Seed size selection by olive baboons.

PubMed

Kunz, Britta Kerstin; Linsenmair, Karl Eduard

2008-10-01

Seed size is an important plant fitness trait that can influence several steps between fruiting and the establishment of a plant's offspring. Seed size varies considerably within many plant species, yet the relevance of the trait for intra-specific fruit choice by primates has received little attention. Primates may select certain seed sizes within a species for a number of reasons, e.g. to decrease indigestible seed load or increase pulp intake per fruit. Olive baboons (Papio anubis, Cercopithecidae) are known to select seed size in unripe and mature pods of Parkia biglobosa (Mimosaceae) differentially, so that pods with small seeds, and an intermediate seed number, contribute most to dispersal by baboons. We tested whether olive baboons likewise select for smaller ripe seeds within each of nine additional fruit species whose fruit pulp baboons commonly consume, and for larger seeds in one species in which baboons feed on the seeds. Species differed in fruit type and seed number per fruit. For five of these species, baboons dispersed seeds that were significantly smaller than seeds extracted manually from randomly collected fresh fruits. In contrast, for three species, baboons swallowed seeds that were significantly longer and/or wider than seeds from fresh fruits. In two species, sizes of ingested seeds and seeds from fresh fruits did not differ significantly. Baboons frequently spat out seeds of Drypetes floribunda (Euphorbiaceae) but not those of other plant species having seeds of equal size. Oral processing of D. floribunda seeds depended on seed size: seeds that were spat out were significantly larger and swallowed seeds smaller, than seeds from randomly collected fresh fruits. We argue that seed size selection in baboons is influenced, among other traits, by the amount of pulp rewarded per fruit relative to seed load, which is likely to vary with fruit and seed shape.

Cloning and transgenesis in mammals: implications for xenotransplantation.

PubMed

Piedrahita, Jorge A; Mir, Bashir

2004-01-01

Availability of suitable organs for transplantation remains of major concern and projections indicate that the problem will continue to increase. Therefore, alternatives to the use of human organs for transplantation, continue to be explored including use of stem cells, artificial organs, and organs from other species (xenotransplantation). In xenotransplantation, the species of choice remains the pig due to its physiological similarities to humans, reduced costs, ease of manipulation, and reduced ethical concerns to its use. However, in order to develop pig organs that are suitable for xenotransplantation, complex genetic modification need to be undertaken. These modifications require the introduction of precise genetic changes into the pig that can only be accomplished at this time using somatic cell nuclear transfer. We cover in this review advances in transgenic manipulation and cloning in swine and how the development of these two technologies is critical to the eventual utilization of the pig as a human organ donor.

Xenotransplantation of neonatal porcine liver cells.

PubMed

Garkavenko, O; Emerich, D F; Muzina, M; Muzina, Z; Vasconcellos, A V; Ferguson, A B; Cooper, I J; Elliott, R B

2005-01-01

Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

Recommendations of the National Heart, Lung, and Blood Institute Heart and Lung Xenotransplantation Working Group.

PubMed

Platt, Jeffrey; DiSesa, Verdi; Gail, Dorothy; Massicot-Fisher, Judith

2002-08-27

The National Heart, Lung, and Blood Institute (NHLBI) recently convened the Heart and Lung Xenotransplantation Working Group to identify hurdles to the clinical application of xenotransplantation, defined as the use of animal organs or tissue for transplantation, and to recommend possible solutions to these problems. The group consisted of experts in xenotransplantation from academia, industry, and federal agencies, and the discussions focused on those areas within the mission of the NHLBI. The areas covered included immunologic and physiological barriers to xenotransplantation, the limitations of the current animal models, the need for collaboration among groups, the high costs of studies using nonhuman primates and genetic engineering of pigs, and the unique problems of lung xenotransplantation. This report is a summary of those discussions.

PROGRESS IN CLINICAL ENCAPSULATED ISLET XENOTRANSPLANTATION

PubMed Central

Cooper, David K.C.; Matsumoto, Shinichi; Abalovich, Adrian; Itoh, Takeshi; Mourad, Nizar I.; Gianello, Pierre R; Wolf, Eckhard; Cozzi, Emanuele

2016-01-01

At the 2015 combined congress of the CTS, IPITA, and IXA, a symposium was held to discuss recent progress in pig islet xenotransplantation. The presentations focused on 5 major topics – (i) the results of 2 recent clinical trials of encapsulated pig islet transplantation, (ii) the inflammatory response to encapsulated pig islets, (iii) methods to improve the secretion of insulin by pig islets, (iv) genetic modifications to the islet-source pigs aimed to protect the islets from the primate immune and/or inflammatory responses, and (v) regulatory aspects of clinical pig islet xenotransplantation. Trials of microencapsulated porcine islet transplantation to treat unstable type 1 diabetic patients have been associated with encouraging preliminary results. Further advances to improve efficacy may include (i) transplantation into a site other than the peritoneal cavity, which might result in better access to blood, oxygen, and nutrients; (ii) the development of a more biocompatible capsule and/or the minimization of a foreign body reaction; (iii) pig genetic modification to induce a greater secretion of insulin by the islets, and/or to reduce the immune response to islets released from damaged capsules; and (iv) reduction of the inflammatory response to the capsules/islets by improvements in the structure of the capsules and/or in genetic-engineering of the pigs and/or in some form of drug therapy. Ethical and regulatory frameworks for islet xenotransplantation are already available in several countries, and there is now a wider international perception of the importance of developing an internationally-harmonized ethical and regulatory framework. PMID:27482959

Pig-to-Primate Islet Xenotransplantation: Past, Present, and Future

PubMed Central

Liu, Zhengzhao; Hu, Wenbao; He, Tian; Dai, Yifan; Hara, Hidetaka; Bottino, Rita; Cooper, David K. C.; Cai, Zhiming; Mou, Lisha

2017-01-01

Islet allotransplantation results in increasing success in treating type 1 diabetes, but the shortage of deceased human donor pancreata limits progress. Islet xenotransplantation, using pigs as a source of islets, is a promising approach to overcome this limitation. The greatest obstacle is the primate immune/inflammatory response to the porcine (pig) islets, which may take the form of rapid early graft rejection (the instant blood-mediated inflammatory reaction) or T-cell-mediated rejection. These problems are being resolved by the genetic engineering of the source pigs combined with improved immunosuppressive therapy. The results of pig-to-diabetic nonhuman primate islet xenotransplantation are steadily improving, with insulin independence being achieved for periods >1 year. An alternative approach is to isolate islets within a micro- or macroencapsulation device aimed at protecting them from the human recipient's immune response. Clinical trials using this approach are currently underway. This review focuses on the major aspects of pig-to-primate islet xenotransplantation and its potential for treatment of type 1 diabetes. PMID:28155815

Jewish, Christian and Muslim theological perspectives about xenotransplantation.

PubMed

Paris, Wayne; Seidler, Rabbi Jerry H; FitzGerald, Kevin; Padela, Aasim I; Cozzi, Emanuele; Cooper, David K C

2018-04-24

This paper is based on a theological symposium presented at the International Xenotransplantation Association's 14th Congress held in Baltimore, MD, September, 2017. The information explores the Jewish, Christian and Muslim theological perceptions and perspectives about cross-species (ie pig-to-human) organ transplantation, the genetic alterations required in the organ-source pig, and their potential to influence individual acceptance of the procedure. This work should not be considered as the ultimate word about individual theological views, but rather as part of an ongoing conversation that will hopefully lead to wider consideration and exploration of these issues as xenotransplantation science advances towards clinical trials. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical xenotransplantation, a closer reality: Literature review.

PubMed

Aristizabal, Ana María; Caicedo, Luis Armando; Martínez, Juan Manuel; Moreno, Manuel; J Echeverri, Gabriel

2017-02-01

Xenotransplantation could provide an unlimited supply of organs and solve the current shortage of organs for transplantation. To become a reality in clinical practice, the immunological and physiological barriers and the risk of xenozoonosis that they possess should be resolved. From the immunological point of view, in the last 30 years a significant progress in the production of transgenic pigs has prevented the hyperacute rejection. About xenozoonosis, attention has been focused on the risk of transmission of porcine endogenous retroviruses; however, today, it is considered that the risk is very low and the inevitable transmission should not prevent the clinical xenotransplantation. Regarding the physiological barriers, encouraging results have been obtained and it's expected that the barriers that still need to be corrected can be solved in the future through genetic modifications. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of bendectin embryotoxicity in nonhuman primates: I. Ventricular septal defects in prenatal macaques and baboon.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Rowland, J

1985-10-01

Cynomolgus monkeys, rhesus monkeys and baboons were administered 10 to 40 times the human dose equivalent of Bendectin throughout the major period of organogenesis (22(+/-3)-50 days of gestation). In animals examined prenatally (100 +/- 2 days gestation) the total incidence of ventricular septal defects (VSD) was 40% in cynomolgus monkeys, 18% in rhesus monkeys, and 23% in baboons. The majority of VSD involved the muscular portion of the septum. No dose response was evident and there were no other cardiac or extracardiac defects found except for one baboon fetus with multiple defects. No defects were observed in cynomolgus monkeys administered Bendectin for 4-day periods between 22 and 41 days of gestation. There was no association of Bendectin treatment with any noncardiac defect. In cynomolgus and rhesus monkeys examined at term there was one mitral valve defect and no incidence of VSD. The increased incidence of VSD observed prenatally in all three species and the absence of defects in macaques at term suggests a delay in closure of the ventricular septum in treated animals. The Bendectin-treated monkey may be a suitable model for the study of the pathogenesis of VSD and the mechanism of spontaneous closure of the defect.

TRANSPLANTATION OF HEPATOCYTES FROM GENETICALLY-ENGINEERED PIGS IN BABOONS

PubMed Central

Iwase, Hayato; Liu, Hong; Schmelzer, Eva; Ezzelarab, Mohamed; Wijkstrom, Martin; Hara, Hidetaka; Lee, Whayoung; Singh, Jagjit; Long, Cassandra; Lagasse, Eric; Gerlach, Jörg C.; Cooper, David K.C.; Gridelli, Bruno

2017-01-01

Background Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically-engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes. Methods Baboons (n=3) were recipients of GTKO/hCD46 pig hepatocytes. All three baboons received anti-thymocyte globulin (ATG) induction and tapering methylprednisolone. Baboon 1 received maintenance immunosuppressive therapy with tacrolimus and rapamycin. Baboons 2 and 3 received an anti-CD40mAb/rapamycin-based regimen that prevents sensitization to pig solid organ grafts. The baboons were euthanized 4 or 5 weeks after hepatocyte transplantation. The baboon immune response was monitored by measurement of anti-nonGal IgM and IgG antibodies (by flow cytometry) and CFSE-mixed lymphocyte reaction. Monitoring for hepatocyte survival and function was by (i) real-time PCR detection of porcine DNA, (ii) real-time PCR for porcine gene expression, and (iii) pig serum albumin levels (by ELISA). The sites of hepatocyte injection were examined microscopically. Results Detection of porcine DNA and porcine gene expression was minimal at all sites of hepatocyte injection. Serum levels of porcine albumen were very low – 500–1,000-fold lower than in baboons with orthotopic pig liver grafts, and approximately 5,000-fold lower than in healthy pigs. No hepatocytes or infiltrating immune cells were seen at any of the injection sites. Two baboons (Baboons 1 and 3) demonstrated a significant increase in anti-pig IgM and an even greater increase in IgG, indicating sensitization to pig antigens. Discussion and Conclusions As a

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

Transplantation of hepatocytes from genetically engineered pigs into baboons.

PubMed

Iwase, Hayato; Liu, Hong; Schmelzer, Eva; Ezzelarab, Mohamed; Wijkstrom, Martin; Hara, Hidetaka; Lee, Whayoung; Singh, Jagjit; Long, Cassandra; Lagasse, Eric; Gerlach, Jörg C; Cooper, David K C; Gridelli, Bruno

2017-03-01

Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes. Baboons (n=3) were recipients of GTKO/hCD46 pig hepatocytes. All three baboons received anti-thymocyte globulin (ATG) induction and tapering methylprednisolone. Baboon 1 received maintenance immunosuppressive therapy with tacrolimus and rapamycin. Baboons 2 and 3 received an anti-CD40mAb/rapamycin-based regimen that prevents sensitization to pig solid organ grafts. The baboons were euthanized 4 or 5 weeks after hepatocyte transplantation. The baboon immune response was monitored by the measurement of anti-non-Gal IgM and IgG antibodies (by flow cytometry) and CFSE-mixed lymphocyte reaction. Monitoring for hepatocyte survival and function was by (i) real-time PCR detection of porcine DNA, (ii) real-time PCR for porcine gene expression, and (iii) pig serum albumin levels (by ELISA). The sites of hepatocyte injection were examined microscopically. Detection of porcine DNA and porcine gene expression was minimal at all sites of hepatocyte injection. Serum levels of porcine albumen were very low-500-1000-fold lower than in baboons with orthotopic pig liver grafts, and approximately 5000-fold lower than in healthy pigs. No hepatocytes or infiltrating immune cells were seen at any of the injection sites. Two baboons (Baboons 1 and 3) demonstrated a significant increase in anti-pig IgM and an even greater increase in IgG, indicating sensitization to pig antigens. As a result of this disappointing experience, the following points

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

PubMed Central

Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

2016-01-01

The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

Translational Model of Zika Virus Disease in Baboons.

PubMed

Gurung, Sunam; Preno, Alisha N; Dubaut, Jamie P; Nadeau, Hugh; Hyatt, Kimberly; Reuter, Nicole; Nehete, Bharti; Wolf, Roman F; Nehete, Pramod; Dittmer, Dirk P; Myers, Dean A; Papin, James F

2018-06-06

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus with devastating outcomes seen recently in the Americas due to the association of maternal ZIKV infection with fetal microcephaly and other fetal malformations not previously associated with flavivirus infections. Here, we have developed the olive baboon ( Papio anubis ) as a non-human primate (NHP) translational model for the study of ZIKV pathogenesis and associated disease outcomes to contrast and compare with humans and other major NHPs such as macaques. Following subcutaneous inoculation of adult male and non-pregnant female baboons, viremia was detected at 3 and 4 days post infection (dpi) with the concordant presentation of a visible rash and conjunctivitis similar to human ZIKV infection. Furthermore, virus was detected in the mucosa and cerebrospinal fluid. A robust ZIKV-specific IgM and IgG antibody response was also observed in all animals. These data show striking similarity between humans and the olive baboon following infection with ZIKV suggesting our model as a suitable translational NHP model to study ZIKV pathogenesis and potential therapeutics. IMPORTANCE ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks where more severe outcomes were reported. Here we present the baboon as a non-human primate model for contrast and comparison to other published animal models of ZIKV such as the mouse and macaque species. Baboons breed year around and are not currently a primary non-human primate species used in biomedical research marking them more readily available for studies other than Human Immunodeficiency virus studies, which many macaque species are designated for. This taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics and size, makes

Myxomatous neoplasms in the perineal region of baboons

PubMed Central

Wallace, Shannon M.; Szabo, Kathleen A.; Schlabritz-Loutsevitch, Natalia E.; Dick, Edward J.; Blanchard, Terrell W.; Hubbard, Gene B.

2012-01-01

Background In baboons, Papio sp. neoplasms tend to affect the hematopoietic system most commonly, with rare documentation of myxomatous neoplasms. In contrast, women can develop myxomatous masses within deep peripelvic tissues with some frequency during their reproductive years. Methods We have identified and examined, retrospectively, myxomatous perineal masses in twelve female baboons within one research facility and compared their histopathologic, immunohistochemical and electron microscopic features to their human variants. Results Our results indicate that these myxomatous neoplasms, in humans and non-human primates, share common features. Conclusion Further research, particularly molecular genetic analysis, may be needed to identify the baboon as a true animal model for myxomatous perineal neoplasms. PMID:19017193

An overview of the role of society and risk in xenotransplantation.

PubMed

Sobbrio, Paola; Jorqui, María

2014-01-01

Over time, the notion of public has evolved. While the concept of public was initially conceived of as a single undifferentiated entity, the common understanding is now that a variety of differentiated, multifaceted and multiple public(s) can be constructed for different purposes. This is equally true in xenotransplantation; the literature shows how different kind of publics can be introduced as relevant. The paper explores the notion of public and the contemporary participatory procedures as participatory rights for citizens in decisions concerning technoscience and society. Its perspective, thus, is normative; namely, it aims at understanding how the political role of citizens is changing in democratic societies where matters of innovation are concerned. It is focused on xenotransplantation whose connections with public discourse and practices are quite paradigmatic among new emerging biomedical technologies, due to its peculiar risks. The paper reviews the historical background of risk communication and public involvement in science-based decision-making and provides an overview of the current roles and meanings of deliberative procedures in xenotransplantation. After a short discussion of the history of the social implementation of xenotransplantation, the construction of the different publics dealing with this biomedical technology is briefly analysed. Publics have been firstly conceived of as objects of research, which has looked at them to quantify people's positive and negative attitudes towards xenotransplantation. Further developments have led to the notion of the public as composed of citizens, empowered as subjects of decisions. In both Canadian and Australian consultations, citizens were engaged in a complex learning process aimed at committing them to a decision. Despite the fact both public consultations represented important forms of experimental democracy, they were still focused on seeking consensus and assessing compliance from citizens. New

Sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons and their perceptual discrimination by baboon listeners

NASA Astrophysics Data System (ADS)

Rendall, Drew; Owren, Michael J.; Weerts, Elise; Hienz, Robert D.

2004-01-01

This study quantifies sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons (Papio spp.) and tests the basic perceptual discriminability of these differences to baboon listeners. Acoustic analyses were performed on 1028 grunts recorded from 27 adult baboons (11 males and 16 females) in southern Africa, focusing specifically on the fundamental frequency (F0) and formant frequencies. The mean F0 and the mean frequencies of the first three formants were all significantly lower in males than they were in females, more dramatically so for F0. Experiments using standard psychophysical procedures subsequently tested the discriminability of adult male and adult female grunts. After learning to discriminate the grunt of one male from that of one female, five baboon subjects subsequently generalized this discrimination both to new call tokens from the same individuals and to grunts from novel males and females. These results are discussed in the context of both the possible vocal anatomical basis for sex differences in call structure and the potential perceptual mechanisms involved in their processing by listeners, particularly as these relate to analogous issues in human speech production and perception.

Charting the neglected West: The social system of Guinea baboons.

PubMed

Fischer, Julia; Kopp, Gisela H; Dal Pesco, Federica; Goffe, Adeelia; Hammerschmidt, Kurt; Kalbitzer, Urs; Klapproth, Matthias; Maciej, Peter; Ndao, Ibrahima; Patzelt, Annika; Zinner, Dietmar

2017-01-01

Primate social systems are remarkably diverse, and thus play a central role in understanding social evolution, including the biological origin of human societies. Although baboons have been prominently featured in this context, historically little was known about the westernmost member of the genus, the Guinea baboon (Papio papio). Here, we summarize the findings from the first years of observations at the field site CRP Simenti in the Niokolo Koba National Park in Senegal. Guinea baboons reveal a nested multi-level social organization, with reproductive units comprising one "primary" male, one to several females, young, and occasionally "secondary" males at the base of the society. Three to five units form "parties," which team up with other parties to form a "gang." Different gangs have largely overlapping home ranges and agonistic interactions between different parties or gangs are rare. Some but not all strongly socially bonded males are highly related, and population genetic and behavioral evidence indicate female-biased dispersal. Females play an important role in intersexual bond formation and maintenance, and female tenure length varies between a few weeks to several years. While the social organization resembles that of hamadryas baboons (P. hamadryas), the social structure differs considerably, specifically in terms of low male aggressiveness and female freedom. Despite substantial differences in social organization and social structure, the acoustic structure of Guinea baboon vocalizations does not differ substantially from that of other baboon taxa. With its multi-level organization, stable bonds between males and females, as well as a high-degree of male-male cooperation and tolerance, Guinea baboons constitute an intriguing model for reconstructing human social evolution. © 2017 American Association of Physical Anthropologists.

Attitude of Nursing Students at the University of Lublin in Poland Toward Xenotransplantation of Organs.

PubMed

Mikla, M; Rios, A; Lopez-Navas, A; Dobrowolska, B; Kilanska, D; Martinez-Alarcon, L; Ramis, G; Ramirez, P; Lopez Montesinos, M J

2015-11-01

Because of the shortage of organs, it has become necessary to look for alternative sources of organs, such as xenotransplantation. The aim of this study was to analyze the attitude of nursing students at a university in the Eastern Poland toward xenotransplantation, to determine factors that affect their acceptance. During the 2011-2012 academic year, nursing students at the University of the Eastern Poland enrolled the 5 nursing courses self-administered a validated questionnaire (the PCID-XenoTx Rios) anonymously. We undertook a descriptive statistical analysis using the Student t test, χ(2) test, and logistic regression analysis. The completion rate was 90% (608 of 672). When asked about the acceptability of organ donation from humans, 62% (n = 379) were in favor, 9% (n = 54) against, and 29% (n = 175) undecided. We found a significant association between the acceptability of transplantation and the university course and the respondents' religion (P ≤ .05). Fourth-year students have a more favorable attitude toward xenotransplantation than third-year students (75% vs 54%; P = .018). Catholics accept this type of donation more readily than those belonging to other faith traditions (63% vs 37%; P = .053). In the multivariate analysis, academic course is a significant influence on attitude toward xenotransplantation (odds ratio, 2.421; 95% CI, 4.347-1.345; P = .003). Nursing students have an unfavorable attitude toward xenotransplantation. This attitude is influenced by the religious beliefs and their academic year. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical porcine islet xenotransplantation under comprehensive regulation.

PubMed

Matsumoto, S; Tan, P; Baker, J; Durbin, K; Tomiya, M; Azuma, K; Doi, M; Elliott, R B

2014-01-01

Xenotransplantation with porcine islets is a promising approach to overcome the shortage of human donors. This is the first report of phase 1/2a xenotransplantation study of encapsulated neonatal porcine islets under the current framework of regulations for xenotransplantation in New Zealand. Newborn piglets were anesthetized and bled, and the pancreata were removed with the use of sterile technique and processed. Encapsulated neonatal porcine islets were implanted with the use of laparoscopy into the peritoneal cavity of 14 patients with unstable type 1 diabetes without any immunosuppressive drugs. The patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4; group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents per kg body weight. Outcome was determined from adverse event reports, HbA1c, total daily insulin dose, and frequency of unaware hypoglycemic events. To assess graft function, transplant estimated function (TEF) scores were calculated. Sufficient or marginal numbers of encapsulated neonatal porcine islets were transplanted into streptozotocin-induced diabetic B6 mice as an in vivo functional assay. There were 4 serious adverse events, of which 3 were considered to be possibly related to the procedure. Tests for porcine endogenous retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia events were reduced after transplantation in all groups. Four of 14 patients attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17, 0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study demonstrated that a sufficient number of the transplanted group reversed diabetes with positive porcine C-peptide. Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo assessment data demonstrated certain graft function. Copyright �

Craniofacial trauma as a clinical marker of seizures in a baboon colony.

PubMed

Szabó, C Akos; Knape, Koyle D; Leland, M Michelle; Bauer, Cassondra; Williams, Jeff T

2014-04-01

Baboons provide a natural model of epilepsy. However, spontaneous seizures are usually sporadic, brief, and may not be observed. We hypothesized that various types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We evaluated the type, demographics, and clinical significance of CFT in a large baboon colony. CFT was categorized according to somatotopic location, propensity to recur, and association with witnessed seizures or abnormal EEG findings. We divided the baboons with CFT into 2 groups: those with known histories of seizures (CFT+Sz, n = 176) and those without seizure histories (CFTonly; n = 515). In CFT+Sz baboons, the 568 injuries identified included periorbital (57%), scalp (27%), muzzle (12%), and facial (4%) injuries; multiple somatotopic locations or body parts were affected in 21 baboons. The most common CFT injuries associated with seizures were periorbital and scalp lesions (43% for each region). Compared with those in CFTonly animals, EEG abnormalities, including interictal epileptic discharges (IED) and photosensitivity were more prevalent in the CFT+Sz group, particularly among baboons with periorbital or scalp injuries. Compared with CFT+Sz animals, CFTonly baboons tended to have later onset and less frequent recurrence of CFT but higher prevalence of muzzle and tooth injuries. IED and photosensitivity were less prevalent in the CFTonly than the CFT+Sz group, with periorbital injuries carrying the highest and muzzle injuries the lowest association with IED or photosensitivity in both groups. Therefore, CFT in general and periorbital injuries in particular may be markers for seizures in baboons.

