Relationships between maternal malaria and malarial immune responses in mothers and neonates

DEFF Research Database (Denmark)

Rasheed, F N; Bulmer, J N; De Francisco, A

1995-01-01

and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation...... responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal...... lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established....

The impact of maternally derived immunity on influenza A virus transmission in neonatal pig populations.

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Allerson, Matt; Deen, John; Detmer, Susan E; Gramer, Marie R; Joo, Han Soo; Romagosa, Anna; Torremorell, Montserrat

2013-01-07

The commonality of influenza A virus (IAV) exposure and vaccination on swine farms in the United States ensures that the majority of neonatal pigs will have some degree of maternal immunity to IAV. The influence of maternal immunity on IAV transmission in neonatal pig populations will impact virus prevalence and infection dynamics across pig populations. The main objective of this study was to assess the impact of maternally derived immunity on IAV transmission in an experimental setting. Neonatal pigs suckled colostrum and derived maternal (passive) immunity from sows in one of three treatment groups: (a) non-vaccinated control (CTRL) or vaccinated with (b) homologous (PASSV-HOM) or (c) heterologous (PASSV-HET) inactivated experimental IAV vaccines. Sentinel neonatal pigs derived from the groups above were challenged with IAV via direct contact with an experimentally infected pig (seeder pig) and monitored for IAV infection daily via nasal swab sampling. A susceptible-infectious-recovered (SIR) experimental model was used to obtain and estimate transmission parameters in each treatment group via a generalized linear model. All sentinel pigs in the CTRL (30/30) and PASSV-HET (30/30) groups were infected with IAV following contact with the seeder pigs and the reproduction ratio estimates (95% confidence interval) were 10.4 (6.6-15.8) and 7.1 (4.2-11.3), respectively. In contrast, 1/20 sentinel pigs in the PASSV-HOM group was infected following contact with the seeder pigs and the reproduction ratio estimate was significantly lower compared to the CTRL and PASSV-HET groups at 0.8 (0.1-3.7). Under the conditions of this study, IAV transmission was reduced in neonatal pigs with homologous maternal immunity compared to seronegative neonatal pigs and pigs with heterologous maternal immunity as defined in this study. This study provides estimates for IAV transmission in pigs with differing types of maternal immunity which may describe the influence of maternal immunity on

Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates.

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Wolsk, H M; Chawes, B L; Følsgaard, N V; Rasmussen, M A; Brix, S; Bisgaard, H

2016-06-01

Siblings have been shown to reduce the risk of childhood asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates, which could represent an underlying immune modulatory pathway. We measured 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosa of 571 one-month-old asymptomatic neonates from the Copenhagen Prospective Studies on Asthma in Childhood2010 birth cohort (COPSAC2010 ). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analysis (PCA). Neonates with siblings had an upregulated level of airway immune mediators, with predominance of Type 1- and Type 17-related mediators. This was supported by the PCA showing a highly significant difference between children with vs without siblings: P Siblings mediate a Type 1/Type 17-related immune-stimulatory effect in the airways of asymptomatic neonates, also after adjustment for pathogenic bacteria and viruses, indicating that siblings exert a transferable early immune modulatory effect. These findings may represent an in utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth, or it could relate to the presence of unidentified microbes, but further studies are needed to confirm our findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunizations, neonatal hyperbilirubinemia and animal-induced injuries.

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Bennett, Sean R; Brennan, Beth; Bernstein, Henry H

2007-08-01

To report recent research findings and new recommendations on immunizations, neonatal hyperbilirubinemia, and animal-induced injuries. Vaccines against rotavirus and human papilloma virus have entered clinical use. Varicella outbreaks among previously vaccinated children have prompted the recommendation for a two-dose varicella vaccine series. Broader coverage for influenza vaccination is now recommended in the US and Canada. Diagnosis and treatment of neonatal hyperbilirubinemia uses population and hour-based norms for total serum bilirubin and assessment of risk factors. Delayed cord clamping is not apparently a risk factor for jaundice but warrants more study. Universal predischarge screening shows promise but is not yet officially recommended. New treatments for hyperbilirubinemia are being evaluated. Dogs are the chief cause of animal bites in children and the largest reservoir for rabies worldwide. In North America and Europe, cats and wild animals cause most human rabies. Postexposure prophylaxis should follow region-appropriate guidelines. New vaccines are available against rotavirus and human papilloma virus. Changes have been made to official immunization recommendations. Appropriate vaccine use can reduce the pediatric disease burden further. Hyperbilirubinemia is the subject of ongoing study, which may lead to improved diagnosis and treatment protocols and reduce the incidence of acute bilirubin encephalopathy. The best tool for rabies prevention after an animal bite is prompt postexposure prophylaxis.

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

OpenAIRE

Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

2015-01-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

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Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

2016-03-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

New strategies to prevent fetal and neonatal complications in Rhesus D immunization

OpenAIRE

Tiblad, Eleonor

2012-01-01

The general purpose of this thesis was to investigate if fetal and neonatal complications due to RhD immunization in the mother could be prevented by 1) reducing procedurerelated complications in intrauterine blood transfusions and by 2) reducing the incidence of RhD immunization by providing routine antenatal anti-D prophylaxis during pregnancy selectively to non-immunized RhD negative women with RhD positive fetuses. Paper I was a retrospective study including 284 intra...

They Are What You Eat: Can Nutritional Factors during Gestation and Early Infancy Modulate the Neonatal Immune Response?

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Sarah Prentice

2017-11-01

Full Text Available The ontogeny of the human immune system is sensitive to nutrition even in the very early embryo, with both deficiency and excess of macro- and micronutrients being potentially detrimental. Neonates are particularly vulnerable to infectious disease due to the immaturity of the immune system and modulation of nutritional immunity may play a role in this sensitivity. This review examines whether nutrition around the time of conception, throughout pregnancy, and in early neonatal life may impact on the developing infant immune system.

Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats.

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Osborne, Brittany F; Caulfield, Jasmine I; Solomotis, Samantha A; Schwarz, Jaclyn M

2017-10-01

The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017. © 2017 Wiley Periodicals, Inc.

The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice.

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McGrath-Morrow, Sharon A; Ndeh, Roland; Collaco, Joseph M; Poupore, Amy K; Dikeman, Dustin; Zhong, Qiong; Singer, Benjamin D; D'Alessio, Franco; Scott, Alan

2017-09-01

Neonates have greater morbidity/mortality from lower respiratory tract infections (LRTI) compared to older children. Lack of conditioning of the pulmonary immune system due to limited environmental exposures and/or infectious challenges likely contributes to the increase susceptibility in the neonate. In this study, we sought to gain insights into the nature and dynamics of the neonatal pulmonary immune response to LRTI using a murine model. Wildtype (WT) and Ccr2 -/- C57BL/6 neonatal and juvenile mice received E. coli or PBS by direct pharyngeal aspiration. Flow cytometry was used to measure immune cell dynamics and identify cytokine-producing cells. Real-time PCR and ELISA were used to measure cytokine/chemokine expression. Innate immune cell recruitment in response to E. coli-induced LRTI was delayed in the neonatal lung compared to juvenile lung. Lung clearance of bacteria was also significantly delayed in the neonate. Ccr2 -/- neonates, which lack an intact CCL2-CCR2 axis, had higher mortality after E. coli challenged than Ccr2 +/+ neonates. A greater percentage of CD8 + T cells and monocytes from WT neonates challenged with E. coli produced TNF compared to controls. The pulmonary immune response to E. coli-induced LRTI differed significantly between neonatal and juvenile mice. Neonates were more susceptible to increasing doses of E. coli and exhibited greater mortality than juveniles. In the absence of an intact CCL2-CCR2 axis, susceptibility to LRTI-induced mortality was further increased in neonatal mice. Taken together these findings underscore the importance of age-related differences in the innate immune response to LRTI during early stages of postnatal life. Copyright © 2017 Elsevier Ltd. All rights reserved.

Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates

DEFF Research Database (Denmark)

Wolsk, Helene Mygind; Chawes, Bo L.; Følsgaard, Nilofar V.

2016-01-01

-related mediators. This was supported by the PCA showing a highly significant difference between children with vs. without siblings: p...BACKGROUND: Siblings have been shown to reduce the risk of later asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates. We hypothesized that siblings exert immune modulatory......-cohort (COPSAC2010). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analyses (PCA). RESULTS: Neonates with siblings had an up-regulated level of airway immune-mediators, with predominance of Type 1- and Type 17...

Prenatal stress, immunity and neonatal health in farm animal species.

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Merlot, E; Quesnel, H; Prunier, A

2013-12-01

The high pre-weaning mortality in farm animal species and poor welfare conditions of reproductive females question modern industrial farming acceptability. A growing body of literature has been produced recently, investigating the impact of maternal stress during gestation on maternal and offspring physiology and behavior in farm animals. Until now, the possible impact of prenatal stress on neonatal health, growth and survival could not be consistently demonstrated, probably because experimental studies use small numbers of animals and thus do not allow accurate estimations. However, the data from literature synthesized in the present review show that in ungulates, maternal stress can sometimes alter important maternal parameters of neonatal survival such as colostrum production (ruminants) and maternal care to the newborn (pigs). Furthermore, maternal stress during gestation can affect maternal immune system and impair her health, which can have an impact on the transfer of pathogens from the mother to her fetus or neonate. Finally, prenatal stress can decrease the ability of the neonate to absorb colostral immunoglobulins, and alter its inflammatory response and lymphocyte functions during the first few weeks of life. Cortisol and reproductive hormones in the case of colostrogenesis are pointed out as possible hormonal mediators. Field data and epidemiological studies are needed to quantify the role of maternal welfare problems in neonatal health and survival.

A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

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Schlieckau, Florian; Schulz, Daniela; Fill Malfertheiner, Sara; Entleutner, Kathrin; Seelbach-Goebel, Birgit; Ernst, Wolfgang

2018-04-19

Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in orally but not muscularly immunized chickens.

Science.gov (United States)

Murai, Atsushi; Kitahara, Kazuki; Okumura, Shouta; Kobayashi, Misato; Horio, Fumihiko

2016-02-01

Recent studies have emphasized the crucial role of gut microbiota in triggering and modulating immune response. We aimed to determine whether the modification of gut microbiota by oral co-administration of two antibiotics, ampicillin and neomycin, would lead to changes in the antibody response to antigens in chickens. Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5 g/L, respectively) in drinking water. At 2 weeks of age, the chicks were muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH), and then serum anti-KLH antibody levels were examined by ELISA. In orally immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM, IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the antibiotics did not enhance antibody responses in the muscularly immunized chicks. Concomitant with their enhancement of antibody responses, the oral antibiotics also lowered the Lactobacillus species in feces. Low doses of antibiotics (10-fold and 100-fold lower than the initial trial), which failed to change the fecal Lactobacillus population, did not modify any antibody responses when chicks were orally immunized with KLH. In conclusion, oral antibiotics treatment enhanced the antibody response to orally exposed antigens in chickens. This enhancement of antibody response was associated with a modification of the fecal Lactobacillus content, suggesting a possible link between gut microbiota and antibody response in chickens. © 2015 Japanese Society of Animal Science.

The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

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Tatiane Ferreira

2012-01-01

Full Text Available The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.

Sculpting humoral immunity through dengue vaccination to enhance protective immunity

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Wayne eCrill

2012-11-01

Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

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Mark R. Schleiss

2013-01-01

Full Text Available Fetal and neonatal infections caused by human cytomegalovirus (CMV are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

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Schleiss, Mark R.

2013-01-01

Fetal and neonatal infections caused by human cytomegalovirus (CMV) are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies. PMID:24023565

Neonatal Vaccination: Challenges and Intervention Strategies.

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Morris, Matthew C; Surendran, Naveen

2016-01-01

While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

OpenAIRE

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for patholog...

Gadolinium-enhanced magnetic resonance angiography in neonates and infants suspected of caval or aortic thrombosis

International Nuclear Information System (INIS)

Greenberg, S. Bruce; Bhutta, Sadaf T.; Buchmann, Robert F.

2004-01-01

Gadolinium-enhanced magnetic resonance angiography (MRA)is a well-established technique in older children and adults. No studies have focused on its use in neonates and small infants. Our objective was to study the use of gadolinium-enhanced MRA in neonates and infants suspected of caval or aortic thrombosis. Materials and Methods:Gadolinium-enhanced MR angiography was performed on seven neonates and small infants for the evaluation of caval or aortic thrombosis. Gadolinium-DTPA at a dose of 0.3 mmol/kg (minimum dose 1 ml) was injected using a power injector (0.2 ml/s). Contrast-enhanced MRA was performed using a 3-D, fast, radiofrequency spoiled gradient-echo sequence (TR/TE: 4.8/1.1, flip angle 45 , matrix 256 x 128, slice thickness 2.6 mm interpolated to 1.3 mm, FOV variable, NEX=1.0). Diagnostic-quality angiograms were obtained in all seven neonates. Superior vena cava thrombosis was identified in two neonates, and abdominal aortic thrombosis was present in one neonate. It is practical to perform gadolinium-enhanced MRA in neonates weighing as little as 600 g for the detection of caval or aortic thrombosis. (orig.)

Gadolinium-enhanced magnetic resonance angiography in neonates and infants suspected of caval or aortic thrombosis

Energy Technology Data Exchange (ETDEWEB)

Greenberg, S. Bruce; Bhutta, Sadaf T.; Buchmann, Robert F. [University of Arkansas for Medical Sciences, Arkansas Children' s Hospital, Little Rock, AR (United States)

2004-12-01

Gadolinium-enhanced magnetic resonance angiography (MRA)is a well-established technique in older children and adults. No studies have focused on its use in neonates and small infants. Our objective was to study the use of gadolinium-enhanced MRA in neonates and infants suspected of caval or aortic thrombosis. Materials and Methods:Gadolinium-enhanced MR angiography was performed on seven neonates and small infants for the evaluation of caval or aortic thrombosis. Gadolinium-DTPA at a dose of 0.3 mmol/kg (minimum dose 1 ml) was injected using a power injector (0.2 ml/s). Contrast-enhanced MRA was performed using a 3-D, fast, radiofrequency spoiled gradient-echo sequence (TR/TE: 4.8/1.1, flip angle 45 , matrix 256 x 128, slice thickness 2.6 mm interpolated to 1.3 mm, FOV variable, NEX=1.0). Diagnostic-quality angiograms were obtained in all seven neonates. Superior vena cava thrombosis was identified in two neonates, and abdominal aortic thrombosis was present in one neonate. It is practical to perform gadolinium-enhanced MRA in neonates weighing as little as 600 g for the detection of caval or aortic thrombosis. (orig.)

Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

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Jafar Majidi-Zolbanin

2014-06-01

Full Text Available Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg on postnatal days (PND 3-5 (early neonatal phase or PND 14-16 (late neonatal phase, and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40 and adulthood (PND 85 or 90. Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice.

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Russell, Ryan F; McDonald, Jacqueline U; Lambert, Laura; Tregoning, John S

2016-05-01

Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example, to Toll-like receptor (TLR) agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger-sensing pathways, focusing on a range of compounds described as inflammasome agonists, including nanoscale silicon dioxide (NanoSiO2), calcium pyrophosphate dihydrate (CPPD) crystals, and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants.In vitro, these compounds induced an interleukin 1-beta (IL-1β) response in the macrophage-like cell line THP1.In vivo, adult CB6F1 female mice were immunized intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD, or M-Tri-DAP and subsequently challenged with H1N1 influenza virus (A/England/195/2009). The adjuvants boosted anti-hemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2-adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle but to little systemic inflammation measured by serum cytokine levels. Blocking IL-1β or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting that it may work through pathways other than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. Vaccines can fail to protect the most at-risk populations, including the very young, the elderly, and the immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunization

Enhancement of Immune Memory Responses to Respiratory Infection

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD...5a. CONTRACT NUMBER Enhancement of Immune Memory Responses to Respiratory Infection 5b. GRANT NUMBER W81XWH-16-1-0360 5c. PROGRAM ELEMENT NUMBER...entitled “ENHANCEMENT OF IMMUNE MEMORY RESPONSES TO RESPIRATORY INFECTION: AUTOPHAGY IN MEMORY B-CELLS RESPONSE TO INFLUENZA VACCINE (AMBRIV

Immunity peculiarities of neonates in case of perinatal pathology

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О. S. Godovanets

2018-02-01

of the evidences of immune system components participation in perinatal pathology pathogenesis is detected correlation between immune disorders severity and clinical manifestation of diseases, as well as immune indices normalization in a long-term organism adaptation formation. Conclusions. Based on the data obtained it has been concluded that immune system status determination is reasonable for diagnostics of disadaptation syndrome severity in early neonatal period.

Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...SUBTITLE Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER...immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or enhance the abscopal in a kidney cancer

Porcine neonatal blood dendritic cells, but not monocytes, are more responsive to TLRs stimulation than their adult counterparts.

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Gael Auray

Full Text Available The neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response. As pigs are becoming more important for vaccine development studies due to their similarity to the human immune system, we decided to compare the activation and maturation of a subpopulation of porcine DCs in adult and neonatal pigs following stimulation with different TLR ligands, which are promising candidates for adjuvants in vaccine formulations. Porcine blood derived DCs (BDCs were directly isolated from blood and consisted of a mix of conventional and plasmacytoid DCs. Following CpG ODN (TLR9 ligand and imiquimod (TLR7 ligand stimulation, neonatal BDCs showed higher levels of expression of costimulatory molecules and similar (CpG ODN or higher (imiquimod levels of IL-12 compared to adult BDCs. Another interesting feature was that only neonatal BDCs produced IFN-α after TLR7 or TLR9 ligand stimulation. Stimulation with CpG ODN and imiquimod also induced enhanced expression of several chemokines. Moreover, in a mixed leukocyte reaction assay, neonatal BDCs displayed a greater ability to induce lymphoproliferation. These findings suggest that when stimulated via TLR7 or TLR9 porcine DCs display similar if not better response than adult porcine DCs.

The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis.

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Torow, Natalia; Hornef, Mathias W

2017-01-15

The existence of a neonatal window was first highlighted by epidemiological studies that revealed the particular importance of this early time in life for the susceptibility to immune-mediated diseases in humans. Recently, the first animal studies emerged that present examples of early-life exposure-triggered persisting immune events, allowing a detailed analysis of the factors that define this particular time period. The enteric microbiota and the innate and adaptive immune system represent prime candidates that impact on the pathogenesis of immune-mediated diseases and are known to reach a lasting homeostatic equilibrium following a dynamic priming period after birth. In this review, we outline the postnatal establishment of the microbiota and maturation of the innate and adaptive immune system and discuss examples of early-life exposure-triggered immune-mediated diseases that start to shed light on the critical importance of the early postnatal period for life-long immune homeostasis. Copyright © 2017 by The American Association of Immunologists, Inc.

Immune cell subsets, cytokine and cortisol levels during the first week of life in neonates born to pre-eclamptic mothers.

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Sava, Florentina; Toldi, Gergely; Treszl, András; Hajdú, Júlia; Harmath, Ágnes; Rigó, János; Tulassay, Tivadar; Vásárhelyi, Barna

2017-06-01

To address the hypothesis that pre-eclampsia (PE) impacts the fetal immune system, we investigated the prevalence of distinct immune cell subsets along with plasma cortisol and cytokine levels in pre-term newborns of PE mothers. Cord blood and peripheral blood samples on the 1st, 3rd and 7th postnatal days of life were collected from 14 pre-term infants affected by PE and 14 non-PE pregnancies. We measured plasma cortisol and cytokine levels with immunoassays and assessed the prevalence of T, NK and DC subsets using flow cytometry. The prevalence of CD4+ cells was lower in PE infants, while that of memory T cells was higher. Myeloid DCs had a lower prevalence in PE neonates. Cytokine and cortisol levels were lower in PE neonates. Our observations show that PE pregnancies are associated with altered newborn immune status during the first week of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neonatal corticosterone administration in rodents as a tool to investigate the maternal programming of emotional and immune domains

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Simone Macrì

2017-02-01

Full Text Available Neonatal experiences exert persistent influences on individual development. These influences encompass numerous domains including emotion, cognition, reactivity to external stressors and immunity. The comprehensive nature of the neonatal programming of individual phenotype is reverberated in the large amount of experimental data collected by many authors in several scientific fields: biomedicine, evolutionary and molecular biology. These data support the view that variations in precocious environmental conditions may calibrate the individual phenotype at many different levels. Environmental influences have been traditionally addressed through experimental paradigms entailing the modification of the neonatal environment and the multifactorial (e.g. behaviour, endocrinology, cellular and molecular biology analysis of the developing individual's phenotype. These protocols suggested that the role of the mother in mediating the offspring's phenotype is often associated with the short-term effects of environmental manipulations on dam's physiology. Specifically, environmental manipulations may induce fluctuations in maternal corticosteroids (corticosterone in rodents which, in turn, are translated to the offspring through lactation. Herein, I propose that this mother-offspring transfer mechanism can be leveraged to devise experimental protocols based on the exogenous administration of corticosterone during lactation. To support this proposition, I refer to a series of studies in which these protocols have been adopted to investigate the neonatal programming of individual phenotype at the level of emotional and immune regulations. While these paradigms cannot replace traditional studies, I suggest that they can be considered a valid complement.

Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk

International Nuclear Information System (INIS)

Berseth, C.L.

1987-01-01

Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formal that contained 1.2, 3.0, and 6.0 μg/ml EGF for 39 h had greater incorporation of [ 3 H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate, in part, breast milk-enhanced neonatal intestinal growth

Immunomodulator-based enhancement of anti smallpox immune responses.

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Osmarie Martínez

Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Immunomodulator-based enhancement of anti smallpox immune responses.

Science.gov (United States)

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1 at Weanling Age.

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Bettina Wagner

Full Text Available Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4 producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC. Neonatal vaccination was performed by oral biotinylated IgE (IgE-bio treatment at birth followed by intramuscular injection of a single dose of streptavidin-conjugated gC/IL-4 fusion protein (Sav-gC/IL-4 for crosslinking of receptor-bound IgE-bio (group 1. Neonates in group 2 received the intramuscular Sav-gC/IL-4 vaccine only. Group 3 remained non-vaccinated at birth. After vaccination, gC antibody production was not detectable. The ability of the vaccine to induce protection was evaluated by an EHV-1 challenge infection after weaning at 7 months of age. Groups 1 and 2 responded to EHV-1 infection with an earlier onset and overall significantly increased anti-gC serum antibody responses compared to control group 3. In addition, group 1 weanlings had a decreased initial fever peak after infection indicating partial protection from EHV-1 infection. This suggested that the neonatal vaccination induced a memory B-cell response at birth that was recalled at weanling age after EHV-1 challenge. In conclusion, early stimulation of neonatal immunity via the innate arm of the immune system can induce partial protection and increased antibody responses against EHV-1.

Three cases of neonatal tetanus in Papua New Guinea lead to development of national action plan for maternal and neonatal tetanus elimination.

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Datta, Siddharta Sankar; Barnabas, Roland; Sitther, Adeline; Guarenti, Laura; Toikilik, Steven; Kariwiga, Grace; Sui, Gerard Pai

2013-01-01

Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is usually the result of poor hygiene during delivery. In 2011, three neonatal tetanus cases were investigated in Papua New Guinea, and all three cases were delivered at home by untrained assistants. The babies were normal at birth but subsequently developed spasms. A neonatal tetanus case must be viewed as a sentinel event indicating a failure of public health services including immunization, antenatal care and delivery care. The confirmation of these cases led to the drafting of the Papua New Guinea National Action Plan for Maternal and Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid supplementary immunization campaign targeting women of childbearing age (WBCA) and strengthening of other clean delivery practices. The first immunization round was conducted in April and May 2012, targeting 1.6 million WBCA and achieved coverage of 77%. The government of Papua New Guinea should ensure detailed investigation of all neonatal tetanus cases reported in the health information system and perform subprovincial analysis of tetanus toxoid coverage following completion of all three immunization rounds. Efforts also should be made to strengthen clean delivery practices to help eliminate maternal and neonatal tetanus in Papua New Guinea.

Three cases of neonatal tetanus in Papua New Guinea lead to development of national action plan for maternal and neonatal tetanus elimination

Directory of Open Access Journals (Sweden)

Grace Kariwiga

2013-06-01

Full Text Available Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is usually the result of poor hygiene during delivery. In 2011, three neonatal tetanus cases were investigated in Papua New Guinea, and all three cases were delivered at home by untrained assistants. The babies were normal at birth but subsequently developed spasms. A neonatal tetanus case must be viewed as a sentinel event indicating a failure of public health services including immunization, antenatal care and delivery care. The confirmation of these cases led to the drafting of the Papua New Guinea National Action Plan for Maternal and Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid supplementary immunization campaign targeting women of childbearing age (WBCA and strengthening of other clean delivery practices. The first immunization round was conducted in April and May 2012, targeting 1.6 million WBCA and achieved coverage of 77%. The government of Papua New Guinea should ensure detailed investigation of all neonatal tetanus cases reported in the health information system and perform sub-provincial analysis of tetanus toxoid coverage following completion of all three immunization rounds. Efforts also should be made to strengthen clean delivery practices to help eliminate maternal and neonatal tetanus in Papua New Guinea.

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

Science.gov (United States)

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform. PMID:25875833

Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

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Navar-Boggan, A M; Halsey, N A; Golden, W C; Escobar, G J; Massolo, M; Klein, N P

2010-09-01

Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, Pimmunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (Pimmunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

Adoptive transfer of immune enhancement of experimental ulcerative colitis.

OpenAIRE

Onderdonk, A B; Steeves, R M; Cisneros, R L; Bronson, R T

1984-01-01

Previous experiments with the carrageenan model for ulcerative colitis have shown that the inflammatory response in guinea pigs can be enhanced by immunization with and subsequent feeding of Bacteroides vulgatus to experimental animals. The present studies showed that only certain strains of B. vulgatus are capable of provoking immune enhancement of ulcerative colitis. Animals were fed carrageenan and various strains of viable B. vulgatus after immunization with a strain of B. vulgatus isolat...

Unusual loss of chymosin in mammalian lineages parallels neo-natal immune transfer strategies.

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Lopes-Marques, Mónica; Ruivo, Raquel; Fonseca, Elza; Teixeira, Ana; Castro, L Filipe C

2017-11-01

Gene duplication and loss are powerful drivers of evolutionary change. The role of loss in phenotypic diversification is notably illustrated by the variable enzymatic repertoire involved in vertebrate protein digestion. Among these we find the pepsin family of aspartic proteinases, including chymosin (Cmy). Previous studies demonstrated that Cmy, a neo-natal digestive pepsin, is inactivated in some primates, including humans. This pseudogenization event was hypothesized to result from the acquisition of maternal immune immunoglobulin G (IgG) transfer. By investigating 94 mammalian subgenomes we reveal an unprecedented level of Cmy erosion in placental mammals, with numerous independent events of gene loss taking place in Primates, Dermoptera, Rodentia, Cetacea and Perissodactyla. Our findings strongly suggest that the recurrent inactivation of Cmy correlates with the evolution of the passive transfer of IgG and uncovers a noteworthy case of evolutionary cross-talk between the digestive and the immune system, modulated by gene loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Neonatal chest image quality addressed through training to enhance radiographer awareness

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Hesta Friedrich-Nel

2018-03-01

Full Text Available Background: Diagnostic radiographers working in the neonatal intensive care unit primarily aim to produce an image of optimal quality using optimal exposure techniques without repeating exposures, to keep neonatal radiation dose to a minimum.   Objectives: The aim of the study was to determine whether radiographers were producing optimal quality chest images and, if not, whether additional training could contribute to reaching this goal in the Free State Province of South Africa.   Methods: Neonatal chest image quality was determined in the Neonatal Intensive Care Unit by using a checklist based on and compiled from published guidelines to evaluate the quality of 450 randomly-selected images. Thereafter, a training programme was designed, based on the evaluation criteria of the checklist and image quality areas identified. The training also referred to positioning techniques that should be applied to ensure optimal image quality. After presentation of the training, 450 newly-produced neonatal chest images were evaluated. These images were selected through purposive sampling as this evaluation only included images of participating radiographers who completed the training.   Results: Image quality that showed significant improvement included a reduction in electrocardiogram lines superimposed on chest anatomy, a tendency to centre closer to thoracic vertebra four, and visible four-sided collimation on images. Image quality areas with no significant enhancement were the absence of lead markers and radiation shielding.   Conclusion: The study has shown that a training programme has the potential to improve neonatal chest image quality.

Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

LENUS (Irish Health Repository)

McCarron, Mark

2012-02-01

In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

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Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

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Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

2015-06-23

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

OpenAIRE

Jafar Majidi-Zolbanin; Mohammad-Hossein Doosti; Behzad Baradaran; Mohammad Amani; Maryam Azarfarin; Ali-Akbar Salari

2014-01-01

Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic dou...

Infections in Neonatal Intensive Care: Prevalence, Prevention and Antibiotic use

NARCIS (Netherlands)

van den Hoogen, A.

2009-01-01

Neonatal infections are an important cause of morbidity in neonatal intensive care units (NICUs). Prematurity or very low birth weight is an important predisposing factor for neonatal infection. In addition, preterm infants have a compromized immune system and they often require invasive procedures

Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

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Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine leu infusion can be used to enhance protein synthes...

Neonatal mucosal immunology.

Science.gov (United States)

Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

2017-01-01

Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.

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Ihssane Zouikr

Full Text Available Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis during postnatal day (PND 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG as well as rostral and caudal axes of the ventrolateral PAG (VLPAG. Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb as compared to medial habenula (MHb, however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

Science.gov (United States)

Zouikr, Ihssane; James, Morgan H.; Campbell, Erin J.; Clifton, Vicki L.; Beagley, Kenneth W.; Dayas, Christopher V.; Hodgson, Deborah M.

2014-01-01

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. PMID:24878577

Strategies to enhance immune function for marathon runners : what can be done?

