over uncorrelated Rayleigh fading channels. Numerical results are provided and show the effects on performance of several system parameters, namely, the HPA parameters, image-leakage ratio, crosstalk, numbers of antennas, length of pilot symbols and phase-shift keying modulation order. © 2011 IEEE.

Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

Science.gov (United States)

Chiang, Chi-Huei

2006-10-31

Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation.

Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy.

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Kirton, Christopher M; Laukkanen, Marja-Leena; Nieminen, Antti; Merinen, Marika; Stolen, Craig M; Armour, Kathryn; Smith, David J; Salmi, Marko; Jalkanen, Sirpa; Clark, Michael R

2005-11-01

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

[A case of severe hemolytic disease of the newborn due to anti-Dia antibody].

Science.gov (United States)

Lee, Sun Min; Im, Sun Ju; Park, Su Eun; Lee, Eun Yup; Kim, Hyung Hoi

2007-10-01

Here we report a severe case of hemolytic anemia of the newborn with kernicterus caused by anti-Di(a) antibody. A full term male infant was transferred due to hyperbilirubinemia on the third day of life. Despite single phototherapy, the baby's total bilirubin had elevated to 30.1 mg/dL. After exchange transfusion, total bilirubin decreased to 11.45 mg/dL. The direct antiglobulin test on the infant's red cells was positive. The maternal and infant's sera showed a negative reaction in routine antibody detection tests, but were positive in Di(a) panel cells. The frequency of the Di(a) antigen among the Korean population is estimated to be 6.4-14.5%. Anti-Di(a) antibody could cause a hemolytic reaction against transfusion or hemolytic disease of the newborn. We suggest the need for reagent red blood cell panels to include Di(a) antigen positive cells in antibody identification test for Korean.

LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

Directory of Open Access Journals (Sweden)

I.A. Meijer

2015-12-01

Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

Directory of Open Access Journals (Sweden)

Silvana Pasetto

Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

Maternal separation modulates short-term behavioral and physiological indices of the stress response.

Science.gov (United States)

Litvin, Yoav; Tovote, Philip; Pentkowski, Nathan S; Zeyda, Thomas; King, Lanikea B; Vasconcellos, Amy J; Dunlap, Christopher; Spiess, Joachim; Blanchard, D Caroline; Blanchard, Robert J

2010-07-01

Early-life stress produces an anxiogenic profile in adulthood, presumably by activating the otherwise quiescent hypothalamic-pituitary-adrenal (HPA) axis during the vulnerable 'stress hyporesponsive period'. While the long-term effects of such early-life manipulations have been extensively characterized, little is known of the short-term effects. Here, we compared the short-term effects of two durations of maternal separation stress and one unseparated group (US) on behavioral and physiological indices of the stress response in rat pups. Separations included 3h on each of 12days, from postnatal day (PND) 2 to 13 (MS2-13) and 3days of daily, 6-h separation from PND11-13 (MS11-13). On PND14 (Experiment 1), both MS2-13 and MS11-13 produced marked reductions in freezing toward an adult male conspecific along with reduced levels of glucocorticoid type 2 (GR) and CRF type-1 (CRF(1)) receptor mRNA in the hippocampus. Group MS2-13 but not MS11-13 produced deficits in stressor-induced corticosterone secretion, accompanied by reductions in body weight. Our results suggest that GR and/or CRF(1) levels, not solely the magnitude of corticosterone secretion, may be involved in the modulation of freezing. In a second experiment, we aimed to extend these findings by testing male and female separated and unseparated pups' unconditioned defensive behaviors to cat odor on PND26, and subsequent cue+context conditioning and extinction throughout postnatal days 27-32. Our results show that maternal separation produced reductions in unconditioned freezing on PND26, with MS2-13 showing stronger deficits than MS11-13. However, separation did not affect any other defensive behaviors. Furthermore, separated rats failed to show conditioned freezing, although they did avoid the no-odor block conditioned cue. There were no sex differences other than weight. We suggest that maternal separation may have produced these changes by disrupting normal development of hippocampal regions involved in

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

Science.gov (United States)

Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

2016-01-01

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are "clean" of different confounding factors. The

Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay.

Science.gov (United States)

Onodera, Rie; Kurita, Emi; Taniguchi, Kikuyo; Karakawa, Shuhei; Okada, Satoshi; Kihara, Hirotaka; Fujii, Teruhisa; Kobayashi, Masao

2017-11-01

Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed. We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA. The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody. EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. © 2017 AABB.