Craniofacial Trauma as a Clinical Marker of Seizures in a Baboon Colony

PubMed Central

Szabó, C Ákos; Knape, Koyle D; Leland, M Michelle; Bauer, Cassondra; Williams, Jeff T

2014-01-01

Baboons provide a natural model of epilepsy. However, spontaneous seizures are usually sporadic, brief, and may not be observed. We hypothesized that various types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We evaluated the type, demographics, and clinical significance of CFT in a large baboon colony. CFT was categorized according to somatotopic location, propensity to recur, and association with witnessed seizures or abnormal EEG findings. We divided the baboons with CFT into 2 groups: those with known histories of seizures (CFT+Sz, n = 176) and those without seizure histories (CFTonly; n = 515). In CFT+Sz baboons, the 568 injuries identified included periorbital (57%), scalp (27%), muzzle (12%), and facial (4%) injuries; multiple somatotopic locations or body parts were affected in 21 baboons. The most common CFT injuries associated with seizures were periorbital and scalp lesions (43% for each region). Compared with those in CFTonly animals, EEG abnormalities, including interictal epileptic discharges (IED) and photosensitivity were more prevalent in the CFT+Sz group, particularly among baboons with periorbital or scalp injuries. Compared with CFT+Sz animals, CFTonly baboons tended to have later onset and less frequent recurrence of CFT but higher prevalence of muzzle and tooth injuries. IED and photosensitivity were less prevalent in the CFTonly than the CFT+Sz group, with periorbital injuries carrying the highest and muzzle injuries the lowest association with IED or photosensitivity in both groups. Therefore, CFT in general and periorbital injuries in particular may be markers for seizures in baboons. PMID:24674589

Liver xenotransplantation.

PubMed

Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

1993-10-01

During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

An efficient model of human endometriosis by induced unopposed estrogenicity in baboons.

PubMed

Nair, Hareesh B; Baker, Robert; Owston, Michael A; Escalona, Renee; Dick, Edward J; VandeBerg, John L; Nickisch, Klaus J

2016-03-08

Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis.

Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon.

PubMed

Clauss, Ralf P; Dormehl, Irene C; Kilian, Elmaré; Louw, Werner K A; Nel, Wally H; Oliver, Douglas W

2002-01-01

Previous studies have shown that zolpidem (CAS 82626-48-0) can lead to improved perfusion in damaged brain tissue. Zolpidem belongs to the imidazopyridine chemical class and it illicits its pharmacological action via the gamma-aminobutyric acid (GABA) receptor system through stimulation of particularly the omega 1 receptors and to a lesser extent omega 2 receptors. Previously it was reported that no cerebral blood flow effects were observed in normal baboons after treatment with zolpidem, whereas an asymmetric regional increase in cerebral blood flow was observed in a neurologically abnormal baboon. In this study, the effect of a combination of the benzodiazepine receptor antagonist flumazenil (CAS 78755-81-4) and zolpidem on brain perfusion was examined by the 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) split dose brain single photon emission computed tomography (SPECT). Four normal baboons and the neurologically abnormal baboon from the previous zolpidem study were examined. In the current study the asymmetric changes observed after zolpidem--only treatment in the abnormal baboon was attenuated by flumazenil intervention. A decreased brain blood flow was observed after combination treatment of zolpidem and flumazenil in the normal baboons. The involvement of the omega receptors is suggested by these results. Up- or down-regulation of omega receptors may also contribute to the observed responses in the abnormal baboon and a brain injured patient.

Extreme behavioural shifts by baboons exploiting risky, resource-rich, human-modified environments.

PubMed

Fehlmann, Gaelle; O'Riain, M Justin; Kerr-Smith, Catherine; Hailes, Stephen; Luckman, Adrian; Shepard, Emily L C; King, Andrew J

2017-11-08

A range of species exploit anthropogenic food resources in behaviour known as 'raiding'. Such behavioural flexibility is considered a central component of a species' ability to cope with human-induced environmental changes. Here, we study the behavioural processes by which raiding male chacma baboons (Papio ursinus) exploit the opportunities and mitigate the risks presented by raiding in the suburbs of Cape Town, South Africa. Ecological sampling and interviews conducted with 'rangers' (employed to manage the baboons' space use) revealed that baboons are at risk of being herded out of urban spaces that contain high-energy anthropogenic food sources. Baboon-attached motion/GPS tracking collars showed that raiding male baboons spent almost all of their time at the urban edge, engaging in short, high-activity forays into the urban space. Moreover, activity levels were increased where the likelihood of deterrence by rangers was greater. Overall, these raiding baboons display a time-activity balance that is drastically altered in comparison to individuals living in more remote regions. We suggest our methods can be used to obtain precise estimates of management impact for this and other species in conflict with people.

Attitudes of primary care professionals in Spain toward xenotransplantation.

PubMed

Conesa, C; Ríos, A; Ramírez, P; Sánchez, J; Sánchez, E; Rodríguez, M M; Martínez, L; Fernández, O M; Ramos, F; Montoya, M J; Parrilla, P

2006-04-01

The deficit in transplantable organs is making it necessary to find alternative sources. One possibility is xenotransplantation. However, the use of animal organs may be rejected by society and among health professionals. Primary Care is fundamental for promoting matters of health; in Spain it has access to nearly 100% of the population. Our objective was to analyze the acceptance of this therapy, although it is experimental, among Primary Care professionals, given that they are the ones most involved in spreading information about this therapy if it was confirmed to be useful. A random sample was stratified by sex, job category, and geographical location among Primary Care personnel, including 428 professionals in 32 health centers among population of 2851 professionals. Attitudes toward xenotransplantation were evaluated using a questionnaire on psychosocial attitudes validated in our geographical area. Contact was made in each center with the Doctor Coordinator for doctors, the Nursing Coordinator for nurses, and an Administrative Officer for ancillary personnel. The chi-square test and Student t test were applied to evaluate categorical and continuous data, respectively. Attitudes toward xenotransplantation were similar to those obtained in human organs: favorable in 79% (n = 325), whereas 19% (n = 78) had doubts and 2% (n = 10) were against. The attitude was more favorable in men (89% vs 72%; P < .000), those who had cared for transplant patients (84% vs 71%; P = .009), those with previous experience in organ donation and transplantation (84% vs 75%; P = .033), those with an attitude in favor of cadaveric organ donation (83% vs 66%; P < .0001), and those in favor of living donation of the kidney (P < .000) or the liver (P < .000), as well as those who believed that they may need a transplant at some time in the future (84% vs 74%; P = .045). There was a clear difference in attitude according to job category (P = .018): approval rates were 89% for doctors, 76

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralimanoharan, Sribalasubashini; Li, Cun; Nakayasu, Ernesto S.

Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased ( SMAD3 and ALK-1 were downregulated in male IUGRs with no differencemore » in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and. females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4α, and NFκB p50). Lipidomics analysis exhibited a net increase in diacylglycerol and plasmalogens, and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.« less

GROUP DECISIONS. Shared decision-making drives collective movement in wild baboons.

PubMed

Strandburg-Peshkin, Ariana; Farine, Damien R; Couzin, Iain D; Crofoot, Margaret C

2015-06-19

Conflicts of interest about where to go and what to do are a primary challenge of group living. However, it remains unclear how consensus is achieved in stable groups with stratified social relationships. Tracking wild baboons with a high-resolution global positioning system and analyzing their movements relative to one another reveals that a process of shared decision-making governs baboon movement. Rather than preferentially following dominant individuals, baboons are more likely to follow when multiple initiators agree. When conflicts arise over the direction of movement, baboons choose one direction over the other when the angle between them is large, but they compromise if it is not. These results are consistent with models of collective motion, suggesting that democratic collective action emerging from simple rules is widespread, even in complex, socially stratified societies. Copyright © 2015, American Association for the Advancement of Science.

Teenagers and Their Future Role in Transplantation: An Analysis of Their Attitudes Toward Solid Organ Xenotransplantation.

PubMed

Febrero, B; Ríos, A; López-Navas, A; Martínez-Alarcón, L; Almela, J; Ramis, G; Ramírez, P; Parrilla, P

2018-03-01

It is important to determine the level of social acceptance of xenotransplantation, especially in places where there are preclinical xenotransplantation projects. In this sense, it is important to know the attitude of teenagers, given that their attitude could have an influence on this kind of donation in the future. The aim of this study is to analyze the attitudes of teenagers toward xenotransplantation and to determine the variables affecting their attitudes. A random simple was obtained of students who were between 12 and 16 years of age in secondary schools in the southeast of Spain (n = 3633). Their attitudes were assessed with the use of a validated psychosocial questionnaire about xenotransplantation (PCID-XenoTx Ríos). The questionnaire was completed anonymously and was self-administered. Descriptive statistical analysis, Student t, and χ 2 tests were used. The completion rate was 97% (n = 3531). With regard to animal organ donation for humans, 44% (n = 1569) would be in favor, 22% (n = 784) against, and 34% (n = 1178) undecided. Attitude was related to knowing a transplantation patient (P = .02), believing that transplant organ needs are not covered (P = .004), having received information about organ donation and transplantation (ODT) on television and from schools (P = .001), family discussion about ODT (P < .001), attitude of the respondent's parents (P < .001), and attitude toward human donation (P < .001). More than half of the teenagers had unfavorable attitudes toward xenotransplantation as this was determined by factors related to knowledge of and previous information about ODT, the attitude of one's family, and attitudes toward the different types of human organ donation. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

PubMed

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

2017-05-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons

PubMed Central

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas

2017-01-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor–β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. PMID:28324053

Differentiation and Characterization of Dopaminergic Neurons From Baboon Induced Pluripotent Stem Cells.

PubMed

Grow, Douglas A; Simmons, DeNard V; Gomez, Jorge A; Wanat, Matthew J; McCarrey, John R; Paladini, Carlos A; Navara, Christopher S

2016-09-01

: The progressive death of dopamine producing neurons in the substantia nigra pars compacta is the principal cause of symptoms of Parkinson's disease (PD). Stem cells have potential therapeutic use in replacing these cells and restoring function. To facilitate development of this approach, we sought to establish a preclinical model based on a large nonhuman primate for testing the efficacy and safety of stem cell-based transplantation. To this end, we differentiated baboon fibroblast-derived induced pluripotent stem cells (biPSCs) into dopaminergic neurons with the application of specific morphogens and growth factors. We confirmed that biPSC-derived dopaminergic neurons resemble those found in the human midbrain based on cell type-specific expression of dopamine markers TH and GIRK2. Using the reverse transcriptase quantitative polymerase chain reaction, we also showed that biPSC-derived dopaminergic neurons express PAX6, FOXA2, LMX1A, NURR1, and TH genes characteristic of this cell type in vivo. We used perforated patch-clamp electrophysiology to demonstrate that biPSC-derived dopaminergic neurons fired spontaneous rhythmic action potentials and high-frequency action potentials with spike frequency adaption upon injection of depolarizing current. Finally, we showed that biPSC-derived neurons released catecholamines in response to electrical stimulation. These results demonstrate the utility of the baboon model for testing and optimizing the efficacy and safety of stem cell-based therapeutic approaches for the treatment of PD. Functional dopamine neurons were produced from baboon induced pluripotent stem cells, and their properties were compared to baboon midbrain cells in vivo. The baboon has advantages as a clinically relevant model in which to optimize the efficacy and safety of stem cell-based therapies for neurodegenerative diseases, such as Parkinson's disease. Baboons possess crucial neuroanatomical and immunological similarities to humans, and baboon

Pig islet xenotransplantation acceptance in a Latin-American diabetic population.

PubMed

Abalovich, Adrián; Wechsler, Carlos; Lara, Silvia; Bervottini, Miguel

2010-01-01

Progress in porcine islet xenotransplantation has been accompanied by studies on acceptance of this new procedure by patients, health professionals or the general public. Such studies have not been done in the Latin-American population. We conducted a questionnaire in 108 diabetes patients (insulin-dependent, n = 53; insulin-independent, n = 55) in a public hospital in Argentina. The questions addressed the general perception of the xenotransplant procedure and specific items related to the outcome (achieving insulin independence, improvement in metabolic control, delay in emergence of diabetic complications, need for repeat procedures, potential of transfer of infectious viruses, association with psychological problems, and anticipated success in relation to achieving a cure). Eighty-six (79%) of the patients accepted islet xenotransplantation; this incidence was not different for insulin-dependent or insulin-independent patients, patients with or without complications, or patients with good or poor metabolic control. Also, over 75% of patients accepted the procedure if this is only associated with a reduction in insulin requirement, if the procedure just delays but not prevents the onset of complications, or if the procedure needs to be performed every 6 months. Fifty-seven percent of patients indicated acceptance even if the potential transmission of a virus infection cannot be completely ruled out: this outcome was not affected by the outbreak of the H1N1 flu epidemic during the conduct of this study. Forty percent of patients indicated that living with porcine cells in their body could give psychological problems. We conclude that this population of Latin-American diabetic patients shows a high acceptance rate of a porcine islet xenotransplantation product. (c) 2010 John Wiley & Sons A/S.

Perspectives on the use of the baboon in embryology and teratology research.

PubMed

Hendrickx, A G; Peterson, P E

1997-01-01

This paper summarizes the developmental stages of the baboon during the period of organ formation and provides comparative information for other primates, including the human. Special attention is directed to the early development of the nervous system, eye, ear and nose/palate. The similarity in development of these structures with humans indicates that the baboon is a suitable model for studies of normal and abnormal neurological development. Spontaneous prenatal loss rates in the baboon (2.4-11.2%) are slightly lower than those reported in rhesus and cynomologus monkeys. The baboon, in addition to the cynomologus monkey and macaque, has been used as a model in teratology research to assess the potential risk of thalidomide, sex steroids, Bendectin and rubella virus, as well as to study the pathogenesis of malformations associated with the corticosteroid triamcinolone acetonide. The rate of spontaneous malformations (<1%) in baboons, similar to that reported for other commonly used primates, supports their continued use as a teratological model. In this regard, a sample protocol is provided for the safety evaluation of biotechnology products using nonhuman primates, which are the most appropriate model for those compounds which are bioactive in species closely related to humans.

Age-related full-field motion change in baboon tympanic membrane

NASA Astrophysics Data System (ADS)

Gan, Rong Z.; Jiang, Shangyuan; Pineda, Mario

2018-05-01

Clinical observations indicate that the structure and function of the middle ear change from newborn to adult. However, due to the lack of young children's temporal bones for investigators, characterizations of the pediatric middle ear function and tissue mechanical properties are limited. Higher primates such as olive baboons (Papio anubis) ear specimens may provide alternative testing sources whose properties are likely to closely resemble those of humans. This paper reports our recent study on measurement of the tympanic membrane (TM) surface motion of baboon temporal bones in the age range from 6 months to young adult using the scanning laser Doppler vibrometry (SLDV). The full-field TM motion and the umbo displacement show that the mobility of the TM at frequencies below 2 kHz increased as age increases and the middle ear input impedance decreased with the age increase. The traveling-wave-like vibration modes in adult TMs started appearing at lower frequencies than that of young baboons. The results show the age-dependent middle ear function changes in baboons which may open a new research dimension to provide urgently needed data for biomechanical properties of young children ears.

Acquisition of joint attention by olive baboons gesturing toward humans.

PubMed

Lamaury, Augustine; Cochet, Hélène; Bourjade, Marie

2017-07-10

Joint attention is a core ability of human social cognition which broadly refers to the coordination of attention with both the presence and activity of social partners. In both human and non-human primates, joint attention can be assessed from behaviour; gestures and gaze alternation between the partner and a distal object are standard behavioural manifestations of joint attention. Here we examined the acquisition of joint attention in olive baboons as a function of their individual experience of a human partner's attentional states during training regimes. Eleven olive baboons (Papio anubis) were observed during their training to perform food-requesting gestures, which occurred either by (1) a human facing them (face condition), or (2) by a human positioned in profile who never turned to them (profile condition). We found neither gestures nor gaze alternation were present at the start of the training but rather developed over the training period. Only baboons in the face condition showed an increase in the number of gaze alternations, and their gaze pattern progressively shifted to a coordinated sequence in which gazes and gestures were coordinated in time. In contrast, baboons trained by a human in profile showed significantly less coordination of gazes with gestures but still learned to request food with their gestures. These results suggest that the partner's social attention plays an important role in the acquisition of visual joint attention and, to a lesser extent, in gesture learning in baboons. Interspecific interactions appear to offer rich opportunities to manipulate and thus identify the social contexts in which socio-communicative skills develop.

What baboons can (not) tell us about natural language grammars.

PubMed

Poletiek, Fenna H; Fitz, Hartmut; Bocanegra, Bruno R

2016-06-01

Rey et al. (2012) present data from a study with baboons that they interpret in support of the idea that center-embedded structures in human language have their origin in low level memory mechanisms and associative learning. Critically, the authors claim that the baboons showed a behavioral preference that is consistent with center-embedded sequences over other types of sequences. We argue that the baboons' response patterns suggest that two mechanisms are involved: first, they can be trained to associate a particular response with a particular stimulus, and, second, when faced with two conditioned stimuli in a row, they respond to the most recent one first, copying behavior they had been rewarded for during training. Although Rey et al. (2012) 'experiment shows that the baboons' behavior is driven by low level mechanisms, it is not clear how the animal behavior reported, bears on the phenomenon of Center Embedded structures in human syntax. Hence, (1) natural language syntax may indeed have been shaped by low level mechanisms, and (2) the baboons' behavior is driven by low level stimulus response learning, as Rey et al. propose. But is the second evidence for the first? We will discuss in what ways this study can and cannot give evidential value for explaining the origin of Center Embedded recursion in human grammar. More generally, their study provokes an interesting reflection on the use of animal studies in order to understand features of the human linguistic system. Copyright © 2015 Elsevier B.V. All rights reserved.

Are baboons learning "orthographic" representations? Probably not

PubMed Central

Bröker, Franziska; Ramscar, Michael; Baayen, Harald

2017-01-01

The ability of Baboons (papio papio) to distinguish between English words and nonwords has been modeled using a deep learning convolutional network model that simulates a ventral pathway in which lexical representations of different granularity develop. However, given that pigeons (columba livia), whose brain morphology is drastically different, can also be trained to distinguish between English words and nonwords, it appears that a less species-specific learning algorithm may be required to explain this behavior. Accordingly, we examined whether the learning model of Rescorla and Wagner, which has proved to be amazingly fruitful in understanding animal and human learning could account for these data. We show that a discrimination learning network using gradient orientation features as input units and word and nonword units as outputs succeeds in predicting baboon lexical decision behavior—including key lexical similarity effects and the ups and downs in accuracy as learning unfolds—with surprising precision. The models performance, in which words are not explicitly represented, is remarkable because it is usually assumed that lexicality decisions, including the decisions made by baboons and pigeons, are mediated by explicit lexical representations. By contrast, our results suggest that in learning to perform lexical decision tasks, baboons and pigeons do not construct a hierarchy of lexical units. Rather, they make optimal use of low-level information obtained through the massively parallel processing of gradient orientation features. Accordingly, we suggest that reading in humans first involves initially learning a high-level system building on letter representations acquired from explicit instruction in literacy, which is then integrated into a conventionalized oral communication system, and that like the latter, fluent reading involves the massively parallel processing of the low-level features encoding semantic contrasts. PMID:28859134

Are baboons learning "orthographic" representations? Probably not.

PubMed

Linke, Maja; Bröker, Franziska; Ramscar, Michael; Baayen, Harald

2017-01-01

The ability of Baboons (papio papio) to distinguish between English words and nonwords has been modeled using a deep learning convolutional network model that simulates a ventral pathway in which lexical representations of different granularity develop. However, given that pigeons (columba livia), whose brain morphology is drastically different, can also be trained to distinguish between English words and nonwords, it appears that a less species-specific learning algorithm may be required to explain this behavior. Accordingly, we examined whether the learning model of Rescorla and Wagner, which has proved to be amazingly fruitful in understanding animal and human learning could account for these data. We show that a discrimination learning network using gradient orientation features as input units and word and nonword units as outputs succeeds in predicting baboon lexical decision behavior-including key lexical similarity effects and the ups and downs in accuracy as learning unfolds-with surprising precision. The models performance, in which words are not explicitly represented, is remarkable because it is usually assumed that lexicality decisions, including the decisions made by baboons and pigeons, are mediated by explicit lexical representations. By contrast, our results suggest that in learning to perform lexical decision tasks, baboons and pigeons do not construct a hierarchy of lexical units. Rather, they make optimal use of low-level information obtained through the massively parallel processing of gradient orientation features. Accordingly, we suggest that reading in humans first involves initially learning a high-level system building on letter representations acquired from explicit instruction in literacy, which is then integrated into a conventionalized oral communication system, and that like the latter, fluent reading involves the massively parallel processing of the low-level features encoding semantic contrasts.

Pharmacokinetics of Fluoxetine in Pregnant Baboons (Papio spp.)

PubMed Central

Shoulson, Rivka L; Stark, Raymond L; Garland, Marianne

2014-01-01

Fluoxetine is used to treat a number of psychiatric conditions in humans and behavioral problems in animals. Its use in pregnancy must balance maternal benefit with potential risk to the fetus. Knowledge of adult and fetal drug disposition can assist clinicians in selecting therapy that minimizes adverse effects to the fetus. Nonhuman primate models are used frequently in drug dose-translation studies, and pregnancy in baboons has many similarities to human pregnancy. Accordingly, pharmacokinetic analysis of a series of fluoxetine and norfluoxetine administrations to pregnant baboons was performed. The mean maternal baboon steady-state clearance of fluoxetine (42 mL/min/kg) was considerably higher than that in humans. Norfluoxetine, the major active metabolite, had a higher metabolite-to-drug ratio (8.7) than that found in humans, particularly with oral dosing. These results are consistent with more extensive metabolism in baboons than in humans and leads to a higher clearance than would be expected from allometric scaling. Fetal-to-maternal fluoxetine and norfluoxetine ratios under steady-state conditions were similar to those in humans, with fetal concentrations of fluoxetine 42% and norfluoxetine 47% of maternal concentrations. The fetal clearance of fluoxetine (303 ± 176 mL/min) and norfluoxetine (450 mL/min) exceeded reported placental blood flow. Understanding these species-associated differences in metabolism is a prerequisite to extrapolating data between species. Nonetheless, nonhuman primates are likely to remain valuable models for pharmacokinetic studies during pregnancy, particularly those directed toward fetal neurodevelopmental effects. Our results also are applicable to determining appropriate dosing of nonhuman primates in clinical settings. PMID:25650979

External cephalic version of the term breech baboon (Papio sp.) fetus.

PubMed

Barrier, Breton F; Joiner, Laura Lee Rihl; Jimenez, Joe B; Leland, M Michelle

2007-06-01

Breech presentation in baboons may be associated with head entrapment and stillbirth during vaginal delivery. For this reason, pregnant dams at our institution typically undergo cesarean delivery for known breech presentation, leading to problems with maternal-infant bonding and increased nursery utilization. This paper describes a simple, non-invasive technique called external cephalic version (ECV) that effectively converts the baboon breech fetus into a cephalic presentation. ECV was successful in each of seven attempted cases, with the consistent development of contractions and vaginal bleeding leading to the delivery of a healthy liveborn infant within 72 hours. ECV may offer a safe and effective alternative to cesarean section for delivery of the breech baboon fetus.