DEFF Research Database (Denmark)

Åkerström, Thorbjörn; Pedersen, Bente K

2007-01-01

immune cells. During this period of immune suppression, by some referred to as an 'open window' in immune function, it has been hypothesised that viruses and bacteria might gain a foothold, which would increase the risk of infections. In light of this, nutritional interventions that can enhance immune...

Neonatal Outcomes of Rh-Negative Pregnancies in a Tertiary Level Neonatal Intensive Care Unit: A Prospective Study

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Chacham

2016-07-01

Full Text Available Background Rhesus incompatibility is a preventable cause for severe neonatal hyperbilirubinemia, hydrops fetalis and still births. The prevalence of the Rh-negative blood group among Indian woman varies from 2% - 10%. Despite declining the incidence of Rhesus incompatibility, due to availability of anti-D immunoglobulin, and improved antenatal care of the Rh-negative pregnant woman, it still accounts for a significant proportion of neonatal hyperbilirubinemia and neuro-morbidity. The prevalence of Rh-negative women having Rh-positive neonates is 60%. Objectives This study aimed to estimate the incidence of Rh iso-immunization and evaluate the outcomes of Rh iso-immunized neonates. Methods This prospective observational study was conducted in a tertiary level neonatal intensive care unit, Princess Esra hospital, Deccan college of medical sciences, Hyderabad, Telangana, India. Consecutive intramural and extramural neonates admitted to neonatal intensive care unit with the Rh-negative mother’s blood group and hyperbilirubinemia were enrolled. Neonates born to Rh+ve mothers were excluded. Neonatal gestational age, birth weight, age at admission, duration of phototherapy, duration of hospitalization, neonatal examination and investigations were recorded in a predesigned, pretested performa. Results A total of 90 neonates were born to Rh-negative mothers, of which 70% (63 had the Rh-positive blood group and 30% had the Rh-negative blood group. Of these 63 neonates, 48 (76.2% had hyperbilirubinemia and 43 neonates (68.3% had significant hyperbilirubinemia (total serum bilirubin > 15mg/dL. Among them, 2%, 75% and 23% were born to primi, multi and grandmutli, respectively. Also, 14.5% of the neonates were large for dates (LFD, 75% appropriate for dates (AFD and 10.5% were small for dates (SFD. Premature and SFD neonates had higher incidence of hyperbilirubinemia. Significantly higher incidence of jaundice occurred within 72 hours of life. The mean

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Narcís Saubi

2011-01-01

Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

2011-01-01

We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216

Can probiotics enhance vaccine-specific immunity in children and adults?

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Kwak, J Y; Lamousé-Smith, E S N

2017-10-13

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

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Liang, Guanxiang; Malmuthuge, Nilusha; Bao, Hua; Stothard, Paul; Griebel, Philip J; Guan, Le Luo

2016-08-11

Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system. Small intestine samples (jejunum and ileum) were collected from newborn male, Holstein calves immediately post-partum (n = 3) and at 7 (n = 5), 21 (n = 5), and 42 (n = 5) days of age and the transcriptomes were profiled using RNA-Seq. When analyzing all time points collectively, greater expression of genes encoding the complement functional pathway, as well as lower expression of genes encoding Toll-like receptors and NOD-like receptors were observed in the jejunum when compared to the ileum. In addition, significant changes in the expression of immune-related genes were detected within the first week post-partum in both jejunum and ileum. For example, increased expression of genes encoding tight junction proteins (claudin 1, claudin 4 and occludin), an antimicrobial peptide (Regenerating Islet-Derived 3-γ), NOD-like receptors (NACHT, LRR and PYD domain-containing protein 3), regulatory T cell marker (forkhead box P3), and both anti-inflammatory (interleukin 10) and pro-inflammatory (interleukin 8) cytokines was observed throughout the small intestine of 7-day-old calves when compared to newborn calves. Moreover, the expression of mucosal immune-related genes were either positively or negatively correlated with total bacterial population depending on both intestinal region and age. The integrated analysis of miRNAs and mRNAs supported the conclusion that miRNAs may regulate temporal changes in the expression of genes encoding tight junction proteins (miR-335), cytokines (miR-335) and

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

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Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico; Ganio, Edward A; Gaudilliere, Dyani K; Tingle, Martha; Lancero, Hope L; McNeil, Leslie S; Spitzer, Matthew H; Wong, Ronald J; Shaw, Gary M; Darmstadt, Gary L; Sylvester, Karl G; Winn, Virginia D; Carvalho, Brendan; Lewis, David B; Stevenson, David K; Nolan, Garry P; Aghaeepour, Nima; Angst, Martin S; Gaudilliere, Brice L

2016-12-01

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 + and CD8 + T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet + CD4 + T cells, CD8 + T cells, B cells, and CD56 lo CD16 + NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. Copyright © 2016 by The American Association of Immunologists, Inc.

Imunidade passiva, morbidade neonatal e desempenho de cabritos em diferentes manejos de colostro Passive immunity, neonatal morbidity and performance of kids in different colostrum management

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Sara Vilar Dantas Simões

2005-12-01

Full Text Available Objetivando determinar o manejo de colostro que permitisse a melhor aquisição de imunidade passiva em cabritos e avaliar possíveis relações entre imunidade, morbidade e desempenho, amostras de sangue foram obtidas de 58 cabritos da raça Saanen antes e 30 horas após a primeira ingestão de colostro. Os cabritos foram distribuídos em cinco grupos experimentais. No Tratamento 1 (T1 o colostro foi ingerido ad libitum durante 24 horas. Nos demais tratamentos o colostro foi fornecido em mamadeira; os cabritos do T2 ingeriram 200mL de colostro após o parto; do T3, ingeriram 400mL de colostro sendo 200mL após o parto e 200mL após 8 horas; do T4, ingeriram também 400mL de colostro, sendo 200mL após o parto, 200mL após 14 horas; e os do T5 ingeriram 600mL de colostro, 200mL após o parto, 200mL as 12 e 200mL as 24 horas. Os valores séricos de gamaglobulinas foram avaliados por eletroforese. O ganho de peso diário foi utilizado para avaliação do desempenho no período de aleitamento. A ocorrência de doenças foi registrada do nascimento até 28 dias. A menor concentração de gamaglobulinas foi encontrada nos animais do Grupo 2 (1,65g/dL e a maior concentração foi observada no Grupo 3 (2,60g/dL. Foi observado no Grupo 3 mais animais com diarréia, porém não foram encontradas diferenças estatísticas significativas ao nível de 5%. Os diferentes manejos de colostro não estiveram associados com o desempenho dos cabritos até o final do período neonatal.The experiment was performed to determine the kid management that ensures the best passive immunity, and to evaluate the relationship between passive immunity, neonatal morbidity and performance. Blood samples were obtained from 58 Saanen kids before colostrum ingestion and 30h after. The kids were submitted to five treatments: (T1 kids were allowed to nurse the dam for 24 hours ingesting colostrum ad libitum; (T2 kids were bottle-fed with 200mL colostrum in the first hour of life; (T

Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

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Qing Zeng

2017-09-01

Full Text Available Escherichia coli (E. coli K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS has a preventive role against neonatal E. coli K1 bacteremia and meningitis. However, the interaction between the neonatal gut barrier, probiotics and E. coli K1 is still not elucidated. The present study aims to investigate how LBS exerts its protective effects on neonatal gut barrier during E. coli K1 infection. The beneficial effects of LBS were explored in vitro and in vivo using human colon carcinoma cell lines HT-29 and rat model of neonatal E. coli K1 infection, respectively. Our results showed that stimulation with E. coli K1 was able to cause intestinal barrier dysfunction, which were reflected by E. coli K1-induced intestinal damage and apoptosis of intestinal epithelial cells, reduction of mucin, immunoglobulin A (IgA and tight junction proteins expression, as well as increase in intestinal permeability, all these changes facilitate E. coli K1 intestinal translocation. However, these changes were alleviated when HT-29 cells were treated with LBS before E. coli K1 infection. Furthermore, we found that LBS-treated neonatal rats (without E. coli K1 infection have showed higher production of mucin, ZO-1, IgA, Ki67 in intestinal mucosa as well as lower intestinal permeability than that of non-treated rats, indicating that LBS could accelerate the development of neonatal intestinal defense. Taken together, our results suggest that enhancement of the neonatal intestinal defense to fight against E. coli K1 translocation could be the potential mechanism to elucidate how LBS confers a protective effect against neonatal E

Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

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Daisuke Ibi

2015-11-01

Full Text Available Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.

The immune enhancement of propolis adjuvant on inactivated porcine parvovirus vaccine in guinea pig.

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Ma, Xia; Guo, Zhenhuan; Shen, Zhiqiang; Wang, Jinliang; Hu, Yuanliang; Wang, Deyun

2011-01-01

Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine. Copyright © 2011 Elsevier Inc. All rights reserved.

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses.

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Dantoft, Widad; Martínez-Vicente, Pablo; Jafali, James; Pérez-Martínez, Lara; Martin, Kim; Kotzamanis, Konstantinos; Craigon, Marie; Auer, Manfred; Young, Neil T; Walsh, Paul; Marchant, Arnaud; Angulo, Ana; Forster, Thorsten; Ghazal, Peter

2017-01-01

Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses

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Widad Dantoft

2017-09-01

Full Text Available Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1 and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1 roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity

Immunological unresponsiveness of the neonatal ruminant to gastrointestinal helminths

International Nuclear Information System (INIS)

Soulsby, E.J.L.

1981-01-01

Parasitic gastro-enteritis of domestic ruminants is a disease syndrome which is most usually seen in young animals in their first grazing season. Although this may be due, in part, to greater susceptibility of young animals to the pathogenic effects of parasitic infection, there is also good evidence that young animals are less able to mount a satisfactory protective immune response or a response which will reject an existing infection. This phenomenon is exemplified by Haemonchus contortus and Trichostrongylus spp. infection in sheep, but the phenomenon is recognized in other species including neonatal rodents (e.g. rats infected with Nippostrongylus brasiliensis) and has been demonstrated in neonatal cattle infected with Taenia saginata. The present consideration will deal mainly with the failure of lambs to mount an effective immune response to gastrointestinal nematodes during the neonatal period. (author)

Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

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Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

2011-09-01

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

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Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

2018-04-23

Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

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Maiko Satomoto

2016-01-01

Full Text Available In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB. Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150% in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

Super-enhancers: Asset management in immune cell genomes.

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Witte, Steven; O'Shea, John J; Vahedi, Golnaz

2015-09-01

Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival

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Kozlowski, Elyse; Matsuura, Kori Y.; Ferrari, Joseph D.; Morris, Samantha A.; Powers, John T.; Daley, George Q.; Quinton, Lee J.; Mizgerd, Joseph P.

2012-01-01

The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3′ terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression. PMID:23209448

Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival.

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Matthew R Jones

Full Text Available The Zcchc11 enzyme is implicated in microRNA (miRNA regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3' terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression.

Nongenetically modified Lactococcus lactis-adjuvanted vaccination enhanced innate immunity against Helicobacter pylori.

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Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqin; Luo, Shuanghui; Yang, Huimin; Zheng, Lufeng; Xi, Tao; Xing, Yingying

2017-10-01

Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4 + T cells and promote S100A8 expression. These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection. © 2017 John Wiley & Sons Ltd.

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

Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

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Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

2003-01-01

To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

γ-Oryzanol-Rich Black Rice Bran Extract Enhances the Innate Immune Response.

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Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Lim, Yoongho; Kim, Jung-Bong; Lee, Young Han

2017-09-01

The innate immune response is an important host primary defense system against pathogens. γ-Oryzanol is one of the nutritionally important phytoceutical components in rice bran oil. The goal of this study was to investigate the effect of γ-oryzanol-rich extract from black rice bran (γORE) on the activation of the innate immune system. In this study, we show that γORE increased the expression of CD14 and Toll-like receptor 4 and enhanced the phagocytic activity of RAW264.7 macrophages. Furthermore, γORE and its active ingredient γ-oryzanol promoted the secretion of innate cytokines, interleukin-8, and CCL2, which facilitate phagocytosis by RAW264.7 cells. These findings suggest that γ-oryzanol in the γORE enhances innate immune responses.

Time for a neonatal-specific consensus definition for sepsis.

Science.gov (United States)

Wynn, James L; Wong, Hector R; Shanley, Thomas P; Bizzarro, Matthew J; Saiman, Lisa; Polin, Richard A

2014-07-01

To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

Growth and recruitment in the immune network

NARCIS (Netherlands)

Boer, R.J. de; Hogeweg, P.; Perelson, A.S.

1992-01-01

The development of the immune repertoire during neonatal life involves a strong selection process among different clones. We investigate the hypothetis that repertoire selection is carried out during early life by the immune network. There are at least two processes in repertoire selection: clonal

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice.

Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

Science.gov (United States)

Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

2010-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

Elevated DMBT1 levels in neonatal gastrointestinal diseases

DEFF Research Database (Denmark)

Müller, Hanna; Renner, Marcus; Helmke, Burkhard M

2016-01-01

Deleted in malignant brain tumor 1 (DMBT1) is involved in innate immunity and epithelial differentiation. Previous studies in adults indicated a strong intestinal expression of DMBT1 and an important role in inflammatory bowel diseases. Here, we analyzed the DMBT1 expression in the fetal gastroin......, and herniation. DMBT1 may play a role in epithelial differentiation and local innate immunity during neonatal inflammatory bowel processes....

Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism.

Science.gov (United States)

Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

2015-03-06

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. 2015 BMJ Publishing Group Ltd.

Oral sucrose for heel lance enhances adenosine triphosphate use in preterm neonates with respiratory distress.

Science.gov (United States)

Angeles, Danilyn M; Asmerom, Yayesh; Boskovic, Danilo S; Slater, Laurel; Bacot-Carter, Sharon; Bahjri, Khaled; Mukasa, Joseph; Holden, Megan; Fayard, Elba

2015-01-01

To examine the effects of oral sucrose on procedural pain, and on biochemical markers of adenosine triphosphate utilization and oxidative stress in preterm neonates with mild to moderate respiratory distress. Preterm neonates with a clinically required heel lance that met study criteria (n = 49) were randomized into three groups: (1) control (n = 24), (2) heel lance treated with placebo and non-nutritive sucking (n = 15) and (3) heel lance treated with sucrose and non-nutritive sucking (n = 10). Plasma markers of adenosine triphosphate degradation (hypoxanthine, xanthine and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured using the Premature Infant Pain Profile. Data were analyzed using repeated measures analysis of variance, chi-square and one-way analysis of variance. We found that in preterm neonates who were intubated and/or were receiving ⩾30% FiO2, a single dose of oral sucrose given before a heel lance significantly increased markers of adenosine triphosphate use. We found that oral sucrose enhanced adenosine triphosphate use in neonates who were intubated and/or were receiving ⩾30% FiO2. Although oral sucrose decreased pain scores, our data suggest that it also increased energy use as evidenced by increased plasma markers of adenosine triphosphate utilization. These effects of sucrose, specifically the fructose component, on adenosine triphosphate metabolism warrant further investigation.

A review of neonatal tetanus in University of Maiduguri Teaching Hospital, North-eastern Nigeria

OpenAIRE

Alhaji, M. A.; Bello, M. A.; Elechi, H. A.; Akuhwa, R. T.; Bukar, F. L.; Ibrahim, H. A.

2013-01-01

Background: Neonatal tetanus is a vaccine preventable disease and is a leading cause of neonatal mortality in developing countries. The effectiveness of immunization and hygienic umbilical cord care practices in the prevention of the disease has been established. Objective: The objective of this study was to audit the scourge of neonatal tetanus in a tertiary health facility in a resource-limited setting. Materials and Methods: The study was a retrospective study. Case notes of neonates admit...

Apparition of iodinated contrast agents in twin neonatal gastrointestinal tracts after maternal contrast-enhanced computed tomography

International Nuclear Information System (INIS)

Kato, Hiroki; Kanematsu, Masayuki; Kato, Zenichiro; Kondo, Naomi; Orii, Kenji E.; Morimoto, Masahiro

2011-01-01

We describe a case of the appearance of iodinated contrast agents in the same locations of twins' neonatal gastrointestinal tracts 1 day after maternal contrast-enhanced computed tomography (CT). The CT examination had been performed on the expectant mother for suspected deep venous thrombosis on the day previous to the twin delivery. At 23 h after the CT examination and after cesarean section, iodinated contrast agents appeared in the same place in the twins' neonatal gastrointestinal tracts, mainly in the ascending colon, on plain abdominal radiographs. Radiologists, obstetricians, and pediatricians should understand the mechanism of appearance of iodinated contrast agents in fetal gastrointestinal tracts when the expectant mother had been given iodinated contrast agents intravenously shortly before delivery. (author)

Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

Directory of Open Access Journals (Sweden)

Erin Jane Campbell

2015-03-01

Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

Perinatal Environmental Effects on the Neonatal Immune System

DEFF Research Database (Denmark)

Thysen, Anna Hammerich

2014-01-01

are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early...... life. Both are known to be associated with disease. We analyzed the distribution of circulating immune cells from cord blood in the children part of the ongoing unselected COPSAC2010 birth cohort by multi-color flow cytometry. Moreover, airway mucosal cytokines and chemokines of 1-month-old children...

Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

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Nereida Valero

Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

Enhancement of Immune Memory Responses to Respiratory Infection

Science.gov (United States)

2017-08-01

Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0361 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Farrah

Colostrum protein uptake in neonatal lambs examined by descriptive and quantitative liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Hernandez Castellano, Lorenzo E; Argüello, Anastasio; Almeida, André M

2015-01-01

Colostrum intake is a key factor for newborn ruminant survival because the placenta does not allow the transfer of immune components. Therefore, newborn ruminants depend entirely on passive immunity transfer from the mother to the neonate, through the suckling of colostrum. Understanding...... the importance of specific colostrum proteins has gained significant attention in recent years. However, proteomics studies of sheep colostrum and their uptake in neonate lambs has not yet been presented. The aim of this study was to describe the proteomes of sheep colostrum and lamb blood plasma, using sodium...... relative quantification of how neonatal plasma protein concentrations change as an effect of colostrum intake. The results of this study describe the presence of 70 proteins in the ovine colostrum proteome. Furthermore, colostrum intake resulted in an increase of 8 proteins with important immune functions...

Hereditary and microbiological factors influencing the airway immunological profile of neonates

DEFF Research Database (Denmark)

Følsgaard, Nilofar

2012-01-01

is well-recognized, with estimated heritability as high as 60% in asthma. Atopic hereditary disease linkage in the offspring seems stronger for maternal than paternal atopic disease. But it is not known how parental atopic disease may affect early immunity in the target organ, the airways. COPSAC has...... mucosa. There was no paternal linkage to the mucosal immune response pattern, suggesting maternal programming of the fetus or neonate is causing an aberrant local airway immune profile in the newborn child. Furthermore our results suggest an association between maternal atopic disease and the expression...... recently reported an association between abnormal bacterial colonization with M. catarrhalis, S. pneumoniae, H. influenzae of the upper airways of neonates and later development of asthma. This led to the hypothesis that the interaction between genetics and this microbiome in very early life may cause...

Review: Natural killer cells enhance the immune surveillance of ...

African Journals Online (AJOL)

All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer (NK) cells are playing an important role to respond to tumor by enhancing the expression of complementary domain (CD86) on dendritic cells (DCs) and production of IL-12. NK cells demolished tumor ...

Cesarean section changes neonatal gut colonization

DEFF Research Database (Denmark)

Stokholm, Jakob; Thorsen, Jonathan; Chawes, Bo L

2016-01-01

BACKGROUND: Delivery by means of cesarean section has been associated with increased risk of childhood immune-mediated diseases, suggesting a role of early bacterial colonization patterns for immune maturation. OBJECTIVE: We sought to describe the influence of delivery method on gut and airway......-driven partial least squares analyses. The initial airway microbiota was unaffected by birth method. CONCLUSION: Delivery by means of cesarean section was associated with early colonization patterns of the neonatal gut but not of the airways. The differences normalized within the first year of life. We speculate...

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

Science.gov (United States)

Spann, Marisa N; Monk, Catherine; Scheinost, Dustin; Peterson, Bradley S

2018-03-14

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior. SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for

Neonatal Tetanus After Home Delivery: Report of One Case

Directory of Open Access Journals (Sweden)

Shou-Chih Chang

2010-06-01

Full Text Available Neonatal tetanus is a rare disease in developed countries, but remains common in developing countries. Pregnant women immigrating to Taiwan from developing countries may carry a risk of neonatal tetanus to the child, because of inadequate tetanus toxoid immunization and inappropriate postnatal cord care. Many young pediatricians in Taiwan are unfamiliar with this disease. Herein, we describe the clinical course of a newborn with neonatal tetanus, who was admitted with complaints of difficult feeding and muscle rigidity. After mechanical ventilation for 58 days and a prolonged hospital stay, the infant was discharged in good condition. It is important to maintain a high index of suspicion for neonatal sepsis when infants present with seizure-like symptoms, in order to allow its early diagnosis and appropriate treatment.

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

Science.gov (United States)

Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

, when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced. Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment. PMID:23777580

Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis.

Science.gov (United States)

Jain, Nitya; Walker, W Allan

2015-01-01

Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates.

Science.gov (United States)

Rindsjö, E; Joerink, M; Johansson, C; Bremme, K; Malmström, V; Scheynius, A

2010-07-01

It is hypothesized that the in utero environment in allergic mothers can affect the neonatal immune responses. The aim of this study was to analyse the effect of maternal allergic disease on cord blood mononuclear cell (CBMC) phenotype and proliferative responses upon allergen stimulation. Peripheral blood mononuclear cells (PBMC) from 12 allergic and 14 nonallergic mothers and CBMC from their children were analysed. In the mothers, we determined cell proliferation, production of IL-4 and expression of FOXP3 in response to allergen stimulation. In the children, we evaluated cell proliferation and FOXP3 expression following allergen stimulation. Furthermore, expression of different homing markers on T cells and regulatory T cells and maturity of the T cells and B cell subsets were evaluated directly ex vivo. The timothy- and birch-allergic mothers responded with increased proliferation and/or IL-4 production towards timothy and birch extract, respectively, when compared to nonallergic mothers. This could not be explained by impairment of FOXP3(+) regulatory T cells in the allergic mothers. CBMC proliferation and FOXP3 expression in response to allergens were not affected by the allergic status of the mother. Also, phenotype of T cells, FOXP3(+) regulatory T cells and B cells was not affected by the allergic status of the mother. Our results suggest that maternal allergic disease has no effect on the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied here could, however, still affect later development of allergy.

Using appreciative inquiry to bring neonatal nurses and parents together to enhance family-centred care: A collaborative workshop.

Science.gov (United States)

Trajkovski, Suza; Schmied, Virginia; Vickers, Margaret; Jackson, Debra

2015-06-01

Family-centred care (FCC) has been well recognised, accepted and reported in the literature as an optimised way of caring for hospitalised children. While neonatal units strive to adopt this philosophy, published research suggests there are difficulties implementing FCC principles in daily practice. Appreciative inquiry (AI) is a philosophy and methodology that offers a unique, strength-based approach to promoting organisational learning and positive organisational change. As a participatory approach, AI facilitates change from the ground up and lends itself to building effective partnerships or collaborations. This article reports the findings of a one-day workshop using an AI methodology to bring neonatal nurses and parents together to enhance the FCC within a neonatal intensive care unit in Sydney, Australia. Participants (n = 15) developed collaborative insights of optimal FCC that can be built upon to support neonates and their families in the future. Shared visions were formed, strategies identified and a development plan made for ongoing collaborations and partnerships. AI provides a flexible framework that enables the mandatory collaboration needed to develop action plans that can form the catalyst for organizational change in health-care research and practice. © The Author(s) 2013.

Transgenerational effects enhance specific immune response in a wild passerine

Directory of Open Access Journals (Sweden)

Juli Broggi

2016-03-01

Full Text Available Vertebrate mothers transfer diverse compounds to developing embryos that can affect their development and final phenotype (i.e., maternal effects. However, the way such effects modulate offspring phenotype, in particular their immunity, remains unclear. To test the impact of maternal effects on offspring development, we treated wild breeding house sparrows (Passer domesticus in Sevilla, SE Spain with Newcastle disease virus (NDV vaccine. Female parents were vaccinated when caring for first broods, eliciting a specific immune response to NDV. The immune response to the same vaccine, and to the PHA inflammatory test were measured in 11-day-old chicks from their following brood. Vaccinated chicks from vaccinated mothers developed a stronger specific response that was related to maternal NDV antibody concentration while rearing their chicks. The chicks’ carotenoid concentration and total antioxidant capacity in blood were negatively related to NDV antibody concentration, whereas no relation with PHA response was found. Specific NDV antibodies could not be detected in 11-day-old control chicks from vaccinated mothers, implying that maternally transmitted antibodies are not directly involved but may promote offspring specific immunity through a priming effect, while other immunity components remain unaffected. Maternally transmitted antibodies in the house sparrow are short-lived, depend on maternal circulation levels and enhance pre-fledging chick specific immunity when exposed to the same pathogens as the mothers.

SHORT-TERM STRESS ENHANCES CELLULAR IMMUNITY AND INCREASES EARLY RESISTANCE TO SQUAMOUS CELL CARCINOMA

OpenAIRE

Dhabhar, Firdaus S.; Saul, Alison N.; Daugherty, Christine; Holmes, Tyson H.; Bouley, Donna M.; Oberyszyn, Tatiana M.

2009-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposu...

Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

Directory of Open Access Journals (Sweden)

Felix R Stahl

Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

Science.gov (United States)

Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

2001-06-14

Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

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Julio A. Balboa

2009-08-01

Full Text Available Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n. route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay PL1 (Proteoliposome from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1 by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL was significantly higher than AFPL1 (1107 U/mL. AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

Science.gov (United States)

LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

2006-03-15

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine

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Dai, Zhihong [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Quan [College of Veterinary Medicine, Yangzhou University, Yangzhou 225009 (China); Wang, Zaishi [China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Zhongqiu [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Veterinary Bureau, Ministry of Agriculture of the People' s Republic of China, Beijing 100125 (China); Guo, Pengju [Institute of Veterinary Medicine, Guangdong Academy of Agricultural Sciences, Guangdong 510640 (China); Zhao, Deming, E-mail: zhaodm@cau.edu.cn [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

2011-11-11

Highlights: Black-Right-Pointing-Pointer We investigated the immunoadjuvant effects of HVJ-E on killed PRRSV vaccine. Black-Right-Pointing-Pointer HVJ-E enhanced the humoral and cellular responses of the piglets to PRRSV. Black-Right-Pointing-Pointer It is suggested that HVJ-E could be developed as a new-type adjuvant for mammals. -- Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-{gamma} production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

Pathogenic bacteria colonizing the airways in asymptomatic neonates stimulates topical inflammatory mediator release

DEFF Research Database (Denmark)

Følsgaard, Nilofar Vahman; Schjørring, Susanne; Chawes, Bo Lund Krogsgaard

2013-01-01

Rationale: Bacterial colonization of neonatal airways with the pathogenic bacterial species, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, is associated with later development of childhood asthma. Objectives: To study a possible association between colonization...... with pathogenic bacterial strains and the immune signature of the upper airways in healthy neonates. Methods: A total of 20 cytokines and chemokines were quantified in vivo in the airway mucosal lining fluid of 662 neonates from the Copenhagen Prospective Study of Asthma in Childhood 2010 birth cohort...

Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy

DEFF Research Database (Denmark)

Pedersen, Susanne Brix; Bischoff, Anne L.; Folsgaard, Nilofar V.

2015-01-01

, IL-5, IL-13, eotaxin-1, eotaxin-3, TARC, MDC, IL-17, IL-1 beta, IL-8, transforming growth factor beta (TGF)-beta 1, IL-10 and IL-2. Infections were monitored the first year of life by daily diary cards and clinical controls. Results: Neonates of mothers vaccinated during pregnancy had significant up...... significant and positive association to up-regulation of TGF-beta 1 levels (P = 0.0003) and significant negative association to other mediators. The study was not powered to study differences in the incidence of infections in early infancy which did not differ between the study groups. Conclusion: Influenza A......(H1N1) pnd09 vaccination during pregnancy up-regulates TGF-beta 1 and down-regulates key mediators of the protective immunity....

Water immersion in neonatal bereavement photography.

Science.gov (United States)

Duffey, Heather

2014-01-01

Water immersion in neonatal bereavement photography is a new technique intended to enhance the quality of the photographs provided to families following their loss. Water immersion appears to be most helpful following a second trimester fetal demise. This technique can be used by nurses, professional photographers and others in addition to more traditional neonatal bereavement photography. It does not require special skills or equipment and can be implemented in virtually any perinatal setting. The enhanced quality of photographs produced with this method can potentially provide a source of comfort to grieving families. © 2014 AWHONN.

Early Life Microbiota, Neonatal Immune Maturation and Hematopoiesis

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Kristensen, Matilde Bylov

Emerging epidemiologic data supports the hypothesis that early life colonization is a key player in development of a balanced immune system. Events in early life, as birth mode and infant diet, are shown to influence development of immune related diseases, like asthma, diabetes and inflammatory...... bowl disease, later in life. The intestinal epithelium makes up a physical and biochemical barrier between the bacteria in the gut lumen and the immune cells in the submocusal tissue. This monolayer of intestinal epithelial cells (IEC) makes up an extremely large surface and is highly important...... for the synergistic coexistence between trillions of bacteria in the gastrointestinal tract and their mammalian hosts. The IEC actively communicate with the microbiota of the gut lumen and tolerance establishment in the intestine is induced as a result of a balanced and controlled communication between IEC...

Human perinatal immunity in physiological conditions and during infection.

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van Well, Gijs T J; Daalderop, Leonie A; Wolfs, Tim; Kramer, Boris W

2017-12-01

The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established. The lung, gastrointestinal tract, and skin are exposed to amniotic fluid during pregnancy and are probable targets of infection and subsequent inflammation during pregnancy. We found a large number of studies focusing on prenatal infection and the host response. Intrauterine infection and fetal immune responses are well studied, and we describe clinical data on cellular, cytokine, and humoral responses to different microbial challenges. The link to postnatal immunological effects including immune paralysis and/or excessive immune activation, however, turned out to be much more complicated. We found studies relating prenatal infectious or inflammatory hits to well-known neonatal diseases such as respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing enterocolitis. Despite these data, a direct link between prenatal hits and postnatal immunological outcome could not be undisputedly established. We did however identify several unresolved topics and propose questions for further research.

Gadolinium-DTPA enhanced MRI in neonatal osteomyelitis of the cervical-spine

NARCIS (Netherlands)

Martijn, A; van der Vliet, AM; van Waarde, WM; van Aalderen, WMC

Although the radiographic features of neonatal osteomyelitis are well described, spinal localizations are very rare and occur in about 2–4%. Clinical presentation with paresis and paralysis occurs in less than 1% (Resnick & Niwayama, 1988). In the neonate negative bone scintigraphy in the presence

Hugsy : a comforting solution for preterm neonates designed to enhance parent-child bonding

NARCIS (Netherlands)

Claes, S.; Guerra, M.G.; Du, J.; Smits, L.M.; Kommers, D.; Oetomo, S.B.

2017-01-01

Premature neonates frequently need to spend several weeks or months in a Neonatal Intensive Care Unit (NICU). These neonates will experience a significant amount of pain, stress and discomfort during their hospital stay due to various medical interventions they will receive ranging from feeding to

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

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Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

Toll-like receptors in neonatal sepsis.

LENUS (Irish Health Repository)

O'Hare, Fiona M

2013-06-01

Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

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

Science.gov (United States)

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.

Neonatal morphine enhances nociception and decreases analgesia in young rats.

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Zhang, Guo Hua; Sweitzer, Sarah M

2008-03-14

The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

Noise-Immune Cavity-Enhanced Optical Frequency Comb Spectroscopy

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Rutkowski, Lucile; Khodabakhsh, Amir; Johanssson, Alexandra C.; Foltynowicz, Aleksandra

2015-06-01

We present noise-immune cavity-enhanced optical frequency comb spectroscopy (NICE-OFCS), a recently developed technique for sensitive, broadband, and high resolution spectroscopy. In NICE-OFCS an optical frequency comb (OFC) is locked to a high finesse cavity and phase-modulated at a frequency precisely equal to (a multiple of) the cavity free spectral range. Since each comb line and sideband is transmitted through a separate cavity mode in exactly the same way, any residual frequency noise on the OFC relative to the cavity affects each component in an identical manner. The transmitted intensity contains a beat signal at the modulation frequency that is immune to frequency-to-amplitude noise conversion by the cavity, in a way similar to continuous wave noise-immune cavity-enhanced optical heterodyne molecular spectroscopy (NICE-OHMS). The light transmitted through the cavity is detected with a fast-scanning Fourier-transform spectrometer (FTS) and the NICE-OFCS signal is obtained by fast Fourier transform of the synchronously demodulated interferogram. Our NICE-OFCS system is based on an Er:fiber femtosecond laser locked to a cavity with a finesse of ˜9000 and a fast-scanning FTS equipped with a high-bandwidth commercial detector. We measured NICE-OFCS signals from the 3νb{1}+νb{3} overtone band of CO_2 around 1.57 μm and achieved absorption sensitivity 6.4×10-11cm-1 Hz-1/2 per spectral element, corresponding to a minimum detectable CO_2 concentration of 25 ppb after 330 s integration time. We will describe the principles of the technique and its technical implementation, and discuss the spectral lineshapes of the NICE-OFCS signals. A. Khodabakhsh, C. Abd Alrahman, and A. Foltynowicz, Opt. Lett. 39, 5034-5037 (2014). J. Ye, L. S. Ma, and J. L. Hall, J. Opt. Soc. Am. B 15, 6-15 (1998). A. Khodabakhsh, A. C. Johansson, and A. Foltynowicz, Appl. Phys. B (2015) doi:10.1007/s00340-015-6010-7.

Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation.

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Suryawan, Agus; Jeyapalan, Asumthia S; Orellana, Renan A; Wilson, Fiona A; Nguyen, Hanh V; Davis, Teresa A

2008-10-01

Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or G protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. Neither leucine nor rapamycin affected the phosphorylation of AMP-activated protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.

Imaging approach to persistent neonatal jaundice

International Nuclear Information System (INIS)

Kirks, D.; Coleman, R.E.; Filston, H.C.; Rosenberg, E.R.; Merten, D.F.

1984-01-01

Fifteen patients with persistent neonatal jaundice were evaluated by sonography and radionuclide scintigraphy. The sonographic features of both neonatal hepatitis and biliary atresia are nonspecific. Hepatobiliary scintigraphy after phenobarbital pretreatment in patients with neonatal hepatitis demonstrates normal hepatic extraction and delayed tracer excretion into the gastrointestinal tract. If there is neonatal hepatitis with severe hepatocellular damage, the hepatic extraction of tracer activity is decreased and excretion may be delayed or absent. Patients under 3 months of age with biliary atresia have normal hepatic extraction of tracer with no excretion into the gastrointestinal tract. Sonography in patients with a choledochal cyst shows a cystic mass in the porta hepatis with associated bile-duct dilatation. Hepatobiliary scintigraphy confirms that the choledochal cyst communicates with the biliary system. Initial sonography demonstrates hepatobiliary anatomy; subsequent phenobarbital-enhanced radionuclide scintigraphy determines hepatobiliary function. An expedient diagnostic approach is recommended for the evaluation of persistent neonatal jaundice

Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

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Doreen Krumbiegel

2005-01-01

Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

The role of recombinant IL-12 in enhancing immune responses induced by hepatitis B vaccine in mice

International Nuclear Information System (INIS)

Lu Qun; Zhou Lixia; Zhao Yanrong; Miao Xiaoguang; Jin Jie; Ke Jinshan; Qin Xuliang; He Zheng

2007-01-01

Objective: To study the role played by recombinant IL-12 in enhancing the intensity and quality of the immune response to hepatitis B vaccine in mice, and investigate the possibility of adding recombinant IL-12 as adjuvants to hepatitis B therapeutic vaccine. Methods: Recombinant IL-12 was injected together with hepatitis B vaccine into mice and special anti-HBsAb in the mice and the cellular immune responses were examined. Results: Recombinant IL-12 can obviously enhance T lymphocyte multiplication activity, accelerate excretion of cytokines IFN-γ and IL-2, and increase the IgG2a antibody in mice. Conclusion: Recombinant IL-12 can remarkably strengthen the cellular immune responses induced by the hepatitis B vaccine, and modulate the immune responses toward Thl. (authors)

Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

Directory of Open Access Journals (Sweden)

Gold Diane R

2006-03-01

Full Text Available Abstract Background Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2, may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. Methods We analyzed immune responses of cord blood mononuclear cells (CBMC from 50 healthy neonates (31 non-atopic and 19 atopic mothers. Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg or the allergen house dust mite Dermatophagoides farinae (Derf1, and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR, and the cytotoxic lymphocyte antigen 4 (CTLA4. Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Results Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07. Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049. IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001, GITR (r = 0.47, p = 0.004 and CTLA4 (r = 0.49, p = 0.003, independent of maternal atopy. Conclusion TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to

Neonatal tetanus in Turkey; what has changed in the last decade?

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Kocamaz Halil

2008-08-01

Full Text Available Abstract Background Neonatal tetanus (NT is still considered as one of the major causes of neonatal death in many developing countries. The aim of the present study was to assess the characteristics of sixty-seven infants with the diagnosis of neonatal tetanus followed-up in the Pediatric Infectious Diseases Ward of Dicle University Hospital, Diyarbakir, between 1991 and 2006, and to draw attention to factors that may contribute (or may have contributed to the elimination of the disease in Diyarbakir. Methods The data of sixty-seven infants whose epidemiological and clinical findings were compatible with neonatal tetanus were reviewed. Patients were stratified into two groups according to whether they survived or not to assess the effect of certain factors in the prognosis. Factors having a contribution to the higher rate of tetanus among newborn infants were discussed. Results A total of 55 cases of NT had been hospitalized between 1991 and 1996 whereas only 12 patients admitted in the last decade. All of the infants had been delivered at home by untrained traditional birth attendants (TBA, and none of the mothers had been immunized with tetanus toxoid during her pregnancy. Twenty-eight (41.8% of the infants died during their follow-up. Lower birth weight, younger age at onset of symptoms and at the time admission, the presence of opisthotonus, risus sardonicus and were associated with a higher mortality rate. Conclusion Although the number of neonatal tetanus cases admitted to our clinic in recent years is lower than in the last decade efforts including appropriate health education of the masses, ensurement of access to antenatal sevices and increasing the rate of tetanus immunization among mothers still should be made in our region to achieve the goal of neonatal tetanus elimination.

Recent advances in prevention of sepsis in the premature neonates in NICU.

Science.gov (United States)

Manzoni, P; Rizzollo, S; Decembrino, L; Ruffinazzi, G; Rossi Ricci, A; Gallo, E; Stolfi, I; Mostert, M; Stronati, M; Farina, D

2011-03-01

Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding.

Science.gov (United States)

Jost, Ted; Lacroix, Christophe; Braegger, Christian P; Rochat, Florence; Chassard, Christophe

2014-09-01

Breast milk has recently been recognized as source of commensal and potential probiotic bacteria. The present study investigated whether viable strains of gut-associated obligate anaerobes are shared between the maternal and neonatal gut ecosystem via breastfeeding. Maternal faeces, breast milk and corresponding neonatal faeces collected from seven mothers-neonate pairs at three neonatal sampling points were analyzed by culture-independent (pyrosequencing) and culture-dependent methods (16S rRNA gene sequencing, pulsed field gel electrophoresis, random amplified polymorphic DNA and repetitive extragenic palindromic polymerase chain reaction. Pyrosequencing allowed identifying gut-associated obligate anaerobic genera, like Bifidobacterium, Bacteroides, Parabacteroides and members of the Clostridia (Blautia, Clostridium, Collinsella and Veillonella) shared between maternal faeces, breast milk and neonatal faeces. Using culture, a viable strain of Bifidobacterium breve was shown to be shared between all three ecosystems within one mother-neonate pair. Furthermore, pyrosequencing revealed that several butyrate-producing members of the Clostridia (Coprococcus, Faecalibacterium, Roseburia and Subdoligranulum) were shared between maternal faeces and breast milk. This study shows that (viable) obligate gut-associated anaerobes may be vertically transferred from mother to neonate via breastfeeding. Thus, our data support the recently suggested hypothesis of a novel way of mother-neonate communication, in which maternal gut bacteria reach breast milk via an entero-mammary pathway to influence neonatal gut colonization and maturation of the immune system. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

Science.gov (United States)

Wilson, Randall M; Marshall, Nicole E; Jeske, Daniel R; Purnell, Jonathan Q; Thornburg, Kent; Messaoudi, Ilhem

2015-06-01

Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multivalent Porous Silicon Nanoparticles Enhance the Immune Activation Potency of Agonistic CD40 Antibody

Science.gov (United States)

Gu, Luo; Ruff, Laura E.; Qin, Zhengtao; Corr, Maripat P.; Hedrick, Stephen M.; Sailor, Michael J.

2012-01-01

One of the fundamental paradigms in the use of nanoparticles to treat disease is to evade or suppress the immune system in order to minimize systemic side effects and deliver sufficient nanoparticle quantities to the intended tissues. However, the immune system is the body's most important and effective defense against diseases. It protects the host by identifying and eliminating foreign pathogens as well as selfmalignancies. Here we report a nanoparticle engineered to work with the immune system, enhancing the intended activation of antigen presenting cells (APCs). We show that luminescent porous silicon nanoparticles (LPSiNPs), each containing multiple copies of an agonistic antibody (FGK45) to the APC receptor CD40, greatly enhance activation of B cells. The cellular response to the nanoparticle-based stimulators is equivalent to a 30–40 fold larger concentration of free FGK45. The intrinsic near-infrared photoluminescence of LPSiNPs is used to monitor degradation and track the nanoparticles inside APCs. PMID:22689074

Efficacy of screening immune system function in at-risk newborns

OpenAIRE

Pavlovski, Christopher J

2014-01-01

This paper explores the introduction of a screening test to highlight impaired immune system status for newborn infants and its efficacy as a preventative clinical measure. Moreover, it is suggested that screening of the infantile immune system has the potential to highlight susceptibility to a range of infant and childhood diseases, bestowing an opportunity to introduce early intervention to reduce the incidence of these diseases. Development of the neonatal immune system is an important hea...

Kefir milk enhances intestinal immunity in young but not old rats.

Science.gov (United States)

Thoreux, K; Schmucker, D L

2001-03-01

The adjuvant effect of kefir fermented milk on the mucosal and systemic immune systems was examined in young (6 mo old) and old (26 mo old) rats. Kefir-fed rats consisted of young or old rats consuming kefir-fermented milk ad libitum on a daily basis in addition to the standard diet, for 28 d. Control rats consumed only the standard diet. The rats were immunized intraduodenally with cholera toxin (CT) on d 7 and 21 and killed on d 28. The nonspecific serum immunoglobulin (Ig)A titers in kefir-fed and control rats did not differ in either age group. The serum anti-CT IgA antibody concentrations were significantly higher in the kefir-fed young rats compared with their age-matched controls (+86%, P: 120%, P: kefir-fed rats compared with their respective controls. Nevertheless, these results demonstrate that a kefir-supplemented diet affects the intestinal mucosal and systemic immune responses to intraduodenal CT differently in young and old rats. Most importantly, our data suggest that orally administered kefir enhances the specific intestinal mucosal immune response against CT in young adult, but not in senescent rats.

Daidzein enhances immune function in late lactation cows under heat stress.

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Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

2014-01-01

Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

Relation Between Interleukin-1-β And Interleukin-8 Levels In Breast Milk (Colostrum) And Neonatal Physiological Jaundice

International Nuclear Information System (INIS)

Mohamed, A.A.; Moawad, A.T.; Marei, E.S.

2011-01-01

The immune system of neonates is influenced by maternal immunity during pregnancy and lactation. Breast-fed neonates have higher incidence of neonatal jaundice and higher level of total serum bilirubin than formula-fed infants. The aim of this study was to find a relationship between neonatal physiological jaundice and interleukin-1-beta (IL-1-β) and interleukin-8 (IL-8) in the colostrum of nursing mothers. Breast milk (colostrum) was collected from 45 nursing mothers of healthy full term neonates. The sharing mothers and their neonates were divided into two groups according to the presence of neonatal jaundice and the level of total serum bilirubin. All jaundiced neonates had total serum bilirubin level more than 12 mg/dl which appeared on the third postpartum day, all of them were breast-fed only. They were subjected to full history through clinical examination and laboratory investigations including determination of colostral levels of IL-1-β and IL-8, by ELISA, and determination of neonatal total serum bilirubin levels. This study revealed that mothers of neonates with physiological jaundice had higher concentrations of IL-1-β and IL-8 in their colostrums as compared with control group. Moreover, it displayed that total serum bilirubin level of jaundiced neonates was higher than its level in non-jaundiced neonates. There were significant correlations between IL- 1-β and IL-8 with mother's age in all groups, while there were inverse correlations between IL-1-β, IL-8 and gestational age of non- jaundiced neonates. Additionally, there was significant correlation between IL-1-β and IL-8 in the colostrum of all mothers enrolled in this study. On the other hand, no correlation was determined between cytokines IL-1-β, IL-8 and total serum bilirubin in all neonates sharing in this study. This study clearly demonstrated that the levels of immunomodulating agents such as cytokines IL-1-β and IL-8 were elevated in the colostrum of mothers with jaundiced neonates

C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

International Nuclear Information System (INIS)

Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen

2006-01-01

Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28 4 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d 3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD 5 ) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d 3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response

Delayed development of systemic immunity in preterm pigs as a model for preterm infants

DEFF Research Database (Denmark)

Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne

2016-01-01

-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2-3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced......Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life......, relative to those born at near-term or term. Using pigs as a model, we characterized blood leukocyte subsets, antimicrobial activities and TLR-mediated cytokine production during the first weeks after preterm birth. Relative to near-term and term pigs, newborn preterm pigs had low blood leukocyte counts...

Au@Pt nanoparticles as catalase mimics to attenuate tumor hypoxia and enhance immune cell-mediated cytotoxicity

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Liang, Hong; Wu, Ying; Ou, Xiang-Yu; Li, Jing-Ying; Li, Juan

2017-11-01

Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor-1α expression. Furthermore, the integration of high catalytic efficiency of Au@Pt NPs with cytokine-induced killer (CIK) cell immunotherapy, could lead to significantly improve the effect of CIK cell-mediated cytotoxicity. These results suggest great potential of Au@Pt NPs for regulation of the hypoxic TME and enhance immune cell mediated anti-tumor immunity.

Palliative care in the neonatal unit: neonatal nursing staff perceptions of facilitators and barriers in a regional tertiary nursery.

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Kilcullen, Meegan; Ireland, Susan

2017-05-11

Neonatology has made significant advances in the last 30 years. Despite the advances in treatments, not all neonates survive and a palliative care model is required within the neonatal context. Previous research has focused on the barriers of palliative care provision. A holistic approach to enhancing palliative care provision should include identifying both facilitators and barriers. A strengths-based approach would allow barriers to be addressed while also enhancing facilitators. The current study qualitatively explored perceptions of neonatal nurses about facilitators and barriers to delivery of palliative care and also the impact of the regional location of the unit. The study was conducted at the Townsville Hospital, which is the only regional tertiary neonatal unit in Australia. Semi-structured interviews were conducted with a purposive sample of eight neonatal nurses. Thematic analysis of the data was conducted within a phenomenological framework. Six themes emerged regarding family support and staff factors that were perceived to support the provision of palliative care of a high quality. Staff factors included leadership, clinical knowledge, and morals, values, and beliefs. Family support factors included emotional support, communication, and practices within the unit. Five themes emerged from the data that were perceived to be barriers to providing quality palliative care. Staff perceived education, lack of privacy, isolation, staff characteristics and systemic (policy, and procedure) factors to impact upon palliative care provision. The regional location of the unit also presented unique facilitators and barriers to care. This study identified and explored facilitators and barriers in the delivery of quality palliative care for neonates in a regional tertiary setting. Themes identified suggested that a strengths-approach, which engages and amplifies facilitating factors while identified barriers are addressed or minimized, would be successful in

Early Microbes Modify Immune System Development and Metabolic Homeostasis-The "Restaurant" Hypothesis Revisited.

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Nash, Michael J; Frank, Daniel N; Friedman, Jacob E

2017-01-01

The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the "Restaurant" hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate's gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

Vaccination Enhances Early Immune Responses in White Shrimp Litopenaeus vannamei after Secondary Exposure to Vibrio alginolyticus

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Lin, Yong-Chin; Chen, Jiann-Chu; Morni, Wan Zabidii W.; Putra, Dedi Fazriansyah; Huang, Chien-Lun; Li, Chang-Che; Hsieh, Jen-Fang

2013-01-01

Background Recent work suggested that the presence of specific memory or some form of adaptive immunity occurs in insects and shrimp. Hypervariable pattern recognition molecules, known as Down syndrome cell adhesion molecules, are able to mount specific recognition, and immune priming in invertebrates. In the present study, we attempted to understand the immune response pattern of white shrimp Litopenaeus vannamei which received primary (PE) and secondary exposure (SE) to Vibrio alginolyticus. Methodology Immune parameters and proliferation of haematopoietic tissues (HPTs) of shrimp which had received PE and SE to V. alginolyticus were measured. In the PE trial, the immune parameters and proliferation of HPTs of shrimp that received heat-killed V. alginolyticus (HVa) and formalin-inactivated V. alginolyticus (FVa) were measured. Mortality, immune parameters and proliferation of HPTs of 7-day-HVa-PE shrimp (shrimp that received primary exposure to HVa after 7 days) and 7-day-FVa-PE shrimp (shrimp that received primary exposure to FVa after 7 days) following SE to live V. alginolyticus (LVa) were measured. Phagocytic activity and clearance efficiency were examined for the 7∼35-day-HVa-PE and FVa-PE shrimp. Results HVa-receiving shrimp showed an earlier increase in the immune response on day 1, whereas FVa-receiving shrimp showed a late increase in the immune response on day 5. The 7-day-FVa-PE shrimp showed enhancement of immunity when encountering SE to LVa, whereas 7-day-HVa-PE shrimp showed a minor enhancement in immunity. 7-day-FVa-PE shrimp showed higher proliferation and an HPT mitotic index. Both phagocytic activity and clearance maintained higher for both HVa-PE and FVa-PE shrimp after 28 days. Conclusions HVa- and FVa-receiving shrimp showed the bacteria agglutinated prior to being phagocytised. FVa functions as a vaccine, whereas HVa functions as an inducer and can be used as an immune adjuvant. A combined mixture of FVa and HVa can serve as a �

Adverse consequences of neonatal antibiotic exposure.

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Cotten, Charles M

2016-04-01

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

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Yike Jiang

2017-07-01

Full Text Available While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1, we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG, a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

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Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-09-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-01-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

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Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Subcutaneous or oral immunization of mice with Lactococcus lactis expressing F4 fimbrial adhesin FaeG.

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Liu, Shujie; Li, Yongming; Xu, Ziwei; Wang, Yicheng

2013-01-01

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in neonatal and postweaning piglets. Fimbrial adhesion of ETEC has been considered an important colonization factor with antigenicity. To safely and effectively deliver the F4 (K88) fimbrial adhesin FaeG to the immune system, we have previously constructed the secretory expression vector pNZ8112-faeG, and FaeG was produced in cytoplasmic form in Lactococcus lactis. In this work, BALB/c mice were immunized with recombinant L. lactis to further determine the immunogenicity of recombinant FaeG (rFaeG) via the subcutaneous or oral route. Subcutaneous immunization in mice with recombinant L. lactis induced a significant increase in the F4-specific serum IgG titer and the number of antibody-secreting cells (ASCs) in the spleen. Oral immunization of mice with recombinant L. lactis induced mucosal and systemic F4-specific immune responses and increased the number of ASCs in the spleen, mesenteric lymph nodes and Peyer's patches. High-dose (2.8 × 10(11) CFU) recombinant strains and adjuvant cholera toxin B subunit enhanced specific mucosal immune responses. The results suggest the feasibility of delivering rFaeG expressed in L. lactis to the immune system in order to induce an F4-specific immune response.

Enhanced Anti-Mycobacterium tuberculosis Immunity over Time with Combined Drug and Immunotherapy Treatment

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Sasha E. Larsen

2018-05-01

Full Text Available It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb. This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE, in combination with rifampicin, isoniazid, and pyrazinamide (RHZ drug treatment. We assessed the host inflammatory immune responses and lung pathology 7–22 weeks post infection, and determined the therapeutic efficacy of combined treatment by enumeration of the bacterial load and survival in the SWR/J mouse model. We show that drug treatment alone, or with immunotherapy, tempered the inflammatory responses measured in brochoalveolar lavage fluid and plasma compared to untreated cohorts. RHZ combined with therapeutic immunizations significantly enhanced TH1-type cytokine responses in the lung over time, corresponding to decreased pulmonary pathology evidenced by a significant decrease in the percentage of lung lesions and destructive lung inflammation. These data suggest that bacterial burden assessment alone may miss important correlates of lung architecture that directly contribute to therapeutic vaccine efficacy in the preclinical mouse model. We also confirmed our previous finding that in combination with antibiotics therapeutic immunizations provide an additive survival advantage. Moreover, therapeutic immunizations with ID93/GLA-SE induced differential T cell immune responses over the course of infection that correlated

Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

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Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

2017-11-01

Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

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Daly Melissa

2006-08-01

Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

Cross-correlation enhanced stability in a tumor cell growth model with immune surveillance driven by cross-correlated noises

International Nuclear Information System (INIS)

Zeng Chunhua; Zhou Xiaofeng; Tao Shufen

2009-01-01

The transient properties of a tumor cell growth model with immune surveillance driven by cross-correlated multiplicative and additive noises are investigated. The explicit expression of extinction rate from the state of a stable tumor to the state of extinction is obtained. Based on the numerical computations, we find the following: (i) the intensity of multiplicative noise D and the intensity of additive noise α enhance the extinction rate for the case of λ ≤ 0 (i.e. λ denotes cross-correlation intensity between two noises), but for the case of λ > 0, a critical noise intensity D or α exists at which the extinction rate is the smallest; D and α at first weaken the extinction rate and then enhance it. (ii) The immune rate β and the cross-correlation intensity λ play opposite roles on the extinction rate, i.e. β enhances the extinction rate of the tumor cell, while λ weakens the extinction rate of the tumor cell. Namely, the immune rate can enhance the extinction of the tumor cell and the cross-correlation between two noises can enhance stability of the cancer state.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

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Matthew E. Brown

2018-04-01

Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

Computed radiography in neonatal intensive care

International Nuclear Information System (INIS)

Merlo, L.; Bighi, S.; Cervi, P.M.; Lupi, L.

1991-01-01

The Authors report their experience in the employment of a computerized digital radiographic system in Neonatal Intensive Care. The analog screen-film system is replaced by photosensitive imaging plates, scanned after X-ray exposure by a laser that releases the digital image, which can then be manipulated on computer work-stations. In a period of twelve months about 200 chest-abdomen X-ray examinations in Neonatal Intensive Care have been performed using this method with good technical and diagnostic results. The use of digital radiography in the neonatal area is of high interest: this system produces good quality images, there is a reduction in radiation dose and 'retakes', the system allows selective enhancement of different structures and their magnification. (orig.)

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

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Zhe Chen

2017-06-01

Full Text Available Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice.Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI, Wan Fang Database (Wan Fang, Chinese Biomedical Literature Database (CBM, VIP Database for Chinese Technical Periodicals (VIP were searched and the deadline is December 2016. Randomized controlled trials (RCTs of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR or mean difference (MD with a 95% confidence interval (CI was used to measure the effect.Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26, P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: −18.05, 95% CI (−25.51, −10.58, P < 0.00001], 5day [MD: -23.49, 95% CI (−32.80, −14.18, P < 0.00001], 7day [MD: −33.01, 95% CI (−37.31, −28.70, P < 0.00001] treatment, but also decreased time of jaundice fading [MD: −1.91, 95% CI (−2.06, −1.75, P < 0.00001], as

Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate

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Smilowitz, Jennifer T.; Lebrilla, Carlito B.; Mills, David A.; German, J. Bruce; Freeman, Samara L.

2015-01-01

In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate. PMID:24850388

"Trans-generational immune priming": specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor.

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Moret, Yannick

2006-06-07

Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph.

Improving vaccine registries through mobile technologies: a vision for mobile enhanced Immunization information systems.

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Wilson, Kumanan; Atkinson, Katherine M; Deeks, Shelley L; Crowcroft, Natasha S

2016-01-01

Immunization registries or information systems are critical to improving the quality and evaluating the ongoing success of immunization programs. However, the completeness of these systems is challenged by a myriad of factors including the fragmentation of vaccine administration, increasing mobility of individuals, new vaccine development, use of multiple products, and increasingly frequent changes in recommendations. Mobile technologies could offer a solution, which mitigates some of these challenges. Engaging individuals to have more control of their own immunization information using their mobile devices could improve the timeliness and accuracy of data in central immunization information systems. Other opportunities presented by mobile technologies that could be exploited to improve immunization information systems include mobile reporting of adverse events following immunization, the capacity to scan 2D barcodes, and enabling bidirectional communication between individuals and public health officials. Challenges to utilizing mobile solutions include ensuring privacy of data, access, and equity concerns, obtaining consent and ensuring adoption of technology at sufficiently high rates. By empowering individuals with their own health information, mobile technologies can also serve as a mechanism to transfer immunization information as individuals cross local, regional, and national borders. Ultimately, mobile enhanced immunization information systems can help realize the goal of the individual, the healthcare provider, and public health officials always having access to the same immunization information. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

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Ryan T Cleary

Full Text Available Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+-K(+-2 Cl(- cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

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Bilbo, Staci D

2013-05-01

Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Copyright © 2013 Elsevier Inc. All rights reserved.

Soluble CD14 in human breast milk and its role in innate immune responses.

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Vidal, K; Labéta, M O; Schiffrin, E J; Donnet-Hughes, A

2001-10-01

Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

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Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neonatal Platelet Transfusions and Future Areas of Research.

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Sola-Visner, Martha; Bercovitz, Rachel S

2016-10-01

Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence-based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom

Medical improvisation training to enhance the antenatal counseling skills of neonatologists and neonatal fellows: a pilot study.

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Sawyer, Taylor; Fu, Belinda; Gray, Megan; Umoren, Rachel

2017-08-01

Neonatologists must be skilled at providing antenatal counseling to expectant parents of premature infants at the limits of viability. We conducted a medical improvisation workshop with the objective of enhancing antenatal counseling skills. Pre- and postworkshop questionnaires were collected to examine the impact of the training. A follow-up survey was distributed 3 months after the workshop to examine the impact of the training on antenatal counseling skills. Nine neonatologists and three neonatal fellows participated in the workshop. Participants reported the skills learned in the workshop could enhance the quality of antenatal counseling. On follow-up survey, 90% of subjects reported improvements in the quality of their antenatal counseling. Participation in a medical improvisation workshop resulted in enhancements of self-perceived antenatal counseling skills. Medical improvisation training may provide a feasible and effective method of communication training for neonatologists. Further research into this innovative method are needed.

Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans.

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Newburg, D S

2009-04-01

This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These

Enhancing neonatal wellness with home visitation.