The Study of Glioma by Xenotransplantation in Zebrafish Early Life Stages

PubMed Central

Motaln, Helena; Turnšek, Tamara Lah

2015-01-01

Zebrafish (Danio rerio) and their transparent embryos are becoming an increasingly popular tool for studying processes involved in tumor progression and in the search for novel tumor treatment approaches. The xenotransplantation of fluorescently labeled mammalian cancer cells into zebrafish embryos is an approach enabling relatively high-throughput in vivo analyses. The small size of the embryos as well as the relative simplicity of their manipulation and maintenance allow for large numbers of embryos to be processed efficiently in a short time and at low cost. Furthermore, the possibility of fluorescence microscopic imaging of tumor progression within zebrafish embryos and larvae holds unprecedented potential for the real-time visualization of these processes in vivo. This review presents the methodologies of xenotransplantation studies on zebrafish involving research on tumor invasion, proliferation, tumor-induced angiogenesis and screening for antitumor therapeutics. We further focus on the application of these zebrafish to the study of glioma; in particular, its most common and malignant form, glioblastoma. PMID:26109632

GENETIC VARIATION IN BABOON CRANIOFACIAL SEXUAL DIMORPHISM

PubMed Central

Willmore, Katherine E.; Roseman, Charles C.; Rogers, Jeffrey; Richtsmeier, Joan T.; Cheverud, James M.

2010-01-01

Sexual dimorphism is a widespread phenomenon and contributes greatly to intraspecies variation. Despite a long history of active research, the genetic basis of dimorphism for complex traits remains unknown. Understanding the sex-specific differences in genetic architecture for cranial traits in a highly dimorphic species could identify possible mechanisms through which selection acts to produce dimorphism. Using distances calculated from three-dimensional landmark data from CT scans of 402 baboon skulls from a known genealogy, we estimated genetic variance parameters in both sexes to determine the presence of gene-by-sex (G × S) interactions and X-linked heritability. We hypothesize that traits exhibiting the greatest degree of sexual dimorphism (facial traits in baboons) will demonstrate either stronger G × S interactions or X-linked effects. We found G × S interactions and X-linked effects for a few measures that span the areas connecting the face to the neurocranium but for no traits restricted to the face. This finding suggests that facial traits will have a limited response to selection for further evolution of dimorphism in this population. We discuss the implications of our results with respect to the origins of cranial sexual dimorphism in this baboon sample, and how the genetic architecture of these traits affects their potential for future evolution. PMID:19210535

The production of multi-transgenic pigs: update and perspectives for xenotransplantation.

PubMed

Niemann, Heiner; Petersen, Bjoern

2016-06-01

The domestic pig shares many genetic, anatomical and physiological similarities to humans and is thus considered to be a suitable organ donor for xenotransplantation. However, prior to clinical application of porcine xenografts, three major hurdles have to be overcome: (1) various immunological rejection responses, (2) physiological incompatibilities between the porcine organ and the human recipient and (3) the risk of transmitting zoonotic pathogens from pig to humans. With the introduction of genetically engineered pigs expressing high levels of human complement regulatory proteins or lacking expression of α-Gal epitopes, the HAR can be consistently overcome. However, none of the transgenic porcine organs available to date was fully protected against the binding of anti-non-Gal xenoreactive natural antibodies. The present view is that long-term survival of xenografts after transplantation into primates requires additional modifications of the porcine genome and a specifically tailored immunosuppression regimen compliant with current clinical standards. This requires the production and characterization of multi-transgenic pigs to control HAR, AVR and DXR. The recent emergence of new sophisticated molecular tools such as Zinc-Finger nucleases, Transcription-activator like endonucleases, and the CRISPR/Cas9 system has significantly increased efficiency and precision of the production of genetically modified pigs for xenotransplantation. Several candidate genes, incl. hTM, hHO-1, hA20, CTLA4Ig, have been explored in their ability to improve long-term survival of porcine xenografts after transplantation into non-human primates. This review provides an update on the current status in the production of multi-transgenic pigs for xenotransplantation which could bring porcine xenografts closer to clinical application.

Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.

PubMed

Neubauer, R H; Rabin, H; Strnad, B C; Lapin, B A; Yakovleva, L A; Indzie, E

1979-02-01

An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses.

[Shear waves elastography of the placenta in pregnant baboon].

PubMed

Quarello, E; Lacoste, R; Mancini, J; Melot-Dusseau, S; Gorincour, G

2015-03-01

To evaluate tissue characteristics of the placenta by transabdominal ShearWave Elastography in pregnant baboon. For 9 months (03/2013-12/2013) two operators (EQ, GG) performed ultrasound of the placenta during pregnancy pregnant baboons station partner primatology project. The identification of the placenta was performed previously in 2D ultrasound. The elastography method was then activated. Three measurements were carried out by operator for each placenta. The intraclass correlation coefficients within and between observers were calculated for the objective assessment (elastography) of placental maturity. During the study period, 21 pregnant baboons were included and ultrasounds were performed between 1 and 3 times each. The measurements have been carried out by two operators in 100% of cases. The intra- and inter-observer ICC for single values are respectively 0.657 - 95% CI (0.548 to 0.752) and 0.458 - 95% CI (0.167 to 0.675). The intra- and inter-observer ICC for average values are respectively 0.852 - 95% CI (0.784 to 0.901) and 0.628 - 95% CI (0.286 to 0.806). The study by transabdominal ShearWave Elastography of placenta's pregnant baboons is possible. The intra- and inter-operator reproducibility of this method is good using the average of three measurements. The objective study via elastography ShearWave of the degree of placental maturity seems not yet be used in clinical practice. Studies of larger cohorts are needed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Ethics of xenotransplantation: animal issues, consent, and likely transformation of transplant ethics.

PubMed

Daar, A S

1997-01-01

The shortage of organs, breakthroughs in research, involvement of biotechnology companies, absence of ethically more acceptable alternatives, and a vaguely perceived "time to put man on the moon" feeling have contributed to the current reawakening of interest in xenotransplantation. The focus of ethical attention has changed from the moral correctness of using animals for research/therapy to an increasingly appreciated danger of the establishment and spread of xenozoonoses in recipients, their contacts, and the general public. The United Kingdom has established an embargo on clinical trials and has set up a national regulatory authority to oversee and coordinate the development of research, establish guidelines, and decide on when trials can proceed. In the United States, on the other hand, the overall attitude is to "proceed with caution," and the Food and Drug Administration has approved a number of xenotransplant studies. The Public Health Service guidelines on reducing infection risk are still evolving and are likely to end up being more cautions than they are currently. There are a number of reasons for not using subhuman primates for xenotransplantation, including their closeness to humans, the likelihood of passing on infections, their depletability (gorillas, chimpanzees), their slow breeding, and the expense of breeding them under specified-pathogen free conditions. The pig, although domesticated and familiar, is too distant to evoke the same feelings we have for primates, has the correct-size organs, is probably less likely to pass on infections, breeds rapidly, and is not endangered; moreover, millions of them are eaten every year. Although drawing ethical conclusions is difficult, at this stage of knowledge and debate it seems acceptable to manipulate pigs genetically and to proceed to using their organs for xenotransplantation trials when infection control measures and the scientific base justify it. The question of informed consent is likely to be a

Kidney lesions in baboons infected with Schistosoma mansoni.

PubMed Central

Houba, V; Sturrock, R F; Butterworth, A E

1977-01-01

Glomerular lesions in baboons (Papio anubis) infected with different dosage regimes of Schistosoma mansoni were studied by immunofluorescence and light microscopy on kidney sections and by countercurrent immunoelectrophoresis on kidney homogenates and tissue eluates. Mild lesions, characterized by focal and segmental deposits of immune complexes, developed in sixty-two out of 103 baboons, irrespective of the intensity and duration of the infection. Severe, diffuse lesions developed in six baboons after prolonged and heavy infections. Adult worm and soluble egg antigens, together with IgM, IgG and C3, were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in acid homogenates and eluates of kidneys which showed no deposits of immunoglobulins or complement. These observations indicate that renal lesions in S. mansoni infections may be attributable to the deposition of immune complexes pre-formed in the circulation. However, the demonstration of antigens alone in some animals may suggest an alternative possibility, namely that antigens are deposited first with a subsequent binding of antibody and complement. PMID:414868

Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.).

PubMed

Abd Alla, Mohamed D; Wolf, Roman; White, Gary L; Kosanke, Stanley D; Cary, David; Verweij, Jaco J; Zhang, Mie-Jie; Ravdin, Jonathan I

2012-04-26

To determine the efficacy of a Gal-lectin based intranasal synthetic peptide vaccine, we developed a new experimental primate model of Entamoeba histolytica intestinal infection. Release of xenic E. histolytica trophozoites (5×10(6)) into the small bowel of baboons (Papio sp.) resulted in a rapid intestinal anti-amebic antibody response and a brief infection; however, release of trophozoites directly into the cecum (5 baboons) elicited a sustained E. histolytica infection, as determined by quantitative fecal PCR, and an ulcerative, inflammatory colitis observed on colonoscopy and histopathology. In three controlled experiments, baboons received four immunizations at seven day intervals of 1600 μg of the vaccine/nostril, with Cholera toxin, 20 μg/nostril as adjuvant; vaccinated (n=6) and control baboons (n=6) baboons were then challenged via colonoscopy with xenic trophozoites (5×10(6)). During 90 days of follow up, 250 of 415 (60.24%) fecal samples in control baboons had a (+) PCR for E. histolytica, compared to only 36 of 423 (8.51%) samples from vaccinated baboons (P<0.001). All 6 vaccinated baboons were free of infection by the 51st day after challenge, 5 of 6 controls positive had (+) fecal PCRs for up to 126 days post-challenge (P=0.019). Inflammatory colitis developed in 4 of 6 control baboons post-challenge, with invasive E. histolytica trophozoites present in 2 of the 4 on histopathology. There was no evidence of inflammatory colitis or parasite invasion in any of the vaccinated baboons; there was a strong inverse correlation between positive ELISA OD value indicating the presence of intestinal anti-peptide IgA antibodies and baboons having a positive fecal PCR CT value, P<0.001. In conclusion, we developed a novel primate model of E. histolytica intestinal infection and demonstrated that a Gal-lectin-based intranasal synthetic peptide vaccine was highly efficacious in preventing experimental E. histolytica infection and colitis in baboons. Copyright �

Increased thermolability of benzodiazepine receptors in cerebral cortex of a baboon with spontaneous seizures: a case report.

PubMed

Squires, R; Naquet, R; Riche, D; Braestrup, C

1979-06-01

The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.

Ovarian Grafts 10 Days after Xenotransplantation: Folliculogenesis and Recovery of Viable Oocytes

PubMed Central

Campos-Junior, Paulo Henrique Almeida; Alves, Thalys Jair Melo; Dias, Marco Tulio; Assunçao, Carolina Marinho; Munk, Michele; Mattos, Matheus Silvério; Kraemer, Lucas Rocha; Almeida, Brígida Gomes; Russo, Remo Castro; Barcelos, Lucíola; Camargo, Luiz Sérgio Almeida; Viana, Joao Henrique Moreira

2016-01-01

Ovarian xenotransplantation is a promising alternative to preserve fertility of oncologic patients. However, several functional aspects of this procedure remained to be addressed. The aim of this study was evaluate the feasibility of xenotransplantation as a strategy to maintain bovine ovarian grafts and produce oocytes. Adult ovarian cortical pieces were xenotransplanted to the dorsal subcutaneous of female NOD-SCID mice (n = 62). Grafts were recovered ten days after xenotransplantation. Host and graft weights; folliculogenesis progression; blood perfusion, relative gene expression and number of macrophage and neutrophil of xenografts; in vitro developmental competence of graft-derived oocytes were evaluated. Folliculogenesis was supported in the grafts, as indicated by the presence of primordial, primary, secondary, antral, and atretic follicles. The xenografts showed a greater volumetric density of atretic follicles and higher hyperemia and number of host-derived macrophage and neutrophil (P<0.05), when compared to non-grafted fragments. There was a higher blood perfusion under the back skin in the transplantation sites of host animals than in control and non-grafted (P<0.01). BAX and PRDX1 genes were up-regulated, while BCL2, FSHR, IGF1R and IGF2R were down-regulated, when compared to the control (P<0.01). Twenty seven oocytes were successfully harvested from grafts, and some of these oocytes were able to give rise to blastocysts after in vitro fertilization. However, cleavage and blastocyst rates of xenograft derived oocytes were lower than in control (P<0.01). Despite showing some functional modifications, the ovarian xenografts were able to support folliculogenesis and produce functional oocytes. PMID:27362486

Impact of a Hormone-Releasing Intrauterine System on the Vaginal Microbiome: A Prospective Baboon Model

PubMed Central

Hashway, Sara A.; Bergin, Ingrid L.; Bassis, Christine M.; Uchihashi, Mayu; Schmidt, Kelsey C.; Young, Vincent B.; Aronoff, David M.; Patton, Dorothy L.; Bell, Jason D.

2014-01-01

Background Use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in humans may alter vaginal microbial populations and susceptibility to pathogens. This study evaluated the time-dependent effects of an LNG-IUS on the vaginal microbiome of the baboon, a useful animal model for reproductive studies. Methods LNG-IUS were inserted into three reproductively mature, female baboons. The animals were evaluated for six months by physical examination and Gram-stained cytology. The vaginal microbiota was characterized at each timepoint by culture-independent analysis of the16S rRNA-encoding gene. Results Each baboon harbored a diverse vaginal microbiome. Inter-individual variation exceeded intra-individual variation. Diversity declined over time in one baboon and showed mild fluctuations in the other two. There were no significant community differences from early to late post LNG-IUS placement. Conclusions The baboon vaginal microbiome is unique to each individual and is polymicrobial. In this pilot study, the vaginal microbiome remained stable from early to late post LNG-IUS placement. PMID:24266633

Unusually high predation on chacma baboons (Papio ursinus) by female leopards (Panthera pardus) in the Waterberg Mountains, South Africa.

PubMed

Jooste, E; Pitman, R T; van Hoven, W; Swanepoel, L H

2012-01-01

Leopards do not preferentially favour baboons as prey, but they are considered the primary predators of baboons across Africa. Even in areas where baboons are abundant, their contribution to leopard diet seldom exceeds 5% of biomass. It is suggested that the extreme aggressiveness of baboons, group vigilance and their high mobility when escaping may limit leopard predation. Male baboons are particularly aggressive, and retaliation often leads to the death of the leopard. However, evidence suggests that leopards may learn to catch and kill certain dangerous prey. This study reports predation on chacma baboons by 3 female leopards on a private game reserve in the Waterberg Mountains of South Africa. Potential leopard feeding sites were identified using global positioning system (GPS) location clusters obtained from GPS collars. Over a 5-month period, we investigated 200 potential leopard feeding sites and located 96 leopard feeding/kill sites. Baboons constituted 18.7% of the leopards' biomass intake. The majority of baboons preyed upon were adults and 70% of the kills were diurnal. In terms of the measured variables, there were no significant differences in the way the leopards preyed upon baboons, compared to the rest of the prey species. Copyright © 2013 S. Karger AG, Basel.

Efficacy of fenbendazole and milbemycin oxime for treating baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

PubMed

Reichard, Mason V; Wolf, Roman F; Carey, David W; Garrett, Jennifer Jane; Briscoe, Heather A

2007-03-01

We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

PubMed

Clauss, R P; Dormehl, I C; Oliver, D W; Nel, W H; Kilian, E; Louw, W K

2001-01-01

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Metabolism of 17α-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons

PubMed Central

Yan, Ru; Nanovskaya, Tatiana N.; Zharikova, Olga L.; Mattison, Donald R.; Hankins, Gary D.V.; Ahmed, Mahmoud S.

2008-01-01

Recent data from our laboratory revealed the formation of an unknown metabolite of 17 hydroxyprogestrone caproate (17-HPC), used for treatment of preterm deliveries, during its perfusion across the dually perfused human placental lobule. Previously, we demonstrated that the drug is not hydrolyzed, neither in vivo nor in vitro, to progesterone and caproate. Therefore, the hypothesis for this investigation is that 17-HPC is actively metabolized by human and baboon (Papio cynocephalus) hepatic and placental microsomes. Baboon hepatic and placental microsomes were investigated to validate the nonhuman primate as an animal model for drug use during pregnancy. Data presented here indicate that human and baboon hepatic microsomes formed several mono-, di-, and tri-hydroxylated derivatives of 17-HPC. However, microsomes of human and baboon placentas metabolized 17-HPC to its mono-hydroxylated derivatives only in quantities that were a fraction of those formed by their respective livers, except for two metabolites (M16’ and M17’) that are unique for placenta and contributed to 25% and 75% of the total metabolites formed by human and baboon, respectively. The amounts of metabolites formed, relative to each other, by human and baboon microsomes were different suggesting that the affinity of 17-HPC to CYP enzymes and their activity could be species-dependent. PMID:18329004

Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons.

PubMed

Kuo, Anderson H; Li, Cun; Huber, Hillary F; Schwab, Matthias; Nathanielsz, Peter W; Clarke, Geoffrey D

2017-07-01

Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life. We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging. Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences. We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR. This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied. Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min -1 m -2 , P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s -1  m -2 , P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased

Antigen-inducing ability of herpesvirus papio in human and baboon lymphoma lines, compared to Epstein-Barr virus.

PubMed

Klein, G; Falk, L; Falk, K

1978-01-01

Herpesvirus papio(HVP)-carrying baboon lymphoblastoid lines do not express a nuclear antigen like the Epstein-Barr virus(EBV)-determined nuclear antigen (EBNA), as judged by in situ anticomplement fluorescence staining, although the carry multiple viral genomes and, in the case of producerlines, early antigen (EA) and viral capsid antigen (VCA) that cross-react with the corresponding human EBV-determined antigens. To test whether the lack of in situ nuclear antigen expression is a property innate to the baboon virus or the baboon cell, nonproducer HVP-carrying baboon lymphoid cells of the 26 CB-1 line were superinfected with two human EBV strains. B95-8-derived EBV induced brilliant EBNA staining, proving that the baboon lymphoid cell was competent to synthesize EBNA. In the mirror experiment, HVP derived from the 9B or the 18C baboon line was added to the EBV-carrying Raji line, the EBV-negative Ramos and BJAB lines and the HVP-carrying nonproducer 26 CB-1 line, respectively. HVP induced EA and VCA in Raji, and EA in BJAB and 26 CB-1. EBNA was not induced in any of the three EBNA-negative lines, BJAB, Ramos and 26 CB-1. It is concluded that the lack of in situ nuclear staining in HVP-carrying baboon lines is a HVP-associated property and is not due to any innate inability of the baboon lymphoid cell to synthesize an antigen of the EBNA type.

Peripheral Insulin Resistance and Impaired Insulin Signaling Contribute to Abnormal Glucose Metabolism in Preterm Baboons

PubMed Central

McGill-Vargas, Lisa L.; Gastaldelli, Amalia; Seidner, Steven R.; McCurnin, Donald C.; Leland, Michelle M.; Anzueto, Diana G.; Johnson, Marney C.; Liang, Hanyu; DeFronzo, Ralph A.; Musi, Nicolas

2015-01-01

Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors. PMID:25560831

Peripheral insulin resistance and impaired insulin signaling contribute to abnormal glucose metabolism in preterm baboons.

PubMed

Blanco, Cynthia L; McGill-Vargas, Lisa L; Gastaldelli, Amalia; Seidner, Steven R; McCurnin, Donald C; Leland, Michelle M; Anzueto, Diana G; Johnson, Marney C; Liang, Hanyu; DeFronzo, Ralph A; Musi, Nicolas

2015-03-01

Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors.

The Frequency of Gastric Amyloidosis in Baboons. A 22-year Survey at a Large Primate Facility

PubMed Central

Rubio, Carlos A.; Dick, Edward J.; Hubbard, Gene B.

2012-01-01

Background Systemic amyloidosis, caused by abnormal tissue accretion of plasma proteins, affects several organs of the gastrointestinal (GI) tract. Gastric amyloidosis, rare in humans, has only been reported once in animals. Materials and Methods Gastric amyloidosis was sought for in baboons with systemic amyloidosis. Results During the past 22 years (between January 1986 and January 2007) a mean of 3,315 baboons/year (range 2,578–3,931) were housed at the Southwest National Primate Research Center. Gastric amyloidosis was found in 9 (10.2%) of the 88 baboons having a diagnosis of systemic amyloidosis. Consequently, the prevalence of gastric amyloidosis occurring since 1986 at this facility was 0.41 baboons/year. Gastric amyloid deposits were found in the interstitial aspect of the lamina propria, replacing normal mucosal structures, in the submucosal stroma along the interface with the muscularis mucosae and in the interstitial tissue of submucosal lymphoid aggregates. In one of the animals, lumps of amyloid deposits with giant cells were found in the gastric mucosa. Conclusion Baboons with systemic amyloidosis usually show increasing frequency of amyloid deposits in the liver, large intestine, lymph nodes, spleen and the small intestine. We now demonstrate that it may also involve the stomach. Why certain organs of the GI tract in baboons are more susceptible than others to be affected by the process of systemic amyloidosis remains unexplained. The apparent natural resistance of the stomach of baboons to be affected by systemic amyloidosis deserves further investigation. The review of the literature indicates that this is only the second report on gastric amyloidosis in baboons. PMID:19180988

The genetic architecture of gene expression levels in wild baboons.

PubMed

Tung, Jenny; Zhou, Xiang; Alberts, Susan C; Stephens, Matthew; Gilad, Yoav

2015-02-25

Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

Olive baboons: a non-human primate model for testing dengue virus type 2 replication.

PubMed

Valdés, Iris; Gil, Lázaro; Castro, Jorge; Odoyo, Damián; Hitler, Rikoi; Munene, Elephas; Romero, Yaremis; Ochola, Lucy; Cosme, Karelia; Kariuki, Thomas; Guillén, Gerardo; Hermida, Lisset

2013-12-01

This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Vocal communication in a complex multi-level society: constrained acoustic structure and flexible call usage in Guinea baboons.

PubMed

Maciej, Peter; Ndao, Ibrahima; Hammerschmidt, Kurt; Fischer, Julia

2013-09-23

To understand the evolution of acoustic communication in animals, it is important to distinguish between the structure and the usage of vocal signals, since both aspects are subject to different constraints. In terrestrial mammals, the structure of calls is largely innate, while individuals have a greater ability to actively initiate or withhold calls. In closely related taxa, one would therefore predict a higher flexibility in call usage compared to call structure. In the present study, we investigated the vocal repertoire of free living Guinea baboons (Papio papio) and examined the structure and usage of the animals' vocal signals. Guinea baboons live in a complex multi-level social organization and exhibit a largely tolerant and affiliative social style, contrary to most other baboon taxa. To classify the vocal repertoire of male and female Guinea baboons, cluster analyses were used and focal observations were conducted to assess the usage of vocal signals in the particular contexts. In general, the vocal repertoire of Guinea baboons largely corresponded to the vocal repertoire other baboon taxa. The usage of calls, however, differed considerably from other baboon taxa and corresponded with the specific characteristics of the Guinea baboons' social behaviour. While Guinea baboons showed a diminished usage of contest and display vocalizations (a common pattern observed in chacma baboons), they frequently used vocal signals during affiliative and greeting interactions. Our study shows that the call structure of primates is largely unaffected by the species' social system (including grouping patterns and social interactions), while the usage of calls can be more flexibly adjusted, reflecting the quality of social interactions of the individuals. Our results support the view that the primary function of social signals is to regulate social interactions, and therefore the degree of competition and cooperation may be more important to explain variation in call usage

Radioimmunoassay of the marjor group specific protein of endogenous baboon type C viruses: relation to the RD-114/CCC group and detection of antigen in normal baboon tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherr, C.J.; Todaro, G.J.