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Parker, Carlo; Warmuskerken, Geene; Sinclair, Lorna

2015-01-01

We planned and implemented an evidence-based program to screen for jaundice and to try to increase the proportion of women breastfeeding for 6 months. The program involved home visitation by a registered nurse to provide education on and support of breastfeeding, and to perform physical assessment of both mothers and newborns, including screening for neonatal jaundice. Quantitative data showed increased breastfeeding rates at 6 months. In addition, readmission rates for jaundice were higher when compared to regional benchmarks. However, the average length of stay for treatment of jaundice was shorter than regional benchmarks. Qualitative data indicated that the program was effective at achieving its goals and was valued by participants. © 2015 AWHONN.

Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

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Gou, Changlong; Wang, Jiazhen; Wang, Yuqiong; Dong, Wenlong; Shan, Xiaofeng; Lou, Yujie; Gao, Yunhang

2018-01-01

The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1β and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans

Directory of Open Access Journals (Sweden)

Line Larry L

2010-03-01

Full Text Available Abstract Background Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation, and protects against UVA-induced oxidative stress in in vitro and rodent models. Similar clinical studies in humans are unavailable. Our objective is to study the action of dietary astaxanthin in modulating immune response, oxidative status and inflammation in young healthy adult female human subjects. Methods Participants (averaged 21.5 yr received 0, 2, or 8 mg astaxanthin (n = 14/diet daily for 8 wk in a randomized double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed on wk 8. Results Plasma astaxanthin increased (P helper, Tcytotoxic or natural killer cells. A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8. Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects. There was no difference in TNF and IL-2 concentrations, but plasma IFN-γ and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin. Conclusion Therefore, dietary astaxanthin decreases a DNA damage biomarker and acute phase protein, and enhances immune response in young healthy females.

Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.

Directory of Open Access Journals (Sweden)

Daniel P Barry

Full Text Available Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2 is essential for transport of L-arginine (L-Arg into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO produced from inducible NO synthase (iNOS, or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2(-/- mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2(-/- mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2(-/- mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.

Neonatal herpes simplex virus infections.

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Pinninti, Swetha G; Kimberlin, David W

2018-04-01

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease. Copyright © 2018 Elsevier Inc. All rights reserved.

T helper cell 2 immune skewing in pregnancy/early life

DEFF Research Database (Denmark)

McFadden, J P; Thyssen, J P; Basketter, D A

2015-01-01

During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells...... that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider...... the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose...

Enhanced immunity in intradermal vaccination by novel hollow microneedles.

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Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

2018-04-29

The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

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Gessner, Bradford D; Halsey, Neal

2017-06-14

A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

‘Trans-generational immune priming’: specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor

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Moret, Yannick

2006-01-01

Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph. PMID:16777729

Neonatal Death

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... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...

Stimulation of TLR7 with Gardiquimod Enhances Protection and Activation of Immune Cells from γ-Irradiation Exposure

International Nuclear Information System (INIS)

Yang, Young-Mi; Bang, Ji-Young; Lee, Suhl-Hyeong; Moon, Tae-Min; Jung, Yu-Jin

2007-01-01

Radiotherapy for cancer patients is based on the radiation-induced cell death, but high dose of radiation is able to cause break of immune system. Thus, protection of immune cells from radiation damage is required to enhance the efficiency and reduce the harmful side effects during cancer radiotherapy. Toll-like receptors (TLRs) are important not only in initiating innate immunity against microbial infection, but also inducing Th1-mediated immunity with producing cytokines and chemokines. Cell stimulation via TLRs leads to downstream activation of NF-kB and other transcription factors. Consequently, several genes encoding mediators and effector molecules of the innate as well as the adaptive immune response are transcribed. There are several previous findings that activated immune cells via TLR9 inducing pathways are resistant to chemical or radiation exposure. But it is not clear that the other TLRs also have the same abilities to protect immune cells against cellular damages including γ-irradiation. This research was performed to evaluate protective effect of immune cells from γ-irradiation through TLR-7 activation pathway

A strategy for bacterial production of a soluble functional human neonatal Fc receptor

DEFF Research Database (Denmark)

Andersen, Jan Terje; Justesen, Sune; Berntzen, Gøril

2008-01-01

The major histocompatibility complex (MHC) class I related receptor, the neonatal Fc receptor (FcRn), rescues immunoglobulin G (IgG) and albumin from lysosomal degradation by recycling in endothelial cells. FcRn also contributes to passive immunity by mediating transport of IgG from mother to fetus...

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

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Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

2017-01-01

To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

Upregulation of TGF-beta 1 in neonates of mothers receiving Influenza A (H1N1) vaccination during pregnancy

DEFF Research Database (Denmark)

Bischoff, Anne Louise; Folsgaard, N.; Bisgaard, H.

2012-01-01

Background: Influenza vaccination of pregnant women is generally considered safe,but the effects on the immune system of the unborn child are unknown.Objectives: Our primary objective was to explore differences in cytokine and chemokine levels in nasal mucosal lining fluid in neonates of mothers...... vaccinated during or after pregnancy. Method: IFN-c, IL-1b, IL-2, -4, -5, -10, - 12p70, -13, -17, TNF-a, IL-8, eotaxin-1,eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1b, TGF-b1 and TARC were quantified in nasal mucosal lining fluid in neonates of mothers receiving Influenza A (H1N1v) vaccine during (n = 52......) or after pregnancy (n = 118) in our unselected Copenhagen Prospective Study on Asthma in Childhood 2010 birth-cohort. Result: Neonates of mothers vaccinated during pregnancy showed a significant up-regulation of the immune-regulatory TGF-b1 (P = 0.0004), significant down regulation (P

The impact of maternal obesity during pregnancy on offspring immunity.

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Wilson, Randall M; Messaoudi, Ilhem

2015-12-15

In the United States, approximately 64% of women of childbearing age are either overweight or obese. Maternal obesity during pregnancy is associated with a greater risk for adverse maternal-fetal outcomes. Adverse health outcomes for the offspring can persist into adulthood, increasing the incidence of several chronic conditions including cardiovascular disease, diabetes, and asthma. Since these diseases have a significant inflammatory component, these observations are indicative of perturbation of the normal development and maturation of the immune system of the offspring in utero. This hypothesis is strongly supported by data from several rodent studies. Although the mechanisms of these perturbations are not fully understood, it is thought that increased placental inflammation due to obesity may directly affect neonatal development through alterations in nutrient transport. In this review we examine the impact of maternal obesity on the neonatal immune system, and potential mechanisms for the changes observed. Published by Elsevier Ireland Ltd.

Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

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Askenasy, Nadir

2016-04-01

The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

Neonatal tetanus elimination in Pakistan: progress and challenges.

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Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

OpenAIRE

Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor ...

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

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Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neonatal colonisation expands a specific intestinal antigen-presenting cell subset prior to CD4 T-cell expansion, without altering T-cell repertoire.

Directory of Open Access Journals (Sweden)

Charlotte F Inman

Full Text Available Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein α-positive (SIRPα(+ antigen-presenting cell subset, whilst SIRPα(-CD11R1(+ antigen-presenting cells (APCs are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRPα(+ antigen-presenting cells as orchestrators of early-life mucosal immune development.

Clinical application of immune-enhanced enteral nutrition in patients with advanced gastric cancer after total gastrectomy.

Science.gov (United States)

Liu, Hua; Ling, Wei; Shen, Zhi Yong; Jin, Xin; Cao, Hui

2012-08-01

To determine whether immune-enhanced enteral nutrition (EN) was effective on nutritional status, immune function, surgical outcomes and days of hospitalization after total gastrectomy for patients with advanced gastric cancer (AGC). From August 2005 to May 2011, 78 patients with AGC who underwent a total gastrectomy were enrolled and divided randomly into three groups: immune-enhanced EN (EN + glutamine [Gln]) group, standard EN group and control group. Serum parameters including total protein, albumin, proalbumin and transferrin were examined on preoperative day 1, postoperative day 2 and day 12. Levels of immunoglobulin M (IgM), immunoglobulin G (IgG), natural killer (NK) cells, CD4⁺ and CD8⁺ T cells were also compared. The formulas were tolerated well in all the patients except 5 with mild complications. The EN + Gln and EN groups showed a faster onset of flatus and shorter hospitalization duration than the control group. On postoperative day 12, serum total protein, albumin, proalbumin and transferrin levels of the EN + Gln and EN groups were significantly higher than those of the control group (P nutritional status and immune function for the patients with AGC after total gastrectomy. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal Symbiosis and Developmental Programming In Utero and Neonatal Life

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Viridiana Alcántara-Alonso

2017-07-01

Full Text Available A balanced interaction between the homeostatic mechanisms of mother and the developing organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpredictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute consequences (e.g., growth impairment and sometimes delayed (e.g., enhanced susceptibility to disease that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health.

The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice.

Science.gov (United States)

Hong, Se Hyang; Ku, Jin Mo; In Kim, Hyo; Ahn, Chang-Won; Park, Soo-Hyun; Seo, Hye Sook; Shin, Yong Cheol; Ko, Seong-Gyu

2017-09-01

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of Clostridium butyricum supplementation on the development of intestinal flora and the immune system of neonatal mice.

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Miao, Rui-Xue; Zhu, Xin-Xin; Wan, Chao-Min; Wang, Zhi-Ling; Wen, Yang; Li, Yi-Yuan

2018-01-01

The objective of the present study was to examine whether Clostridium butyricum supplementation has a role in the regulation of the intestinal flora and the development of the immune system of neonatal mice. A total of 30 pregnant BALB/c mice, including their offspring, were randomly divided into three groups: In the maternal intervention group (Ba), maternal mice were treated with Clostridium butyricum from birth until weaning at postnatal day 21 (PD21) followed by administration of saline to the offspring at PD21-28; in the offspring intervention group (Ab), breast-feeding maternal mice were supplemented with saline and offspring were directly supplemented with Clostridium butyricum from PD21-28; in the both maternal and offspring intervention group (Bb), both maternal mice and offspring were supplemented with Clostridium butyricum at PD 0-21 and at PD21-28. While mice in the control group were given the same volume of normal saline. Stool samples from the offspring were collected at PD14, -21 and -28 to observe the intestinal flora by colony counts of Enterococcus spp., Enterobacter spp., Bifidobacterium spp. and Lactobacillus spp. Detection of intestinal secreted immunoglobulin A (sIgA) levels and serum cytokine (interferon-γ, and interleukin-12, -4 and -10) levels in offspring was performed to evaluate the effect on their immune system. The results revealed that compared with the control group, offspring in the Ba group displayed significantly decreased stool colony counts of Enterococcus spp. (t=3.123, Pflora balance in their offspring. However, due to insignificant effects on sIgA level and the associated cytokines, Clostridium butyricum had a limited influence on the balance of type 1 vs. type 2 T-helper cells. However, using Clostridium butyricum as an invention may be a safe method for improving the balance of intestinal flora and associated processes in offspring.

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

Science.gov (United States)

Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

Science.gov (United States)

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Innate Immunity and Human Milk MicroRNAs Content: A New Perspective for Premature Newborns

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Erika Cione

2017-02-01

Full Text Available Context The premature newborns are prone to develop both early onset and late onset neonatal sepsis. The major causes of this phenomenon rely on the immaturity of the immune system, which has reduced capability to respond adequately to pathogens. Evidence Acquisition Titles and abstracts of previous papers were scanned before reading the full-text, in order to retrieve appropriate information. The databases used for searching were PubMed, Cochrane, and Embase for articles published before 1st of July, 2016. Secondary search for articles cited in reference lists were identified by the primary search. This review focused on neonatal sepsis incidence and the associated immune response with regards to microRNAs of human milk as a new microelement that enables regulation of innate immunity functions. Results Since human milk is a valuable source of microRNAs, a better understanding of its content will open a new therapeutic avenue for the clinical management of infectious diseases affecting premature newborns. The variation in miRNAs quantity in human milk needs to be considered. Mother’s milk can have different amounts of miRNAs and the identification of a microMilk batch richer of miRNAs can be a nutrition intervention method for modulating innate immunity in clinical management of premature newborns. Conclusions Routine translation of the microMilk concept for neonatal intensive care unit (NICU, in the management of premature newborns could be a way of defending premature newborns and Very Low Birth Weight (VLBW infants from both early and late sepsis.

The risks of using allogeneic cell lines for vaccine production : The example of Bovine Neonatal Pancytopenia

NARCIS (Netherlands)

Benedictus, Lindert; Bell, Charlotte R

2017-01-01

INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for

Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine

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Wei Li

2013-12-01

Full Text Available Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis. Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.

Dietary N-Carbamylglutamate Supplementation Boosts Intestinal Mucosal Immunity in Escherichia coli Challenged Piglets.

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Fengrui Zhang

Full Text Available N-carbamylglutamate (NCG has been shown to enhance performance in neonatal piglets. However, few studies have demonstrated the effect of NCG on the intestinal mucosal barrier. This study was conducted to determine the effects of dietary NCG supplementation on intestinal mucosal immunity in neonatal piglets after an Escherichia coli (E. coli challenge. New-born piglets (4 d old were assigned randomly to one of four treatments (n = 7, including (I sham challenge, (II sham challenge +50 mg/kg NCG, (III E. coli challenge, and (IV E. coli challenge +50 mg/kg NCG. On d 8, pigs in the E. coli challenge groups (III and IV were orally challenged with 5 mL of E. coli K88 (10(8 CFU/mL, whereas pigs in the sham challenge groups (I and II were orally dosed with an equal volume of water. On d 13, all piglets were sacrificed, and samples were collected and examined. The results show that average daily gain in the E. coli challenged piglets (III and IV was decreased (PE.coli<0.05. However, it tended to be higher in the NCG treated piglets (II and IV. Ileum secretory IgA, as well as IFN-γ, IL-2, IL-4 and IL-10 in ileal homogenates, were increased in E. coli challenged piglets (III and IV. Similarly, ileum SIgA and IL-10 levels, and CD4(+ percentage in NCG treated piglets (II and IV were higher than no-NCG treated piglets (PNCG<0.05. However, the IL-2 level was only decreased in the piglets of E. coli challenge + NCG group (IV compared with E. coli challenge group (III (P<0.05. No change in the IL-2 level of the sham challenged piglets (III was observed. In conclusion, dietary NCG supplementation has some beneficial effects on intestinal mucosal immunity in E. coli challenged piglets, which might be associated with stimulated lymphocyte proliferation and cytokine synthesis. Our findings have an important implication that NCG may be used to reduce diarrhea in neonatal piglets.

Transient neonatal diabetes or neonatal hyperglycaemia: A case ...

African Journals Online (AJOL)

Transient neonatal diabetes and neonatal hyperglycaemia both present in the neonatal period with features of hyperglycaemia, dehydration and weight loss. Differentiating these conditions clinically is difficult. We describe the case of a 13 day old female whom we managed recently who could have had either condition.

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

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N. Fargas-Berríos

2015-01-01

Full Text Available Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM and transient neonatal diabetes mellitus (TNDM. We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL, glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate’s hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

Science.gov (United States)

Kirchner, Elizabeth; Ruffing, Victoria

2017-02-01

For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Codevelopment of Microbiota and Innate Immunity and the Risk for Group B Streptococcal Disease

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Julia Kolter

2017-11-01

Full Text Available The pathogenesis of neonatal late-onset sepsis (LOD, which manifests between the third day and the third month of life, remains poorly understood. Group B Streptococcus (GBS is the most important cause of LOD in infants without underlying diseases or prematurity and the third most frequent cause of meningitis in the Western world. On the other hand, GBS is a common intestinal colonizer in infants. Accordingly, despite its adaption to the human lower gastrointestinal tract, GBS has retained its potential virulence and its transition from a commensal to a dangerous pathogen is unpredictable in the individual. Several cellular innate immune mechanisms, in particular Toll-like receptors, the inflammasome and the cGAS pathway, are engaged by GBS effectors like nucleic acids. These are likely to impact on the GBS-specific host resistance. Given the long evolution of streptococci as a normal constituent of the human microbiota, the emergence of GBS as the dominant neonatal sepsis cause just about 50 years ago is remarkable. It appears that intensive usage of tetracycline starting in the 1940s has been a selection advantage for the currently dominant GBS clones with superior adhesive and invasive properties. The historical replacement of Group A by Group B streptococci as a leading neonatal pathogen and the higher frequency of other β-hemolytic streptococci in areas with low GBS prevalence suggests the existence of a confined streptococcal niche, where locally competing streptococcal species are subject to environmental and immunological selection pressure. Thus, it seems pivotal to resolve neonatal innate immunity at mucous surfaces and its impact on microbiome composition and quality, i.e., genetic heterogeneity and metabolism, at the microanatomical level. Then, designer pro- and prebiotics, such as attenuated strains of GBS, and oligonucleotide priming of mucosal immunity may unfold their potential and facilitate adaptation of potentially

Codevelopment of Microbiota and Innate Immunity and the Risk for Group B Streptococcal Disease.

Science.gov (United States)

Kolter, Julia; Henneke, Philipp

2017-01-01

The pathogenesis of neonatal late-onset sepsis (LOD), which manifests between the third day and the third month of life, remains poorly understood. Group B Streptococcus (GBS) is the most important cause of LOD in infants without underlying diseases or prematurity and the third most frequent cause of meningitis in the Western world. On the other hand, GBS is a common intestinal colonizer in infants. Accordingly, despite its adaption to the human lower gastrointestinal tract, GBS has retained its potential virulence and its transition from a commensal to a dangerous pathogen is unpredictable in the individual. Several cellular innate immune mechanisms, in particular Toll-like receptors, the inflammasome and the cGAS pathway, are engaged by GBS effectors like nucleic acids. These are likely to impact on the GBS-specific host resistance. Given the long evolution of streptococci as a normal constituent of the human microbiota, the emergence of GBS as the dominant neonatal sepsis cause just about 50 years ago is remarkable. It appears that intensive usage of tetracycline starting in the 1940s has been a selection advantage for the currently dominant GBS clones with superior adhesive and invasive properties. The historical replacement of Group A by Group B streptococci as a leading neonatal pathogen and the higher frequency of other β-hemolytic streptococci in areas with low GBS prevalence suggests the existence of a confined streptococcal niche, where locally competing streptococcal species are subject to environmental and immunological selection pressure. Thus, it seems pivotal to resolve neonatal innate immunity at mucous surfaces and its impact on microbiome composition and quality, i.e., genetic heterogeneity and metabolism, at the microanatomical level. Then, designer pro- and prebiotics, such as attenuated strains of GBS, and oligonucleotide priming of mucosal immunity may unfold their potential and facilitate adaptation of potentially hazardous streptococci as

Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1978-01-01

The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased (a) the incidence of benign and malignant tumors and (b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased the incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Science.gov (United States)

Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

2017-01-01

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

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Sarah L Sherrington

2017-05-01

Full Text Available Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

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Wheatley, Scott M.; El-Kadi, Samer W.; Suryawan, Agus; Boutry, Claire; Orellana, Renán A.; Nguyen, Hanh V.; Davis, Steven R.

2013-01-01

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 μmol·kg body wt−1·h−1 for 1 h (HMB 0, HMB 20, HMB 100, or HMB 400). Plasma HMB concentrations increased with infusion and were 10, 98, 316, and 1,400 nmol/ml in the HMB 0, HMB 20, HMB 100, and HMB 400 pigs. Protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles, lung, and spleen were greater in HMB 20 than in HMB 0, and in the LD were greater in HMB 100 than in HMB 0. HMB 400 had no effect on protein synthesis. Eukaryotic initiation factor (eIF)4E·eIF4G complex formation and ribosomal protein S6 kinase-1 and 4E-binding protein-1 phosphorylation increased in LD, gastrocnemius, and soleus muscles with HMB 20 and HMB 100 and in diaphragm with HMB 20. Phosphorylation of eIF2α and elongation factor 2 and expression of system A transporter (SNAT2), system L transporter (LAT1), muscle RING finger 1 protein (MuRF1), muscle atrophy F-box (atrogin-1), and microtubule-associated protein light chain 3 (LC3-II) were unchanged. Results suggest that supplemental HMB enhances protein synthesis in skeletal muscle of neonates by stimulating translation initiation. PMID:24192287

Cephalic Tetanus in an Immunized Teenager: An Unusual Case Report.

Science.gov (United States)

Felter, Robert A; Zinns, Lauren E

2015-07-01

Tetanus is a rare disease in developed countries but is prevalent worldwide. It has significant morbidity and mortality. The causative agent Clostridium tetani is ubiquitous in nature. In the United States, approximately 50 to 100 cases are reported per year but rarely in immunocompetent, fully immunized patients. Of the four types of tetanus (generalized, neonatal, cephalic, and localized), cephalic is the least common. We present a case of cephalic tetanus in a 14-year-old boy who completed his primary immunizations with a video of his physical examination findings.

Pediatric and neonatal cardiovascular pharmacology.

Science.gov (United States)

Miller-Hoover, Suzan R

2003-01-01

Advances in cardiology, surgical techniques, postoperative care, and medications have improved the chances of long-term survival of the neonatal and pediatric patient with complex congenital cardiac anomalies. Rather than undergoing palliative repair, these children are now frequently taken to the operating room for complete repair. As complete repair becomes the norm, collaborative management and a thorough understanding of the pre and postoperative medications used become essential to the care of these patients. The nurse's ability to understand preop, postop, and management medications is enhanced by an understanding of the principles of cardiac anatomy and physiology, as well as developmental changes in cardiac function. All of these are reviewed. In addition, since the safe and effective administration of these drugs depends on the pediatric intensive care unit (PICU) and neonatal intensive care unit (NICU) nurse's thorough knowledge of these medications and their effects on the cardiovascular system, a brief review of these medications is presented. While new technology and techniques are improving survival rates for children with congenital heart anomalies, it is the postoperative care that these children receive that enhances the patient's survival even more.

Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

Science.gov (United States)

de Vos, Paul; Mujagic, Zlatan; de Haan, Bart J.; Siezen, Roland J.; Bron, Peter A.; Meijerink, Marjolein; Wells, Jerry M.; Masclee, Ad A. M.; Boekschoten, Mark V.; Faas, Marijke M.; Troost, Freddy J.

2017-01-01

Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on

Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

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Paul de Vos

2017-08-01

Full Text Available Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1 or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L

The neonatal brain

International Nuclear Information System (INIS)

Flodmark, O.

1987-01-01

The clinical examination of the CNS in the neonate is often difficult in cases of complex pathology. Diagnostic imaging of the neonatal brain has become extremely useful and in the last decade has developed in two main directions: CT and US. MR imaging has been used recently with varying success in the diagnosis of pathology in the neonatal brain. Despite technical difficulties, this imaging method is likely to become increasingly important in the neonate. The paper examines the normal neonatal brain anatomy as seen with the different modalities, followed by pathologic conditions. Attention is directed to the common pathology, in asphyxiated newborns, the patholphysiology of intraventicular hemorrhage and periventricular leukomalacia in the preterm neonate, and hypoxic-ischemic brain injury in the term neonate. Pitfalls, artifacts, and problems in image interpretation are illustrated. Finally, the subsequent appearance of neonatal pathology later in infancy and childhood is discussed

Prenatal and neonatal radiation injury and lymphohematopoietic development in the dog

International Nuclear Information System (INIS)

Nold, J.B.

1985-01-01

Immunologic and hematopoietic responses were studied in beagle dogs following prenatal or neonatal irradiation to evaluate the effects of ionizing radiation on the developing lymphohematopoietic system. In prenatally-irradiated dogs thymic medullary volumes were significantly reduced at birth, but had returned to control levels by 12 weeks of age. Irradiated dogs exhibited a significant reduction in primary humoral antibody responses and showed a concurrent decrease in T helper lymphocytes in the peripheral blood. In neonatally-irradiated dogs lymphocyte blastogenic responses were sharply decreased at 8 weeks, but returned to control levels by 12 weeks of age. Contact sensitivity to dinitrochlorobenzene was decreased, indicating reduced cell-mediated immune responses. Alterations in peripheral blood lymphocyte subpopulations included decreases in B cells and increases in T cells, possibly due to increased numbers of T suppressor cells. There were significant reductions in body size and body tissue weights in all irradiated dogs, although these were more severe and persistent in the prenatally-irradiated dogs. These data show that prenatally or neonatally-irradiated dogs have significantly postnatal immunologic and hematopoietic defects. The effect on bone marrow function in prenatally-irradiated dogs was more severe and persistent than in neonatally-irradiated animals; however, the neonatally-irradiated dogs exhibited more severe alterations in lymphocyte subpopulations than did the prenatally-irradiated dogs. The observation of altered lymphocyte subpopulations suggests altered immunoregulation and raises some important questions relating to radiation-induced immunodeficiency and increased susceptibility to clinical disease, including neoplasia

Neonatal hypertension.

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Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2017-03-01

Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

T-cell proliferative responses following sepsis in neonatal rats.

Science.gov (United States)

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis. Copyright 2003 S. Karger AG, Basel

Gold nanoparticles conjugating recombinant influenza hemagglutinin trimers and flagellin enhanced mucosal cellular immunity.

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Wang, Chao; Zhu, Wandi; Luo, Yuan; Wang, Bao-Zhong

2018-04-09

The immunogenicity of subunit vaccines can be augmented by formulating them into nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2) hemagglutinin (HA) onto functionalized gold nanoparticles (AuNPs) surfaces in a repetitive, oriented configuration. To further improve the immunogenicity, we generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC particle mixture elicited strong mucosal and systemic immune responses that protected hosts against lethal influenza challenges. Compared with the AuNP-HA alone group, the addition of AuNP-FliC improved mucosal B cell responses as characterized by elevated influenza specific IgA and IgG levels in nasal, tracheal, and lung washes. AuNP-HA/AuNP-FliC also stimulated antigen-specific interferon-γ (IFN-γ)-secreting CD4 + cell proliferation and induced strong effector CD8 + T cell activation. Our results indicate that intranasal co-delivery of antigen and adjuvant-displaying AuNPs enhanced vaccine efficacy by inducing potent cellular immune responses. Copyright © 2018. Published by Elsevier Inc.

[Establishment and validation of a neonatal pig model of hemolytic jaundice].

Science.gov (United States)

Li, Yong-Fu; Ma, Yue-Lan; Nie, Ling; Chen, Shuan; Jin, Mei-Fang; Wang, San-Lan

2016-05-01

To establish a neonatal pig model of hemolytic jaundice. Twelve seven-day-old purebred Yorkshire pigs were randomly divided into an experimental group and a control group (n=6 each). Immunization of New Zealand white rabbits was used to prepare rabbit anti-porcine red blood cell antibodies, and rabbit anti-porcine red blood cell serum was separated. The neonatal pigs in the experimental group were given an intravenous injection of rabbit anti-porcine red blood cell serum (5 mL), and those in the control group were given an intravenous injection of normal saline (5 mL). Venous blood samples were collected every 6 hours for routine blood test and liver function evaluation. The experimental group had a significantly higher serum bilirubin level than the control group at 18 hours after the injection of rabbit anti-porcine red blood cell serum (64±30 μmol/L vs 20±4 μmol/L; Pjaundice simulates the pathological process of human hemolytic jaundice well and provides good biological and material bases for further investigation of neonatal hemolysis.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

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Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

2014-08-21

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

Science.gov (United States)

Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

2014-01-01

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

Etiologies of Prolonged Unconjugated Hyperbilirubinemia in Neonates Admitted to Neonatal Wards

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Mohammad Kazem Sabzehei

2015-12-01

Full Text Available Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran. Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia. Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants. Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.

Dynamic Interaction of Enterovirus 71 and Dendritic Cells in Infected Neonatal Rhesus Macaques.

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Zhao, Ting; Zhang, Zhixiao; Zhang, Ying; Feng, Min; Fan, Shengtao; Wang, Lichun; Liu, Longding; Wang, Xi; Wang, Qinglin; Zhang, Xiaolong; Wang, Jingjing; Liao, Yun; He, Zhanlong; Lu, Shuaiyao; Yang, Huai; Li, Qihan

2017-01-01

Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.

Children developing asthma by school-age display aberrant immune responses to pathogenic airway bacteria as infants

DEFF Research Database (Denmark)

Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich

2014-01-01

Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonisation of neonatal airways with the pathogenic bacterial strains H. influenzae, M. catarrhalis and S. pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that c...... that children developing asthma have an abnormal immune response to pathogenic bacteria in infancy. We aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years.......Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonisation of neonatal airways with the pathogenic bacterial strains H. influenzae, M. catarrhalis and S. pneumoniae is associated with increased risk of later childhood asthma. We hypothesized...

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

Science.gov (United States)

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

Rearing environment affects development of the immune system in neonates

NARCIS (Netherlands)

Inman, C.F.; Haverson, K.; Konstantinov, S.R.; Jones, P.H.; Harris, C.; Smidt, H.; Miller, B.; Bailey, M.; Stokes, C.

2010-01-01

P>Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect

Radiation-induced life shortening in neonatally thymectomized germ-free mice

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1980-01-01

Radiation in sufficient amounts is carcinogenic, immunosuppressive, and results in a reduced life span. Similar consequences follow neonatal thymectomy (nTx) in some strains of rodents. The tumorigenic effects of irradiation appear to be partly mediated via suppression of the thymus-dependent portion of the immune response. Our purpose was to determine whether a similar relationship exists for radiation-induced accelerated aging. Female germ-free Charles River mice had neonatal or sham thymectomies within 24 hours of birth. Half of each group was exposed to 700 rads at 6 weeks of age. When mice with histologically malignant tumors were excluded, the combined life-shortening effects of nTx and irradiation were less pronounced than the sum of the individual effects. This suggests that some of the decreased longevity associated with irradiation may be mediated by T-cell injury

Knowledge, attitudes and practices of neonatal staff concerning neonatal pain management

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Sizakele L.T. Khoza

2014-11-01

Full Text Available Background: Neonatal pain management has received increasing attention over the past four decades. Research into the effects of neonatal pain emphasises the professional, ethical and moral obligations of staff to manage pain for positive patient outcomes. However, evaluation studies continuously report evidence of inadequate neonate pain management and a gap between theory and practice. Objective: This study reviewed current practice in neonatal pain management to describe the knowledge, attitudes and practices of nurses and doctors regarding pain management for neonates in two academic hospitals. Method: A non-experimental, prospective quantitative survey, the modified Infant Pain Questionnaire, was used to collect data from 150 nurses and doctors working in the neonatal wards of two academic hospitals in central Gauteng. Results: The response rate was 35.33% (n = 53, most respondents being professional nurses (88.68%; n = 47 working in neonatal intensive care units (80.77%; n = 42; 24 (45.28% had less than 5 years’ and 29 respondents 6 or more years’ working experience in neonatal care. A review of pain management in the study setting indicated a preference for pharmacological interventions to relieve moderate to severe pain. An association (p < 0.05 was found between pain ratings on 5 procedures and frequency of administration of pharmacological pain management. Two-thirds of respondents (64% reported that there were no pain management guidelines in the neonatal wards in which they worked. Conclusion: The interventions to manage moderate neonatal pain are in line with international guidelines. However, neonatal pain management may not occur systematically based on prior assessment of neonatal pain, choice of most appropriate intervention and evaluation. This study recommends implementation of a guideline to standardise practice and ensure consistent and adequate pain management in neonates.

Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

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Sarah M. Dinces

2014-06-01

Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

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Shulei Qiu

Full Text Available The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4 to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

Science.gov (United States)

Pamornpathomkul, Boonnada; Rojanarata, Theerasak; Opanasopit, Praneet; Ngawhirunpat, Tanasait

2017-10-01

The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

Enhancement of anamnestic immunospecific antibody response in orally immunized chickens

DEFF Research Database (Denmark)

Mayo, Susan; Carlsson, Hans-Erik; Zagon, Andrea

2008-01-01

Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying hens through oral immunization is an attractive alternative to conventional antibody production in mammals for economic reasons as well as for animal welfare reasons. Oral immunization results in a systemic humoral...... of the immunization in week 18, demonstrating the presence of memory cells following the two initial oral immunizations. Considering that oral immunization results in approximately ten times lower concentrations of immunospecific antibodies in the egg yolk, compared to traditional subcutaneous immunization schemes...

Neonatal retinoblastoma

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Tero T Kivelä

2017-01-01

Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support

Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

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Elisa Ramos-Sevillano

Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

A case of Panton–Valentine leucocidin toxin‐positive Staphylococcus aureus‐mediated neonatal mastitis

LENUS (Irish Health Repository)

O’Connor, Ciara

2014-09-01

Introduction: Neonatal mastitis is an inflammatory condition of the breast frequently associated with Staphylococcus aureus. While Panton–Valentine leucocidin (PVL), a B‐pore‐forming cytotoxin, is commonly associated with enhanced virulence in community‐acquired methicillin‐resistant S. aureus isolates, this is the first report to our knowledge of neonatal mastitis caused by PVL‐positive S. aureus.\\r\

Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep.

Science.gov (United States)

Downs, Cynthia J; Boan, Brianne V; Lohuis, Thomas D; Stewart, Kelley M

2018-01-01

Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep ( Ovis dalli dalli ) in Southcentral Alaska. Specifically, we (i) tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii) tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

Science.gov (United States)

Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

2016-11-04

In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

Science.gov (United States)

Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

construct self-adjuvanting polymer-based intranasal mRNA vaccines to enhance lymph node trafficking and further improve immune responses. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Vaginal seeding or vaginal microbial transfer from the mother to the cesarean born neonate

DEFF Research Database (Denmark)

Haahr, Thor; Glavind, Julie; Axelsson, Paul

2017-01-01

Recent evidence suggests cesarean delivery (CD) to be a risk factor for inflammatory and metabolic diseases such as asthma, allergies and other chronic immune disorders in the child. One hypothetical pathogenesis of these associations has been proposed to be a disruption of the neonatal colonizat...... to children delivered vaginally. This article is protected by copyright. All rights reserved....

Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

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Guohui eCai

2015-01-01

Full Text Available Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS. Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

A regional multilevel analysis: can skilled birth attendants uniformly decrease neonatal mortality?

Science.gov (United States)

Singh, Kavita; Brodish, Paul; Suchindran, Chirayath

2014-01-01

Globally 40 % of deaths to children under-five occur in the very first month of life with three-quarters of these deaths occurring during the first week of life. The promotion of delivery with a skilled birth attendant (SBA) is being promoted as a strategy to reduce neonatal mortality. This study explored whether SBAs had a protective effect against neonatal mortality in three different regions of the world. The analysis pooled data from nine diverse countries for which recent Demographic and Health Survey data were available. Multilevel logistic regression was used to understand the influence of skilled delivery on two outcomes-neonatal mortality during the first week of life and during the first day of life. Control variables included age, parity, education, wealth, residence (urban/rural), geographic region (Africa, Asia and Latin America/Caribbean), antenatal care and tetanus immunization. The direction of the effect of skilled delivery on neonatal mortality was dependent on geographic region. While having a SBA at delivery was protective against neonatal mortality in Latin America/Caribbean, in Asia there was only a protective effect for births in the first week of life. In Africa SBAs were associated with higher neonatal mortality for both outcomes, and the same was true for deaths on the first day of life in Asia. Many women in Africa and Asia deliver at home unless a complication occurs, and thus skilled birth attendants may be seeing more women with complications than their unskilled counterparts. In addition there are issues with the definition of a SBA with many attendants in both Africa and Asia not actually having the needed training and equipment to prevent neonatal mortality. Considerable investment is needed in terms of training and health infrastructure to enable these providers to save the youngest lives.

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

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Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

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Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

2014-06-01

Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

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Siggers, Richard H.; Siggers, Jayda; Thymann, Thomas

2011-01-01

on the nutritional, microbial and immunological interactions during the early feeding-induced mucosal dysfunction and later NEC development. We show that introduction of suboptimal enteral formula diets, coupled with parenteral nutrition, predispose to disease, while advancing amounts of mother's milk from birth...... (particularly colostrum) protects against disease. Hence, the transition from parenteral to enteral nutrition shortly after birth plays a pivotal role to secure gut growth, digestive maturation and an appropriate response to bacterial colonization in the sensitive gut of preterm neonates.......The gastrointestinal inflammatory disorder, necrotizing enterocolitis (NEC), is among the most serious diseases for preterm neonates. Nutritional, microbiological and immunological dysfunctions all play a role in disease progression but the relationship among these determinants is not understood...

Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response.

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Csongor I Vágási

Full Text Available Glucocorticoid (GC hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long as well as on their circulating levels (baseline vs. stress-induced. Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation and physiological state (humoral innate immune system activity and oxidative balance. We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days elevation of baseline CORT might have a positive and stimulatory effect on animal physiology.

Identification and characterization of the related immune-enhancing proteins in crab Scylla paramamosain stimulated with rhubarb polysaccharides.

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Cao, Jingsong; Wang, Zehuan; Zhang, Yueling; Qu, Fengliang; Guo, Lingling; Zhong, Mingqi; Li, Shengkang; Zou, Haiying; Chen, Jiehui; Wang, Xiuying

2014-02-01

Recently, considerable interest has been focused on immunostimulants to reduce diseases in crab aquaculture. However, information regarding to the related immune-enhancing proteins in crabs is not available yet. In this study, rhubarb polysaccharides were tested for enhancement of the immune activity in crab Scylla paramamosain. Compared with those in the control group, values of, phenoloxidase (PO), alkaline phosphatase (AKP) and alkaline phosphatasein (ACP) activity in the, experimental group were improved significantly 4 d after the treatment. Furthermore, 15 and 17 altered proteins from haemocytes and hepatopancreas, respectively, were found in rhubarb polysaccharide-treated crabs using 2-DE approach. Of these, hemocyanin, chymotrypsin, cryptocyanin, C-type lectin receptor, and ferritin protein were identified by mass spectrometry. In addition, RT-PCR, analysis showed that the mRNA levels of hemocyanin and chymotrypsin increased about 2.4- and 1.4-fold in the experiment group. Moreover, the hemocyanin gene in S. paramamosain (SpHMC) was, cloned and characterized. SpHMC contains one open reading frame of 2022 bp and encodes a polypeptide of 673 amino acids. It is clustered into one branch along with crab hemocyanin in a phylogenetic tree. The mRNA transcripts of SpHMC were detected mainly in the tissues of, hepatopancreas, hemocyte and intestines, and its levels were up-regulated significantly in hemocytes, of S. paramamosain treated with Vibrio parahemolyticus, Beta streptococcus or poly I:C for 6-48 h. Taken together, these studies found 5 related immune-enhancing proteins and a novel heomcyanin homologue with potential pathogen-resistant activities in crab. Copyright © 2013 Elsevier Ltd. All rights reserved.

Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

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Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.

2017-01-01

The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657

Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

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Mirjam E Belderbos

Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

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Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

2012-01-01

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

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Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

2017-01-05

CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-neonatal drop in alveolar SP-A expression

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Stray-Pedersen, Arne; Vege, Ashild; Stray-Pedersen, Asbjorg

2008-01-01

BACKGROUND: Surfactant protein A (SP-A) is synthesized in the lung and is a part of the innate immune system. The aim of this study was to evaluate the expression of SP-A in lung tissue from fetuses, infants, children and adults with special regard to sudden infant death syndrome (SIDS). METHODS......: A total of 160 cases were studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1 year of age, 19 toddlers and 14 adults. Immunohistochemical detection of SP-A using monoclonal antibodies was performed by microscopy of lung tissue specimens collected at autopsy. A scoring system...

Proteomic identification of the related immune-enhancing proteins in shrimp Litopenaeus vannamei stimulated with vitamin C and Chinese herbs.

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Qiao, Jie; Du, Zhiheng; Zhang, Yueling; Du, Hong; Guo, Lingling; Zhong, Mingqi; Cao, Jingsong; Wang, Xiuying

2011-12-01

Recently, strong interest has been focused on immunostimulants to reducing the diseases in shrimp aquaculture. However, information regarding to the related immune-enhancing proteins in shrimps is not available yet. In this study, vitamin C (Vc), Chinese herbs (CH), and the mixture of vitamin C and Chinese herbs (Mix) were tested for their enhancement on shrimp's immune activity. Compared with those in the control group, values of phenoloxidase (PO), superoxide dismutase (SOD) and antibacterial (Ua) activity in the Mix-treated group were improved significantly 12 or 24 days after the treatment. The cumulative mortality was also lower in the Mix-treated group after infection with Vibrio parahemolyticus. Furthermore, comparative proteomic approach was used to assess the protein expression profile in shrimps. Approximately 220-290 and 300-400 protein spots were observed in the 2-DE gels. Among them, 29 and 28 altered proteins from hemocytes and hepatopancreas, respectively, were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The results revealed that the main altered proteins showed high homologies with Litopenaeus vannamei hemocyanin, hemolymph clottable protein, hemoglobin beta, cytosolic MnSOD, trypsin, cathepsin I(L) and zinc proteinase Mpc1. Together, these studies found Vc and CH were suitable immunostimulants to shrimp L. vannamei, and 7 altered proteins could be involved in the enhanced immune activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

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Qing Zeng; Xiaolong He; Santhosh Puthiyakunnon; Hansen Xiao; Zelong Gong; Swapna Boddu; Lecheng Chen; Huiwen Tian; Huiwen Tian; Sheng-He Huang; Sheng-He Huang; Hong Cao

2017-01-01

Escherichia coli (E. coli) K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS) has a preventive role against neonatal E. coli K1 bacteremia and men...

Advancing Neurologic Care in the Neonatal Intensive Care Unit with a Neonatal Neurologist

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Mulkey, Sarah B.; Swearingen, Christopher J.

2014-01-01

Neonatal neurology is a growing sub-specialty area. Given the considerable amount of neurologic problems present in the neonatal intensive care unit, a neurologist with expertise in neonates is becoming more important. We sought to evaluate the change in neurologic care in the neonatal intensive care unit at our tertiary care hospital by having a dedicated neonatal neurologist. The period post-neonatal neurologist showed a greater number of neurology consultations (Pneurology encounters per patient (Pneurology became part of the multi-disciplinary team providing focused neurologic care to newborns. PMID:23271754

Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep

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Cynthia J. Downs

2018-01-01

Full Text Available Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep (Ovis dalli dalli in Southcentral Alaska. Specifically, we (i tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

Ureaplasma-associated prenatal, perinatal, and neonatal morbidities.

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Silwedel, Christine; Speer, Christian P; Glaser, Kirsten

2017-11-01

Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Furthermore, a potential causal relation with other inflammation-induced morbidities, such as intraventricular hemorrhage, white matter injury, necrotizing enterocolitis, and retinopathy of prematurity, has been debated. Areas covered: This review will summarize current knowledge on the role of Ureaplasma spp. in prenatal, perinatal, and neonatal morbidities, while furthermore examining mutual underlying mechanisms. We try to elaborate who is at particular risk of Ureaplasma-induced inflammation and subsequent secondary morbidities. Expert commentary: Most likely by complex interactions with immunological processes, Ureaplasma spp. can induce pro-inflammation, but may also downregulate the immune system. Tissue damage, possibly causing the above mentioned complications, is likely to result from both ways: either directly cytokine-associated, or due to a higher host vulnerability to secondary impact factors. These events are very likely to begin in prenatal stages, with the most immature preterm infants being most susceptible and at highest risk.

Enhancing immune responses to inactivated porcine parvovirus oil emulsion vaccine by co-inoculating porcine transfer factor in mice.

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Wang, Rui-ning; Wang, Ya-bin; Geng, Jing-wei; Guo, Dong-hui; Liu, Fang; Chen, Hong-ying; Zhang, Hong-ying; Cui, Bao-an; Wei, Zhan-yong

2012-07-27

Inactivated porcine parvovirus (PPV) vaccines are available commercially and widely used in the breeding herds. However, inactivated PPV vaccines have deficiencies in induction of specific cellular immune response. Transfer factor (TF) is a material that obtained from the leukocytes, and is a novel immune-stimulatory reagent that as a modulator of the immune system. In this study, the immunogenicity of PPV oil emulsion vaccine and the immuno-regulatory activities of TF were investigated. The inactivated PPV oil emulsion vaccines with or without TF were inoculated into BALB/c mice by subcutaneous injection. Then humoral and cellular immune responses were evaluated by indirect enzyme-linked immunosorbent assays (ELISA), fluorescence-activated cell sorter analyses (FACS). The results showed that the PPV specific immune responses could be evoked in mice by inoculating with PPV oil emulsion vaccine alone or by co-inoculation with TF. The cellular immune response levels in the co-inoculation groups were higher than those groups receiving the PPV oil emulsion vaccine alone, with the phenomena of higher level of IFN-γ, a little IL-6 and a trace of IL-4 in serum, and a vigorous T-cell response. However, there was no significant difference in antibody titers between TF synergy inactivated vaccine and the inactivated vaccine group (P>0.05). In conclusion, these results suggest that TF possess better cellular immune-enhancing capability and would be exploited into an effective immune-adjuvant for inactivated vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

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Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

2017-01-01

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

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Kuender D. Yang

2017-04-01

Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways

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Qishi Zheng

2015-09-01

Full Text Available Background/Aims: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. Methods: We recruited members of a university badminton club as the regular exercise (RE group and healthy sedentary students as the sedentary control (SC group. We investigated the distribution of peripheral blood mononuclear cell (PBMC subsets and functions in the two groups. Results: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-γ, TNF-α, IL-6, IFN-α and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-α and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or α-galactosylceramide. Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. Conclusion: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

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Zhao JH

2017-07-01

Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

Immune cells in term and preterm labor

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Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

2014-01-01

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

Neonatal Bartter syndrome and unilateral ectopic renal cyst as new renal causes of hydrops fetalis: two case reports and review of the literature.

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Çetinkaya, Merih; Durmaz, Oguzhan; Büyükkale, Gökhan; Ozbek, Sibel; Acar, Deniz; Kilicaslan, Isin; Kavuncuoglu, Sultan

2013-07-01

Non-immune hydrops fetalis (NIHF) is a challenging entity as it represents the end stage of several different disorders. Renal and genitourinary causes of NIHF are rare and include congenital renal malformations, tumors and ureter-urethra disorders. Herein, two NIHF cases with different renal causes were presented. The first case that had antenatal NIHF was diagnosed neonatal Bartter syndrome. The second case of NIHF with antenatal large cyst in the surrenal gland area required surgery and ectopic renal cyst was diagnosed. To our best of knowledge, these are the first reports of NIHF associated with neonatal Bartter syndrome and ectopic renal cyst in neonates. Although it may be coincidental, these cases suggest that both neonatal Bartter syndrome and unilateral ectopic renal cyst may cause NIHF development in neonates by several different mechanisms. Therefore, these two rare entities should be suspected in cases of NIHF with similar findings.

Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.

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Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre; Katz, Nathan; Zhu, Yanqing; Lin, Gloria; Choa, Ruth; Bagel, Jessica; O'Donnell, Patricia; Fitzgerald, Caitlin A; Langan, Therese; Wang, Ping; Casal, Margret L; Haskins, Mark E; Wilson, James M

2016-09-01

High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

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Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.

2015-01-01

Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047

A tritherapy combination of inactivated allogeneic leukocytes infusion and cell vaccine with cyclophosphamide in a sequential regimen enhances antitumor immunity

OpenAIRE

Yishu Tang; Wenbo Ma; Chunxia Zhou; Dongmei Wang; Shuren Zhang

2018-01-01

Background: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses. Methods: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell ...

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

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Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

2011-02-01

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Post-oral and perioral stimulations during nursing enhance appetitive olfactory memory in neonatal rabbits.

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Serra, J; Ferreira, G; Mirabito, L; Lévy, F; Nowak, R

2009-06-01

Nursing-suckling interactions facilitate olfactory learning in newborns as long as suckling and the olfactory stimulus temporally overlap. We tested the hypothesis that olfactory preferences would develop even with a long delay between odor presentation and nursing. Thyme was presented to 2-day-old rabbit pups by placing an odorized plate 2 cm above their nest box. Duration and time of nursing were controlled and occurred before, during, or after odor presentation. Controls were not nursed. When exposed to the odor for 15 min, control pups preferred thyme to a novel odor in a 2-choice test immediately after exposure but not 3 and 22 h later. When pups were nursed immediately before thyme exposure or during exposure, they preferred the familiar odorant until 22 h later. Identically, when nursing occurred 30 min before odor exposure, a preference for thyme was maintained up to 22 h. This was not observed when nursing occurred 60 min before odor presentation. We concluded that enhancement of olfactory memory occurs in neonates during nursing but also after post-oral stimulation by postprandial internal state.

Immune reaction and colorectal cancer: friends or foes?

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Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario

2014-09-21

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

Overexpression of angiotensin-converting enzyme in myelomonocytic cells enhances the immune response [version 1; referees: 3 approved

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Kenneth E. Bernstein

2016-03-01

Full Text Available Angiotensin-converting enzyme (ACE converts angiotensin I to the vasoconstrictor angiotensin II and thereby plays an important role in blood pressure control. However, ACE is relatively non-specific in its substrate specificity and cleaves many other peptides. Recent analysis of mice overexpressing ACE in monocytes, macrophages, and other myelomonocytic cells shows that these animals have a marked increase in resistance to experimental melanoma and to infection by Listeria monocytogenes or methicillin-resistant Staphylococcus aureus (MRSA. Several other measures of immune responsiveness, including antibody production, are enhanced in these animals. These studies complement a variety of studies indicating an important role of ACE in the immune response.

Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination.

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Paul K S Chan

Full Text Available Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question.The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future.A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults.Among 212 students, 17-23-year-old, born after adoption of neonatal immunization, 2 (0.9% were HBsAg positive, 40 (18.9% were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs 100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047. At 2-4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10-100 mIU/mL.Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.

Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

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Michael J. Nash

2017-12-01

Full Text Available The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD. This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

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Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

2008-06-01

Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

Regulation of IgE antibody production by serum molecules. I. Serum from complete Freund's adjuvant-immune donors suppresses irradiation-enhanced IgE production in low responder mouse strains

International Nuclear Information System (INIS)

Tung, A.S.; Chiorazzi, N.; Katz, D.H.

1978-01-01

Exposure of mice to low doses of x irradiation at or near the time of primary immunization with 2,4-dinitrophenyl (DNP)-Ascaris suum extract (ASC) results in substantial enhancement of IgE anti-DNP antibody responses; the IgG antibody responses of such mice do not increase after such manipulations. This selective enhancement of IgE antibody production occurs in mice of both high and low IgE responder phenotype, although the extent of enhancement compared to unmanipulated control animals is more striking in low IgE responder mice. The studies presented here demonstrate that the irradiation-enhanced IgE antibody responses of low responder SJL and C57BL/6 mice as well as of intermediate responder AKR mice can be effectively suppressed by passive transfer of CFA-immune serum obtained from isologous donor mice. Moreover, adoptive secondary IgE antibody responses in SJL recipients of primed syngeneic spleen cells can be totally abolished by passive transfer of CFA-immune serum or ascitic fluid from CFA-immune mice. The suppressive activity of CFA-immune serum can be diminished or eliminated by exposure of CFA-primed donor mice to low dose x irradiation at an appropriate point during the priming regimen, after a single inoculation of CFA, and before collection of serum. Low dose x irradiation was not effective in eliminating suppressive activity of CFA-induced ascites fluid obtained from donor mice inoculated repeatedly with CFA. In contrast to the capacity of CFA-immune serum from isologous donors to suppress irradiation-enhanced IgE responses of low responder mice, similar sera or ascites fluids were ineffective in suppressing irradiation-enhanced responses of high responder BALB/c or (SJL x BALB/c)F 1 hybrid mice

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

OpenAIRE

Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

2014-01-01

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delive...

Failure to thrive among neonates, associated factors and early neonatal outcome

International Nuclear Information System (INIS)

Thomas, Erica; Manji, Karim; Mpembeni Rose

2005-01-01

Failure to thrive or growth failure is an important feature of problems prevalent in the neonate. It remains one of the greatest challenges for the practicing pediatrician and it is a common pathway or outcome of several different underlaying infant and maternal conditions. To determine the prevalence, possible causes and early neonatal outcome of failure to thrive among young infants admitted to the Neonatal Unit in this hospital. A cross-sectional descriptive hospital based study, was carried for 10 months from April 2001 to January 2002 at the Neonatal Unit at Muhimbili National Hospital. (author)

Role of maternally derived immunity in fish.

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Swain, P; Nayak, S K

2009-08-01

Maternal immunity is of paramount importance for protection of young ones at early stage of life since the immune factors of an immunocompetent female are transferred transplacentally or through colostrum, milk or yolk to an immunologically naive neonate. Both innate and adaptive type of immunity are transferred of from mother to offspring in fishes. These factors include immunoglobulin (Ig)/antibody, complement factors, lysozymes, protease inhibitors like alpha macroglobulin, different types of lectins and serine proteases like molecules. Among different types of Ig viz. IgM, IgD, IgT/IgZ and IgM-IgZ chimera types, IgM is present in most of the teleostean fishes. In teleosts, IgM either as a reduced/breakdown product or monomeric form is usually transferred to the offsprings. The maternally derived IgM usually persists for a limited duration, exhausts within the completion of yolk absorption process, and completely disappears thereafter during larval stages. Maternal transfer of immunity which provides defense to embryo and larvae depends upon the health as well as the immune status of brood fish. The overall health status of brood fish can affect breeding performances, quality seed production and protection of offsprings. However, factors such as age, maturation, reproductive behaviour and nutrition (micro and macro-nutrients) may affect the immunity in brood fishes. Besides these, seasonal changes such as photoperiods, temperature, adverse environmental conditions, and stress conditions like handling, crowding, and water pollution/contamination can also affect the immunity of brood fishes. The maintenance of the brood stock immunity at high level during vitellogenesis and oogenesis, is utmost important for reducing mortalities at larval/post larval stages through maximum/optimum transfer of maternal immunity. Brood stock immunization prior to breeding as well as selective breeding among the disease resistant families might be the ideal criteria for producing

Risk Factors for Neonatal Mortality Among Very Low Birth Weight Neonates

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Fatemeh Nayeri

2013-05-01

Full Text Available The objective of this study is to determine risk factors causing increase in very low birth way (VLBW neonatal mortality. The medical files of all neonates weighing ≤1500 g, born in Vali-e-Asr hospital (2001-2004 were studied. Two groups of neonates (living and dead were compared up to the time of hospital discharge or death. A total of 317 neonates were enrolled. A meaningful relationship existed between occurrence of death and low gestational age (P=0.02, low birth weight, lower than 1000 g (P=0.001, Apgar score <6 at 5th minutes (P=0.001, resuscitation at birth (P=0.001, respiratory distress syndrome (P=0.001 need for mechanical ventilation (P=0.001, neurological complications (P=0.001 and intraventricular hemorrhage (P=0.001. Regression analysis indicated that each 250 g weight increase up to 1250 g had protective effect, and reduced mortality rate. The causes of death of those neonates weighting over 1250 g should be sought in factors other than weight. Survival rate was calculated to be 80.4% for neonates weighing more than 1000 g. The most important high risk factors affecting mortality of neonates are: low birth weight, need for resuscitation at birth, need for ventilator use and intraventricular hemorrhage.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

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Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-01-01

ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental Ig

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

Science.gov (United States)

Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-05-04

Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or

Protective effect of enterovirus‑71 (EV71) virus‑like particle vaccine against lethal EV71 infection in a neonatal mouse model.

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Cao, Lei; Mao, Fengfeng; Pang, Zheng; Yi, Yao; Qiu, Feng; Tian, Ruiguang; Meng, Qingling; Jia, Zhiyuan; Bi, Shengli

2015-08-01

Enterovirus-71 (EV71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (HFMD) among young children, with significant mortality. Effective vaccines against HFMD are urgently required. Several EV71 virus-like particle (VLP) vaccine candidates were found to be protective in the neonatal mouse EV71 challenge model. However, to what extent the VLP vaccine protects susceptible organs against EV71 infection in vivo has remained elusive. In the present study, the comprehensive immunogenicity of a potential EV71 vaccine candidate based on VLPs was evaluated in a neonatal mouse model. Despite lower levels of neutralizing antibodies to EV71 in the sera of VLP-immunized mice compared with those in mice vaccinated with inactivated EV71, the VLP-based vaccine was shown to be able to induce immunoglobulin (Ig)G and IgA memory-associated cellular immune responses to EV71. Of note, the EV71 VLP vaccine candidate was capable of inhibiting viral proliferation in cardiac muscle, skeletal muscle, lung and intestine of immunized mice and provided effective protection against the pathological damage caused by viral attack. In particular, the VLP vaccine was able to inhibit the transportation of EV71 from the central nervous system to the muscle tissue and greatly protected muscle tissue from infection, along with recovery from the viral infection. This led to nearly 100% immunoprotective efficacy, enabling neonatal mice delivered by VLP-immunized female adult mice to survive and grow with good health. The present study provided valuable additional knowledge of the specific protective efficacy of the EV71 VLP vaccine in vivo, which also indicated that it is a promising potential candidate for being developed into an EV71 vaccine.

Age-related differences in plasma proteins: how plasma proteins change from neonates to adults.

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Vera Ignjatovic

Full Text Available The incidence of major diseases such as cardiovascular disease, thrombosis and cancer increases with age and is the major cause of mortality world-wide, with neonates and children somehow protected from such diseases of ageing. We hypothesized that there are major developmental differences in plasma proteins and that these contribute to age-related changes in the incidence of major diseases. We evaluated the human plasma proteome in healthy neonates, children and adults using the 2D-DIGE approach. We demonstrate significant changes in number and abundance of up to 100 protein spots that have marked differences in during the transition of the plasma proteome from neonate and child through to adult. These proteins are known to be involved in numerous physiological processes such as iron transport and homeostasis, immune response, haemostasis and apoptosis, amongst others. Importantly, we determined that the proteins that are differentially expressed with age are not the same proteins that are differentially expressed with gender and that the degree of phosphorylation of plasma proteins also changes with age. Given the multi-functionality of these proteins in human physiology, understanding the differences in the plasma proteome in neonates and children compared to adults will make a major contribution to our understanding of developmental biology in humans.

Guidance on management of asymptomatic neonates born to women with active genital herpes lesions.

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Kimberlin, David W; Baley, Jill

2013-02-01

Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.

Effect of oral administration of Lactobacillus paracasei L9 on mouse systemic immunity and the immune response in the intestine

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Zhu Yuanbo

2016-01-01

Full Text Available A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-γ/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.

Transient hepatic attenuation differences in neonates

International Nuclear Information System (INIS)

Towbin, Alexander J.; Fleck, Robert; Ying, Jun

2009-01-01

A transient hepatic attenuation difference (THAD) is a hepatic perfusion anomaly seen on contrast-enhanced CT scans caused by an alteration in the dual blood supply of the liver. Although THADs have been described in adolescents and adults, they have not previously been described in neonates. We describe the appearance and evaluate the frequency of THADs in neonates ≤1 month of age compared to other infants younger than 2 years. A retrospective study was performed looking at all CT angiograms from 2000 to 2007 in infants <2 years of age. The incidence of THADs was compared among four age groups. Significance was determined using a logistic regression model. The study included 128 CT angiograms. A THAD was seen in 9/26 infants <1 month of age, in 3/50 infants 1 to 6 months of age, in 1/23 infants 6 months to 1 year of age, and in 1/29 infants 1 to 2 years of age. A THAD was found significantly more frequently in infants <1 month of age than in the older age groups (P<0.05). THADs are benign entities that can be seen normally in the neonatal age group. When the characteristic appearance is seen on CT, no further imaging is needed. (orig.)

Hiperbilirrubinemia neonatal agravada Aggravated neonatal hyperbilirubinemia

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Ana Campo González

2010-09-01

Full Text Available INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al Departamento de Neonatología con diagnóstico de hiperbilirrubinemia agravada. RESULTADOS. La incidencia de hiperbilirrubinemia neonatal agravada fue del 3,67 % y predominó en hermanos con antecedentes de ictericia (56,65 %. El tiempo de aparición fue de 48 a 72 h (76,87 % y entre los factores agravantes se hallaron el nacimiento pretérmino y el bajo peso al nacer. La mayoría de los pacientes fueron tratados con luminoterapia (90,17 %. CONCLUSIÓN. La hiperbilirrubinemia neonatal agravada constituye un problema de salud. Los factores agravantes son la prematuridad y el bajo peso al nacer. La luminoterapia es una medida terapéutica eficaz para su tratamiento.INTRODUCTION. Most of times jaundice in newborn is a physiological fact due to hyperbilirubinemia of indirect predominance, secondary to liver immaturity and to bilirubin hyperproduction. The aim of present of present study was to determine the behavior of neonatal hyperbilirubinemia in the Gynecology and Obstetrics Teaching Hospital of Guanabacoa municipality from 2007 to 2009. METHODS. A retrospective and descriptive study was conducted in 173 newborn patients admitted in the Neonatology Department diagnosed with severe hyperbilirubinemia. RESULTS. The incidence of severe neonatal hyperbilirubinemia was of 3,67% with predominance in brothers with a history of jaundice (56,65%. The time of appearance was of 48 to 72 hrs (76,87% and among the aggravating factors were the preterm birth and

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.

Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity

Directory of Open Access Journals (Sweden)

Mari Hirvinen

2016-01-01

Full Text Available In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI to boost the innate immune system and to activate adaptive immune cells in the tumor. We showed that infection with DAI-expressing VV increases expression of several genes related to important immunological pathways. Treatment with DAI-armed VV resulted in significant reduction in the size of syngeneic melanoma tumors in mice. When the mice were rechallenged with the same tumor, DAI-VV-treated mice completely rejected growth of the new tumor, which indicates immunity established against the tumor. We also showed enhanced control of growth of human melanoma tumors and elevated levels of human T-cells in DAI-VV-treated mice humanized with human peripheral blood mononuclear cells. We conclude that expression of DAI by an oncolytic VV is a promising way to amplify the vaccine potency of an oncolytic vaccinia virus to trigger the innate—and eventually the long-lasting adaptive immunity against cancer.

Effects of in ovo exposure to PCBs (coplanar congener, kanechlor mixture, hydroxylated metabolite) on the developing cell-mediated immunity in chickens

Energy Technology Data Exchange (ETDEWEB)

Hasegawa, J.; Matsuda, M.; Kawano, M.; Wakimoto, T. [Faculty of Agriculture, Ehime Univ., Matsuyama, Ehime (Japan); Kashima, Y. [Dept. of Hygiene, Yokohama City Univ. School of Medicine, Yokohama (Japan)

2004-09-15

Polychlorinated biphenyls (PCBs) are wide spread environmental contaminants and known to cause various adverse effects on health of human and wildlife. Immune system is one of the several targets for toxic effects of PCBs and its normal balance is often disrupted by the exposure of the compounds. For example, PCBs may induce immune suppression and result in increased susceptibility to bacterial and viral infections, or conversely, excessive immune enhancement may cause adverse outcomes including as autoimmune disease and anergy. Therefore immune function is regarded as one of an important endpoint in toxicological risk assessment. There are a number of studies shown that neonatal organisms perinatally exposed to polyhalogenated aromatic hydrocarbons (PHAHs) such as PCBs have severer effects on their immune system than adult. Dioxins and coplanar PCB congeners, structurally planar PHAHs are known to have high affinity for aryl hydrocarbon receptor (AhR). 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) have the strongest affinity among such compounds and these are considered to act on immune system through AhR. On the other hand, such as non-planar PCB congeners with low affinity for AhR, which are abundantly contained in commercial PCB preparations have non-additive (antagonistic) effects on immune function. Prenatal exposure of TCDD to rodent induced abnormal lymphoid development in the thymus and thymus-dependent immune functions were remarkably disturbed. Although several experimental studies in mammals have been carried out on the developmental immunotoxicity of PCBs, there are still limited information available on avian species. Thus in this study, prenatal exposure to low level of PCBs and the effects on the developing immune system were investigated with chicken as a model animal of avian species, especially it is focused on the cell-mediated immune function.

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

Science.gov (United States)

Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

2013-01-01

We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

Early immune response patterns to pathogenic bacteria are associated to increased risk of lower respiratory infections in children

DEFF Research Database (Denmark)

Vissing, N. H.; Larsen, Jeppe Madura; Rasmussen, Mette Annelie

2014-01-01

Neonatal colonisation of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood (1). Therefore, we hypothesized that children developing LRI have an abnormal immune response to pathogenic bacteria in infancy. We aimed...... to characterise the systemic immune response to pathogenic bacteria at the age of 6 months and study the association with incidence of LRI during the first 3 years of life....

Colostrum and milk protein rankings and ratios of importance to neonatal calf health using a proteomics approach

DEFF Research Database (Denmark)

Nissen, Asger; Andersen, Pia Haubro; Bendixen, Emøke

2017-01-01

Administration of colostrum to the newborn calf before gut closure is pivotal to its health, because of the transfer of passive immunity. Traditionally, passive immunity has been attributed to the transfer of immunoglobulins although it is increasingly clear that multiple other factors contribute......, including innate immune proteins, developmental factors, immunomodulatory factors, and the presence of cellular immunity. The objective of this study was to produce a comprehensive comparison of the bovine colostrum proteome and the milk proteome by applying 2-dimensional liquid chromatography-tandem mass...... spectrometry. Further, the objectives were to rank proteins mutually and generate protein ratios from the spectral counts of the 2 proteomes and ELISA to gain insight into which proteins could be of most relevance to neonatal calf health. To obtain an in-depth picture of the bovine colostrum and milk proteome...

Pathogen-induced maternal effects result in enhanced immune responsiveness across generations.

Science.gov (United States)

Rosengaus, Rebeca B; Hays, Nicole; Biro, Colette; Kemos, James; Zaman, Muizz; Murray, Joseph; Gezahegn, Bruck; Smith, Wendy

2017-05-01

Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo "clearance of infection" assay, we also show that challenged larvae born to heat-killed- or live- Serratia -injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life-history theories and highlights the significant role that pathogen-induced maternal effects play as generators and modulators of evolutionary change.

Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles.

Science.gov (United States)

Mui, B; Raney, S G; Semple, S C; Hope, M J

2001-09-01

The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN) containing immune stimulatory sequences (ISS) has been demonstrated in animal models of cancer and infection. In particular, when CpG-containing PS ODN are administered to mice, activation of macrophages and dendritic, NK, T, and B cells occurs, resulting in the release of an array of cytokines, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We have previously described stabilized antisense-lipid particles (SALP) for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001) 1510:152--166]. Given the propensity for SALP to target macrophages in vivo it was of interest to determine whether they could enhance the potency of CpG ODN to induce an immune response. In this report we show that when CpG-containing SALP are administered intravenously to ICR mice the plasma concentrations of IL-12, IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly increased compared with the same dose of free ODN. The pattern of cytokine induction indicates that the immune response is T helper cell type 1-biased, similar to that observed for PS CpG ODN ISS in general. Furthermore, when phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation cytokine induction is even greater at the early time points, in marked contrast to free PO ODN, which is inactive. These results demonstrate that the immunogenicity of ISS is not only enhanced by encapsulation in lipid particles, which more closely mimic the way ISS DNA would normally be presented to antigen presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN to be used as immune stimulants.

Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

Science.gov (United States)

Ebner, Nina; Rohrmeister, Klaudia; Winklbaur, Bernadette; Baewert, Andjela; Jagsch, Reinhold; Peternell, Alexandra; Thau, Kenneth; Fischer, Gabriele

2007-03-16

Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

Dextran sodium sulfate (DSS induces necrotizing enterocolitis-like lesions in neonatal mice.

Directory of Open Access Journals (Sweden)

Marco Ginzel

Full Text Available Necrotizing enterocolitis (NEC is an inflammatory bowel disease of preterm human newborns with yet unresolved etiology. An established neonatal murine model for NEC employs oral administration of lipopolysaccharides (LPS combined with hypoxia/hypothermia. In adult mice, feeding dextran sodium sulfate (DSS represents a well-established model for experimental inflammatory bowel disease. Here we investigated the effect of DSS administration on the neonatal murine intestine in comparison with the established NEC model.3-day-old C57BL/6J mice were either fed formula containing DSS or LPS. LPS treated animals were additionally stressed by hypoxia/hypothermia twice daily. After 72 h, mice were euthanized, their intestinal tissue harvested and analyzed by histology, qRT-PCR and flow cytometry. For comparison, adult C57BL/6J mice were fed with DSS for 8 days and examined likewise. Untreated, age matched animals served as controls.Adult mice treated with DSS exhibited colonic inflammation with significantly increased Cxcl2 mRNA expression. In contrast, tissue inflammation in neonatal mice treated with DSS or LPS plus hypoxia/hypothermia was present in colon and small intestine as well. Comparative analysis of neonatal mice revealed a significantly increased lesion size and intestinal Cxcl2 mRNA expression after DSS exposure. Whereas LPS administration mainly induced local neutrophil recruitment, DSS treated animals displayed increased monocytes/macrophages infiltration.Our study demonstrates the potential of DSS to induce NEC-like lesions accompanied by a significant humoral and cellular immune response in the small and large intestine of neonatal mice. The new model therefore represents a good alternative to LPS plus hypoxia/hypothermia administration requiring no additional physical stress.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

2014-01-01

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang

2014-06-11

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The impact of prenatal care quality on neonatal, infant and child mortality in Zimbabwe: evidence from the demographic and health surveys.

Science.gov (United States)

Makate, Marshall; Makate, Clifton

2017-04-01

The impact of the quality of prenatal care on child mortality outcomes has received less attention in sub-Saharan Africa. This study endeavoured to explore the effect of the quality of prenatal care and its individual components on neonatal, infant and under-five mortality. The empirical analysis uses data from the three most recent waves of the nationally representative Demographic and Health Survey for Zimbabwe conducted in 1999, 2005/06 and 2010/11. The results indicate that a one-unit increase in the quality of prenatal care lowers the prospect of neonatal, infant and under-five mortality by approximately 42.33, 30.86 and 28.65%, respectively. These findings remained roughly the same even after adjusting for potential mediating factors. Examining the effect of individual prenatal care components on child mortality revealed that women who receive information on possible complications arising during pregnancy are less liable to experience a neonatal death. Similarly, women who had blood pressure checks and tetanus immunizations were less likely to experience an infant or under-five death. We did not find any statistically meaningful impact on child mortality outcomes of blood and urine sample checks, iron tablet consumption, and the receipt of malarial tablets. Overall, our results suggest the need for public health policymakers to focus on ensuring high-quality prenatal care to enhance the survival prospects of Zimbabwe's infants. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neonatal pain

Science.gov (United States)

Walker, Suellen M

2014-01-01

Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

International Nuclear Information System (INIS)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

2011-01-01

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

Energy Technology Data Exchange (ETDEWEB)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2011-11-11

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

Science.gov (United States)

Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

2014-07-01

Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

Tuberculosis neonatal

OpenAIRE

Pastor Durán, Xavier

1986-01-01

PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..

Outgrowing the Immaturity Myth: The Cost of Defending From Neonatal Infectious Disease

Directory of Open Access Journals (Sweden)

Danny Harbeson

2018-05-01

Full Text Available Newborns suffer high rates of mortality due to infectious disease—this has been generally regarded to be the result of an “immature” immune system with a diminished disease-fighting capacity. However, the immaturity dogma fails to explain (i greater pro-inflammatory responses than adults in vivo and (ii the ability of neonates to survive a significantly higher blood pathogen burden than of adults. To reconcile the apparent contradiction of clinical susceptibility to disease and the host immune response findings when contrasting newborn to adult, it will be essential to capture the entirety of available host-defense strategies at the newborn’s disposal. Adults focus heavily on the disease resistance approach: pathogen reduction and elimination. Newborn hyperactive innate immunity, sensitivity to immunopathology, and the energetic requirements of growth and development (immune and energy costs, however, preclude them from having an adult-like resistance response. Instead, newborns also may avail themselves of disease tolerance (minimizing immunopathology without reducing pathogen load, as a disease tolerance approach provides a counterbalance to the dangers of a heightened innate immunity and has lower-associated immune costs. Further, disease tolerance allows for the establishment of a commensal bacterial community without mounting an unnecessarily dangerous immune resistance response. Since disease tolerance has its own associated costs (immune suppression leading to unchecked pathogen proliferation, it is the maintenance of homeostasis between disease tolerance and disease resistance that is critical to safe and effective defense against infections in early life. This paradigm is consistent with nearly all of the existing evidence.

Maternal immunization increases nestling energy expenditure, immune function, and fledging success in a passerine bird

Directory of Open Access Journals (Sweden)

Gary Burness

2018-04-01

Full Text Available Female birds transfer maternally derived antibodies (matAb to their nestlings, via the egg yolk. These antibodies are thought to provide passive protection, and allow nestlings to avoid the costs associated with mounting an innate immune response. To test whether there is an energetic benefit to nestlings from receiving matAb, we challenged adult female tree swallows (Tachycineta bicolor prior to clutch initiation with either lipopolysaccharide (LPS or saline (Control. Following hatching, one half of each female's nestlings were immunized on day 8 post-hatch with LPS or saline, and the 4-h post-immunization nestling metabolic rate (MR was measured. There was no difference in either LPS-reactive antibodies or total Ig levels between offspring of immunized and non-immunized mothers on day 6 or 14 post-hatch, possibly reflecting a relatively short half-life of matAbs in altricial birds. Additionally, we found no evidence that nestlings from LPS-immunized mothers could avoid the growth suppression that may result from activation of an inflammatory response. Unexpectedly, we found that control nestlings from LPS mothers had higher resting MR than control nestlings of control mothers. We attribute the increased MR to the costs associated with a general non-specific enhancement of immune function in nestlings from LPS-immunized mothers. Consistent with enhanced immune function, nestlings of immunized mothers had a more robust inflammatory response to phytohaemagglutinin and higher fledging success. Our results suggest that maternal antigen exposure pre-laying can result in increased fitness for both mothers and offspring, depending on food availability.

N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: An immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice.

Science.gov (United States)

Tao, Wei; Zheng, Hai-Qun; Fu, Ting; He, Zhuo-Jing; Hong, Yan

2017-08-03

Adjuvants are essential for enhancing vaccine potency by improving the humoral and/or cell-mediated immune response to vaccine antigens. This study was performed to evaluate the immuno-enhancing characteristic of N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, as an adjuvant for hepatitis E virus (HEV) recombinant polypeptide vaccine. Animal experiments showed that HTCC provides adjuvant activity when co-administered with HEV recombinant polypeptide vaccine by intramuscularly route. Vaccination using HTCC as an adjuvant was associated with increases of the serum HEV-specific IgG antibodies, splenocytes proliferation and the growths of CD4 + CD8 - T lymphocytes and IFN-γ-secreting T lymphocytes in peripheral blood. These findings suggested that HTCC had strong immuno-enhancing effect. Our findings are the first to demonstrate that HTCC is safe and effective in inducing a good antibody response and stimulating Th1-biased immune responses for HEV recombinant polypeptide vaccine.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

Science.gov (United States)

Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Neonatal CD8+ T-cell differentiation is dependent on interleukin-12.

LENUS (Irish Health Repository)

McCarron, Mark J

2012-02-01

Neonatal CD8(+) T-cell activation is significantly impaired compared with that in adults. Recent studies have demonstrated that interleukin (IL)-12 is necessary as a third signal, in addition to antigen and co-stimulation, to authorize the differentiation of naive CD8(+) T cells. We examined whether human neonatal CD8(+) T cells, which possess an exclusively naive T-cell phenotype, required a third signal to authorize a productive T-cell response. IL-12 enhanced activated naive CD8(+) T-cell survival, expansion, CD25 expression, and IL-2 production. Activated CD8(+) T cells produced interferon-gamma and intracellular granzyme B and were cytotoxic only in the presence of IL-12. Sustained IL-12 signaling for 72 hours was required for optimal interferon-gamma production. IL-12, in concert with T cell receptor (TCR) stimulation, sustained late-stage (48-72 hours) intracellular phosphorylation and particularly total protein levels of the proximal TCR components, Lck, and CD3xi. The requirement for a third signal for productive human neonatal CD8(+) T-cell differentiation may have implications for neonatal vaccination strategies.

Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects.

Science.gov (United States)

Moro-García, Marco Antonio; Alonso-Arias, Rebeca; Baltadjieva, Maria; Fernández Benítez, Carlos; Fernández Barrial, Manuel Amadeo; Díaz Ruisánchez, Enrique; Alonso Santos, Ricardo; Alvarez Sánchez, Magdalena; Saavedra Miján, Juan; López-Larrea, Carlos

2013-08-01

Throughout life, there is an aging of the immune system that causes impairment of its defense capability. Prevention or delay of this deterioration is considered crucial to maintain general health and increase longevity. We evaluated whether dietary supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 could enhance the immune response in the elderly. This multi-center, double-blind, and placebo controlled study enrolled 61 elderly volunteers who were randomly assigned to receive either placebo or probiotics. Each capsule of probiotics contained at least 3 × 10(7)  L. delbrueckii subsp. bulgaricus 8481. Individuals in the study were administered three capsules per day for 6 months. Blood samples were obtained at baseline (time 0), end of month 3, and month 6. We characterized cell subpopulations, measured cytokines by flow cytometry, quantified T cell receptor excision circle (TREC) by real-time PCR (RT-PCR), and determined human β-defensin-2 (hBD-2) concentrations and human cytomegalovirus (CMV) titers by enzyme-linked immunosorbent assay (ELISA). Elderly responded to the intake of probiotic with an increase in the percentage of NK cells, an improvement in the parameters defining the immune risk profile (IRP), and an increase in the T cell subsets that are less differentiated. The probiotic group also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but increased antimicrobial peptide hBD-2. These effects disappeared within 6 months of stopping the probiotic intake. Immunomodulation induced by L. delbrueckii subsp. bulgaricus 8481 could favor the maintenance of an adequate immune response, mainly by slowing the aging of the T cell subpopulations and increasing the number of immature T cells which are potential responders to new antigens.

The isolator piglet: a model for studying the development of adaptive immunity

Czech Academy of Sciences Publication Activity Database

Butler, J. E.; Šinkora, Marek

2007-01-01

Roč. 39, 1-3 (2007), s. 33-51 ISSN 0257-277X R&D Projects: GA ČR GA524/07/0087; GA ČR GA523/07/0088; GA AV ČR IAA5020303 Institutional research plan: CEZ:AV0Z50200510 Keywords : neonatal development * colonization * immune homeostasis Subject RIV: EE - Microbiology, Virology Impact factor: 2.364, year: 2007

Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.

Science.gov (United States)

Greenstein, Robert J; Su, Liya; Shahidi, Azra; Brown, William D; Clifford, Anya; Brown, Sheldon T

2014-09-01

The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents. Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D. All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP. We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

Energy Technology Data Exchange (ETDEWEB)

Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T

2003-07-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)

Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

International Nuclear Information System (INIS)

Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T.

2003-01-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)

INVISIBLE MURDERER: NEONATAL TETANUS

Directory of Open Access Journals (Sweden)

Yonca SONMEZ

2006-06-01

Full Text Available Neonatal tetanus (NNT has been secondary in the whole world in the death list of diseases which can be protected by the help of vaccine. It’s an important community health problem in the less-developed countries in which pre-birth care services are limited, assisting a mother at childbirth by uneducated people in dirty atmosphere and the immunity against tetanus is not enough. Studies have shown that minor part of the cases have been expressed in most of the countries. Because of that NNT have been called as “silent/invisible murderer”. In Turkey, in the year of 2003 it has been seen 15 cases, and 12 of them have been resulted in death. The methods which will be applied to carry out the elimination of NNT are; the vaccination of pregnant women with at least two doses tetanus toxoid and providing clean birth conditions for all of the pregnant women. However, in Turkey the proportion of the women who have two doses of tetanus vaccine is 41%. To eliminate NNT in our country, all the pregnant women must be attained, the ones who are attained must be presented with qualified pre-birth care service which also includes tetanus immunity and the births must be carried out under healty conditions. As smallpox and polio eradication, NNT elimination will also be accomplished by self-sacrificing works of personnel in primary health care. [TAF Prev Med Bull 2006; 5(3.000: 229-233

Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

Science.gov (United States)

Kaleeswaran, B; Ilavenil, S; Ravikumar, S

2011-12-01

Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the experimental diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

Energy Technology Data Exchange (ETDEWEB)

Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

2011-08-05

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

International Nuclear Information System (INIS)

Weir, Genevieve M.; Liwski, Robert S.; Mansour, Marc

2011-01-01

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments

Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.

Science.gov (United States)

Tršan, Tihana; Vuković, Kristina; Filipović, Petra; Brizić, Ana Lesac; Lemmermann, Niels A W; Schober, Kilian; Busch, Dirk H; Britt, William J; Messerle, Martin; Krmpotić, Astrid; Jonjić, Stipan

2017-08-01

Designing CD8 + T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 + T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1 + CD8 + T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 + T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 + T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 + T-cell sensitive tumors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maternal and neonatal tetanus elimination: from protecting women and newborns to protecting all

Directory of Open Access Journals (Sweden)

Khan R

2015-02-01

Full Text Available Rownak Khan,1 Jos Vandelaer,1 Ahmadu Yakubu,2 Azhar Abid Raza,1 Flint Zulu1 1Health Section, Programme Division, UNICEF, New York, NY, USA; 2Family, Women and Children’s Health Cluster, World Health Organization, Geneva, Switzerland Abstract: A total of 35 of the 59 countries that had not eliminated maternal and neonatal tetanus (MNT as a public health problem in 1999 have since achieved the MNT-elimination goal. Neonatal tetanus deaths have decreased globally from 200,000 in 2000 to 49,000 in 2013. This is the result of increased immunization coverage with tetanus toxoid-containing vaccines among pregnant women, improved access to skilled birth attendance during delivery, and targeted campaigns with these vaccines for women of reproductive age in high-risk areas. In the process, inequities have been reduced, private–public partnerships fostered, and innovations triggered. However, lack of funding, poor accessibility to some areas, suboptimal surveillance, and a perceived low priority for the disease are among the main obstacles. To ensure MNT elimination is sustained, countries must build and maintain strong routine programs that reach people with vaccination and with clean deliveries. This should also be an opportunity to shift programs into preventing tetanus among all people. Regular assessments, and where needed appropriate action, are key to prevent increases in MNT incidence over time, especially in areas that are at higher risk. The main objective of the paper is to provide a detailed update on the progress toward MNT elimination between 1999 and 2014. It elaborates on the challenges and opportunities, and discusses how MNT elimination can be sustained and to shift the program to protect wider populations against tetanus. Keywords: maternal, neonatal, tetanus, elimination, high risk, immunization, vaccination, clean delivery

The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome.

Science.gov (United States)

Emami, Tara; Rezayat, Seyed Mahdi; Khamesipour, Ali; Madani, Rasool; Habibi, Gholamreza; Hojatizade, Mansure; Jaafari, Mahmoud Reza

2018-04-01

Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative. BALB/c mice were immunized by liposomal formulations of lip/SLA, lip/MPL/SLA, lip/IMQ/SLA, lip/MPL/IMQ/SLA, lip/SLA + lip/IMQ, lip/SLA + lip/MPL, lip/SLA + lip/MPL/IMQ and five controls of SLA, lip/MPL, lip/IMQ, lip/MPL/IMQ and buffer by subcutaneously (SC) injections, three times in 2 weeks intervals. The synergic effect of two adjuvants when they are used in one formulation showed significantly (p MPL and IMQ adjuvants and antigen in nanoliposome carrier could be an appropriate delivery system to induce cellular immunity pathway against leishmaniasis.

Neonatal neurosonography

Energy Technology Data Exchange (ETDEWEB)

Riccabona, Michael, E-mail: michael.riccabona@klinikum-graz.at

2014-09-15

Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance – either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.

Clinical case of using discrete plasmapheresis in infant with early neonatal sepsis and hemolytic disease

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S. V. Aborin

2017-01-01

Full Text Available Currently in the literature there are insufficient data on the use of efferent hemocorrection methods in neonatal practice. The basic principle of this method is the removal of plasma containing endotoxins and exotoxins and other pathological substances, replacing it with donor plasma, colloid and crystalloid solutions. The therapeutic effect of plasmapheresis includes detoxification, anti-inflammatory and immunomodulatory effects by removing toxins and removal of circulating immune complexes, inflammatory mediators, and activated structures of the complement system. Discrete plasmapheresis in neonatal practice may be used in any body mass of the patient. This article describes a clinical case of successful application of discrete plasmapheresis in full-term newborn baby is in critical condition. The severity was due to severe early neonatal sepsis, development of multiple organ failure and accompanying RH-conflict. After two sessions of plasmapheresis was observed a positive clinical effect in reducing intoxication, systemic inflammatory response syndrome. Reducing the level of bilirubin is allowed to avoid the operation replacement blood transfusion.

Socioeconomic factors and adolescent pregnancy outcomes: distinctions between neonatal and post-neonatal deaths?

Directory of Open Access Journals (Sweden)

Flick Louise H

2005-07-01

Full Text Available Abstract Background Young maternal age has long been associated with higher infant mortality rates, but the role of socioeconomic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post-neonatal deaths, socioeconomic status and maternal age in a large, retrospective cohort study. Methods We conducted a population-based cohort study using linked birth-death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10,131; 18–19 years, n = 18,954 were compared to those for older women (20–35 years, n = 28,899. Logistic regression was used to estimate adjusted odds ratios (OR and 95% confidence intervals (CI for all potential associations. Results The risk of infant (OR 1.95, CI 1.54–2.48, neonatal (1.69, 1.24–2.31 and post-neonatal mortality (2.47, 1.70–3.59 were significantly higher for younger adolescent (12–17 years than older (20–34 years mothers. After adjusting for race, marital status, age-appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid, the risk of post-neonatal mortality (1.73, 1.14–2.64 but not neonatal mortality (1.43, 0.98–2.08 remained significant for younger adolescent mothers. There were no differences in neonatal or post-neonatal mortality risks for older adolescent (18–19 years mothers. Conclusion Socioeconomic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post-neonatal mortality risk.

Neonatal adrenal hemorrhage presenting as late onset neonatal jaundice

OpenAIRE

Qureshi, Umar Amin; Ahmad, Nisar; Rasool, Akhter; Choh, Suhail

2009-01-01

Clinical manifestations of adrenal hemorrhage vary depending on the degree and rate of hemorrhage, as well as the amount of adrenal cortex compromised by hemorrhage. We report here a case of neonatal adrenal hemorrhage that presented with late onset neonatal jaundice. The cause of adrenal hemorrhage was birth asphyxia.

Recombinant Secreted Antigens from Mycoplasma hyopneumoniae Delivered as a Cocktail Vaccine Enhance the Immune Response of Mice

Science.gov (United States)

Galli, Vanessa; Simionatto, Simone; Marchioro, Silvana Beutinger; Klabunde, Gustavo Henrique Ferrero; Conceição, Fabricio Rochedo

2013-01-01

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (EP), which is a respiratory disease responsible for huge economic losses in the pig industry worldwide. The commercially available vaccines provide only partial protection and are expensive. Thus, the development of alternatives for the prophylaxis of EP is critical for improving pig health. The use of multiple antigens in the same immunization may represent a promising alternative. In the present study, seven secreted proteins of M. hyopneumoniae were cloned, expressed in Escherichia coli, and evaluated for antigenicity using serum from naturally and experimentally infected pigs. In addition, the immunogenicity of the seven recombinant proteins delivered individually or in protein cocktail vaccines was evaluated in mice. In Western blot assays and enzyme-linked immunosorbent assays, most of the recombinant proteins evaluated were recognized by convalescent-phase serum from the animals, indicating that they are expressed during the infectious process. The recombinant proteins were also immunogenic, and most induced a mixed IgG1/IgG2a humoral immune response. The use of these proteins in a cocktail vaccine formulation enhanced the immune response compared to their use as antigens delivered individually, providing evidence of the efficacy of the multiple-antigen administration strategy for the induction of an immune response against M. hyopneumoniae. PMID:23803903

Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

International Nuclear Information System (INIS)

Besser, T.E.

1986-01-01

High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G 1 (IgG 1 ) is transferred to the gastrointestinal tract, 125 I-labelled bovine IgG 1 anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of 125 I-IgG 1 from the blood was measured and compared to the rate of 125 I-IgG 1 appearance in the gastrointestinal tract, as measured (1) by the rate of fecal 125 I-IgG 1 excretion, and (2) by the amount of 125 I-IgG 1 in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity

Bacillus Coagulans Enhance the Immune Function of the Intestinal Mucosa of Yellow Broilers

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L Xu

Full Text Available ABSTRACT This experiment was conducted to investigate the effects of Bacillus coagulans on the growth performance and immune functions of the intestinal mucosa of yellow broilers. Three hundred and sixty one-day-old yellow chicks were randomly allocated to four treatments groups with six replicates of 15 chicks each. The broilers were randomly subjected to one of the following treatments for 28 days: control group (group1, fed a basal diet and three treatments (group 2, 3, 4 fed the basal diet supplemented with 100, 200, or 300 mg/kg Bacillus coagulans , respectively. The results showed that for 28 days, compared with the control diet, the dietary addition of 200 mg/kg Bacillus coagulans significantly decreased the feed/gain ratio (F/G (p<0.05, improved the thymus index, spleen index and bursa index (p<0.05, increased the villus height to crypt depth ratio (V/C in the duodenum (p<0.05, increased the number of secretory immunoglobulin (sIgA positive cells ( p<0.05. The dietary addition of 200 mg/kg Bacillus coagulans promoted a significant increase in Lactobacillus spp. populations and suppressed Escherichia coli replication in cecum, compared with the control (p<0.05. Moreover, the dietary addition of 200 mg/kg Bacillus coagulans also significantly enhanced the levels of interferon alpha (IFNα, toll-like receptor (TLR3, and melanoma differentiation-associated protein 5(MDA5 in the duodenum (p<0.05. In conclusion, the dietary addition of Bacillus coagulans significantly improved broiler performance, and enhanced the intestinal mucosal barrier and immune function. The optimal dosage of Bacillus coagulans for yellow broilers was determined as 2×108 cfu/kg.