1974-09-01

The major group specific (gs) protein of the endogenous baboon type C virus M7 was purified to homogeneity by gel filtration and isoelectric focusing. The protein has a molecular weight of approximately 33,000, as determined by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate, and an isoelectric point (pl) of 7.1, different from the pls of similarly purified gs proteins from six other mammalian type C viruses. Detergent disrupted M7 virus, whether grown in canine thymus or human rhabdomyosarcoma cells, fully displaced radiolabeled M7 gs protein from antigen-antibody complexes in a competitive radioimmunoassay. No antigenic differences were detected among themore » gs proteins of five independent isolates of baboon type C viruses grown in various cultured cell lines. The gs proteins of six independently isolated feline viruses of the RD-114/CCC group were antigenically related to, but could be distinguished from, the gs proteins of baboon type C viruses. No significant cross-reactions were observed in the radioimmunoassay for M7 gs protein using several other type C viruses, including two previously isolated from a woolly monkey and a gibbon ape. Group specific antigen was found in normal baboon testicular and splenic tissues using the M7 radioimmunoassay; no gs antigen could be detected in these same tissues using a radioimmunoassay for the gs protein of the woolly monkey type C virus. No gs antigen was found in baboon liver or in the tissues of several other primates. (auth)« less

Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

PubMed

Sithaldeen, Riashna; Ackermann, Rebecca Rogers; Bishop, Jacqueline M

2015-01-01

Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp.) supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef) through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

Application of Carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy.

PubMed

Santolaya-Forgas, Joaquin; De Leon-Luis, Juan; Friel, Lara A; Wolf, Roman

2007-09-01

The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n=18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n=82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p>0.01). Significant correlations (p>0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p>0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis.

Molecular cloning of the myo-inositol oxygenase gene from the kidney of baboons.

PubMed

González-Álvarez, Rafael; Pérez-Ibave, Diana Cristina; Garza-Rodríguez, María Lourdes; Lugo-Trampe, Ángel; Delgado-Enciso, Iván; Tejero-Barrera, María Elizabeth; Martínez-De-Villarreal, Laura Elia; Garza-Guajardo, Raquel; Sánchez-Chaparro, María Marisela; Ruiz-Ayma, Gabriel; Barboza-Quintana, Oralia; Barrera-Saldaña, Hugo Alberto; Rocha-Pizaña, María Del Refugio; Rodríguez-Sánchez, Irám Pablo

2017-10-01

The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney-specific member of the aldo-keto reductase family. MIOX catalyzes the first reaction involved in the myo-inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo-Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo-Inositol is achieved by utilizing the Fe 2+ /Fe 3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription-polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces.

A tethering system for direct measurement of cardiovascular function in the caged baboon

NASA Technical Reports Server (NTRS)

Byrd, L. D.

1979-01-01

A device suitable for the continuous measurement of physiological activity in large, conscious monkeys has permitted the direct recording of systemic arterial blood pressure and heart rate in caged baboons. The device comprises a lightweight fiberglass backpack, retained in place on the baboon by a thoracic elastic band and shoulder straps, and a flexible stainless steel tether connecting the pack to an electrocannular slip-ring in the top center of the baboon's cage. A chronically indwelling arterial catheter inserted retrograde into the abdominal aorta via the internal iliac artery and connected to a small pressure transducer on the pack provides direct measurement of blood pressure and heart rate. Body fluids can be sampled or drugs administered via an indwelling catheter in the inferior vena cava. Electrical and fluid connections between the fiberglass pack and recording and infusion equipment located outside the cage pass through the flexible tether and remain protected from the subject. The reliability of the tethering system has been demonstrated in physiological, pharmacological, and behavioral experiments with baboons.

Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

PubMed Central

Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

2017-01-01

Abstract Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection. PMID:28535276

The genetic architecture of gene expression levels in wild baboons

PubMed Central

Tung, Jenny; Zhou, Xiang; Alberts, Susan C; Stephens, Matthew; Gilad, Yoav

2015-01-01

Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates. DOI: http://dx.doi.org/10.7554/eLife.04729.001 PMID:25714927

Vocal communication in a complex multi-level society: constrained acoustic structure and flexible call usage in Guinea baboons

PubMed Central

2013-01-01

Background To understand the evolution of acoustic communication in animals, it is important to distinguish between the structure and the usage of vocal signals, since both aspects are subject to different constraints. In terrestrial mammals, the structure of calls is largely innate, while individuals have a greater ability to actively initiate or withhold calls. In closely related taxa, one would therefore predict a higher flexibility in call usage compared to call structure. In the present study, we investigated the vocal repertoire of free living Guinea baboons (Papio papio) and examined the structure and usage of the animals’ vocal signals. Guinea baboons live in a complex multi-level social organization and exhibit a largely tolerant and affiliative social style, contrary to most other baboon taxa. To classify the vocal repertoire of male and female Guinea baboons, cluster analyses were used and focal observations were conducted to assess the usage of vocal signals in the particular contexts. Results In general, the vocal repertoire of Guinea baboons largely corresponded to the vocal repertoire other baboon taxa. The usage of calls, however, differed considerably from other baboon taxa and corresponded with the specific characteristics of the Guinea baboons’ social behaviour. While Guinea baboons showed a diminished usage of contest and display vocalizations (a common pattern observed in chacma baboons), they frequently used vocal signals during affiliative and greeting interactions. Conclusions Our study shows that the call structure of primates is largely unaffected by the species’ social system (including grouping patterns and social interactions), while the usage of calls can be more flexibly adjusted, reflecting the quality of social interactions of the individuals. Our results support the view that the primary function of social signals is to regulate social interactions, and therefore the degree of competition and cooperation may be more important

Functional PET Evaluation of the Photosensitive Baboon

PubMed Central

Szabó, C. Ákos; Salinas, Felipe S; Narayana, Shalini

2011-01-01

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes. PMID:22276085

Efficacy of fenbendazole formulated in a commercial primate diet for treating specific pathogen-free baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

PubMed

Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

2008-11-01

Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura.

Efficacy of Fenbendazole Formulated in a Commercial Primate Diet for Treating Specific Pathogen-free Baboons (Papio cynocephalus anubis) Infected with Trichuris trichiura

PubMed Central

Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

2008-01-01

Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura. PMID:19049254

Molecular cloning of the myo-inositol oxygenase gene from the kidney of baboons

PubMed Central

González-Álvarez, Rafael; Pérez-Ibave, Diana Cristina; Garza-Rodríguez, María Lourdes; Lugo-Trampe, Ángel; Delgado-Enciso, Iván; Tejero-Barrera, María Elizabeth; Martínez-De-Villarreal, Laura Elia; Garza-Guajardo, Raquel; Sánchez-Chaparro, María Marisela; Ruiz-Ayma, Gabriel; Barboza-Quintana, Oralia; Barrera-Saldaña, Hugo Alberto; Rocha-Pizaña, María Del Refugio; Rodríguez-Sánchez, Irám Pablo

2017-01-01

The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney-specific member of the aldo-keto reductase family. MIOX catalyzes the first reaction involved in the myo-inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo-Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo-Inositol is achieved by utilizing the Fe2+/Fe3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription-polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces. PMID:29085625

Deep Learning of Orthographic Representations in Baboons

PubMed Central

Hannagan, Thomas; Ziegler, Johannes C.; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

2014-01-01

What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords [1]. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process. PMID:24416300

Deep learning of orthographic representations in baboons.

PubMed

Hannagan, Thomas; Ziegler, Johannes C; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

2014-01-01

What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process.

Genome-wide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons

PubMed Central

Wall, Jeffrey D; Schlebusch, Stephen A; Alberts, Susan C; Cox, Laura A; Snyder-Mackler, Noah; Nevonen, Kimberly; Carbone, Lucia; Tung, Jenny

2017-01-01

Naturally occurring admixture has now been documented in every major primate lineage, suggesting its key role in primate evolutionary history. Active primate hybrid zones can provide valuable insight into this process. Here, we investigate the history of admixture in one of the best-studied natural primate hybrid zones, between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in the Amboseli ecosystem of Kenya. We generated a new genome assembly for yellow baboon and low coverage genome-wide resequencing data from yellow baboons, anubis baboons, and known hybrids (n=44). Using a novel composite likelihood method for estimating local ancestry from low coverage data, we found high levels of genetic diversity and genetic differentiation between the parent taxa, and excellent agreement between genome-scale ancestry estimates and a priori pedigree, life history, and morphology-based estimates (r2=0.899). However, even putatively unadmixed Amboseli yellow individuals carried a substantial proportion of anubis ancestry, presumably due to historical admixture. Further, the distribution of shared versus fixed differences between a putatively unadmixed Amboseli yellow baboon and an unadmixed anubis baboon, both sequenced at high coverage, are inconsistent with simple isolation-migration or equilibrium migration models. Our findings suggest a complex process of intermittent contact that has occurred multiple times in baboon evolutionary history, despite no obvious fitness costs to hybrids or major geographic or behavioral barriers. In combination with the extensive phenotypic data available for baboon hybrids, our results provide valuable context for understanding the history of admixture in primates, including in our own lineage. PMID:27145036

Institutional policy learning and public consultation: the Canadian xenotransplantation experience.

PubMed

Jones, Mavis; Einsiedel, Edna

2011-09-01

Attempts to evaluate public consultations, participatory technology assessment, and deliberative democracy have typically considered impacts on either policy or participants. The determination of impacts on policy institutions has been limited due to the challenges of tracing effects through the policy process, or penetrating bureaucratic walls. This paper presents findings from a retrospective study exploring the institutional lessons learned from a 2001 Canadian national public consultation on xenotransplantation. The consultation was conducted through an arm's-length process and involved the use of citizen juries in six regional sites. We conducted in-depth interviews of regulatory and policy actors who were engaged in early policy discussions and the consultation process. We reviewed evaluations of this process, both internal and external, which gave us richer insights into what institutional actors saw as the impacts of this consultative experience on their policy environment. Participants in our research identified a broader shift toward openness in policy culture which they linked specifically to the innovative consultation process employed for xenotransplantation. We argue that beyond input into policy decisions, a consultation may have an impact in terms of its contribution to overall shifts in institutional culture (related to institutional learning), such as an "opening" of technological decision processes to a broader range of actors, knowledge, and values. Copyright © 2011 Elsevier Ltd. All rights reserved.

The ontogeny of insulin signaling in the preterm baboon model.

PubMed

Blanco, Cynthia L; Liang, Hanyu; Joya-Galeana, Joaquin; DeFronzo, Ralph A; McCurnin, Donald; Musi, Nicolas

2010-05-01

Hyperglycemia, a prevalent condition in premature infants, is thought to be a consequence of incomplete suppression of endogenous glucose production and reduced insulin-stimulated glucose disposal in peripheral tissues. However, the molecular basis for these conditions remains unclear. To test the hypothesis that the insulin transduction pathway is underdeveloped with prematurity, fetal baboons were delivered, anesthetized, and euthanized at 125 d gestational age (GA), 140 d GA, or near term at 175 d GA. Vastus lateralis muscle and liver tissues were obtained, and protein content of insulin signaling molecules [insulin receptor (IR)-beta, IR substate-1, p85 subunit of phosphatidylinositol 3-kinase, Akt, and AS160] and glucose transporters (GLUT)-1 and GLUT4 was measured by Western blotting. Muscle from 125 d GA baboons had markedly reduced GLUT1 protein content (16% of 140 d GA and 9% of 175 d GA fetuses). GLUT4 and AS160 also were severely reduced in 125 d GA fetal muscle (43% of 175 d GA and 35% of 175 d GA, respectively). In contrast, the protein content of IR-beta, IR substate-1, and Akt was elevated by 1.7-, 5.2-, and 1.9-fold, respectively, in muscle from 125 d GA baboons when compared with 175 d GA fetuses. No differences were found in the content of insulin signaling proteins in liver. In conclusion, significant gestational differences exist in the protein content of several insulin signaling proteins in the muscle of fetal baboons. Reduced muscle content of key glucose transport-regulating proteins (GLUT1, GLUT4, AS160) could play a role in the pathogenesis of neonatal hyperglycemia and reduced insulin-stimulated glucose disposal.

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

PubMed Central

Castro, Iris; Giret, Teresa M.; Magnani, Diogo M.; Maxwell, Helen S.; Umland, Oliver; Perry, Jessica K.; Pecotte, Jerilyn K.; Brasky, Kathleen M.; Barber, Glen N.; Desrosiers, Ronald C.

2016-01-01

ABSTRACT There are currently 5 million to 10 million human T-lymphotropic virus type 1 (HTLV-1)-infected people, and many of them will develop severe complications resulting from this infection. A vaccine is urgently needed in areas where HTLV-1 is endemic. Many vaccines are best tested in nonhuman primate animal models. As a first step in designing an effective HTLV-1 vaccine, we defined the CD8+ and CD4+ T cell response against simian T-lymphotropic virus type 1 (STLV-1), a virus closely related to HTLV-1, in olive baboons (Papio anubis). Consistent with persistent antigenic exposure, we observed that STLV-1-specific CD8+ T cells displayed an effector memory phenotype and usually expressed CD107a, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α). To assess the viral targets of the cellular immune response in STLV-1-infected animals, we used intracellular cytokine staining to detect responses against overlapping peptides covering the entire STLV-1 proteome. Our results show that, similarly to humans, the baboon CD8+ T cell response narrowly targeted the Tax protein. Our findings suggest that the STLV-1-infected baboon model may recapitulate some of the important aspects of the human response against HTLV-1 and could be an important tool for the development of immune-based therapy and prophylaxis. IMPORTANCE HTLV-1 infection can lead to many different and often fatal conditions. A vaccine deployed in areas of high prevalence might reduce the incidence of HTLV-1-induced disease. Unfortunately, there are very few animal models of HTLV-1 infection useful for testing vaccine approaches. Here we describe cellular immune responses in baboons against a closely related virus, STLV-1. We show for the first time that the immune response against STLV-1 in naturally infected baboons is largely directed against the Tax protein. Similar findings in humans and the sequence similarity between the human and baboon viruses suggest that the STLV-1-infected baboon

Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

PubMed

Reichart, B; Niemann, H; Chavakis, T; Denner, J; Jaeckel, E; Ludwig, B; Marckmann, G; Schnieke, A; Schwinzer, R; Seissler, J; Tönjes, R R; Klymiuk, N; Wolf, E; Bornstein, S R

2015-01-01

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation. © Georg Thieme Verlag KG Stuttgart · New York.

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

PubMed Central

Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

2014-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

PubMed

Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

2015-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. Copyright © 2014 Elsevier Inc. All rights reserved.

GPS-identified, low-level nocturnal activity of vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) in Laikipia, Kenya.

PubMed

Isbell, Lynne A; Bidner, Laura R; Crofoot, Margaret C; Matsumoto-Oda, Akiko; Farine, Damien R

2017-09-01

Except for owl monkeys (Aotus spp.), all anthropoid primates are considered strictly diurnal. Recent studies leveraging new technologies have shown, however, that some diurnal anthropoids also engage in nocturnal activity. Here we examine the extent to which vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) are active at night. We deployed GPS collars with tri-axial accelerometer data loggers on 18 free-ranging adult females: 12 vervets spread among 5 social groups, and 6 olive baboons spread among 4 groups. Their locations were recorded every 15 min, and their activity levels, for 3 s/min over 7.5 months. We also used camera traps that were triggered by heat and movement at seven sleeping sites. Travel was detected on 0.4% of 2,029 vervet-nights involving 3 vervets and 1.1% of 1,109 baboon-nights involving 5 baboons. Travel was mainly arboreal for vervets but mainly terrestrial for baboons. During the night, vervets and baboons were active 13% and 15% of the time, respectively. Activity varied little throughout the night and appeared unaffected by moon phase. Our results confirm the low nocturnality of vervets and olive baboons, which we suggest is related to living near the equator with consistent 12-hr days, in contrast to other anthropoids that are more active at night. Since anthropoid primates are thought to have evolved in northern latitudes, with later dispersal to tropical latitudes, our results may have implications for understanding the evolution of anthropoid diurnality. © 2017 Wiley Periodicals, Inc.

Antelope Predation by Nigerian Forest Baboons: Ecological and Behavioural Correlates.

PubMed

Sommer, Volker; Lowe, Adriana; Jesus, Gonçalo; Alberts, Nienke; Bouquet, Yaëlle; Inglis, David M; Petersdorf, Megan; van Riel, Eelco; Thompson, James; Ross, Caroline

2016-01-01

Baboons are well studied in savannah but less so in more closed habitats. We investigated predation on mammals by olive baboons (Papio anubis) at a geographical and climatic outlier, Gashaka Gumti National Park (Nigeria), the wettest and most forested site so far studied. Despite abundant wildlife, meat eating was rare and selective. Over 16 years, baboons killed 7 bushbuck (Tragelaphus scriptus) and 3 red-flanked duiker (Cephalophus rufilatus), mostly still-lying 'parked' infants. Taking observation time into account, this is 1 predation per group every 3.3 months - far lower than at other sites. Some features of meat eating resemble those elsewhere; predation is opportunistic, adult males monopolize most prey, a targeted killing bite is lacking and begging or active sharing is absent. Carcass owners employ evasive tactics, as meat is often competed over, but satiated owners may tolerate others taking meat. Other features are unusual; this is only the second study site with predation records for bushbuck and the only one for red-flanked duiker. The atypical prey and rarity of eating mammals probably reflects the difficulty of acquiring prey animals when vegetation cover is dense. Our data support the general prediction of the socioecological model that environments shape behavioural patterns, while acknowledging their intraspecific or intrageneric plasticity. © 2016 S. Karger AG, Basel.

The Endocannabinoid System in the Baboon (Papio SPP.) as a Complex Framework for Developmental Pharmacology

PubMed Central

Rodriguez-Sanchez, Iram P.; Guindon, Josee; Ruiz, Marco; Tejero, Maria E.; Hubbard, Gene; Martinez-De-Villarreal, Laura E.; Barrera-Saldaña, Hugo A.; Dick, Edward J.; Commuzzie, Anthony G; Schlabritz-Loutsevitch, Natalia E

2017-01-01

Introduction The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or “endocannabinoid” (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha). Reports regarding the toxic and therapeutic effects of pharmacological compounds targeting the ECS are sometimes contradictory. This may be caused by the fact that structure of the eCBs varies in the species studied. Objectives First: to clone and characterize the cDNAs of selected members of ECS in a non-human primate (baboon, Papio spp.), and second: to compare those cDNA sequences to known human structural variants (single nucleotide polymorphisms and haplotypes). Materials and methods Polymerase chain reaction-amplified gene products from baboon tissues were transformed into Escherichia coli. Amplicon-positive clones were sequenced, and the obtained sequences were conceptually translated into amino-acid sequences using the genetic code. Results Among the ECS members, CNR1 was the best conserved gene between humans and baboons. The phenotypes associated with mutations in the untranslated regions of this gene in humans have not been described in baboons. One difference in the structure of CNR2 between humans and baboons was detected in the region with the only known clinically relevant polymorphism in a human receptor. All of the differences in the amino-acid structure of DAGL-α between humans and baboons were located in the hydroxylase domain, close to phosphorylation sites. None of the differences in the amino-acid structure of MAGL observed between baboons and humans were located in

The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology.

PubMed

Rodriguez-Sanchez, Iram P; Guindon, Josee; Ruiz, Marco; Tejero, M Elizabeth; Hubbard, Gene; Martinez-de-Villarreal, Laura E; Barrera-Saldaña, Hugo A; Dick, Edward J; Comuzzie, Anthony G; Schlabritz-Loutsevitch, Natalia E

The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha). Reports regarding the toxic and therapeutic effects of pharmacological compounds targeting the ECS are sometimes contradictory. This may be caused by the fact that structure of the eCBs varies in the species studied. First: to clone and characterize the cDNAs of selected members of ECS in a non-human primate (baboon, Papio spp.), and second: to compare those cDNA sequences to known human structural variants (single nucleotide polymorphisms and haplotypes). Polymerase chain reaction-amplified gene products from baboon tissues were transformed into Escherichia coli. Amplicon-positive clones were sequenced, and the obtained sequences were conceptually translated into amino-acid sequences using the genetic code. Among the ECS members, CNR1 was the best conserved gene between humans and baboons. The phenotypes associated with mutations in the untranslated regions of this gene in humans have not been described in baboons. One difference in the structure of CNR2 between humans and baboons was detected in the region with the only known clinically relevant polymorphism in a human receptor. All of the differences in the amino-acid structure of DAGL-α between humans and baboons were located in the hydroxylase domain, close to phosphorylation sites. None of the differences in the amino-acid structure of MAGL observed between baboons and humans were located in the area critical for enzyme function. The evaluation of

Influence of Age, Reproductive Cycling Status, and Menstruation on the Vaginal Microbiome in Baboons (Papio anubis)

PubMed Central

UCHIHASHI, M.; BERGIN, I. L.; BASSIS, C. M.; HASHWAY, S. A.; CHAI, D.; BELL, J. D.

2015-01-01

The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal microbiome compared to that of humans, which is most commonly dominated by Lactobacillus spp. We evaluated the influence of age, reproductive cycling status (cycling vs. non-cycling) and menstruation on the vaginal microbiome of 38 wild-caught, captive female olive baboons (Papio anubis) by culture-independent sequencing of the V3–V5 region of the bacterial 16S rRNA gene. All baboons had highly diverse vaginal microbial communities. Adult baboons had significantly lower microbial diversity in comparison to subadult baboons, which was attributable to decreased relative abundance of minor taxa. No significant differences were detected based on cycling state or menstruation. Predictive metagenomic analysis showed uniformity in relative abundance of metabolic pathways regardless of age, cycle stage, or menstruation, indicating conservation of microbial community functions. This study suggests that selection of an optimal vaginal microbial community occurs at puberty. Since decreased diversity occurs in both baboons and humans at puberty, this may reflect a general strategy for selection of adult vaginal microbial communities. Comparative evaluation of vaginal microbial community development and composition may elucidate mechanisms of community formation and function that are conserved across host species or across microbial community types. These findings have implications for host health, evolutionary biology, and microbe-host ecosystems. PMID:25676781

Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons (Papio anubis).

PubMed

Uchihashi, M; Bergin, I L; Bassis, C M; Hashway, S A; Chai, D; Bell, J D

2015-05-01

The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal microbiome compared to that of humans, which is most commonly dominated by Lactobacillus spp. We evaluated the influence of age, reproductive cycling status (cycling vs. non-cycling) and menstruation on the vaginal microbiome of 38 wild-caught, captive female olive baboons (Papio anubis) by culture-independent sequencing of the V3-V5 region of the bacterial 16S rRNA gene. All baboons had highly diverse vaginal microbial communities. Adult baboons had significantly lower microbial diversity in comparison to subadult baboons, which was attributable to decreased relative abundance of minor taxa. No significant differences were detected based on cycling state or menstruation. Predictive metagenomic analysis showed uniformity in relative abundance of metabolic pathways regardless of age, cycle stage, or menstruation, indicating conservation of microbial community functions. This study suggests that selection of an optimal vaginal microbial community occurs at puberty. Since decreased diversity occurs in both baboons and humans at puberty, this may reflect a general strategy for selection of adult vaginal microbial communities. Comparative evaluation of vaginal microbial community development and composition may elucidate mechanisms of community formation and function that are conserved across host species or across microbial community types. These findings have implications for host health, evolutionary biology, and microbe-host ecosystems. © 2015 Wiley Periodicals, Inc.

Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

PubMed Central

Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar

2008-01-01

Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925

Ovarian cycling and reproductive state shape the vaginal microbiota in wild baboons.

PubMed

Miller, Elizabeth A; Livermore, Joshua A; Alberts, Susan C; Tung, Jenny; Archie, Elizabeth A

2017-01-19

The vaginal microbiome is an important site of bacterial-mammalian symbiosis. This symbiosis is currently best characterized for humans, where lactobacilli dominate the microbial community and may help defend women against infectious disease. However, lactobacilli do not dominate the vaginal microbiota of any other mammal studied to date, raising key questions about the forces that shape the vaginal microbiome in non-human mammals. We used Illumina sequencing of the bacterial 16S rRNA gene to investigate variation in the taxonomic composition of the vaginal microbiota in 48 baboons (Papio cynocephalus), members of a well-studied wild population in Kenya. Similar to prior studies, we found that the baboon vaginal microbiota was not dominated by lactobacilli. Despite this difference, and similar to humans, reproductive state was the dominant predictor of baboon vaginal microbiota, with pregnancy, postpartum amenorrhea, and ovarian cycling explaining 18% of the variance in community composition. Furthermore, among cycling females, a striking 39% of variance in community composition was explained by ovarian cycle phase, with an especially distinctive microbial community around ovulation. Periovulatory females exhibited the highest relative abundance of lactic acid-producing bacteria compared to any other phase, with a mean relative abundance of 44%. To a lesser extent, sexual behavior, especially a history of shared sexual partners, also predicted vaginal microbial similarity between baboons. Despite striking differences in their dominant microbes, both human and baboon vaginal microbiota exhibit profound changes in composition in response to reproductive state, ovarian cycle phase, and sexual behavior. We found major shifts in composition during ovulation, which may have implications for disease risk and conception success. These findings highlight the need for future studies to account for fine-scale differences in reproductive state, particularly differences between

Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle.

PubMed

Blanco, Cynthia L; Moreira, Alvaro G; McGill-Vargas, Lisa L; Anzueto, Diana G; Nathanielsz, Peter; Musi, Nicolas

2014-05-01

We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 μg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure the protein content and gene expression of insulin receptor β (IRβ; INSR), IRβ Tyr 1361 phosphorylation (pIRβ), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKT and AKT1 (respectively, 73 and 72% from 0.67 GA control, P<0.001); IRβ and pIRβ were also decreased (respectively, 94 and 85%, P<0.01) in the muscle of premature GC-exposed fetuses but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P<0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.

Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

PubMed

Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

2014-04-01

Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species. © 2013 Wiley Periodicals, Inc.

Antenatal Corticosteroids Alter Insulin Signaling Pathways in Fetal Baboon Skeletal Muscle

PubMed Central

BLANCO, Cynthia L.; MOREIRA, Alvaro G.; McGILL, Lisa L.; ANZUETO, Diana G.; NATHANIELSZ, Peter; MUSI, Nicolas

2015-01-01

Objective We hypothesize that prenatal exposure to glucocorticoids (GCs) will negatively alter the insulin signal transduction pathway and has differing effects on the fetus according to gestational age at exposure. Methods Twenty-three fetal baboons were delivered from twenty-three healthy, non-diabetic mothers. Twelve preterm (0.67 gestational age) and eleven near term (0.95 gestational age) baboons were euthanized immediately after delivery. Half of the pregnant baboons at each gestation received two doses of intramuscular betamethasone 24-hours apart (170 μg.kg−1) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure protein content and gene expression of insulin receptor (IR)-β, IR-β Tyr 1361 phosphorylation (pIR-β), IR substate-1 (IRS-1), IRS-1 tyrosine phosphorylation (pIRS-1), p85 subunit of PI3-kinase (p85), Akt (Protein Kinase B), phospho-Akt Ser473 (pAkt), Akt-1, Akt-2, and glucose transporters (GLUT1 and GLUT4). Results Skeletal muscle from preterm baboons exposed to glucocorticoids had markedly reduced protein content of Akt and Akt-1 (respectively, 73% and 72% from 0.67 gestational age Control, P<0.001); IR-β and pIR-β were decreased (respectively, 94% and 85%, P<0.01) in the muscle of premature GC exposed fetuses, but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased 6.0 fold in term animals after GC exposure (P<0.05). Conclusion Exposure to a single course of antenatal GCs during fetal life alters the insulin-signaling pathway in fetal muscle in a manner dependent on the stage of gestation. PMID:24756099

Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment

PubMed Central

Liang, Fan; Wamala, Isaac; Scalea, Joseph; Tena, Aseda; Cormack, Taylor; Pratts, Shannon; Struuck, Raimon Duran; Elias, Nahel; Hertl, Martin; Huang, Christene A.; Sachs, David H.

2013-01-01

Background The development of genetically modified pigs which lack the expression of alpha 1–3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation [8]. Two baboons with low levels of pre-transplant anti-non-Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor-specific hypo-responsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre-transplant anti-non-Gal IgG levels might improve engraftment levels following GalT-KO pig-to-baboon bone marrow transplantation. Methods Five baboons, with low pre-transplant anti-non-Gal IgG levels, received transplantation of bone marrow cells (1–5 × 10^9/kg of recipient weight) from GalT-KO pigs. They received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation (150cGy), thymic irradiation (700cGy), anti-thymocyte globulin (ATG) and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal antibody levels were assessed by serum binding towards GalT-KO PBMC using flow cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.

PubMed

Cohen, Philip R

2015-08-15

Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

Cloning and expression of porcine β1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen.

PubMed

Byrne, Guerard W; Du, Zeji; Stalboerger, Paul; Kogelberg, Heide; McGregor, Christopher G A

2014-01-01

porcine endothelial cells and shows a broadly distributed expression pattern. Expression of porcine B4GALNT2 in human HEK cells (HEK-B4T) results in increased binding of antibody to the B4GALNT2 enzyme, and increased reactivity with anti-Sd(a) and DBA. HEK-B4T cells show increased sensitivity to complement mediated lysis when challenged with serum from primates after pig to primate cardiac xenotransplantation. In GTKO and GTKO:CD55 cardiac xenotransplantation recipients there is a significant correlation between the induction of a non-Gal antibody, measured using GTKO PAECs, and the induction of antibodies which preferentially bind to HEK-B4T cells. The functional isolation of the porcine B4GALNT2 gene from a PAEC expression library, the pattern of B4GALNT2 gene expression and its sensitization of HEK-B4T cells to antibody binding and complement mediated lysis indicates that the enzymatic activity of porcine B4GALNT2 produces a new immunogenic non-Gal glycan which contributes in part to the non-Gal immune response detected after pig-to-baboon cardiac xenotransplantation. © 2014 The Authors. Xenotransplantation Published by John Wiley & Sons Ltd.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework.

PubMed

Cozzi, Emanuele; Tallacchini, Mariachiara; Flanagan, Enda B; Pierson, Richard N; Sykes, Megan; Vanderpool, Harold Y

2009-01-01

The outstanding results recently obtained in islet xenotransplantation suggest that porcine islet clinical trials may soon be scientifically appropriate. Before the initiation of such clinical studies, however, it is essential that a series of key ethical and regulatory conditions are satisfied. As far as ethics is concerned, the fundamental requirements have been previously reported in a position paper of the Ethics Committee of the International Xenotransplantation Association. These include aspects related to the selection of adequately informed, appropriate recipients; animal breeding and welfare; safety issues and the need for a favorable risk/benefit assessment based on strong efficacy data in relevant xenotransplantation studies in the primate. As most diabetic patients are not at risk of short-term mortality without islet transplantation, only a small subset of patients could currently be considered for any type of islet transplant. However, there are potential advantages to xenotransplantation that could result in a favorable benefit-over-harm determination for islet xenotransplantation in this subpopulation and ultimately in a broader population of diabetic patients. With regard to regulatory aspects, the key concepts underlying the development of the regulatory models in existence in the United States, Europe and New Zealand are discussed. Each of these models provides an example of a well-defined regulatory approach to ensure the initiation of well-regulated and ethically acceptable clinical islet xenotransplantation trials. At this stage, it becomes apparent that only a well-coordinated international effort such as that initiated by the World Health Organization, aimed at harmonizing xenotransplantation procedures according to the highest ethical and regulatory standards on a global scale, will enable the initiation of clinical xenotransplantation trials under the best auspices for its success and minimize any risk of failure.

Extended Microbiological Characterization of Göttingen Minipigs in the Context of Xenotransplantation: Detection and Vertical Transmission of Hepatitis E Virus

PubMed Central

Morozov, Vladimir A.; Morozov, Alexey V.; Rotem, Avi; Barkai, Uriel; Bornstein, Stefan; Denner, Joachim

2015-01-01

Xenotransplantation has been proposed as a solution to the shortage of suitable human donors. Pigs are currently favoured as donor animals for xenotransplantation of cells, including islet cells, or organs. To reduce the xenotransplantation-associated risk of infection of the recipient the pig donor should be carefully characterised. Göttingen minipigs from Ellegaard are often used for biomedical research and are regularly tested by their vendor for the presence of numerous bacteria, fungi, viruses and parasites. However, screening for some pathogens transmittable to humans had not been performed.The presence of microorganisms was examined in Göttingen Minipigs by PCR methods. Since zoonotic transmission of porcine hepatitis E virus HEV to humans has been demonstrated, extended search for HEV was considered as a priority. RNA from sera, islet and other cells from 40 minipigs were examined for HEV using different real-time reverse transcription (RT)-PCRs, among them two newly established. In addition, sera were examined by Western blot analysis using two recombinant capsid proteins of HEV as antigens. HEV RNA was not detected in pigs older than one year including gilts, but it was detected in the sera of three of ten animals younger than 1 year. Furthermore, HEV was also detected in the sera of three sows six days after delivery and their offspring, indicating vertical transmission of the virus. PCR amplicons were cloned, sequenced and the viruses were found to belong to the HEV genotype (gt) 3/4. Anti-HEV immunoglobulins G were detected in one sow and maternal antibodies in her six day old piglet. Since Göttingen minipigs were negative for many xenotransplantation-relevant microorganisms, they can now be classified as safe. HEV may be eliminated from the Ellegaard herd by selection of negative animals and/or by treatment of the animals. PMID:26466154

Attitudes of Swedes to marginal donors and xenotransplantation

PubMed Central

Lundin, S; Idvall, M

2003-01-01

The aim of our survey was to capture the attitudes of Swedes to marginal donors and xenotransplantation. Modern biotechnology makes it possible to replace non-functioning organs, cells, and genes. Nonetheless, people may have reservations and fears about such treatments. With the survey, Attitudes of the General Public to Transplants, we have sought to expose the ambivalence that arises when medical possibilities are juxtaposed with ideas of risk. The design of the questionnaire originates from the interdisciplinary cooperation between ethnologists, medical scientists, and geneticists. By combining qualitative and quantitative methods, it is possible to illustrate the complexity that characterises people's view of modern biomedicine. People's reflections are based on a personal and situation bound morality, which does not necessarily coincide with what they generally consider as ethically justifiable. PMID:12796443

Herpesvirus papio: state and properties of intracellular viral DNA in baboon lymphoblastoid cell lines.

PubMed

Falk, L; Lindahl, T; Bjursell, G; Klein, G

1979-07-15

Herpesvirus papio (HVP) is an indigenous B-lymphotropic virus of baboons (Papio sp.) present in latent form in baboon lymphoblastoid cell lines. It shares cross-reacting viral capsid and early antigens with the Epstein-Barr virus (EBV), and HVP DNA and EBV DNA show partial sequence homology. EBV-specific complementary RNA was employed here as a probe to investigate the physical state of the HVP DNA component in baboon lymphoblastoid cells after fractionation of cellular DNA by density gradient centrifugation. Five virus-producing cultures contained both free and integrated HVP DNA sequences while one non-producing cell line had two or three viral genome equivalents per cell in an apparently integrated form. Further analysis of one virus-producing line showed that the free HVP DNA fraction was composed of both linear and circular viral DNA. Contour length measurements of HVP circular DNA molecules by electron microscopy revealed that they were similar in length to the EBV circular DNA present in human lymphoblastoid cells.

EXPRESSION OF NeuGc ON PIG CORNEAS AND ITS POTENTIAL SIGNIFICANCE IN PIG CORNEAL XENOTRANSPLANTATION

PubMed Central

Lee, Whayoung; Miyagawa, Yuko; Long, Cassandra; Ekser, Burcin; Walters, Eric; Ramsoondar, Jagdeece; Ayares, David; Tector, A. Joseph; Cooper, David K. C.; Hara, Hidetaka

2016-01-01

Purpose Pigs expressing neither galactose-α1,3-galactose (Gal) nor N-glycolylneuraminic acid (NeuGc) take xenotransplantation one step closer to the clinic. Our aims were (i) to document the lack of NeuGc expression on corneas and aortas, and cultured endothelial cells (aortic [AECs]; corneal [CECs]) of GTKO/NeuGcKO pigs, and (ii) to investigate whether the absence of NeuGc reduced human antibody binding to the tissues and cells. Methods Wild-type (WT), GTKO, and GTKO/NeuGcKO pig were used for the study. Human tissues and cultured cells were negative controls. Immunofluorescence staining was performed using anti-Gal and anti-NeuGc antibodies, and to determine human IgM and IgG binding to tissues. Flow cytometric analysis was used to determine Gal and NeuGc expression on cultured CECs and AECs and to measure human IgM/IgG binding to these cells. Results Both Gal and NeuGc were detected on WT pig corneas and aortas. Although GTKO pigs expressed NeuGc, neither human nor GTKO/NeuGcKO pigs expressed Gal or NeuGc. Human IgM/IgG binding to corneas and aortas from GTKO and GTKO/NeuGcKO pigs was reduced compared to binding to WT pigs. Human antibody binding to GTKO/NeuGcKO AECs was significantly less than to GTKO AECs, but there was no significant difference in binding between GTKO and GTKO/NeuGcKO CECs. Conclusions The absence of NeuGc on GTKO aortic tissue and AECs is associated with reduced human antibody binding, and possibly will provide better outcome in clinical xenotransplantation using vascularized organs. For clinical corneal xenotransplantation, the absence of NeuGc expression on GTKO/NeuGcKO pig corneas may not prove an advantage over GTKO corneas. PMID:26418433

Homeothermy and primate bipedalism: is water shortage or solar radiation the main threat to baboon (Papio hamadryas) homeothermy?

PubMed

Mitchell, Duncan; Fuller, Andrea; Maloney, Shane K

2009-05-01

Other than the hominin lineage, baboons are the diurnally active primates that have colonized the arid plains of Africa most successfully. While the hominin lineage adopted bipedalism before colonizing the open, dry plains, baboons retained a quadrupedal mode of locomotion. Because bipedalism has been considered to reduce the thermoregulatory stress of inhabiting open dry plains, we investigated how baboons cope with thermal loads and water restriction. Using implanted data loggers, we measured abdominal temperature every 5 min in six unrestrained baboons while they were exposed to simulated desert conditions (15 degrees C at night rising to 35 degrees C during the day, with and without extra radiant heating), or an ambient temperature of 22 degrees C. At 22 degrees C, core temperature averaged 37.9 degrees C and cycled nychthemerally by 1.7 degrees C. Mean, minimum, and maximum daily core temperatures in euhydrated baboons in the simulated desert environments did not differ from the temperatures displayed in the 22 degrees C environment, even when radiant heating was applied. At 22 degrees C, restricting water intake did not affect core temperature. During the desert simulations, maximum core temperature increased significantly on each day of water deprivation, with the highest temperatures (>40 degrees C) on the third day in the simulation that included radiant heat. When drinking water heated to 38 degrees C was returned, core temperature decreased rapidly to a level lower than normal for that time of day. We conclude that baboons with access to water can maintain homeothermy in the face of high air temperatures and radiant heat loads, but that a lack of access to drinking water poses a major threat to baboon homeothermy. We speculate that any competitive thermoregulatory advantage of bipedalism in early hominins was related to coping with water shortage in hot environments, and that their freed hands might have enabled them to transport enough water to avoid

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

PubMed

Franke, Katja; Clarke, Geoffrey D; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years ( p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition

PubMed Central

Franke, Katja; Clarke, Geoffrey D.; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H.; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W.

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4–7 years; human equivalent 14–24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans. PMID:28443017

Suggestions for the diagnosis and elimination of hepatitis E virus in pigs used for xenotransplantation.

PubMed

Busby, Stacey-Ann; Crossan, Claire; Godwin, Jon; Petersen, Bjoern; Galli, Cesare; Cozzi, Emanuele; Takeuchi, Yasu; Scobie, Linda

2013-01-01

The hepatitis E virus (HEV) is considered a zoonotic pathogen. In xenotransplantation, given the high prevalence of HEV infection in pigs, the risk of zoonotic transmission from a porcine source is considered high. Currently no clear data are available on how to diagnose and eliminate HEV in herds used for medical purposes and the importance of viral infection at the stage of harvest. In this study, several groups of animals currently used for medical purposes were found RNA positive in both serum and faeces for HEV genotype 3. In addition, viraemia was found in animals up to 3.6 yr of age, which is much longer than originally expected. Herd transmission rates appeared to be significantly lower in animals kept under minimal barrier conditions, compared with those observed for commercial animals, and as expected, segregation of animals at an early age prevented spread of infection. This study makes suggestions to ensure appropriate detection and eradication of HEV from a donor herd to be used for xenotransplantation purposes. © 2013 John Wiley & Sons A/S.

Resource base influences genome-wide DNA methylation levels in wild baboons (Papio cynocephalus)

PubMed Central

Lea, Amanda J.; Altmann, Jeanne; Alberts, Susan C.; Tung, Jenny

2015-01-01

Variation in resource availability commonly exerts strong effects on fitness-related traits in wild animals. However, we know little about the molecular mechanisms that mediate these effects, or about their persistence over time. To address these questions, we profiled genome-wide whole blood DNA methylation levels in two sets of wild baboons: (i) ‘wild-feeding’ baboons that foraged naturally in a savanna environment and (ii) ‘Lodge’ baboons that had ready access to spatially concentrated human food scraps, resulting in high feeding efficiency and low daily travel distances. We identified 1,014 sites (0.20% of sites tested) that were differentially methylated between wild-feeding and Lodge baboons, providing the first evidence that resource availability shapes the epigenome in a wild mammal. Differentially methylated sites tended to occur in contiguous stretches (i.e., in differentially methylated regions or DMRs), in promoters and enhancers, and near metabolism-related genes, supporting their functional importance in gene regulation. In agreement, reporter assay experiments confirmed that methylation at the largest identified DMR, located in the promoter of a key glycolysis-related gene, was sufficient to causally drive changes in gene expression. Intriguingly, all dispersing males carried a consistent epigenetic signature of their membership in a wild-feeding group, regardless of whether males dispersed into or out of this group as adults. Together, our findings support a role for DNA methylation in mediating ecological effects on phenotypic traits in the wild, and emphasize the dynamic environmental sensitivity of DNA methylation levels across the life course. PMID:26508127

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mackey, W.C.; Connolly, R.J.; Callow, A.D.

The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotidmore » interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.« less

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon).

PubMed

Pérez-Ibave, Diana Cristina; González-Alvarez, Rafael; de La Luz Martinez-Fierro, Margarita; Ruiz-Ayma, Gabriel; Luna-Muñoz, Maricela; Martínez-De-Villarreal, Laura Elia; De Lourdes Garza-Rodríguez, María; Reséndez-Pérez, Diana; Mohamed-Noriega, Jibran; Garza-Guajardo, Raquel; Bautista-De-Lucío, Víctor Manuel; Mohamed-Noriega, Karim; Barboza-Quintana, Oralia; Arámburo-De-La-Hoz, Carlos; Barrera-Saldaña, Hugo Alberto; Rodríguez-Sánchez, Irám Pablo

2016-11-08

The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Schistosoma egg-induced liver pathology resolution by Sm-p80-based schistosomiasis vaccine in baboons.

PubMed

Le, Loc; Molehin, Adebayo J; Nash, Stewart; Sennoune, Souad R; Ahmad, Gul; Torben, Workineh; Zhang, Weidong; Siddiqui, Afzal A

2018-05-05

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Molecular pathways mediating differential responses to lipopolysaccharide between human and baboon arterial endothelial cells.

PubMed

Shi, Qiang; Cox, Laura A; Glenn, Jeremy; Tejero, Maria E; Hondara, Vida; Vandeberg, John L; Wang, Xing Li

2010-02-01

1. Vascular inflammation plays a critical role in atherogenesis. Previously, we showed that baboon arterial endothelial cells (BAEC) were hyporesponsive to lipopolysaccharide (LPS) compared with human arterial endothelial cells (HAEC). 2. In the present study, we investigated mechanisms underlying differential responses between HAEC and BAEC to tumour necrosis factor (TNF)-alpha and LPS. 3. Both HAEC and BAEC responded similarly to TNF-alpha. However, BAEC showed retarded responses to LPS in expression of E-selectin, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and interleukin-8 (P < 0.05). These changes were confirmed at the mRNA level. Tumour necrosis factor-alpha activated nuclear factor-kappaB members such as p50, p52, p65, c-rel and RelB in both HAEC and BAEC. In contrast, LPS activated p50 and p65 only in HAEC. Using microarray assays, we found that TNF receptor-associated factor 2 (TRAF-2), TNF receptor superfamily, member 1A-associated via death domain (TRADD) and nuclear factors such as nuclear factor of kappa in B-cells inhibitor, alpha (NFKBIA) and nuclear factor of kappa in B-cells inhibitor, beta (NFKBIB) were upregulated by LPS only in HAEC. Although the baseline expression of Toll-like receptor (TLR) 4 was low in both HAEC and BAEC, TNF-alpha activated TLR4 expression in both cell types. Although LPS increased TLR4 expression only in HAEC, human and baboon peripheral blood mononuclear cells exhibited similar TLR4 expression and response to LPS. Transfecting BAEC with TLR4/myeloid differentiation protein-2 overexpression vector conferred BAEC responsiveness to LPS. 4. The findings of the present study indicate that an altered TLR4 system may be responsible for the resistance of baboon endothelial cells to LPS. Given the importance of TLR4 in human immune responses and vascular diseases, the natural resistance of baboons to LPS/TLR4-initiated inflammation could make the baboon a valuable animal model in which to study how

Future issues in transplantation ethics: ethical and legal controversies in xenotransplantation, stem cell, and cloning research.

PubMed

Shapiro, Robyn S

2008-07-01

With little prospect of developing a sufficient supply of human transplantable organs to meet the large and growing demand, attention has turned to xenotransplantation, as well as stem cell and cloning research, as possible approaches for alleviating this allograft shortage. This article explores ethical and legal issues that surround developments in these fields.

Occurrence of specific humoral non-responsiveness to swine antigens following administration of GalT-KO bone marrow to baboons

PubMed Central

Griesemer, Adam; Liang, Fan; Hirakata, Atsushi; Hirsh, Erica; Lo, Diana; Okumi, Masayoshi; Sykes, Megan; Yamada, Kazuhiko; Huang, Christene A.; Sachs, David H.

2010-01-01

Background Hematopoietic chimerism induces transplantation tolerance across allogeneic and xenogeneic barriers, but has been difficult to achieve in the pig-to-primate model. We have now utilized swine with knockout of the gene coding for α-1,3-galactosyltransferase (GalT-KO pigs) as bone marrow donors in an attempt to achieve chimerism and tolerance by avoiding the effects of natural antibodies to Gal determinants on pig hematopoietic cells. Methods Baboons (n = 4; Baboons 1 to 4 = B156, B158, B167, and B175, respectively) were splenectomized and conditioned with TBI (150 cGy), thymic irradiation (700 cGy), T cell depletion with rabbit anti-thymocyte globulin (rATG) and rat anti-primate CD2 (LoCD2b), and received FK506 and supportive therapy for 28 days. All animals received GalT-KO bone marrow (1 to 2 × 109 cells/kg) in two fractions on days 0 and 2, and were thereafter monitored for the presence of pig cells by flow cytometry, for porcine progenitor cells by PCR of BM colony-forming units, and for cellular reactivity to pig cells by mixed lymphocyte reaction (MLR). In vitro antibody formation to LoCD2b and rATG was tested by ELISA; antibody reactivity to GalT-KO pig cells was tested by flow cytometry and cytotoxicity assays. Additionally, Baboons 3 and 4 received orthotopic kidney transplants on days 17 and 2, respectively, to test the potential impact of the protocol on renal transplantation. Results None of the animals showed detectable pig cells by flow cytometry for more than 12 h post-BM infusion. However, porcine progenitor cell engraftment, as evidenced by pig-derived colony forming units in the BM, as well as peripheral microchimerism in the thymus, lymph node, and peripheral blood was detected by PCR in baboons 1 and 2 for at least 28 days post-transplant. ELISA results confirmed humoral immunocompetence at time of transplantation as antibody titers to rat (LoCD2b) and rabbit (ATG) increased within 2 weeks. However, no induced antibodies to Gal

Evaluation of reproduction and raising offspring in a nursery-reared SPF baboon (Papio hamadryas anubis) colony.