Enhancing crop innate immunity: new promising trends

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Pin-Yao eHuang

2014-11-01

Full Text Available Plants are constantly exposed to potentially pathogenic microbes present in their surrounding environment. Due to the activation of the pattern-triggered immunity (PTI response that largely relies on accurate detection of pathogen- or microbe-associated molecular patterns by pattern-recognition receptors (PRRs, plants are resistant to the majority of potential pathogens. However, adapted pathogens may avoid recognition or repress plant PTI and resulting diseases significantly affect crop yield worldwide. PTI provides protection against a wide range of pathogens. Reinforcement of PTI through genetic engineering may thus generate crops with broad-spectrum field resistance. In this review, new approaches based on fundamental discoveries in PTI to improve crop immunity are discussed. Notably, we highlight recent studies describing the interfamily transfer of PRRs or key regulators of PTI signalling.

Monolateral suppurative parotitis in a neonate and review of literature.

Science.gov (United States)

Decembrino, Lidia; Ruffinazzi, Giulia; Russo, Fabio; Manzoni, Paolo; Stronati, Mauro

2012-07-01

Neonatal suppurative parotitis is a rare condition characterized by swelling, pain, and erythema over the affected gland. Antimicrobials and adequate hydration are an essential part of treatment. Surgical intervention is reserved for organized abscesses and for infections not responding to medical management. A case report and review of the literature. Only few case reports and case series are reported in literature on neonatal parotitis. Transmission of bacteria seems to occur mainly by ascending spread through Stensen's duct, or by hematogenous spread from a distant focus. Dehydration, low birth weight, immune suppression, ductal obstruction, oral trauma and structural abnormalities of the parotid gland are recognised as risk factors. The most common pathogen is Staphylococcus aureus. Other less frequent agents are other Gram-positive cocci, Gram-negative bacilli and rarely anaerobic bacteria. Advances in antimicrobial therapy have improved both outcome and prognosis. Thanks to the prompt antibiotic treatment complications are now drastically reduced. Ultrasound examination may help in the diagnosis and monitoring of clinical course. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Placental Inflammatory Changes and Bacterial Infection in Premature Neonates with Respiratory Failure

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S. A. Perepelitsa

2012-01-01

Full Text Available Objective: to reveal a relationship of placental inflammatory changes to bacterial infection in premature neonates with respiratory failure. Material and methods. Bronchoalveolar aspirate was bacteriologically studied in 157 premature neonates with respiratory distress syndrome (NRDS; the total and differential leukocyte counts were measured in their peripheral blood. The levels of the cytokines IL-1^3, IL-4, IL-6, and TNF-a were studied in different biological fluids of mothers and their babies; the placentas were also morphologically examined. Results. An analysis of bacterial cultures from the tracheobronchial tree revealed no growth of bacterial microflora in 61.8% of cases, Enterococcus faecalis and Staphylococcus epidermidis were isolated in 6.4 and 8.3% of the infants, respectively; Staphylococcus haemolyticus, Staphylococcus capitis, Enterobacter agglomerans, and hemolytic group A Streptococcus were seen in 1.9% each; moreover, 1.3% of the newborn infants were found to have Bacillus spp., Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Serratia marcescens. Other microorganisms and a microbial association were encountered in 8.9% of cases. Placental morphological examination revealed different inflammatory changes concurrent with chronic and acute placental insufficiency. The investigation demonstrated that the maternal peripheral plasma levels of IL-1^, IL-4, IL-6, and TNF-a were within the physiological range at the end of the first period of delivery. The amniotic fluid displayed elevated IL-6 and TNF-a concentrations and normal IL-4 and IL-1e levels, suggesting that there was an intrauterine inflammatory process. Conclusion. Premature birth is associated with various placental inflammatory changes, which causes intrauterine stimulation of macrophages in the chorionic villi. Specific immune defense mechanisms that prevent the development of a fetal infectious process, i.e. the maternal infectious process, may induce

Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

Science.gov (United States)

Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

2017-08-03

The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

Exposure assessment of neonates in israel to x-ray radiation during hospitalization at neonatal intensive care unit

International Nuclear Information System (INIS)

Datz, H.

2005-03-01

Nowadays nearly 10% of all births in western countries are premature. In the last decade, there has been an increase of 45% in the number of neonates that were born in Israel. At the same time, the survival of neonates, especially those with very low birth weight, VLBW, (less than 1,500 gr), has increased dramatically. Diagnostic radiology plays an important role in the assessment and treatment of neonates requiring intensive care. During their prolonged and complex hospitalization, these infants are exposed to multiple radiographic examinations involving X-ray radiation. The extent of the examinations that the infant undergoes depends on its birth weight, gestational age and its medical problems, where most of the treatment effort is focused especially on VLBW neonates. Most of the diagnostic X-ray examinations taken during the hospitalization of neonates in the neonatal intensive care unit (NICU) consist of imaging of the respiratory and gastrointestinal systems, namely, the chest and abdomen. The imaging process is done using mobile X-ray units located at the NICUs. Due to their long hospitalization periods and complex medical condition, all neonates, and neonates with VLBW in particular, are exposed to a much higher level of diagnostic radiation, compared to normal newborns. The goal of this research was to assess the extent of the exposure of neonates in Israel to X-ray radiation during their hospitalization at the neonatal intensive care unit. Five NICUs, located at different geographical zones in Israel and treating 20% of all newborns in Israel every year, participated in this research. The research was conducted in three phases: Phase I: Collection of information on radiographic techniques and exposure parameters (e.g. kV, mAs, focus to skin distance (FSD), examination borders). 499 X-ray examinations (from 157 neonates) were evaluated for necessary and unnecessary exposure of the neonate's organs to X-ray radiation during these examinations. Phase II

The role of TLR2 and bacterial lipoprotein in enhancing airway inflammation and immunity

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Amit A Lugade

2011-04-01

Full Text Available Non-typeable Haemophilus influenzae (NTHI colonizes the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD and also causes exacerbations of the disease. The 16-kDa lipoprotein P6 has been widely studied as a potential vaccine antigen due to its highly conserved expression amongst NTHI strains. Although P6 is known to induce potent inflammatory responses, its role in the pathogenesis of NTHI infection in vivo has not been examined. Additionally, the presence of an amino-terminal lipid motif on P6 serves to activate host TLR2 signaling. The role of host Toll-like receptor 2 (TLR2 and NTHI expression of the lipoprotein P6 on the induction of airway inflammation and generation of adaptive immune responses following chronic NTHI stimulation was evaluated with TLR2-deficient mice and a P6-deficient NTHI strain. Absence of either host TLR2 or bacterial P6 resulted in diminished levels of immune cell infiltration within lungs of mice exposed to NTHI. Pro-inflammatory cytokine secretion was also reduced in lungs that did not express TLR2 or were exposed to NTHI devoid of P6. Induction of specific antibodies to P6 was severely limited in TLR2-deficient mice. Although mice exposed to the P6-deficient NTHI strain were capable of generating antibodies to other surface antigens of NTHI, these levels were lower compared to those observed in mice exposed to P6-expressing NTHI. Therefore, cognate interaction between host TLR2 and bacterial P6 serves to enhance lung inflammation and elicit robust adaptive immune responses during NTHI exposure. Strategies to limit NTHI inflammation while simultaneously promoting robust immune responses may benefit from targeting the TLR2:P6 signaling axis.

Neonatal pain management

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Tarun Bhalla

2014-01-01

Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.

Causes of Neonatal Mortality in the Neonatal Intensive Care Unit of Taleghani Hospital

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Ali Hossein Zeinalzadeh

2017-09-01

Full Text Available Background: Neonatal survival is one of the most important challenges today. Over 99% of neonatal mortalities occur in the developing countries, and epidemiologic studies emphasize on this issue in the developed countries, as well. In this study, we attempted to investigate the causes of neonatal mortality in Taleghani Hospital, Tabriz, Iran.Methods: In this cross-sectional study, we studied causes of neonatal mortality in neonatal intensive care unit (NICU of Taleghani Hospital, Tabriz, Iran, during 2013-2014. Data collection was performed by the head nurse and treating physician using a pre-designed questionnaire. Most of the data were extracted from the neonatal records. Information regarding maternal underlying diseases and health care during pregnancy was extracted from mothers' records.Results: A total of 891 neonates were admitted to NICU of Taleghani Hospital of Tabriz, Iran, during 2013-2014, 68 (7.5% of whom died. Among these cases, 37 (%54.4 were male, 29 (29.4% were extremely low birth weight, and 16 (23.5% weighed more than 2.5 kg. The main causes of mortality were congenital anomalies (35.3%, prematurity (26.5%, and sepsis (10.3%, respectively.Conclusion: Congenital anomaly is the most common cause of mortality, and the pattern of death is changing from preventable diseases to unavoidable mortalities

Enhanced acquired antibodies to a chimeric Plasmodium falciparum antigen; UB05-09 is associated with protective immunity against malaria.

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Dinga, J N; Gamua, S D; Titanji, V P K

2017-08-01

It has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritize such a chimera for malaria vaccine development, it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here, we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05-09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross-sectional study, recombinant UB05-09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria-endemic zone, using the enzyme-linked immunosorbent assay (ELISA). Anti-UB05-09 antibody levels doubled that of its constituent antigens, UB09 and UB05, and this correlated with protection against malaria. The presence of enhanced UB05-09-specific antibody correlated with the absence of fever and parasitaemia, which are the main symptoms of malaria infection. The chimera is more effective in detecting and distinguishing acquired protective immunity against malaria than any of its constituents taken alone. Online B-cell epitope prediction tools confirmed the presence of B-cell epitopes in the study antigens. UB05-09 chimera is a marker of protective immunity against malaria that needs to be studied further. © 2017 John Wiley & Sons Ltd.

Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths

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Gause, William C.; Wynn, Thomas A.; Allen, Judith E.

2013-01-01

Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance. PMID:23827958

Developments in neonatal care and nursing responses.

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Healy, Patricia; Fallon, Anne

This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.

Enhancement of innate immune system in monocot rice by transferring the dicotyledonous elongation factor Tu receptor EFR

Institute of Scientific and Technical Information of China (English)

Fen Lu; Huiqin Wang; Shanzhi Wang; Wendi Jiang; Changlin Shan; Bin Li; Jun Yang; Shiyong Zhang; Wenxian Sun

2015-01-01

The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifical y recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrated that Arabidopsis EFR confers broad-spectrum bacterial resistance in the EFR transgenic solanaceous plants. Here, the transgenic rice plants (Oryza sativa L. ssp. japonica cv. Zhonghua 17) and cel cultures with constitutive expression of AtEFR were developed to investigate whether AtEFR senses EF-Tu and thus enhances bacterial resistance in the monocot plants. We demonstrated that the Xanthomonas oryzae-derived elf18 peptide induced oxidative burst and mitogen-activated protein kinase activa-tion in the AtEFR transgenic rice cel s and plants, respectively. Pathogenesis-related genes, such as OsPBZ1, were upregulated dramatical y in transgenic rice plant and cel lines in response to elf18 stimulation. Importantly, pretreatment with elf18 trig-gered strong resistance to X. oryzae pv. oryzae in the transgenic plants, which was largely dependent on the AtEFR expression level. These plants also exhibited enhanced resistance to rice bacterial brown stripe, but not to rice fungal blast. Col ectively, the results indicate that the rice plants with heterologous expression of AtEFR recognize bacterial EF-Tu and exhibit enhanced broad-spectrum bacterial disease resistance and that pattern recognition receptor-mediated immunity may be manipulated across the two plant classes, dicots and monocots.

Patterns of admission and factors associated with neonatal mortality among neonates admitted to the neonatal intensive care unit of University of Gondar Hospital, Northwest Ethiopia

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Demisse AG

2017-05-01

Full Text Available Abayneh Girma Demisse, Fentahun Alemu, Mahlet Abayneh Gizaw, Zemene Tigabu School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia Introduction: The neonatal period is a highly vulnerable time for an infant completing many of the physiologic adjustments required for life outside the uterus. As a result, there are high rates of morbidity and mortality. The three major causes of mortality in developing countries include prematurity, infection, and perinatal asphyxia. The aim of this study was to identify the patterns of neonatal admission and factors associated with mortality among neonates admitted at the Neonatal Intensive Care Unit (NICU of University of Gondar Hospital.Materials and methods: A retrospective cross-sectional study was conducted among all admitted neonates in the NICU of University of Gondar referral hospital from December 1, 2015 to August 31, 2016. Information was extracted retrospectively during admission from patient records and death certificates, using a pretested questionnaire. The data were entered and analyzed using SPSS version 20, and p-values <0.05 were considered statistically significant.Results: A total of 769 neonates was included in the study. There were 448 (58.3% male neonates, and 398 (51.8% neonates were rural residents. More than two-thirds of the 587 deliveries (76.3% were performed in tertiary hospitals. Neonatal morbidity included hypothermia 546 (71%, sepsis 522 (67.9%, prematurity 250 (34.9%, polycythemia 242 (31.5%, hypoglycemia 142 (18.5, meconium aspiration syndrome 113 (14.7%, and perinatal asphyxia 96 (12.5%. The overall mortality was 110 (14.3%; 95% confidence interval [CI]: 11.9–16.9 of which 69 (62.7% deaths occurred in the first 24 hours of age. In the multivariate analysis, mortality was associated with perinatal asphyxia (adjusted odds ratio [AOR]: 5.97; 95% CI: 3.06–11.64, instrumental delivery (AOR: 2.99; 95% CI: 1.08–8.31, and early onset

Volume and leak measurements during neonatal CPAP in neonates

OpenAIRE

Fischer, Hendrik S.

2011-01-01

As yet, little is known about the effects of air leakages during CPAP in newborns. The present doctoral dissertation investigates tidal volume and leak measurements during nasal continuous positive airway pressure in neonates using a commercial ventilatory device. Investigations include in vitro studies, modelling and computer simulation as well as a clinical randomized cross-over trial in neonates.

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

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Azevedo, Raimunda S S; de Sousa, Jorge R; Araujo, Marialva T F; Martins Filho, Arnaldo J; de Alcantara, Bianca N; Araujo, Fernanda M C; Queiroz, Maria G L; Cruz, Ana C R; Vasconcelos, Beatriz H Baldez; Chiang, Jannifer O; Martins, Lívia C; Casseb, Livia M N; da Silva, Eliana V; Carvalho, Valéria L; Vasconcelos, Barbara C Baldez; Rodrigues, Sueli G; Oliveira, Consuelo S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

2018-01-08

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

Capacity building of nurses providing neonatal care in Rio de Janeiro, Brazil: methods for the POINTS of care project to enhance nursing education and reduce adverse neonatal outcomes

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Darlow Brian A

2012-03-01

Full Text Available Abstract Background Increased survival of preterm infants in developing countries has often been accompanied by increased morbidity. A previous study found rates of severe retinopathy of prematurity varied widely between different neonatal units in Rio de Janeiro. Nurses have a key role in the care of high-risk infants but often do not have access to ongoing education programmes. We set out to design a quality improvement project that would provide nurses with the training and tools to decrease neonatal mortality and morbidity. The purpose of this report is to describe the methods and make the teaching package (POINTS of care--six modules addressing Pain control; optimal Oxygenation; Infection control; Nutrition interventions; Temperature control; Supportive care available to others. Methods/Design Six neonatal units, caring for 40% of preterm infants in Rio de Janeiro were invited to participate. In Phase 1 of the study multidisciplinary workshops were held in each neonatal unit to identify the neonatal morbidities of interest and to plan for data collection. In Phase 2 the teaching package was developed and tested. Phase 3 consisted of 12 months data collection utilizing a simple tick-sheet for recording. In Phase 4 (the Intervention all nurses were asked to complete all six modules of the POINTS of care package, which was supplemented by practical demonstrations. Phase 5 consisted of a further 12 months data collection. In Phase 1 it was agreed to include inborn infants with birthweight ≤ 1500 g or gestational age of ≤ 34 weeks. The primary outcome was death before discharge and secondary outcomes included retinopathy of prematurity and bronchopulmonary dysplasia. Assuming 400-450 infants in both pre- and post-intervention periods the study had 80% power at p = Discussion The results of the POINTS of Care intervention will be presented in a separate publication. Trial registration Current Controlled Trials: ISRCTN83110114

Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

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Rafael Fenutría

Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

Prenatal vitamin A deficiency impairs adaptive immune responses to pentavalent rotavirus vaccine (RotaTeq®) in a neonatal gnotobiotic pig model.

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Kandasamy, Sukumar; Chattha, Kuldeep S; Vlasova, Anastasia N; Saif, Linda J

2014-02-07

Vitamin A deficiency (VAD) is associated with increased childhood mortality and morbidity in impoverished Asian and African countries, but the impact of VAD on rotavirus (RV) vaccine or infection is poorly understood. We assessed effects of gestational and dietary induced pre- and post-natal VAD and vitamin A supplementation on immune responses to a pentavalent rotavirus vaccine, RotaTeq(®) in a neonatal gnotobiotic pig model. Vaccine efficacy was assessed against virulent G1P[8] human rotavirus (HRV) challenge. VAD and vitamin A sufficient (VAS) piglets were derived from dietary VAD and VAS sows, respectively. VAD piglets had significantly lower levels of hepatic vitamin A compared to that of VAS piglets. RotaTeq(®)-vaccinated VAD piglets had 350-fold higher fecal virus shedding titers compared to vaccinated VAS piglets post-challenge. Only 25% of vaccinated non-vitamin A supplemented VAD piglets were protected against diarrhea compared with 100% protection rate in vaccinated non-supplemented VAS piglets post-challenge. Intestinal HRV specific immune responses were compromised in VAD piglets. Vaccinated VAD piglets had significantly lower ileal HRV IgG antibody secreting cell (ASC) responses (pre-challenge) and duodenal HRV IgA ASC responses (post-challenge) compared to vaccinated VAS piglets. Also, intestinal HRV IgA antibody titers were 11-fold lower in vaccinated VAD compared to vaccinated VAS piglets post-challenge. Persistently elevated levels of IL-8, a pro-inflammatory mediator, and lower IL-10 responses (anti-inflammatory) in vaccinated VAD compared to VAS piglets suggest more severe inflammatory responses in VAD piglets post-challenge. Moreover higher IFN-γ responses pre-challenge were observed in VAD compared to VAS piglets. The impaired vaccine-specific intestinal antibody responses and decreased immunoregulatory cytokine responses coincided with reduced protective efficacy of the RV vaccine against virulent HRV challenge in VAD piglets. In

Telemedicine in Neonatal Home Care

DEFF Research Database (Denmark)

Holm, Kristina Garne; Brødsgaard, Anne; Zachariassen, Gitte

2016-01-01

participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care......BACKGROUND: For the majority of preterm infants, the last weeks of hospital admission mainly concerns tube feeding and establishment of breastfeeding. Neonatal home care (NH) was developed to allow infants to remain at home for tube feeding and establishment of breastfeeding with regular home...... visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used...

Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

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Romain Ballet

2014-12-01

Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

Neonatal Informatics: Transforming Neonatal Care Through Translational Bioinformatics

Science.gov (United States)

Palma, Jonathan P.; Benitz, William E.; Tarczy-Hornoch, Peter; Butte, Atul J.; Longhurst, Christopher A.

2012-01-01

The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized. PMID:22924023

The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates

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Kludka-Sternik M

2010-04-01

Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendriticcells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty ninehealthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. Theexpression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performedusing a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentageof BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood ofhealthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatorymolecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 moleculesenable appropriate development of immune response.

The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates.

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S Radej

2011-04-01

Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty nine healthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. The expression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performed using a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4 expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentage of BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood of healthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatory molecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 molecules enable appropriate development of immune response.

Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat.

Science.gov (United States)

Bhardwaj, S K; Forcelli, P A; Palchik, G; Gale, K; Srivastava, L K; Kondratyev, A

2012-06-01

Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maternal haemoglobin and short-term neonatal outcome in preterm neonates.

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Elodie Savajols

Full Text Available To determine whether there is a significant association between maternal haemoglobin measured before delivery and short-term neonatal outcome in very preterm neonates.We included prospectively all live births occurring from 25 to 32+6 weeks of gestation in a tertiary care centre between January 1(st 2009 and December 31(st 2011. Outborn infants and infants presenting with lethal malformations were excluded. Three hundred and thirty-nine mothers and 409 infants met the inclusion criteria. For each mother-infant pair a prospective record of epidemiologic data was performed and maternal haemoglobin concentration recorded within 24 hours before delivery was retrospectively researched. Maternal haemoglobin was divided into quartiles with the second and the third one regarded as reference as they were composed of normal haemoglobin values. Short-term outcome was defined as poor in case of death during hospital stay and/or grades III/IV intraventricular haemorrhage and/or periventricular leukomalacia and/or necessity of ventriculoperitoneal shunt.The global rate of poor short-term neonatal outcome was 11.4% and was significantly associated with low maternal haemoglobin values. This association remained significant after adjustment for antenatal corticosteroids therapy, gestational age, parity, mechanism of preterm birth, mode of delivery and birth weight (aOR = 2.97 CI 95% [1.36-6.47]. There was no relation between short-term neonatal outcome and high maternal haemoglobin concentration values.We show that low maternal haemoglobin concentration at delivery is an independent risk factor for poor short-term neonatal outcome in very preterm neonates. This study is one of the first to show such an association within the preterm population.

Therapeutic enhancement of protective immunity during experimental leishmaniasis.

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Senad Divanovic

2011-09-01

Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

Neonates need tailored drug formulations.

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Allegaert, Karel

2013-02-08

Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

In vitro study of acetylcholine and histamine induced contractions in colon and rectum of adult and neonate rats.

Science.gov (United States)

Singh, Shuchita; Mandal, Maloy B

2013-01-01

Contractile mechanisms of different parts of the gut in adult and neonate may not be identical due to developmental processes. The present study was undertaken to investigate acetylcholine (ACh) and histamine induced contractile responses of colon and rectum in adult and neonatal albino rats. Contractile responses were recorded from isolated in vitro preparations. The dose-response curve for ACh (0.001-100 microM) revealed dose dependent increase in contractile responses. A significantly (P pheniramine (100 microM) in adult rectum. This potentiating response of pheniramine was absent in neonate rectum. Such effect was also not seen in colon of both adult and neonate. The present investigation indicates that the contractile responses induced by ACh are similar in both adult and neonate, excepting that the blocking effect of atropine in colon was more pronounced in adult as compared to neonate. Further, the results also indicated different mechanism of histamine action in adults and neonates as evidenced by the significant enhancement of contractions by pheniramine only in adult rectum. Therefore, the present results indicate the existence of a different cholinergic and histaminergic activity in adult and neonate as well as in rectal and colonic tissue.

25-Hydroxyvitamin D and Peripheral Immune Mediators

DEFF Research Database (Denmark)

Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin

2017-01-01

Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470...... patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared...... to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH...

Natural material adsorbed onto a polymer to enhance immune function

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Reinaque AP

2012-08-01

Full Text Available Ana Paula Barcelos Reinaque,1 Eduardo Luzía França,2 Edson Fredulin Scherer,3 Mayra Aparecida Côrtes,1 Francisco José Dutra Souto,4 Adenilda Cristina Honorio-França51Post Graduate Program in Material Science, 2Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, 3Post Graduate Program in Material Science, Institute of Biological and Health Science, Federal University of Mato Grosso, Pontal do Araguaia, 4Faculty of Medical Sciences, Federal University of Mato Grosso, Cuiabá, 5Institute of Biological and Health Science, Federal University of Mato Grosso, Pontal do Araguaia, MT, BrazilBackground: In this study, we produced poly(ethylene glycol (PEG microspheres of different sizes and adsorbing a medicinal plant mixture, and verified their effect in vitro on the viability, superoxide production, and bactericidal activity of phagocytes in the blood.Methods: The medicinal plant mixture was adsorbed onto PEG microspheres and its effects were evaluated by flow cytometry and fluorescence microscopy.Results: Adsorption of the herbal mixture onto the PEG microspheres was achieved and the particles were internalized by phagocytes. PEG microspheres bearing the adsorbed herbal mixture stimulated superoxide release, and activated scavenging and microbicidal activity in phagocytes. No differences in functional activity were observed when the phagocytes were not incubated with PEG microspheres bearing the adsorbed herbal mixture.Conclusion: This system may be useful for the delivery of a variety of medicinal plants and can confer additional protection against infection. The data reported here suggest that a polymer adsorbed with a natural product is a treatment alternative for enhancing immune function.Keywords: natural product, polymer, adsorption, immune function, phagocytes

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

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Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

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Neide M. Silva

2017-04-01

Full Text Available Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70. Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

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Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

2016-01-01

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Enhancement of collective immunity in Tokyo metropolitan area by selective vaccination against an emerging influenza pandemic.

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Masaya M Saito

Full Text Available Vaccination is a preventive measure against influenza that does not require placing restrictions on social activities. However, since the stockpile of vaccine that can be prepared before the arrival of an emerging pandemic strain is generally quite limited, one has to select priority target groups to which the first stockpile is distributed. In this paper, we study a simulation-based priority target selection method with the goal of enhancing the collective immunity of the whole population. To model the region in which the disease spreads, we consider an urban area composed of suburbs and central areas connected by a single commuter train line. Human activity is modelled following an agent-based approach. The degree to which collective immunity is enhanced is judged by the attack rate in unvaccinated people. The simulation results show that if students and office workers are given exclusive priority in the first three months, the attack rate can be reduced from [Formula: see text] in the baseline case down to 1-2%. In contrast, random vaccination only slightly reduces the attack rate. It should be noted that giving preference to active social groups does not mean sacrificing those at high risk, which corresponds to the elderly in our simulation model. Compared with the random administration of vaccine to all social groups, this design successfully reduces the attack rate across all age groups.

Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

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Besser, T.E.

1986-01-01

High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G/sub 1/ (IgG/sub 1/) is transferred to the gastrointestinal tract, /sup 125/I-labelled bovine IgG/sub 1/ anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of /sup 125/I-IgG/sub 1/ from the blood was measured and compared to the rate of /sup 125/I-IgG/sub 1/ appearance in the gastrointestinal tract, as measured (1) by the rate of fecal /sup 125/I-IgG/sub 1/ excretion, and (2) by the amount of /sup 125/I-IgG/sub 1/ in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity.

Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

International Nuclear Information System (INIS)

Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

2007-01-01

Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

Newborn Jaundice Technologies: Unbound Bilirubin and Bilirubin Binding Capacity In Neonates

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Amin, Sanjiv B.; Lamola, Angelo A.

2011-01-01

Neonatal jaundice (hyperbilirubinemia), extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or “free”) bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates including premature infants, there currently exists no widely available method to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need. PMID:21641486

Pneumococcal conjugate vaccination at birth in a high-risk setting: no evidence for neonatal T-cell tolerance.

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van den Biggelaar, Anita H J; Pomat, William; Bosco, Anthony; Phuanukoonnon, Suparat; Devitt, Catherine J; Nadal-Sims, Marie A; Siba, Peter M; Richmond, Peter C; Lehmann, Deborah; Holt, Patrick G

2011-07-26

Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neonatal Nursing

OpenAIRE

Crawford, Doreen; Morris, Maryke

1994-01-01

"Neonatal Nursing" offers a systematic approach to the nursing care of the sick newborn baby. Nursing actions and responsibilities are the focus of the text with relevant research findings, clinical applications, anatomy, physiology and pathology provided where necessary. This comprehensive text covers all areas of neonatal nursing including ethics, continuing care in the community, intranatal care, statistics and pharmokinetics so that holistic care of the infant is described. This book shou...

Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients

NARCIS (Netherlands)

Tepaske, Robert; te Velthuis, Henk; Oudemans-van Straaten, Heleen M.; Bossuyt, Patrick M. M.; Schultz, Marcus J.; Eijsman, Leon; Vroom, Margreeth

2007-01-01

Background: Elderly patients and patients with a poor cardiac function have increased morbidity rates when undergoing cardiac surgery. The aim of this study was to determine whether addition of glycine to a standard preoperative oral immune-enhancing nutrition supplement (OIENS) improves outcome.

SERUM SODIUM CHANGES IN NEONATES RECEIVING PHOTOTHERAPY FOR NEONATAL HYPERBILIRUBINEMIA

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Sunil Kumar

2015-07-01

Full Text Available BACKGROUND : Neonates receiving phototherapy have side effects like hypocalcemia and electrolyte changes. Our study is hereby intended to study the serum sodium changes due to phototherapy. AIMS : To evaluate the serum sodium changes in neonates receiving phototherapy f or neonatal hyperbilirubinemia. SETTINGS AND DESIGN : A prospective hospital based comparative study conducted on neonates admitted in the Neonatal Intensive Care Unit receiving phototherapy. METHODS AND MATERIAL : A predesigned proforma has aided the enroll ment of 252 newborns into the study. Serum bilirubin and serum sodium were determined before and after termination of phototherapy. The first samples were considered as controls. A comparative study was made between before and after phototherapy groups to determine the incidence of serum sodium imbalances. STATISTICAL ANALYSIS USED : Proportions will be compared using chi - square test. All data of various groups will be tabulated and statistically analyzed using suitable statistical tests (Student's t test. RESULTS : Male to Female ratio was 1.45 : 1. Incidence of low birth weight babies was 23% and preterm was 20.2%. Mean birth weight and gestational age was 2.84±0.51 kg and 38.44±1.98 wks respectively. Mean duration of phototherapy was 37.65±11.06 hrs. The incidence of hyponatremia post phototherapy found to be 6% which was more in low birth weight (LBW babies (17.2% , p48 hrs (p<0.001. Even the decline in mean serum sodium values after phototherapy found to be statistically significant. CONCLUSION : Our study shows that neonates u nder phototherapy are at higher risk of hyponatremia. This risk is greater in premature and LBW babies and hence this group of babies should be closely monitored for changes in serum sodium and should be managed accordingly.