PubMed

Budda, Madeline L; Ely, John J; Doan, Sandra; Chavez-Suarez, Maria; White, Gary L; Wolf, Roman F

2013-08-01

Baboons (Papio hamadryas anubis) of a conventional breeding colony were nursery-reared to create a specific pathogen-free (SPF) baboon-breeding program. Because the founding generations were nursery-reared until 2 years of age, it was suspected that the SPF baboons would exhibit increased reproductive challenges as adults. Mothering behavior was of interest, because SPF females were not exposed to parental role models during the nursery-rearing process. We compared reproductive data from the SPF baboon breeding program during its first 10 years with data from age-matched baboons during the same period from an established, genetically-similar conventional breeding colony. We also evaluated records documenting mother-infant behaviors within the SPF colony. The average age of menarche in SPF females was 3.3 years. The overall live birth rate of both SPF and conventional females was approximately 90%, with no difference in pregnancy outcome between the two colonies. The average age at first conception for SPF females was earlier (4.2 years) than that of the conventional females (4.7 years). In both colonies, primiparous females were more likely to abort than multiparous females. Similarly, primiparous females were more likely to lose their infants to death or human intervention. A mothering score system was developed in the SPF colony to facilitate intervention of poor mother-infant relationships. Records revealed 70% of SPF mothers were able to raise one or more of their infants successfully to at least 180 days of age, which did not differ from conventional mothers. SPF females returned to post-partum amenorrhea 27 days sooner on average than the conventional females, independent of dam age. The nursery-rearing process used for recruitment into the SPF colony therefore did not have an adverse effect on reproduction or rearing offspring. © 2013 Wiley Periodicals, Inc.

Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions.

PubMed

Hawash, Mohamed B F; Andersen, Lee O; Gasser, Robin B; Stensvold, Christen Rune; Nejsum, Peter

2015-01-01

The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates. We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related. Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates.

Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions

PubMed Central

Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.; Stensvold, Christen Rune; Nejsum, Peter

2015-01-01

Background The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates. Methods and Findings We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois’ leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois’ leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related. Conclusion and Significance Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates

Reflexive Research Ethics in Fetal Tissue Xenotransplantation Research

PubMed Central

Panikkar, Bindu; Smith, Natasha; Brown, Phil

2013-01-01

For biomedical research in which the only involvement of the human subject is the provision of tissue or organ samples, a blanket consent, i.e. consent to use the tissue for anything researchers wish to do, is considered by many to be adequate for legal and IRB requirements. Alternatively, a detailed informed consent provides patients or study participants with more thorough information about the research topic. We document here the beliefs and opinions of the research staff on informed consent and the discussion-based reflexive research ethics process that we employed in our fetal tissue xenotransplantion research on the impact of environmental exposures on fetal development. Reflexive research ethics entails the continued adjustment of research practice according to relational and reflexive understandings of what might be beneficent or harmful. Such reflexivity is not solely an individual endeavor, but rather a collective relationship between all actors in the research process. PMID:23074992

Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura.

PubMed

Reichard, Mason V; Thomas, Jennifer E; Chavez-Suarez, Maria; Cullin, Cassandra O; White, Gary L; Wydysh, Emily C; Wolf, Roman F

2017-01-01

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.

Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura

PubMed Central

Reichard, Mason V; Thomas, Jennifer E; Chavez-Suarez, Maria; Cullin, Cassandra O; White, Gary L; Wydysh, Emily C; Wolf, Roman F

2017-01-01

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM–FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM–FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM–FBZ. All baboons treated with IVM–FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM–FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura. PMID:28905715

Associative learning in baboons (Papio papio) and humans (Homo sapiens): species differences in learned attention to visual features.

PubMed

Fagot, J; Kruschke, J K; Dépy, D; Vauclair, J

1998-10-01

We examined attention shifting in baboons and humans during the learning of visual categories. Within a conditional matching-to-sample task, participants of the two species sequentially learned two two-feature categories which shared a common feature. Results showed that humans encoded both features of the initially learned category, but predominantly only the distinctive feature of the subsequently learned category. Although baboons initially encoded both features of the first category, they ultimately retained only the distinctive features of each category. Empirical data from the two species were analyzed with the 1996 ADIT connectionist model of Kruschke. ADIT fits the baboon data when the attentional shift rate is zero, and the human data when the attentional shift rate is not zero. These empirical and modeling results suggest species differences in learned attention to visual features.

Isotopic assessment of marine food consumption by natural-foraging chacma baboons on the Cape Peninsula, South Africa.

PubMed

Lewis, Matthew C; West, Adam G; O'Riain, M Justin

2018-01-01

Stable isotope analysis has been used to investigate consumption of marine resources in a variety of terrestrial mammals, including humans, but not yet in extant nonhuman primates. We sought to test the efficacy of stable isotope analysis as a tool for such studies by comparing isotope- and observation-based estimates of marine food consumption by a troop of noncommensal, free-ranging chacma baboons. We determined δ 13 C and δ 15 N values of baboon hair (n = 9) and fecal samples (n = 144), and principal food items (n = 362). These values were used as input for diet models, the outputs of which were compared to observation-based estimates of marine food consumption. Fecal δ 13 C values ranged from -29.3‰ to -25.6‰. δ 15 N values ranged from 0.9‰ to 6.3‰ and were positively correlated with a measure of marine foraging during the dietary integration period. Mean (± SD) δ 13 C values of adult male and female baboon hairs were -21.6‰ (± 0.1) and -21.8‰ (± 0.3) respectively, and corresponding δ 15 N values were 5.0‰ (± 0.3) and 3.9‰ (± 0.2). Models indicated that marine contributions were ≤10% of baboon diet within any season, and contributed ≤17% of dietary protein through the year. Model output and observational data were in agreement, both indicating that despite their abundance in the intertidal region, marine foods comprised only a small proportion of baboon diet. This suggests that stable isotope analysis is a viable tool for investigating marine food consumption by natural-foraging primates in temperate regions. © 2017 Wiley Periodicals, Inc.

Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero.

PubMed

Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D

2013-12-01

Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen.

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

PubMed Central

Zhou, Ming; Hara, Hidetaka; Dai, Yifan; Mou, Lisha; Cooper, David K. C.; Wu, Changyou; Cai, Zhiming

2016-01-01

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation. PMID:27490531

Periodontitis in Pregnant Baboons: Systemic Inflammation and Adaptive Immune Responses and Pregnancy Outcomes in a Baboon Model

PubMed Central

Ebersole, Jeffrey L.; Holt, Stanley C.; Cappelli, David

2014-01-01

Chronic periodontal infections have been suggested to contribute to the risk of adverse pregnancy outcomes. This study describes the relationship of patterns of systemic inflammatory mediators and IgG antibody to 20 oral bacteria in pregnant female baboons (Papio anubis) coupled with clinical features of ligature-induced periodontitis, as risk indicators for adverse pregnancy outcomes. Animals showing a preterm delivery and/or low birth weight newborns, as well as those pregnancies resulting in spontaneous abortion, stillbirth, or fetal demise were tabulated as adverse pregnancy outcomes. A significantly greater frequency of the periodontitis group neonates had a low birth weight (18.1%; p=0.008) and decreased gestational age (9.8%). Spontaneous abortion/stillbirth/fetal demise were increased in the periodontitis (8.7%) versus the control group (3.8%) (p=0.054). The baseline oral clinical presentation of the experimental animals did not relate to the adverse pregnancy outcomes. Animals with the greatest extent/severity of periodontitis progression during the initial ½ of gestation (ie. to mid-pregnancy) had the greatest risk for adverse pregnancy outcomes. Baseline biological parameters indicating historical responses of the animals to periodontal challenge demonstrated individual variation in selected mediators, some of which became more differential during ligature-induced periodontitis. The relationship of clinical parameters to systemic inflammatory responses was consistent with a temporal contribution to adverse pregnancy outcomes in a subset of the animals. These results support a link between periodontitis and adverse pregnancy outcomes in the baboons and provide a prospective experimental model for delineating the biologic parameters that contribute to a causal relationship between chronic oral infections and birth events. PMID:23710643

Regulation of Baboon Fetal Ovarian Development by Placental Estrogen: Onset of Puberty Is Delayed in Offspring Deprived of Estrogen In Utero1

PubMed Central

Pepe, Gerald J.; Lynch, Terrie J.; Albrecht, Eugene D.

2013-01-01

ABSTRACT Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen. PMID:24132960

Analysis of swine leukocyte antigen class I gene profiles and porcine endogenous retrovirus viremia level in a transgenic porcine herd inbred for xenotransplantation research

PubMed Central

Sypniewski, Daniel; Gałka, Sabina; Sołtysik, Dagna; Loch, Tomasz; Nowak, Ewa; Smorąg, Zdzisław; Bednarek, Ilona

2018-01-01

Molecular characterization of swine leukocyte antigen (SLA) genes is important for elucidating the immune responses between swine-donor and human-recipient in xenotransplantation. Examination of associations between alleles of SLA class I genes, type of pig genetic modification, porcine endogenous retrovirus (PERV) viral titer, and PERV subtypes may shed light on the nature of xenograft acceptance or rejection and the safety of xenotransplantation. No significant difference in PERV gag RNA level between transgenic and non-transgenic pigs was noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA-1 gene profile type may correspond with PERV level in blood and thereby influence infectiveness. Screening of pigs should provide selection of animals with low PERV expression and exclusion of specimens with PERV-C in the genome due to possible recombination between A and C subtypes, which may lead to autoinfection. Presence of PERV-C integrated in the genome was detected in 31.25% of specimens, but statistically significant increased viremia in specimens with PERV-C was not observed. There is a need for multidirectional molecular characterization (SLA typing, viremia estimation, and PERV subtype screening) of animals intended for xenotransplantation research in the interest of xeno-recipient safety. PMID:29366300

Virotherapy of the Malignant U87 Human Glioblastoma in the Orthotopic Xenotransplantation Mouse SCID Model.

PubMed

Shchelkunov, S N; Razumov, I A; Kolosova, I V; Romashchenko, A V; Zavjalov, E L

2018-01-01

The possibility of glioblastoma virotherapy at intravenous injection of the LIVP-GFP recombinant virus was studied in experimental model of orthotopic xenotransplantation of human glioblastoma cell line U87 to SCID laboratory mice. The LIVP-GFP recombinant virus deficient for thymidine kinase exhibited a significantly greater oncolytic capacity than the original LIVP virus, and an intravenous injection of LIVP-GFP at the early stages of tumorigenesis in mouse brain in most cases resulted in the lysis of the tumor.

Genetic variations in the beta-tubulin gene and the internal transcribed spacer 2 region of Trichuris species from man and baboons.

PubMed

Hansen, Tina V A; Thamsborg, Stig M; Olsen, Annette; Prichard, Roger K; Nejsum, Peter

2013-08-12

The whipworm Trichuris trichiura has been estimated to infect 604 - 795 million people worldwide. The current control strategy against trichuriasis using the benzimidazoles (BZs) albendazole (400 mg) or mebendazole (500 mg) as single-dose treatment is not satisfactory. The occurrence of single nucleotide polymorphisms (SNPs) in codons 167, 198 or 200 of the beta-tubulin gene has been reported to convey BZ-resistance in intestinal nematodes of veterinary importance. It was hypothesised that the low susceptibility of T. trichiura to BZ could be due to a natural occurrence of such SNPs. The aim of this study was to investigate whether these SNPs were present in the beta-tubulin gene of Trichuris spp. from humans and baboons. As a secondary objective, the degree of identity between T. trichiura from humans and Trichuris spp. from baboons was evaluated based on the beta-tubulin gene and the internal transcribed spacer 2 region (ITS2). Nucleotide sequences of the beta-tubulin gene were generated by PCR using degenerate primers, specific primers and DNA from worms and eggs of T. trichiura and worms of Trichuris spp. from baboons. The ITS2 region was amplified using adult Trichuris spp. from baboons. PCR products were sequenced and analysed. The beta-tubulin fragments were studied for SNPs in codons 167, 198 or 200 and the ITS2 amplicons were compared with GenBank records of T. trichiura. No SNPs in codons 167, 198 or 200 were identified in any of the analysed Trichuris spp. from humans and baboons. Based on the ITS2 region, the similarity between Trichuris spp. from baboons and GenBank records of T. trichiura was found to be 98 - 99%. Single nucleotide polymorphisms in codon 167, 198 and 200, known to confer BZ-resistance in other nematodes, were absent in the studied material. This study does not provide data that could explain previous reports of poor BZ treatment efficacy in terms of polymorphism in these codons of beta-tubulin. Based on a fragment of the beta

Genetic variations in the beta-tubulin gene and the internal transcribed spacer 2 region of Trichuris species from man and baboons

PubMed Central

2013-01-01

Background The whipworm Trichuris trichiura has been estimated to infect 604 – 795 million people worldwide. The current control strategy against trichuriasis using the benzimidazoles (BZs) albendazole (400 mg) or mebendazole (500 mg) as single-dose treatment is not satisfactory. The occurrence of single nucleotide polymorphisms (SNPs) in codons 167, 198 or 200 of the beta-tubulin gene has been reported to convey BZ-resistance in intestinal nematodes of veterinary importance. It was hypothesised that the low susceptibility of T. trichiura to BZ could be due to a natural occurrence of such SNPs. The aim of this study was to investigate whether these SNPs were present in the beta-tubulin gene of Trichuris spp. from humans and baboons. As a secondary objective, the degree of identity between T. trichiura from humans and Trichuris spp. from baboons was evaluated based on the beta-tubulin gene and the internal transcribed spacer 2 region (ITS2). Methods Nucleotide sequences of the beta-tubulin gene were generated by PCR using degenerate primers, specific primers and DNA from worms and eggs of T. trichiura and worms of Trichuris spp. from baboons. The ITS2 region was amplified using adult Trichuris spp. from baboons. PCR products were sequenced and analysed. The beta-tubulin fragments were studied for SNPs in codons 167, 198 or 200 and the ITS2 amplicons were compared with GenBank records of T. trichiura. Results No SNPs in codons 167, 198 or 200 were identified in any of the analysed Trichuris spp. from humans and baboons. Based on the ITS2 region, the similarity between Trichuris spp. from baboons and GenBank records of T. trichiura was found to be 98 – 99%. Conclusions Single nucleotide polymorphisms in codon 167, 198 and 200, known to confer BZ-resistance in other nematodes, were absent in the studied material. This study does not provide data that could explain previous reports of poor BZ treatment efficacy in terms of polymorphism in these codons of beta

A review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a "humanized" tilapia insulin.

PubMed

Wright, James R; Yang, Hua; Hyrtsenko, Olga; Xu, Bao-You; Yu, Weiming; Pohajdak, Bill

2014-01-01

Most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. Teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called Brockmann bodies which can be inexpensively harvested. When transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. Like porcine islets, when transplanted into euthymic mice, they are rejected in a CD4 T-cell-dependent manner. However, unlike pigs, tilapia are so phylogenetically primitive that their cells do not express α(1,3)Gal and, because tilapia are highly evolved to live in warm stagnant waters nearly devoid of dissolved oxygen, their islet cells are exceedingly resistant to hypoxia, making them ideal for transplantation within encapsulation devices. Encapsulation, especially when combined with co-stimulatory blockade, markedly prolongs tilapia islet xenograft survival in small animal recipients, and a collaborator has shown function in diabetic cynomolgus monkeys. In anticipation of preclinical xenotransplantation studies, we have extensively characterized tilapia islets (morphology, embryologic development, cell biology, peptides, etc.) and their regulation of glucose homeostasis. Because tilapia insulin differs structurally from human insulin by 17 amino acids, we have produced transgenic tilapia whose islets stably express physiological levels of humanized insulin and have now bred these to homozygosity. These transgenic fish can serve as a platform for further development into a cell therapy product for diabetes. © 2014 The Authors. Xenotransplantation Published by John Wiley & Sons Ltd.

Skeletal and dental morphology supports diphyletic origin of baboons and mandrills

PubMed Central

Fleagle, John G.; McGraw, W. Scott

1999-01-01

Numerous biomolecular studies from the past 20 years have indicated that the large African monkeys Papio, Theropithecus, and Mandrillus have a diphyletic relationship with different species groups of mangabeys. According to the results of these studies, mandrills and drills (Mandrillus) are most closely related to the torquatus–galeritus group of mangabeys placed in the genus Cercocebus, whereas baboons (Papio) and geladas (Theropithecus) are most closely related to the albigena–aterrimus mangabeys, now commonly placed in the genus Lophocebus. However, there has been very little morphological evidence linking mandrills on the one hand and baboons and geladas on the other with different groups of mangabeys. In a study of mangabey locomotion and skeletal anatomy, we have identified features of the postcranial skeleton and the dentition that support the molecular phylogeny and clearly link mandrills with Cercocebus and Papio with Lophocebus. Moreover, the features linking Cercocebus and Mandrillus accord with ecological studies of these species indicating that these two genera are a cryptic clade characterized by unique adaptations for gleaning insects, hard nuts, and seeds from the forest floor. PMID:9927710

Role of Grooming in Reducing Tick Load in Wild Baboons (Papio cynocephalus)

PubMed Central

Akinyi, Mercy Y.; Tung, Jenny; Jeneby, Maamun; Patel, Nilesh B.; Altmann, Jeanne; Alberts, Susan C.

2013-01-01

Nonhuman primate species spend a conspicuous amount of time grooming during social interactions, a behavior that probably serves both social and health-related functions. While the social implications of grooming have been relatively well studied, less attention has been paid to the health benefits, especially the removal of ectoparasites, which may act as vectors in disease transmission. In this study, we examined the relationship between grooming behavior, tick load (number of ticks), and haemoprotozoan infection status in a population of wild free-ranging baboons (Papio cynocephalus). We found that the amount of grooming received was influenced by an individual’s age, sex and dominance rank. The amount of grooming received, in turn, affected the tick load of an individual. Baboons with higher tick loads had lower packed red cell volume (PCV or haematocrit), one general measure of health status. We detected a tick-borne haemoprotozoan, Babesia microti, but its low prevalence in the population precluded identifying sources of variance in infection. PMID:24659824

Testosterone positively associated with both male mating effort and paternal behavior in savanna baboons (Papio cynocephalus)

PubMed Central

Onyango, Patrick Ogola; Gesquiere, Laurence R.; Altmann, Jeanne; Alberts, Susan C.

2012-01-01

Testosterone (T) is often positively associated with male sexual behavior and negatively associated with paternal care. These associations have primarily been demonstrated in species where investment in paternal care begins well after mating activity is complete, when offspring are hatched or born. Different patterns may emerge in studies of species where investment in mating and paternal care overlap temporally, for instance in non-seasonal breeders in which males mate with multiple females sequentially and may simultaneously have multiple offspring of different ages. In a 9-year data set on levels of T in male baboons, fecal concentrations of T (fT) were positively associated with both mate guarding (“consortship”) – a measure of current reproductive activity – and with the number of immature offspring a male had in his social group – a measure of past reproductive activity and an indicator of likely paternal behavior. To further examine the relationship between T and potential paternal behavior, we next drew on an intensive 8-month study of male behavior, and found that fathers were more likely to be in close proximity to their offspring than expected by chance. Because male baboons are known to provide paternal care, and because time in proximity to offspring would facilitate such care, this suggests that T concentrations in wild male baboons may be associated with both current reproductive activity and with current paternal behavior. These results are consistent with the predicted positive association between T a mating effort but not nd with a negative association between T a paternal care; in male baboons, high levels of nd T occur in males that are differentially associating with their offspring. PMID:23206991

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

Failure of transplantation tolerance induction by autologous regulatory T cells in the pig-to-non-human primate islet xenotransplantation model.

PubMed

Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jong-Min; Kim, Jung-Sik; Yoon, Il Hee; Kim, Hyun Je; Kim, Yong-Hee; Jang, Jae Yool; Kang, Hee Jung; Lim, Dong-Gyun; Ha, Jongwon; Kim, Sang-Joon; Park, Chung-Gyu

2016-07-01

Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40-CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue.

PubMed

Amorim, Christiani A; Jacobs, Sophie; Devireddy, Ram V; Van Langendonckt, Anne; Vanacker, Julie; Jaeger, Jonathan; Luyckx, Valérie; Donnez, Jacques; Dolmans, Marie-Madeleine

2013-08-01

Can a vitrification protocol using an ethylene glycol/dimethyl sulphoxide-based solution and a cryopin successfully cryopreserve baboon ovarian tissue? Our results show that baboon ovarian tissue can be successfully cryopreserved with our vitrification protocol. Non-human primates have already been used as an animal model to test vitrification protocols for human ovarian tissue cryopreservation. Ovarian biopsies from five adult baboons were vitrified, warmed and autografted for 5 months. After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. The influence of the vitrification procedure on the cooling rate was evaluated by a computer model. After vitrification, warming and long-term grafting, follicles were able to grow and maintain their function, as illustrated by Ki67, anti-Müllerian hormone (AMH) and growth differentiation factor-9 (GDF-9) immunostaining. Corpora lutea were also observed, evidencing successful ovulation in all the animals. Stromal tissue quality did not appear to be negatively affected by our cryopreservation procedure, as demonstrated by vascularization and proportions of fibrotic areas, which were similar to those found in fresh ungrafted ovarian tissue. Despite our promising findings, before applying this technique in a clinical setting, we need to validate it by achieving pregnancies. In addition to encouraging results obtained with our vitrification procedure for non-human ovarian tissue, this study also showed, for the first time, expression of AMH and GDF-9 in ovarian follicles. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4507.10, grant 3.4.590.08 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Department of Mechanical Engineering at Louisiana State University (support to Ram Devireddy), and

IMMUNOLOGIC AND PHYSIOLOGIC OBSERVATIONS IN BABOONS WITH LIFE-SUPPORTING GENETICALLY-ENGINEERED PIG KIDNEY GRAFTS

PubMed Central

Iwase, Hayato; Hara, Hidetaka; Ezzelarab, Mohamed; Li, Tao; Zhang, Zhongqiang; Gao, Bingsi; Liu, Hong; Long, Cassandra; Wang, Yi; Cassano, Amy; Klein, Edwin; Phelps, Carol; Ayares, David; Humar, Abhinav; Wijkstrom, Martin; Cooper, David KC

2017-01-01

Background Genetically-engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 days and 310 days, but graft survival >30 days has been unusual until recently. Methods Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement-regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation-regulatory protein. Two baboons received a kidney from a 6-gene pig (Group A) and two from a 3-gene pig (Group B). Immunosuppressive therapy was identical in all 4 cases, and consisted of anti-thymoglobulin (ATG) + anti-CD20mAb (induction) and anti-CD40mAb + rapamycin + corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy. Results The two Group A baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, e.g., thrombocytopenia, reduction of fibrinogen, or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both Group B baboons developed features of a consumptive coagulopathy and required euthanasia on day 12. Conclusions The combination of (i) a graft from a specific 6-gene genetically-modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory therapy prevented immune injury, a protein-losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is

Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough.

PubMed

Kapil, Parul; Papin, James F; Wolf, Roman F; Zimmerman, Lindsey I; Wagner, Leslie D; Merkel, Tod J

2018-03-28

Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

Extracellular matrix metalloproteinase inducer expression in the baboon endometrium: menstrual cycle and endometriosis

PubMed Central

Braundmeier, A G; Fazleabas, A T; Nowak, R A

2016-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN; BSG) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates, endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, BSG and MMPs are expressed in the endometrium of cycling baboons, and their expression is hormonally regulated by ovarian hormones, but endometriosis disrupts this regulation. BSG expression was evaluated in the baboon endometrium by q-PCR and immunohistochemistry. In the endometrium of control cycling animals, BSG mRNA levels were highest in late secretory stage tissue. BSG protein localized to glandular epithelial cells during the proliferative phase; whereas, secretory stage tissues expressed BSG in glandular and luminal epithelia with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with the highest levels found during menstruation. In ovariectomized animals, BSG endometrial mRNA levels were highest with treatment of both estrogen and progesterone than that with only estrogen. Estrogen alone resulted in BSG protein localization primarily in the endometrial glandular epithelia, while estrogen and progesterone treatment displayed BSG protein localization in both the glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared with the control cycling animals. In the eutopic endometrium of endometriotic animals, BSG mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP7 compared with the control animals. In baboons, BSG and MMP endometrial expression is regulated by both ovarian hormones, and their expression patterns are dysregulated in endometriotic animals. PMID:20841363

Xenotransplantation of uterine leiomyoma in Wistar rats: a pilot study.

PubMed

Sousa, Willane Bandeira de; Garcia, João Batista Santos; Nogueira Neto, João; Furtado, Pablo Gustavo Ribeiro; Anjos, Jonhnathan Adriano Araújo dos

2015-07-01

=0.039). This study demonstrates that the xenotransplantation of uterine leiomyoma into the parietal peritoneum is more effective than the xenotransplantation of uterine leiomyoma into the subcutaneous tissue, and it describes a promising new model for the study of leiomyoma in vivo. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stek, M.; Minard, P.; Dean, D.A.

1981-06-01

Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

Immunization of baboons with Schistosoma mansoni cercariae attenuated by gamma irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stek, M. Jr.; Minard, P.; Dean, D.A.

1981-06-26

Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70%) and egg excretion rates (82%). These results support immunization as a potential method for schistosomiasis control.

Ontogenetic scaling of fore limb and hind limb joint posture and limb bone cross-sectional geometry in vervets and baboons.

PubMed

Burgess, M Loring; Schmitt, Daniel; Zeininger, Angel; McFarlin, Shannon C; Zihlman, Adrienne L; Polk, John D; Ruff, Christopher B

2016-09-01

Previous studies suggest that the postures habitually adopted by an animal influence the mechanical loading of its long bones. Relatively extended limb postures in larger animals should preferentially reduce anteroposterior (A-P) relative to mediolateral (M-L) bending of the limb bones and therefore decrease A-P/M-L rigidity. We test this hypothesis by examining growth-related changes in limb bone structure in two primate taxa that differ in ontogenetic patterns of joint posture. Knee and elbow angles of adult and immature vervets (Chlorocebus aethiops, n = 16) were compared to published data for baboons (Papio hamadryas ursinus, n = 33, Patel et al., ). Ontogenetic changes in ratios of A-P/M-L bending rigidity in the femur and humerus were compared in skeletal samples (C. aethiops, n = 28; P. cynocephalus, n = 39). Size changes were assessed with linear regression, and age group differences tested with ANOVA. Only the knee of baboons shows significant postural change, becoming more extended with age and mass. A-P/M-L bending rigidity of the femur decreases during ontogeny in immature and adult female baboons only. Trends in the humerus are less marked. Adult male baboons have higher A-P/M-L bending rigidity of the femur than females. The hypothesized relationship between more extended joints and reduced A-P/M-L bending rigidity is supported by our results for immature and adult female baboon hind limbs, and the lack of significant age changes in either parameter in forelimbs and vervets. Adult males of both species depart from general ontogenetic trends, possibly due to socially mediated behavioral differences between sexes. Am J Phys Anthropol 161:72-83, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Increased antibody responses to Herpes virus papio (HVP) antigens in pre-lymphomatous baboons (Papio hamadryas) of the Sukhumi high lymphoma stock.

PubMed

Voevodin, A F; Yakovleva, L A; Lapin, B A; Ponomarjeva, T I

1983-11-15

Antibody responses to Herpes virus papio (HVP) antigens were studied in 21 pre-lymphoma baboons (which subsequently died of malignant lymphoma), 21 paired controls, i.e. age-, sex- and population-matched healthy baboons, and 185 randomly selected healthy baboons of the same population. The sera were all collected at the same time and were tested blind in the fixed-cell indirect immunofluorescence test against HVP viral capsid antigen (VCA)-positive, early antigen (EA)-positive cell targets before and after absorption with HVP. Eleven of the pre-lymphoma sera were anti-EA-positive whereas none of the paired controls contained anti-EA. Anti-VCA titers of pre-lymphoma sera were higher than those of paired controls in thirteen cases. Only in four cases were anti-VCA titers of pre-lymphoma sera lower than those of paired controls. Qualitatively, the same results were obtained when anti-VCA and anti-EA titers of pre-lymphoma sera were compared with respective mean population values. The differences between pre-lymphoma group and control groups, especially in the case of anti-EA, were statistically highly significant. Thus, elevated anti-HVP titers in healthy baboons of the Sukhumi lymphoma-prone stock can be considered as a marker of high risk for development of malignant lymphoma.

Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Qian-fei; Liu, Xin; O'Connell, Jeff

2003-09-15

Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent withmore » haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.« less

Defense of the lungs in oxygen-injured baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, S.R.; Rawlinson, W.K.; Roach, F.M.

1986-03-05

Pneumonia and subsequent sepsis have been linked with multiple organ failure and death in patients with adult respiratory distress syndrome. This suggests that lung defense may be impaired. In a model of ARDS, 13 baboons were intubated and ventilated with 80% O/sub 2/ for 6 days, following which 7 were inoculated intratracheally with Pseudomonas aeruginosa (PA) strain DGI-RI30. After 5 days on 50% O/sub 2/ the animals were sacrificed. Bronchoalveolar lavage (BAL) was performed before O/sub 2/ exposure, after 6 days of 80% O/sub 2/, and at sacrifice. Total WBC and differential counts were determined for BAL cells. Mononuclear BALmore » cells were isolated for in vitro phagocytosis assays. BAL fluid (BALF) was tested for in vitro PMN chemotactic activity. An index of bacterial infection (sum of log CFU/g lung homogenate) was greater for infected animals (p < 0.01). Percentage of PMN in BALF was significantly increased at sacrifice in PA-inoculated animals. BALF from PA-inoculated animals at sacrifice elicited increased in vitro PMN chemotaxis, which was destroyed at 100/sup 0/C but not 56/sup 0/C, extracted by ether, and not degraded by proteases. Mononuclear BAL cells from inoculated animals at sacrifice were phagocytially more active than baseline cells. These data suggest that oxygen injury does not inhibit recruitment of PMN or phagocytosis of bacteria by alveolar macrophages in baboons; however, the addition of bacterial inoculation results in clinical deterioration despite unimpaired local defense.« less

Xenotransplantation as a model for human testicular development.

PubMed

Hutka, Marsida; Smith, Lee B; Mitchell, Rod T

The developing male reproductive system may be sensitive to disruption by a wide range of exogenous 'endocrine disruptors'. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific 'window of susceptibility' in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect future fertility. Much of our current knowledge about fetal and early postnatal human testicular development derives from studies conducted in animal models predictive for humans. Therefore, over recent years, testicular transplantation has been employed as a 'direct' approach to understand the development of human fetal and prepubertal testis in health and disease. In this review we describe the potential use of human testis xenotransplantation to study testicular development and its application for (i) assessing the effects of environmental exposures in humans, and (ii) establishing fertility preservation options for prepubertal boys with cancer. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model

PubMed Central

Ebersole, J L; Steffen, M J; Holt, S C; Kesavalu, L; Chu, L; Cappelli, D

2010-01-01

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals. PMID:21070210

Complement inhibition decreases early fibrogenic events in the lung of septic baboons.

PubMed

Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

2015-11-01

Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 10(9) cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. © 2015 The Authors

Other better versus self better in baboons: an evolutionary approach of social comparison

PubMed Central

2017-01-01

Comparing oneself with others is an important characteristic of human social life, but the link between human and non-human forms of social comparison remains largely unknown. The present study used a computerized task presented in a social context to explore psychological mechanisms supporting social comparison in baboons and compare major findings with those usually observed in humans. We found that the effects of social comparison on subject's performance were guided both by similarity (same versus different sex) and by task complexity. Comparing oneself with a better-off other (upward comparison) increased performance when the other was similar rather than dissimilar, and a reverse effect was obtained when the self was better (downward comparison). Furthermore, when the other was similar, upward comparison led to a better performance than downward comparison. Interestingly, the beneficial effect of upward comparison on baboons' performance was only observed during simple task. Our results support the hypothesis of shared social comparison mechanisms in human and non-human primates. PMID:28539512

Fatigue of immature baboon cortical bone.

PubMed

Keller, T S; Lovin, J D; Spengler, D M; Carter, D R

1985-01-01

Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance.

A BRIEF HISTORY OF CLINICAL XENOTRANSPLANTATION

PubMed Central

Cooper, David K. C.; Ekser, Burcin; Tector, A. Joseph

2015-01-01

Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century, with grafts from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into elderly men, believing that the hormones produced by the testis would rejuvenate his patients. In 1963–4, when human organs were not available and dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within two hours. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992 he obtained patient survival for 70 days following a baboon liver transplant. The first clinical pig islet transplant was carried out by Groth in 1993. Today, genetically-modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant. PMID:26118617

Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts.

PubMed

Iwase, Hayato; Hara, Hidetaka; Ezzelarab, Mohamed; Li, Tao; Zhang, Zhongqiang; Gao, Bingsi; Liu, Hong; Long, Cassandra; Wang, Yi; Cassano, Amy; Klein, Edwin; Phelps, Carol; Ayares, David; Humar, Abhinav; Wijkstrom, Martin; Cooper, David K C

2017-03-01

Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein. Two baboons received a kidney from a six-gene pig (GroupA) and two from a three-gene pig (GroupB). Immunosuppressive therapy was identical in all four cases and consisted of anti-thymoglobulin (ATG)+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy. The two GroupA baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, eg, thrombocytopenia and reduction of fibrinogen, or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both GroupB baboons developed features of a consumptive coagulopathy and required euthanasia on day 12. The combination of (i) a graft from a specific six-gene genetically modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory therapy prevented immune injury, a protein-losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is that expression of human endothelial

Prevalence of antibodies to soluble antigen of Epstein-Barr virus-producing cells (P3HR-1) in the sera of hamadryas baboons of the high lymphoma incidence stock.

PubMed

Voevodin, A F; Lapin, B A; Yakovleva, L A; Ponomarjova, T I; Agrba, V Z

1979-01-01

Soluble antigen of P3HR-1 cells (SA-P3HR-1) was identified in indirect double immunodiffusion enhanced with tannic acid using serum of a nasopharyngeal carcinoma patient containing high-titer antibodies to Epstein-Barr virus (EBV) antigens. SA-P3HR-1 was nonidentical to soluble antigen of Raji cells. Human and baboon sera containing antibodies to all the known antigen of EBV and HVP respectively were anti-SA-3HR-1-positive. Human and baboon sera containing antibodies to all the known antigens of EBV and herpesvirus Papio (HVP) were also anti-SA-P3HR-1-negative. Prevalence of anti-SA-P3HR-1 was very high in two groups of the high-lymphoma incidence stock of hamadryas baboons of the Sukhumi monkey colony. 54% (15 of 28) and 38% (13 of 34) of clinically lymphomatous and clinical normal monkeys, respectively, were anti-SA-P3HR-1-positive.. Only 1 of 30 normal baboons studied, living in the forest and having no contacts with the baboons in the main stock of the Sukhumi monkey colony, was anti-SA-P3HR-1-positive (3%).

Derivation and characterization of novel nonhuman primate embryonic stem cell lines from in vitro-fertilized baboon preimplantation embryos.

PubMed

Chang, Tien-Cheng; Liu, Ya-Guang; Eddy, Carlton A; Jacoby, Ethan S; Binkley, Peter A; Brzyski, Robert G; Schenken, Robert S

2011-06-01

The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol. The inner cell mass of blastocyst was laser-dissected and plated on mouse embryonic fibroblast feeder cell monolayer in the NHP ESC culture medium. Three cell lines with characteristic ESC morphology have been cultured through an extended period (>14 months), with 2 male cell lines (UT-1 and -2) and 1 female cell line (UT-3) displaying normal baboon karyotypes. Reverse transcription-polymerase chain reaction analysis confirmed that all 3 lines express primate ESC pluripotency markers, including OCT-4, NANOG, SOX-2, TERT, TDGF, LEFTYA, and REX-1. All 3 lines demonstrated positive immunocytochemical staining for OCT-4, stage-specific embryonic antigen-3, stage-specific embryonic antigen-4, TRA-1-60, and TRA-1-81. Baboon ESCs injected into NOD/SCID mice formed teratomas with all 3 germ layers. In addition, embryoid body-like spherical structures were derived and initial outgrowth was observed when embedded into extracellular matrix Matrigel. The ESC lines established in this NHP model have the potential to extend our knowledge in the fields of developmental biology, regenerative medicine, and future applications, including preclinical safety assessment of in vivo stem cell therapy.

Endocrinology of year-round reproduction in a highly seasonal habitat: environmental variability in testosterone and glucocorticoids in baboon males

PubMed Central

Gesquiere, Laurence R.; Onyango, Patrick O.; Alberts, Susan C.; Altmann, Jeanne

2010-01-01

In conditions characterized by energetic constraints, such as in periods of low food availability, some trade-offs between reproduction and self-maintenance may be necessary; even year-round breeders may then be forced to exhibit some reproductive seasonality. Prior research has largely focused on female reproduction and physiology, and few studies have evaluated the impact of environmental factors on males. Here we assessed the effects of season and ambient temperatures on fecal glucocorticoid (fGC) and testosterone (fT) levels in male baboons in Amboseli, Kenya. The Amboseli basin is a highly challenging, semi-arid tropical habitat that is characterized by strongly seasonal patterns of rainfall and by high ambient temperatures. We previously reported that female baboons were impacted by these challenging environmental conditions. We ask here whether male baboons in the same environment and groups as females exhibit similar physiological effects. We found that after accounting for male age and individual variability, males exhibited higher fGC levels and lower fT levels during the dry season than during the wet season. Furthermore, fT but not fGC levels were lower in months of high average daily maximum temperatures, suggesting a direct impact of heat on testes. Our results demonstrate that male baboons, like females, experience ecological stress that alters their reproductive physiology. The impact of the environment on male reproduction deserves more attention both in its own right and because alteration in male physiology may contribute to the reduction in female fertility observed in challenging environments. PMID:20721938

Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

PubMed

Mubiru, James N; Yang, Alice S; Olsen, Christian; Nayak, Sudhir; Livi, Carolina B; Dick, Edward J; Owston, Michael; Garcia-Forey, Magdalena; Shade, Robert E; Rogers, Jeffrey

2014-01-01

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

A brief history of clinical xenotransplantation.

PubMed

Cooper, David K C; Ekser, Burcin; Tector, A Joseph

2015-11-01

Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century, with grafts from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into elderly men, believing that the hormones produced by the testis would rejuvenate his patients. In 1963-4, when human organs were not available and dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 h. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992 he obtained patient survival for 70 days following a baboon liver transplant. The first clinical pig islet transplant was carried out by Groth in 1993. Today, genetically-modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Genetic integration of molar cusp size variation in baboons

PubMed Central

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

2010-01-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the non-occluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. PMID:20034010

Genetic integration of molar cusp size variation in baboons.

PubMed

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T; Fletcher, Zachary; Mahaney, Michael C; Hlusko, Leslea J

2010-06-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the nonoccluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. Copyright 2009 Wiley-Liss, Inc.

Financial aspects of organ procurement from deceased donors in the USA-Relevance to xenotransplantation.

PubMed

Saari, Ryan J; Cooper, David K C

2017-07-01

When clinical xenotransplantation is introduced, the costs associated with acquisition of a genetically engineered pig organ are as yet unknown. How will these costs compare with those currently associated with the acquisition of deceased human organs? An understanding of the financial aspects of deceased organ and tissue procurement in the USA is therefore worthwhile. We have therefore attempted to review certain economic aspects of non-profit and for-profit organizations that provide cadaveric organs and/or tissues for purposes of transplantation into patients with end-stage organ failure, cellular deficiencies, or in need of reconstructive procedures. We briefly consider the laws, organizations, and business practices that govern the acquisition, processing, and/or distribution of cadaveric organs and tissues, and the economic implications of industry practices. In particular, we explore and highlight what we perceive as a lack of transparency and oversight with regard to financial practices, and we question whether donor families would be entirely happy with the business environment that has developed from their altruistic donations. Until xenotransplantation becomes established clinically, which will negate the need for any system of organ procurement and allocation, we suggest that those involved in organ and cell transplantation, as well as those who participate in reconstructive surgery, should take responsibility to ensure that the financial practices associated with procurement are transparent, and overseen/regulated by a responsible authority. We suggest the major transplant societies should take a lead in this respect. The ability to acquire a genetically engineered pig organ whenever required through a simple commercial transaction (as in the acquisition of a life-saving drug) will be greatly to the patient's benefit. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Of Pigs and Men: Understanding Students' Reasoning About the Use of Pigs as Donors for Xenotransplantation

NASA Astrophysics Data System (ADS)

Lindahl, Mats Gunnar

2010-09-01

Two important roles of education are to provide students with knowledge for their democratic participation in society and to provide knowledge for a future profession. In science education, students encounter values that may be in conflict with their worldview. Such conflicts may, for example, lead to constructive reflections as well as rejection of scientific knowledge and technology. Students’ ways of reasoning are important starting points for discussing problematic issues and may be crucial for constructive dialogues in the classroom. This study investigates students’ reasoning about conflicting values concerning the human-animal relationship exemplified by the use of genetically modified pigs as organ donors for xenotransplantation. Students’ reasoning is analyzed using Giddens’ concepts of disembedded and embedded practices in parallel with moral philosophical theories in a framework based on human-animal relationships. Thirteen students were interviewed and their stances categorized. Kantian deontological and classical utilitarian ethics were found within the patronage and the partnership models. These students appreciated expert knowledge but those using the partnership model could not accept xenotransplantation if pigs were to be killed. Students using care ethics did not appreciate expert knowledge since it threatened naturalness. The results suggest that stances against the use of scientific knowledge are more problematic than knowledge per se, and that conflicting stances have similarities that present opportunities for understanding and development of students’ argumentation skills for future participation in societal discourse on utilizing expert knowledge. Furthermore it is argued that science education could benefit from a higher awareness of the presence of different morals.

Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon.

PubMed

Pantham, Priyadarshini; Rosario, Fredrick J; Nijland, Mark; Cheung, Alex; Nathanielsz, Peter W; Powell, Theresa L; Galan, Henry L; Li, Cun; Jansson, Thomas

2015-10-01

Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood. We hypothesized that MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplacental transfer of AAs. Pregnant baboons were fed either a control (ad libitum, n = 7), or MNR diet (70% of control diet, n = 7) from gestational day (GD) 30. At GD 165 (0.9 gestation), placentas (n = 7 in each group) were collected, and microvillous plasma membrane vesicles (MVM) isolated. MVM system A and system L AA transport was determined in vitro using radiolabeled substrates and rapid filtration techniques. In vivo transplacental AA transport was assessed by infusing nine (13)C- or (2)H-labeled essential AA as a bolus into the maternal circulation (n = 5 control, n = 4 MNR) at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each essential AA was calculated. Fetal and placental weights were significantly reduced in the MNR group compared with controls (P < 0.01). The activity of system A and system L was markedly reduced by 73 and 84%, respectively, in MVM isolated from baboon placentas at GD 165 following MNR (P < 0.01). In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly reduced for leucine, isoleucine, methionine, phenylalanine, threonine, and tryptophan in MNR baboons (P < 0.05). This is the first study to investigate placental AA transport in a nonhuman primate model of MNR. We demonstrate that the downregulation of system A and system L activity in syncytiotrophoblast MVM in MNR leads to decreased transplacental AA transport and, consequently, reduced circulating fetal AA concentrations, a potential mechanism linking maternal undernutrition to reduced fetal growth. Copyright © 2015 the American Physiological Society.

Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons

PubMed Central

Guardado-Mendoza, Rodolfo; Davalli, Alberto M.; Chavez, Alberto O.; Hubbard, Gene B.; Dick, Edward J.; Majluf-Cruz, Abraham; Tene-Perez, Carlos E.; Goldschmidt, Lukasz; Hart, John; Perego, Carla; Comuzzie, Anthony G.; Tejero, Maria Elizabeth; Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo; Halff, Glenn; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco

2009-01-01

β-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative β-cell volume, and increased relative α-cell volume and hyperglucagonemia. These results strongly support the concept that IA and β-cell apoptosis in concert with α-cell proliferation and hypertrophy are key determinants of islets of Langerhans “dysfunctional remodeling” and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R2 = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. PMID:19666551

Electromyography of wrist and finger flexor muscles in olive baboons (Papio anubis).

PubMed

Patel, Biren A; Larson, Susan G; Stern, Jack T

2012-01-01

Some non-human primates use digitigrade hand postures when walking slowly on the ground. As a component of an extended limb, a digitigrade posture can help minimize wrist joint moments thereby requiring little force production directly from wrist flexors (and/or from the assistance of finger flexors) to maintain limb posture. As a consequence, less active muscle volume would be required from these anti-gravity muscles and overall metabolic costs associated with locomotion could be reduced. To investigate whether the use of digitigrade hand postures during walking in primates entails minimal use of anti-gravity muscles, this study examined electromyography (EMG) patterns in both the wrist and finger flexor muscles in facultatively digitigrade olive baboons (Papio anubis) across a range of speeds. The results demonstrate that baboons can adopt a digitigrade hand posture when standing and moving at slow speeds without requiring substantial EMG activity from distal anti-gravity muscles. Higher speed locomotion, however, entails increasing EMG activity and is accompanied by a dynamic shift to a more palmigrade-like limb posture. Thus, the ability to adopt a digitigrade hand posture by monkeys is an adaptation for ground living, but it was never co-opted for fast locomotion. Rather, digitigrady in primates appears to be related to energetic efficiency for walking long distances.

Knockouts of high-ranking males have limited impact on baboon social networks.

PubMed

Franz, Mathias; Altmann, Jeanne; Alberts, Susan C

Social network structures can crucially impact complex social processes such as collective behaviour or the transmission of information and diseases. However, currently it is poorly understood how social networks change over time. Previous studies on primates suggest that `knockouts' (due to death or dispersal) of high-ranking individuals might be important drivers for structural changes in animal social networks. Here we test this hypothesis using long-term data on a natural population of baboons, examining the effects of 29 natural knockouts of alpha or beta males on adult female social networks. We investigated whether and how knockouts affected (1) changes in grooming and association rates among adult females, and (2) changes in mean degree and global clustering coefficient in these networks. The only significant effect that we found was a decrease in mean degree in grooming networks in the first month after knockouts, but this decrease was rather small, and grooming networks rebounded to baseline levels by the second month after knockouts. Taken together our results indicate that the removal of high-ranking males has only limited or no lasting effects on social networks of adult female baboons. This finding calls into question the hypothesis that the removal of high-ranking individuals has a destabilizing effect on social network structures in social animals.

Seroepizootiology of the herpesvirus Papio (HVP) infection in healthy baboons (Papio hamadryas) of high- and low-lymphoma risk populations.

PubMed

Voevodin, A F; Ponomarjeva, T I; Lapin, B A

1985-01-01

Seroepizootiology of Herpesvirus Papio (HVP) infection was studied in three groups of healthy hamadryas baboons (Papio hamadryas): the main Sukhumi (high-lymphoma) stock, forest Sukhumi (lymphoma-free) stock and newly imported wild animals. The prevalence to HVP infection, as judged by anti-VCA-HVP positivity, was approximately the same in both Sukhumi stocks (86% and 90% respectively) and it was significantly lower in the pooled group of newly imported baboons. It is interesting that prevalence of HVP infection in the different independent groups varied markedly (35-79%). Geometric mean titers of positives in all groups were approximately the same. The prevalence of HVP infection was age-dependent. It increased during the first years of life reaching the maximum (about 100%) at the age of 5 years being stable up to the age of 18 years and "decreased" at very old ages (over 18 years). The prevalence of HVP infection in newly imported baboons increased with age up to 71% in a group of the "oldest" monkeys and did not plateau. No significant sex differences in anti-HVP titers were found. Anti-EA-HVP-positive (with one exception) and anti-HUPNA-positive animals were found only in the main Sukhumi stock. Thus, "serologic activity" against HVP infection was the highest in the ligh-lymphoma stock.