Immune Evasion, Immunopathology and the Regulation of the Immune System

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Bruno Faivre

2013-02-01

Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

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Nicholas Glanville

Full Text Available Human rhinovirus (RV infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2 capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.

Neonatal plasmacytoid dendritic cells (pDCs display subset variation but can elicit potent anti-viral innate responses.

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Xiaoming Zhang

Full Text Available Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV, human immunodeficiency virus (HIV or herpes-simplex virus (HSV by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.

Special Considerations in Neonatal Mechanical Ventilation.

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Dalgleish, Stacey; Kostecky, Linda; Charania, Irina

2016-12-01

Care of infants supported with mechanical ventilation is complex, time intensive, and requires constant vigilance by an expertly prepared health care team. Current evidence must guide nursing practice regarding ventilated neonates. This article highlights the importance of common language to establish a shared mental model and enhance clear communication among the interprofessional team. Knowledge regarding the underpinnings of an open lung strategy and the interplay between the pathophysiology and individual infant's response to a specific ventilator strategy is most likely to result in a positive clinical outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Pleurocidin Peptide Enhances Grouper Anti-Vibrio harveyi Immunity Elicited by Poly(lactide-co-glycolide)-Encapsulated Recombinant Glyceraldehyde-3-phosphate Dehydrogenase.

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Chuang, Shu-Chun; Huang, Wan-Ling; Kau, Sau-Wei; Yang, Yun-Pei; Yang, Chung-Da

2014-05-14

Outer membrane proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are considered immunodominant antigens for eliciting protective immunity against Vibrio harveyi, the main etiological agent of vibriosis in fish. Cationic antimicrobial peptides (AMPs), such as pleurocidin (PLE), play important roles in activating and recruiting immune cells, thereby contributing to subsequent innate and adaptive immune responses. In the present study, we aimed to use PLE peptide as a potent adjuvant to improve the immunogenicity of V. harveyi recombinant GAPDH (rGAPDH). In order to prepare a controlled-release vaccine, PLE peptide and rGAPDH protein were simultaneously encapsulated into polymeric microparticles made from the biodegradable poly(lactide-co-glycolide) (PLG) polymer. The resulting PLG-encapsulated PLE plus rGAPDH (PLG-PLE/rGAPDH) microparticles, 3.21-6.27 μm in diameter, showed 72%-83% entrapment efficiency and durably released both PLE and rGAPDH for a long 30-day period. Following peritoneal immunization in grouper (Epinephelus coioides), PLG-PLE/rGAPDH microparticles resulted in significantly higher (p PLE/rGAPDH microparticles conferred a high survival rate (85%), which was significantly higher (p PLE peptide exhibits an efficacious adjuvant effect to elicit not only improved immunity, but also enhanced protection against V. harveyi in grouper induced by rGAPDH protein encapsulated in PLG microparticles.

Neonatal ghrelin programs development of hypothalamic feeding circuits

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Steculorum, Sophie M.; Collden, Gustav; Coupe, Berengere; Croizier, Sophie; Lockie, Sarah; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sebastien G.

2015-01-01

A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation. PMID:25607843

Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

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Nigel J Stevenson

Full Text Available The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.

A stressful microenvironment: opposing effects of the endoplasmic reticulum stress response in the suppression and enhancement of adaptive tumor immunity.

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Rausch, Matthew P; Sertil, Aparna Ranganathan

2015-03-01

The recent clinical success of immunotherapy in the treatment of certain types of cancer has demonstrated the powerful ability of the immune system to control tumor growth, leading to significantly improved patient survival. However, despite these promising results current immunotherapeutic strategies are still limited and have not yet achieved broad acceptance outside the context of metastatic melanoma. The limitations of current immunotherapeutic approaches can be attributed in part to suppressive mechanisms present in the tumor microenvironment that hamper the generation of robust antitumor immune responses thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic reticulum (ER) stress response has recently emerged as a potent regulator of tumor immunity. The ER stress response is an adaptive mechanism that allows tumor cells to survive in the harsh growth conditions inherent to the tumor milieu such as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER stress can also alter the cancer cell response to therapies. In addition, the ER stress response promotes tumor immune evasion by inducing the production of protumorigenic inflammatory cytokines and impairing tumor antigen presentation. However, the ER stress response can boost antitumor immunity in some situations by enhancing the processing and presentation of tumor antigens and by inducing the release of immunogenic factors from stressed tumor cells. Here, we discuss the dualistic role of the ER stress response in the modulation of tumor immunity and highlight how strategies to either induce or block ER stress can be employed to improve the clinical efficacy of tumor immunotherapy.

The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree.

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Zhang, Guiqiang; Cheng, Gong; Jia, Peiyuan; Jiao, Siming; Feng, Cui; Hu, Tao; Liu, Hongtao; Du, Yuguang

2017-07-26

Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS-PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1)/T-helper 2 (Th2) response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides)-PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree)-PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree)-PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant) group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

OpenAIRE

Wheatley, Scott M.; El-Kadi, Samer W.; Suryawan, Agus; Boutry, Claire; Orellana, Renán A.; Nguyen, Hanh V.; Davis, Steven R.; Davis, Teresa A.

2013-01-01

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 μmol·kg body wt−1·h−1 for 1 h (HMB 0, HMB 20, HMB 100, ...

Human study of the herbal preparation(HemoHIM) on enhancement of immune and hematopoietic functions

Energy Technology Data Exchange (ETDEWEB)

Choi, Hee-Jeong; Park, Jong-Nam; Jeon, Sun-Hee [Eulji Univ. Hospital, Daejeon (Korea, Republic of)

2006-01-15

This study was aimed to evaluate the human efficacy of the herbal preparation(HemoHIM) on the immune and hematopoiesis enhancement in sub-healthy volunteers. It was conducted as a double-blind, placebo-controlled human study. The sub-healthy volunteers with peripheral White Blood Cell (WBC) counts below 5000/μl were recruited and randomly allocated to 3 groups and administered with HemoHIM 6g/day, HemoHIM 12g/day, or placebo throughout the test. Peripheral blood was collected 4 times before or after the administration and analyzed for the hematological and serum biochemical values, immune cell activities, antioxidant status of plasma. The data of 38 volunteers were finally included in the analysis. Although there were no statistical significances, a trend was observed that the dose and duration of HemoHIM administration was correlated to the increased number of immune cells (white blood cells and lymphocytes). NK cell activity was increased significantly in the male group administered with HemoHIM 6g/day. The cytokines involved in immune activation (IL-2, IFN-γ, IL-6) were significantly increased or showed the trends of increases in HemoHIM administered groups, while IL-4 involved in allergy and asthma was not changed or showed the trends of decreases in HemoHIM administered groups. On the other hand, the antioxidant biomarkers such as total GSH, MDA, and TAS, were not affected by HemoHIM administration. The toxicological safety of HemoHIM administration was confirmed by the serum biochemical analysis of liver and kidney function markers and the questionnaire of HemoHIM administration and the consultation with the doctor, which showed no side effects of HemoHIM administration. The results of this study may provide the basic data for further clinical study on HemoHIM.

[Different aluminum adjuvants significantly enhances the effect of immunization on Brucella Omp31].

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Qing, Rui; Xiang, Qingke; Liu, Zhongqi; Xiao, Fei; Yang, Fan

2018-02-01

Objective To investigate the effect of aluminum phosphate (AP) and aluminum hydroxide (AH) as adjuvants on Brucella outer membrane protein 31 (Omp31) in inducing humoral and cellular immune responses and immune protection. Methods AP and AH adjuvants were prepared and separately mixed with Brucella Omp31 protein to measure the adsorption rates. The AP- and AH-absorbed Omp31 protein were intraperitoneally injected into BLAB/c mice at 0, 2, and 4 weeks, and meanwhile, unabsorbed Omp31 protein and PBS were used as controls. The levels of serum IgG, IgG1, IgG2a and genital tract secretion sIgA were determined by ELISA at 0, 2, 4 and 6 weeks. Spleen cells were collected for culture at 6 weeks, and the cells were stimulated by Omp31 for 48 hours followed by the analysis of IFN-γ and IL-10 levels in the supernatants by ELISA, and the determination of lymphocyte proliferation by CCK-8 assay. The mice were challenged with Brucella at 6 weeks, and bacterial content in spleen tissue was determined 1 and 2 weeks later. Results AP and AH could absorb over 70% and 85% of the Omp31 protein, respectively, for solutions at all the tested concentrations. ELISA suggested that serum IgG, IgG1, IgG2a and genital tract sIgA levels peaked 2 weeks after the last immunization for both AP and AH groups, and antibody level was higher in the AP and AH groups than the control groups, and higher in the AH group than in the AP group. CCK-8 assay showed that the proliferating rate of lymphocytes induced by the AH group was significantly higher than that by the AP group, and the AH group also showed significantly higher IFN-γ level in the supernatant than the AP group, but no significant difference in IL-10 level. The AH group had remarkably lower bacterial load in the spleen than the AP group 2 weeks after challenged by Brucella 16M strain. Conclusion Both AP and AH adjuvants effectively enhanced immunogenicity and immune protection of the Brucella Omp31 protein, and AH was superior to AP in

Therapies for neonates with congenital malformations admitted to a neonatal unit

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Maria Vera Lúcia Moreira Leitão Cardoso

2015-03-01

Full Text Available The aim of this study was to characterize the treatments applied to newborns with congenital malformation hospitalized in a neonatal unit and to identify whether there is an association among the treatments used and the type of malformation. A descriptive, prospective and quantitative study was developed in a public institution in Fortaleza, Ceará, Brazil. Data were collected using the medical records of 30 neonates with congenital malformations. The incidence of malformations was higher among females, regardless of the mother’s age, gestational age or weight at birth; malformations of the central nervous and musculoskeletal systems prevailed. The treatments used varied according to the clinical evolution of the neonate. The data collected did not present statistical significance when associated with the variable of congenital malformation and the treatments used (p>0.05. The treatments are not directly related to the type of malformation, but to the clinical condition of the neonate.

Intraoperative fluid therapy in neonates

African Journals Online (AJOL)

Differences from adults and children in physiology and anatomy of neonates inform our ... is based on energy expenditure indexed to bodyweight.2 Energy ... fragile and poorly keratinised.5 ... neonates means that very conservative fluid regimes in neonates ..... I make an estimation of insensible loss from the skin, viscera,.

Influence of iron on plutonium absorption by the adult and neonatal rat

International Nuclear Information System (INIS)

Sullivan, M.F.; Ruemmler, P.S.; Buschbom, R.L.

1986-01-01

To determine how iron affects plutonium absorption, adult rats were gavaged with 238 Pu nitrate (pH 2) after they had been fed an iron-deficient diet or treated with iron supplements. Neonatal rats born to dams on an iron-deficient diet were also gavaged with 238 Pu. An iron-deficient diet resulted in enhanced 238 Pu absorption both in the adults and in neonates born to iron-deficient dams. Ferric iron increased 238 Pu absorption 12-fold in adult rats; injected iron-dextran reduced that increase; gavaged ferrous iron reduced 238 Pu absorption to one-third of the control value. Rat neonates absorbed 30 to 40 times as much 238 Pu as adults; absorption was lowered in groups that received iron supplements: Iron-dextran caused a 50% reduction; ferric iron, 95%; and ferrous iron, greater than 95%. The results demonstrate an effect of the oxidation state of iron on plutonium absorption in adult rats different from that observed in suckling rats. The results suggest that the high rate of 238 Pu absorption by neonatal animals is due not only to the permeability of their intestines but also to their high demand for iron

Neonatal Tele-Homecare

DEFF Research Database (Denmark)

Holm, Kristina Garne

Neonatal homecare (NH) implies that parents manage tube feeding and care of their preterm infant at home supported by home visits from neonatal nurses, to monitor infant growth and the well-being of the family. Home visits are costly and time consuming in rural areas. The overall aim of this study...

[Neonatal tumours and congenital malformations].

Science.gov (United States)

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

Rebuilding immunity with Remune.

Science.gov (United States)

Whitfield, L

1998-01-01

Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

Science.gov (United States)

Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

2014-01-01

Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

Maternal Vaccination as an Essential Component of Life-Course Immunization and Its Contribution to Preventive Neonatology

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Naomi Bergin

2018-04-01

Full Text Available Maternal immunisation schedules are increasingly coming under the spotlight as part of the development of lifetime immunisation programmes for the role that they play in improving maternal, foetal, and neonatal health. Maternally-acquired antibodies are critical in protecting infants during the first months of their lives. Maternal immunisation was previously overlooked owing to concerns regarding vaccinations in this untested and high-risk population but is now acknowledged for its potential impact on the outcomes in many domains of foetal and neonatal health, aside from its maternal benefits. This article highlights the role that maternal immunisation may play in reducing infections in preterm and term infants. It explores the barriers to antenatal vaccinations and the optimisation of the immunisation uptake. This review also probes the part that maternal immunisation may hold in the reduction of perinatal antimicrobial resistance and the prevention of non-infectious diseases. Both healthcare providers and expectant mothers should continue to be educated on the importance and safety of the appropriate immunizations during pregnancy. Maternal vaccination merits its deserved priority in a life-course immunization approach and it is perhaps the only immunization whereby two generations benefit directly from a single input. We outline the current recommendations for antenatal vaccinations and highlight the potential advances in the field contributing to “preventive neonatology”.

In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

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Tânia A Costa

Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

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Wu Li

2012-01-01

Full Text Available Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host’s defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.

Immunization of Mice with a Live Transconjugant Shigella Hybrid Strain Induced Th1 and Th17 Cell-Mediated Immune Responses and Confirmed Passive Protection Against Heterologous Shigellae.

Science.gov (United States)

Nag, D; Koley, H; Sinha, R; Mukherjee, P; Sarkar, C; Withey, J H; Gachhui, R

2016-02-01

An avirulent, live transconjugant Shigella hybrid (LTSHΔstx) strain was constructed in our earlier study by introducing a plasmid vector, pPR1347, into a Shiga toxin gene deleted Shigella dysenteriae 1. Three successive oral administrations of LTSHΔstx to female adult mice produced comprehensive passive heterologous protection in their offspring against challenge with wild-type shigellae. Production of NO and different cytokines such asIL-12p70, IL-1β and IL-23 in peritoneal mice macrophages indicated that LTSHΔstx induced innate and adaptive immunity in mice. Furthermore, production of IFN-γ, IL-10 and IL-17 in LTSH-primed splenic CD4+ T cell suggested that LTSHΔstx may induce Th1 and Th17 cell-mediated immune responses. Exponential increase of the serum IgG and IgA titre against whole shigellae was observed in immunized adult mice during and after the immunization with the highest peak on day 35. Antigen-specific sIgA was also determined from intestinal lavage of immunized mice. The stomach extracts of neonates from immunized mice, mainly containing mother's milk, contained significant levels of anti-LTSHΔstx immunoglobulin. These studies suggest that the LTSHΔstx could be a new live oral vaccine candidate against shigellosis in the near future. © 2015 The Foundation for the Scandinavian Journal of Immunology.

[Immunization with Bifidobacterium bifidum-vectored OprI vaccine of Pseudomonas aeruginosa enhances inhibitory effect on P. aeruginosa in mice].

Science.gov (United States)

Liu, Xiao; Li, Wengui

2017-08-01

Objective To study the pulmonary bacterial loads, splenocyte proliferation, distributions of T cell subsets and cell apoptosis in mice immunized with Bifidobacterium bifidum-vectored OprI (Bb-OprI) vaccine of Pseudomonas aeruginosa and challenged with P. aeruginosa PA01 strain. Methods BALB/c mice were immunized with 5×10 9 CFUs of vaccine by intragastric administration, 3 times a week for 3 weeks, and challenged intranasally with 5×10 6 CFUs of PA01 strain at the fourth week after the first immunization. At the second week after the challenge, all mice were sacrificed to separate their lungs and spleens, and the pulmonary bacterial loads were counted. The proliferation of the splenocytes was determined by MTT assay. The splenic CD4 + , CD8 + T cell subsets and the apoptotic rate of splenocytes were detected by flow cytometry. Results The number of pulmonary bacterial colonies in the mice immunized with the vaccine and challenged with PA01 strain decreased, while the proliferation of splenocytes and the proportion of CD4 + T cells markedly increased, and the apoptosis of splenocytes was notably reduced. Conclusion The intragastric vaccination of recombinant Bb-OprI vaccine can increase the proportion of CD4 + T cells and enhance the inhibitory effect on P. aeruginosa.

Neonatal mortality in Utah.

Science.gov (United States)

Woolley, F R; Schuman, K L; Lyon, J L

1982-09-01

A cohort study of neonatal mortality (N = 106) in white singleton births (N = 14,486) in Utah for January-June 1975 was conducted. Using membership and activity in the Church of Jesus Christ of Latter-day Saints (LDS or Mormon) as a proxy for parental health practices, i.e., tobacco and alcohol abstinence, differential neonatal mortality rates were calculated. The influence of potential confounding factors was evaluated. Low activity LDS members were found to have an excess risk of neonatal death five times greater than high activity LDS, with an upper bound of a two-sided 95% confidence interval of 7.9. The data consistently indicate a lower neonatal mortality rate for active LDS members. Non-LDS were found to have a lower rate than either medium or low activity LDS.

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

Science.gov (United States)

Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

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Karen A.O. Martins

2016-01-01

Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Splenic rupture and intracranial haemorrhage in a haemophilic neonate: Case report and literature review

Directory of Open Access Journals (Sweden)

Ibrahim Adamu

2012-01-01

Full Text Available Splenic rupture and intracranial haemorrhage are life-threatening conditions infrequently encountered in neonates without history of birth trauma. External manifestations of birth trauma; namely, capput succadeneum and cephalhematoma, when present raise suspicions for more serious intracranial or visceral damage. Rupture of normal spleen without an obvious source of trauma in haemophilic neonate is a rare event. The concurrence of both conditions and the unusual presentation make this case a rare one that is seldom encountered in the literature. Additionally, when splenic rupture occurs, the consensus is to employ all non-operative techniques aimed at salvaging the spleen, thus avoiding the immune-compromised state associated with splenectomy. However, in this case, we present a 3-day-old male with family history of haemophilia A, who was diagnosed with splenic rupture and bilateral subdural haematomas and underwent splenectomy, albeit with post-operative complications, in light of haemodynamic instability and high ongoing transfusion requirements.

Localized skin changes at the site of immunization with highly irradiated cercariae of Schistosoma mansoni are associated with enhanced resistance to a challenge infection

International Nuclear Information System (INIS)

Miller, K.L.; Smithers, S.R.

1982-01-01

The level of immunity to a percutaneous cercarial challenge with Schistosoma mansoni was assayed 4-6 weeks after immunization of mice with highly irradiated (20 krad.) cercariae or schistosomula. When immunization and challenge occurred through the same skin site, resistance, particularly that which occurred in the skin, was greater than that observed when immunization and challenge occurred in different sites. The enhanced resistance is believed to be due to localized changes in the skin; 4 weeks after exposure to irradiated cercariae, abdominal skin is characterized by a thickened epidermis, changes in the ground substance and a cellular infiltration of the dermis. A convenient mouse model is described in which one or both ear pinnae are exposed to irradiated cercariae and a percutaneous challenge is given via the abdomen, thus eliminating the effects of local skin changes. In this model, the majority of the challenge infection which succumbs to the immune response appears to be killed in the skin. (author)

Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania

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Jeremiah Seni

2010-06-01

Full Text Available Abstract Background Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC, Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. Methods This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Results Among 770 neonates admitted during the study period; 300 (38.9% neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40% and 179(60% had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1% and 92 (51.4% among neonates with early and late onset neonatal sepsis respectively (p = 0.466. Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA. Deaths occurred in 57 (19% of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001, gram negative sepsis (p = 0.0001 and

NEONATAL TOBACCO SYNDROME

Directory of Open Access Journals (Sweden)

R.A.Kireev

2008-12-01

Full Text Available The objective of the research is to study neonatal adaptation in new-born children from the tobacco abused mothers. A comparative analysis of clinical and neuroendochnal status and lipid metabolism in new-born children from smoking and non-smoking mothers was carried out Neonatal adaptation disorders were revealed in new-born children from the smoking mothers.

Pelayanan Kesehatan Ibu dan Kematian Neonatal

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Desy Fitri Yani

2013-03-01

Full Text Available Indonesia bersama seluruh negara berkembang berupaya mencapai kesepakatan Millenium Development Goals (MDGs dengan salah satu sasaran menurunkan angka kematian neonatal dari 20 per 1.000 kelahiran hidup menjadi 15 per 1.000 kelahiran hidup. Penelitian ini bertujuan mengetahui hubungan pelayanan kesehatan ibu dengan kematian neonatal di Kabupaten Lampung Timur tahun 2011. Penelitian dengan desain studi kasus kontrol ini mengamati kasus ibu yang mengalami kematian neonatal dan kontrol ibu yang tidak mengalami kematian neonatal. Analisis multivariat menemukan pelayanan antenatal dan pertolongan persalinan berhubungan secara signifikan dengan kematian neonatal, setelah mengendalikan variabel umur ibu dan riwayat kehamilan (OR = 16,32; nilai p = 0,000; dan (OR = 18,36; nilai p = 0,31. Bayi yang dilahirkan dari Ibu dengan pelayanan antenatal tidak lengkap berisiko mengalami kematian neonatal 16,32 dan 18,36 kali lebih besar daripada bayi yang dilahirkan. Ibu dengan pelayanan antenatal lengkap dan penolong persalinan profesional. Tidak ada hubungan penolong persalinan dengan kematian neonatal, setelah mengontrol variabel pelayanan antenatal, umur ibu, riwayat kehamilan, riwayat penyakit, dan riwayat persalinan. Disarankan meningkatkan kualitas pelayanan antenatal dengan memerhatikan faktor umur ibu dan riwayat persalinan, mengembangkan kegiatan audit maternal perinatal serta meningkatkan keterampilan petugas penolong persalinan. All developing countries including Indonesia seek to reach agreement the Millennium Development Goals (MDG’s. It is objectives include reducing neonatal mortality by 25 percent from 20 per 1,000 live birth to 15 per 1,000 live births. This study aimed to determine the relationship of maternal health services with neonatal mortality in East Lampung District in 2011. This study used case control design to compare between the groups of mother whom have neonatal deaths (cases and neonatal life (control in East Lampung District in

T-regulatory cells depletion is the main cause for enhanced antitumor immunity during radio-sensitization of tumors by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Farooque, Abdullah; Verma, Amit; Singh, Niharika; Chauhan, Sachin Kumar Singh; Jethani, Jyoti; Adhikari, J.S.; Dwarakanath, B.S.; Afrin, Farhat

2014-01-01

Regulatory T cells (Tregs) are known to have profound effects in blocking anti-tumor immunity. Therefore, Tregs are seen as a major hurdle that must be overcome in order to improve the efficacy of cancer therapy. The glycolytic inhibitor, 2-deoxy-d-glucose (2-DG) enhances radiation and chemotherapeutics induced death of many cancer cells in vitro and local tumor control in vivo, which was found to be associated with the enhanced anti-tumor immunity. Therefore, we investigated the role of Tregs in determining the tumor response to the combined treatment of 2-DG plus ionizing radiation. Ehrlich ascites tumor bearing mice were administered with a single dose of 2-DG (2 gm/Kg/b.wt) intravenously just before focal irradiation (10 Gy). Immuno-phenotyping of Tregs in secondary lymphoid organs was carried out using flow cytometry, while related cytokines were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells and CD4 + CD25 + using real time PCR and Western blot techniques. Results clearly showed depletion (TRAIL mediated apoptosis) of T regs (CD4 + CD25 + FoxP3 + CD39 + FR4 + GITR + CD127 - ), in blood, spleen, lymph node and tumor following the combined treatment. This led to the immune activation in the periphery, secondary lymphoid organs and massive infiltration of CD4 + , CD8 + and NK cells in the tumor, which correlated well with the complete response (cure; tumor free survival). Association of Treg depletion with the tumor response was further confirmed using low doses of cyclophosphamide (which depletes Tegs) and rapamycin (activator of Tregs),wherein the depletor of Tregs enhanced the efficacy of combined treatment, while Tregs enhancer compromised the efficacy. These studies unequivocally established the role of Tregs in determining the therapeutic response and can be used as a target for enhancing the efficacy of this combined treatment, besides establishing the potential of

Interpretation of neonatal chest radiography

International Nuclear Information System (INIS)

Yoon, Hye Kyung

2016-01-01

Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice

Interpretation of neonatal chest radiography

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hye Kyung [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

2016-05-15

Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice.

Radiation doses and risks to neonates undergoing common radiographic examinations in the neonatal intensive care unit

International Nuclear Information System (INIS)

McParland, B.J.; Lee, R.

1996-01-01

Neonates in the-Neonatal Intensive Care Unit (NICU) can receive large numbers of radiographs owing to the clinical conditions they may present. More neonatal radiation dosimetry data are required for three fundamental reasons: (1.) to aid in the establishment of reference dose levels for interinstitutional comparisons; (2.) to improve childhood cancer risk estimates following neonatal exposure; and (3.) to indicate appropriate directions for dose reduction. This paper describes an investigation of two different NICU radiological techniques with significantly different neonate doses. While patient-matched images taken with both techniques were assessed in a blind review, this component of the study is beyond the scope of this paper and is not discussed here. (author)

Jungle Honey Enhances Immune Function and Antitumor Activity

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Miki Fukuda

2011-01-01

Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

PROFIL TETANUS NEONATORUM DALAM RANGKA KEBIJAKAN ELIMINASI TETANUS MATERNAL DAN NEONATAL DI KABUPATEN BANGKALAN PROVINSI JAWA TIMUR TAHUN 2012–2014

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Mugeni Sugiharto

2017-01-01

: Infants in their golden period are particularly vulnerable to infectious diseases, such as neonatal tetanus. Bangkalan District Government supports policy on Elimination Maternal Neonatal Tetanus (EMNT to save infants from neonatal tetanus infection. The study aims to identify profiles of tetanus cases among infants for support the policy on EMNT in Bangkalan District, East Java Province year 2012–2014. Methods: The study used secondary data on Tetanus Toxoid immmunization and tetanus neonatorum from Bangkalan District Health Office. In Depth interview on the policy on EMNT for the Programmer of immunization. Result: Every year there were tetanus neonatorum cases in Bangkalan District that caused deats because their mothers were not immunized by TT during pregnancies, deliveries assisted by traditional birth attendants, unhygienic cord care such as unsterile scissors and using traditional herbs for curing. To prevent tetanus neonatorum, Bangkalan District issued policy on EMNT as in the operational strategies that must conducted by all related staffs. Implementation of the EMNT policy is not as expected because there were still TN cases are each year, TT coverage tended lower as 61.7% in 2012 to 59.18% in 2014. In accordance, DPT for infants were from 92.8% to 88.0% during the same. Conclusion: Bangkalan District are prone to tetanus, including tetanus neonatorum, due to declining coverages of TT immunization among pregnant women and DPT immunization among infants each year. The policy of tetanus neonatorum elimination was appropriate to increase immunization coverage and prevents TN among infants in Bangkalan. Suggestion: Programmer immunization should be more active to disseminate TT immunization through the ANC among pregnant women and DPT for infants to prevent tetanus cases. 

Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

International Nuclear Information System (INIS)

Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

2006-01-01

Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

Murine and bovine γδ T cells enhance innate immunity against Brucella abortus infections.

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Jerod A Skyberg

Full Text Available γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ(-/- mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα(-/-, and GMCSF(-/- mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ(-/- mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.

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Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J

2015-01-23

Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Combined effect of x irradiation and cell-mediated immune reaction

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Song, C.W.; Guertin, D.P.

1978-01-01

The combined effect of radiation and cell-mediated immune reaction on tumor cells was investigated in vitro. Mastocytoma P815-X2 cells of DBA mice either were irradiated first and subjected to immune lysis by immune splenic lymphocytes of C57Bl mice, or the tumor cells were subjected to immune reaction first and then irradiated. Cell survival was quantitated by colony formation in soft agar medium. It was observed that cellular immune damage to tumor cells did not influence the response of tumor cells to subsequent radiation. Irradiation of tumor cells first, followed by subjection of the cells to cellular immune reaction, slightly enhanced the death of the tumor cells. It appears that this enhanced death might have resulted from a relative increase in the ratio of the number of cytotoxic immune cells to the number of target tumor cells in the incubation mixture as a consequence of the decrease in the number of viable tumor cells by radiation

Neonatal Meningoventriculitis Due to Proteus Mirabilis – A Case Report

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Juyal, Deepak; Rathaur, Vyas Kumar; Sharma, Neelam

2013-01-01

A five day old full term born baby was admitted to our Neonatal Intensive Care Unit with seizures, opisthotonous posture and was icteric upto thigh. Baby had a three day history of poor feeding, lethargy and abnormal body movements. Mother was a 29 years old primigravida and had a normal vaginal delivery at home. Sepsis profile of the patient was requested, lumbar puncture and ventricular tap was performed. Patient was put on third generation cephalosporins, aminoglycosides and phenobarbitone. Culture and sensitivity report of blood, Cerebro spinal fluid and ventricular fluid showed Proteus mirabilis. Computerized Tomography scan showed a large parenchymal lesion in the right frontal lobe and diffuse ependymal enhancement along both the lateral ventricles suggestive of meningoventriculitis. We hereby present a fatal case of neonatal meningoventriculitis due to Proteus mirabilis. PMID:23543669

Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.