Zoonotic intestinal parasites in Papio anubis (baboon) and Cercopithecus aethiops (vervet) from four localities in Ethiopia.

PubMed

Legesse, Mengistu; Erko, Berhanu

2004-05-01

A total of 59 faecal samples from ranging Papio anubis (baboons) and another 41 from Cercopithecus aethiops (vervet) from the Rift Valley areas of Ethiopia were microscopically examined to determine the prevalence and species of major gastro-intestinal parasites of zoonotic importance. Faecal smears were prepared from fresh faecal samples, stained using modified Ziehl-Neelsen method and microscopically examined. About 3 gm of the dropping was also preserved separately in clean and properly labelled containers containing 10% formalin. The specimens were microscopically examined after formalin-ether concentration for ova, larvae, cysts and oocyst of intestinal parasites. The results of microscopic examination of faecal samples of baboons demonstrated the presence of Trichuris sp. (27.1%), Strongyloides sp. (37.3%), Trichostrongylus sp. (8.5%), Oesophagostomum sp. (10.2%), Schistosoma mansoni (20.3%), Entamoeba coli (83.1%), Entamoeba histolytica/dispar (16.9%), Blastocystis hominis (3.3%), Cyclospora sp. (13.3%) and Cryptosporidium sp. (11.9%). Likewise, the results of microscopic examination of faecal samples of vervets demonstrated the presence of Trichuris sp. (36.6%), Oesophagostomum sp. (4.9%), E. coli (61.0%), E. histolytica/dispar (24.4%), B. hominis (34.2%), Cyclospora sp. (22.0%) and Cryptosporidium sp. (29.3%). The presence of parasitic protozoa and helminths in baboons and vervets in the study areas is a high risk to human welfare because these non-human primates use the same water sources as humans and range freely in human habitats. An implication of such parasitic infection for the control programme is discussed.

The influence of quarantine on reproductive cycling in wild-caught Baboons (Papio anubis).

PubMed

Liechty, Emma R; Wang, Diane Y; Chen, Emily; Chai, Daniel; Bell, Jason D; Bergin, Ingrid L

2015-12-01

Stress impacts nonhuman primate menstrual cycle length but the impact of quarantine is unknown. A retrospective analysis was performed on cycle data from 31 wild-caught baboons during and following quarantine. Cycling initiated in 94 days (19-181) and length normalized within 4-6 cycles. Quarantine significantly impacts menstrual cycle length. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Frankenswine, or bringing home the bacon

PubMed Central

2008-01-01

Xenotransplantation—specifically from pig into human—could resolve the critical shortage of organs, tissues and cells for clinical transplantation. Genetic engineering techniques in pigs are relatively well-developed and to date have largely been aimed at producing pigs that either (1) express high levels of one or more human complement-regulatory protein(s), such as decay-accelerating factor or membrane cofactor protein, or (2) have deletion of the gene responsible for the expression of the oligosaccharide, Galα1,3Gal (Gal), the major target for human anti-pig antibodies, or (3) have both manipulations. Currently the transplantation of pig organs in adequately-immunosuppressed baboons results in graft function for periods of 2–6 months (auxiliary hearts) and 2–3 months (life-supporting kidneys). Pig islets have maintained normoglycemia in diabetic monkeys for >6 months. The remaining immunologic barriers to successful xenotransplantation are discussed, and brief reviews made of (1) the potential risk of the transmission of an infectious microorganism from pig to patient and possibly to the public at large, (2) the potential physiologic incompatibilities between a pig organ and its human counterpart, (3) the major ethical considerations of clinical xenotransplantation, and (4) the possible alternatives that compete with xenotransplantation in the field of organ or cell replacement, such as mechanical devices, tissue engineering, stem cell biology and organogenesis. Finally, the proximity of clinical trials is discussed. Islet xenotransplantation is already at the stage where clinical trials are actively being considered, but the transplantation of pig organs will probably require further genetic modifications to be made to the organ-source pigs to protect their tissues from the coagulation/anticoagulation dysfunction that plays a significant role in pig graft failure after transplantation in primates. PMID:19279708

Dietary wheaten bran in baboons: long-term effect on the morphology of the digestive tract and aorta, and on tissue mineral concentrations.

PubMed Central

Kriek, N. P.; Sly, M. R.; du Bruyn, D. B.; de Klerk, W. A.; Renan, M. J.; Van Schalkwyk, D. J.; Van Rensburg, S. J.

1982-01-01

Two groups of 13 young baboons, each consisting of 8 males and 8 females, were fed on either high- or low-bran diets (based on wheat of either high or low extraction rate) for a period of 26 months. All animals grew well and remained in good condition throughout. Male (but not female) baboons on the high-bran diet had lower (p less than 0.05) concentrations of zinc in serum and bone, despite a low phytate: zinc molar ratio and a high intake of zinc. Particle-induced X-ray emission analysis showed there to be lower concentrations of calcium, copper, zinc, sulphur, potassium and nickel in the livers of baboons on the high-bran diet (P less than 0.005). Baboons on the low-bran diet passed smaller quantities of softer faeces, they had fewer nodules of lymphoid tissue in the distal portion of the colon (P less than 0.05), and within mucosal microherniations of their ileo-caecal valves the epithelial cells showed a greater tendency to squamous transformation (P less than 0.05). Mucosal microherniations of the ileo-caecal valves tended to be more frequent and larger in size (P less than 0.05) in animals of the low-bran group. Morphometrical studies did not reveal any differences in the general structural development of the digestive tract. The high-bran diet had no effect on serum cholesterol concentrations, nor on the incidence or severity of atherosclerotic lesions of the aorta. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6284191

Proteomic Identification of Non-Gal Antibody Targets After Pig-to-Primate Cardiac Xenotransplantation

PubMed Central

Byrne, Guerard W.; Stalboerger, Paul G.; Davila, Eduardo; Heppelmann, Carrie J.; Gazi, Mozammel H.; McGregor, Hugh C. J.; LaBreche, Peter T.; Davies, William R.; Rao, Vinay P.; Oi, Keiji; Tazelaar, Henry D.; Logan, John S.; McGregor, Christopher G. A.

2008-01-01

Background Experience with non-antigenic galactose α1,3 galactose (αGal) polymers and development of αGal deficient pigs has reduced or eliminated the significance of this antigen in xenograft rejection. Despite these advances, delayed xenograft rejection (DXR) continues to occur most likely due to antibody responses to non-Gal endothelial cell (EC) antigens. Methods To gauge the diversity of the non-Gal antibody response we used antibody derived from CD46 transgenic heterotopic cardiac xenografts performed without T-cell immunosuppression, Group A (n = 4) and Gal knockout (GT-KO) heart transplants under tacrolimus and sirolimus immunosuppression, Group B (n = 8). Non-Gal antibody was measured by flow cytometry and by Western blots using GT-KO EC membrane antigens. A nanoLC/MS/MS analysis of proteins recovered from 2D gels was used to identify target antigens. Results Group A recipients exhibited a mixed cellular and humoral rejection. Group B recipients mainly exhibited classical DXR. Western blot analysis showed a non-Gal antibody response induced by GT+ and GT-KO hearts to an overlapping set of pig aortic EC membrane antigens. Proteomic analysis identified 14 potential target antigens but failed to define several immunodominant targets. Conclusions These experiments indicate that the non-Gal antibody response is directed to a number of stress response and inflammation related pig EC antigens and a few undefined targets. Further analysis of these antibody specificities using alternative methods is required to more fully define the repertoire of non-Gal antibody responses. PMID:18957049

Developmental Regulation of p66Shc Is Altered by Bronchopulmonary Dysplasia in Baboons and Humans

PubMed Central

Lee, Matt K.; Pryhuber, Gloria S.; Schwarz, Margaret A.; Smith, Susan M.; Pavlova, Zdena; Sunday, Mary E.

2005-01-01

Rationale: The p66Shc adapter protein antagonizes mitogen-activated protein, or MAP, kinase, mediates oxidative stress, and is developmentally regulated in fetal mouse lungs. Objectives: To determine if p66Shc is similarly regulated in primates and in bronchopulmonary dysplasia (BPD), which results from oxidative injury to immature lungs. Methods: Normal and injured lungs from humans and baboons were evaluated by Western analysis and immunohistochemistry. Measurements and Main Results: In baboons, p66Shc decreased 80% between 125 and 175 days' gestation (p = 0.025), then doubled after term delivery at 185 days (p = 0.0013). In the hyperoxic 140-day fetal baboon BPD model, p66Shc expression persisted, and its localization shifted from the epithelium of gestational controls to the mesenchyme of diseased lungs, coincident with expression of proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase, a marker of apoptosis. Treatment with the antibombesin antibody 2A11 attenuated BPD, reduced cell proliferation, increased p66Shc expression 10.5-fold, and preserved epithelial p66Shc localization. p66Shc also decreased during normal human lung development, falling 87% between 18 and 24 weeks' gestation (p = 0.02). p66Shc was expressed throughout 18-week human lungs, became restricted to scattered epithelial cells by 24 weeks, and localized to isolated mesenchymal cells after term delivery. In contrast, p66Shc remained prominent in the epithelium of lungs with acute injury or mild BPD, and in the mesenchyme of lungs with severe disease. p66Shc localized to tissues expressing proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase. Conclusions: p66Shc expression, cell proliferation, and apoptosis are concomitantly altered during lung development and in BPD. PMID:15778491

Development of a consensus protocol to quantify primate anti-non-Gal xenoreactive antibodies using pig aortic endothelial cells.

PubMed

Azimzadeh, Agnes M; Byrne, Guerard W; Ezzelarab, Mohamed; Welty, Emily; Braileanu, Gheorghe; Cheng, Xiangfei; Robson, Simon C; McGregor, Christopher G A; Cooper, David K C; Pierson, Richard N

2014-01-01

Scientists working in the field of xenotransplantation do not employ a uniform method to measure and report natural and induced antibody responses to non-Galα(1,3)Gal (non-Gal) epitopes. Such humoral responses are thought to be particularly pathogenic after transplantation of vascularized GalTKO pig organs and having a more uniform assay and reporting format would greatly facilitate comparisons between laboratories. Flow cytometry allows examination of antibody reactivity to intact antigens in their natural location and conformation on cell membranes. We have established a simple and reproducible flow cytometric assay to detect antibodies specific for non-Gal pig antigens using primary porcine aortic endothelial cells (pAECs) and cell culture-adapted pAEC cell lines generated from wild type and α1,3galactosyl transferase knockout (GalTKO) swine. The consensus protocol we propose here is based on procedures routinely used in four xenotransplantation centers and was independently evaluated at three sites using shared cells and serum samples. Our observation support use of the cell culture-adapted GalTKO pAEC KO:15502 cells as a routine method to determine the reactivity of anti-non-Gal antibodies in human and baboon serum. We have developed an assay that allows the detection of natural and induced non-Gal xenoreactive antibodies present in human or baboon serum in a reliable and consistent manner. This consensus assay and format for reporting the data should be accessible to laboratories and will be useful for assessing experimental results between multiple research centers. Adopting this assay and format for reporting the data should facilitate the detection, monitoring, and detailed characterization of non-Gal antibody responses. © 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

The effects of vitamine C on lipid metabolism.

PubMed

Kotzé, J P

1975-09-20

Evidence is presented showing that vitamin C had definite effects on lipid metabolism. The stress of captivity on free-living baboons causes a decrease in serum vitamin C levels and an increase in serum cholesterol levels. Increased dietary intake of vitamin C during the initial stages of captivity significantly decreases the serum cholesterol values. Dietary vitamin C stimulates the synthesis of cholesterol from 14C-labelled acetate and mevalonate in baboon liver homogenates and increases the turnover rate of the cholesterol body pool. Vitamin C inhibits baboon cardiac lipoprotein lipase activity.

Emotion-Cognition Interaction in Nonhuman Primates: Cognitive Avoidance of Negative Stimuli in Baboons (Papio papio)

PubMed

Blanchette, Isabelle; Marzouki, Yousri; Claidière, Nicolas; Gullstrand, Julie; Fagot, Joël

2017-01-01

It is well established that emotion and cognition interact in humans, but such an interaction has not been extensively studied in nonhuman primates. We investigated whether emotional value can affect nonhuman primates' processing of stimuli that are only mentally represented, not visually available. In a short-term memory task, baboons memorized the location of two target squares of the same color, which were presented with a distractor of a different color. Through prior long-term conditioning, one of the two colors had acquired a negative valence. Subjects were slower and less accurate on the memory task when the targets were negative than when they were neutral. In contrast, subjects were faster and more accurate when the distractors were negative than when they were neutral. Some of these effects were modulated by individual differences in emotional disposition. Overall, the results reveal a pattern of cognitive avoidance of negative stimuli, and show that emotional value alters cognitive processing in baboons even when the stimuli are not physically present. This suggests that emotional influences on cognition are deeply rooted in evolutionary continuity.

Canine Length in Wild Male Baboons: Maturation, Aging and Social Dominance Rank

PubMed Central

Galbany, Jordi; Tung, Jenny; Altmann, Jeanne; Alberts, Susan C.

2015-01-01

Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04–20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size. PMID:25950700

Increased circulating D-lactate levels predict risk of mortality after hemorrhage and surgical trauma in baboons.

PubMed

Sobhian, Babak; Kröpfl, Albert; Hölzenbein, Thomas; Khadem, Anna; Redl, Heinz; Bahrami, Soheyl

2012-05-01

Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.

Chimpanzees empathize with group mates and humans, but not with baboons or unfamiliar chimpanzees

PubMed Central

Campbell, Matthew W.; de Waal, Frans B. M.

2014-01-01

Human empathy can extend to strangers and even other species, but it is unknown whether non-humans are similarly broad in their empathic responses. We explored the breadth and flexibility of empathy in chimpanzees, a close relative of humans. We used contagious yawning to measure involuntary empathy and showed chimpanzees videos of familiar humans, unfamiliar humans and gelada baboons (an unfamiliar species). We tested whether each class of stimuli elicited contagion by comparing the effect of yawn and control videos. After including previous data on the response to ingroup and outgroup chimpanzees, we found that familiar and unfamiliar humans elicited contagion equal to that of ingroup chimpanzees. Gelada baboons did not elicit contagion, and the response to them was equal to that of outgroup chimpanzees. However, the chimpanzees watched the outgroup chimpanzee videos more than any other. The combination of high interest and low contagion may stem from hostility towards unfamiliar chimpanzees, which may interfere with an empathic response. Overall, chimpanzees showed flexibility in that they formed an empathic connection with a different species, including unknown members of that species. These results imply that human empathic flexibility is shared with related species. PMID:24619445

Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

PubMed

Marchand, Sandrine; Bouchene, Salim; de Monte, Michèle; Guilleminault, Laurent; Montharu, Jérôme; Cabrera, Maria; Grégoire, Nicolas; Gobin, Patrice; Diot, Patrice; Couet, William; Vecellio, Laurent

2015-10-01

The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs.

PubMed

Keane, Fiona M; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G; Chowdhury, Sumaiya; Poplawski, Sarah E; Lai, Jack H; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M T; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M; McLennan, Susan V; McCaughan, Geoffrey W; Bachovchin, William W; Gorrell, Mark D

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs☆

PubMed Central

Keane, Fiona M.; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G.; Chowdhury, Sumaiya; Poplawski, Sarah E.; Lai, Jack H.; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M.T.; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A. Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M.; McLennan, Susan V.; McCaughan, Geoffrey W.; Bachovchin, William W.; Gorrell, Mark D.

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis. PMID:24371721

M Protein-Deficient Respiratory Syncytial Virus (RSV) Vaccine Protects Infant Baboons Against RSV Challenge

PubMed Central

Welliver, Robert C; Oomens, Antonius; Wolf, Roman; Papin, James; Ivanov, Vadim; Preno, Alisha; Staats, Rachel; Piedra, Pedro; Yu, Zhongxin

2017-01-01

Abstract Background RSV bronchiolitis is the most common cause of hospitalization of infants in the US, and may lead to the development of long-term airway disease. Inactivated vaccines may lead to enhanced disease, while replicating vaccines have caused unacceptable degrees of illness, and may revert back to wild type. We developed an RSV vaccine lacking the gene for the M protein (Mnull RSV). The M protein is responsible for reassembly of the virus after it infects cells and expresses its proteins. Infant baboons vaccinated intranasally (IN) with Mnull RSV develop serum neutralizing antibody (NA) responses, but the virus does not replicate. Methods 2-week-old baboons (n = 12) were primed IN with 107 vaccine units of Mnull RSV or a control preparation, and a similar booster dose was given 4 weeks later. Mnull RSV vaccination did not cause tachypnea, airway inflammation or other signs of illness when compared with sham-vaccinated controls. Two weeks after boosting, all infants were challenged intratracheally with human RSV A2. We continuously monitored respiratory rates and levels of overall activity. On various days following challenge, we obtained BAL fluids for leukocyte counts and degree of virus replication, and evaluated alveolar-arterial oxygen gradients (A-a O2). Results Vaccinated animals (vs. unvaccinated controls) had lower respiratory rates (P = 0.0014), improved A-a O2 (P = 0.0063) and reduced viral replication (P = 0.0014). Activity scores were higher in vaccine recipients than in unvaccinated animals. Vaccine recipients also were primed for earlier serum and secretory neutralizing antibody responses, and greater airway lymphocyte responses. Airway lymphocyte numbers (but not antibody responses) were associated with lower respiratory rates and reduced viral replication (P < 0.01). Conclusion Vaccination intranasally with Mnull RSV protected infant baboons against an RSV challenge without causing respiratory disease or enhanced illness, and

Exaggerated sexual swellings and male mate choice in primates: testing the reliable indicator hypothesis in the Amboseli baboons.

PubMed

Fitzpatrick, Courtney L; Altmann, Jeanne; Alberts, Susan C

2015-06-01

The paradigm of competitive males vying to influence female mate choice has been repeatedly upheld, but, increasingly, studies also report competitive females and choosy males. One female trait that is commonly proposed to influence male mate choice is the exaggerated sexual swelling displayed by females of many Old World primate species. The reliable indicator hypothesis posits that females use the exaggerated swellings to compete for access to mates, and that the swellings advertise variation in female fitness. We tested the two main predictions of this hypothesis in a wild population of baboons ( Papio cynocephalus) . First, we examined the effect of swelling size on the probability of mate-guarding ('consortship') by the highest-ranking male and the behavior of those males that trailed consorshipts ('follower males'). Second, we asked whether a female's swelling size predicted several fitness measures. We found that high-ranking males do not prefer females with larger swellings (when controlling for cycle number and conception) and that females with larger swellings did not have higher reproductive success. Our study-the only complete test of the reliable indicator hypothesis in a primate population-rejects the idea that female baboons compete for mates by advertising heritable fitness differences. Furthermore, we found unambiguous evidence that males biased their mating decisions in favor of females who had experienced more sexual cycles since their most recent pregnancy. Thus, rather than tracking the potential differences in fitness between females, male baboons appear to track and target the potential for a given reproductive opportunity to result in fertilization.

Exaggerated sexual swellings and male mate choice in primates: testing the reliable indicator hypothesis in the Amboseli baboons

PubMed Central

Fitzpatrick, Courtney L.; Altmann, Jeanne; Alberts, Susan C.

2015-01-01

The paradigm of competitive males vying to influence female mate choice has been repeatedly upheld, but, increasingly, studies also report competitive females and choosy males. One female trait that is commonly proposed to influence male mate choice is the exaggerated sexual swelling displayed by females of many Old World primate species. The reliable indicator hypothesis posits that females use the exaggerated swellings to compete for access to mates, and that the swellings advertise variation in female fitness. We tested the two main predictions of this hypothesis in a wild population of baboons (Papio cynocephalus). First, we examined the effect of swelling size on the probability of mate-guarding (‘consortship’) by the highest-ranking male and the behavior of those males that trailed consorshipts (‘follower males’). Second, we asked whether a female’s swelling size predicted several fitness measures. We found that high-ranking males do not prefer females with larger swellings (when controlling for cycle number and conception) and that females with larger swellings did not have higher reproductive success. Our study—the only complete test of the reliable indicator hypothesis in a primate population—rejects the idea that female baboons compete for mates by advertising heritable fitness differences. Furthermore, we found unambiguous evidence that males biased their mating decisions in favor of females who had experienced more sexual cycles since their most recent pregnancy. Thus, rather than tracking the potential differences in fitness between females, male baboons appear to track and target the potential for a given reproductive opportunity to result in fertilization. PMID:26752790

Pharmacokinetics of doxylamine given as Bendectin in the pregnant monkey and baboon.

PubMed

Rowland, J M; Slikker, W; Holder, C L; Denton, R; Prahalada, S; Young, J F; Hendrickx, A G

1989-01-01

The object of the present study was to determine the maternal plasma pharmacokinetics of doxylamine (the antihistamine component of Bendectin) following Bendectin administration. Bendectin was administered daily, po, at a dosage approximately 10 times the maximum human therapeutic dosage (7 mg/kg/day) throughout organogenesis (approximately days 22 through 50 of gestation) to three cynomolgus monkeys, four rhesus monkeys, and five baboons. Two pharmacokinetic experiments were performed in each animal, one on the first day of treatment and one on the last day of treatment. Although this study was not designed specifically as a teratologic examination, no morphologic abnormalities were observed when the fetuses were examined on approximately day 100 of gestation. A single-compartment, parallel first- and second-order elimination model was used to analyze the data. Although considerable interindividual variation was evident, no significant differences between species were observed when the half-life for the absorption of doxylamine from the gut or the elimination of doxylamine and metabolites from the plasma were compared. The plasma elimination half-lives and the clearance values were not altered by the 29 days of Bendectin treatment for any of the species. Only the half-life for the absorption of doxylamine in the baboon was reduced by daily dosing with Bendectin, but this did not alter doxylamine elimination. Thus, the pharmacokinetics of doxylamine administered as Bendectin were similar in the three nonhuman primate species examined and were not altered by repeated daily administration.

Localization of /sup 3/H-estradiol in the reproductive organs of male and female baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaker, F.J.; Sheridan, P.J.

1982-05-01

The uptake and retention of radiolabeled estradiol by both the male and female reproductive organs were examined in the baboon. Two male and two female baboons were injected intracardially with 1 microgram/kg body weight of /sup 3/H-estradiol and two animals, one male and one female, were injected with both labeled and 100 micrograms/kg body weight of unlabeled estradiol. One and a half hours after the injections, the animals were sacrificed and the uterus, cervix, vagina, oviduct, seminal vesicles, and prostate gland were removed and processed for autoradiography. The stratified squamous epithelia of the cervix and vagina demonstrated a light uptakemore » of the label in the germinative, but not in the superficial cell layers. The columnar cells lining the oviduct and uterine glands were labeled, whereas the luminal epithelium of the uterus and the glandular epithelia of the seminal vesicles and prostate gland did not sequester the tritiated steroid. The interstitial cells of all the organs studied demonstrated a moderate to heavy uptake of the radioactivity, whereas the smooth muscle cells were lightly labeled except in the vagina, in which these cells displayed a moderate number of silver grains.« less

Effects of food availability on serum insulin and lipid concentrations in free-ranging baboons.

PubMed

Kemnitz, Joseph W; Sapolsky, Robert M; Altmann, Jeanne; Muruthi, Philip; Mott, Glen E; Stefanick, Marcia L

2002-05-01

The relationship between food availability and metabolic physiology was studied in groups of free-ranging baboons (Papio spp.) living in the Amboseli National Park and the Masai Mara National Reserve of Kenya. Three groups subsisted entirely on natural forage, while two other groups lived near tourist facilities and often consumed food wastes from these lodges. The refuse provided a very accessible food source with relatively high caloric density. Consumption of the refuse was associated with reduced locomotion. Sexually mature individuals from all five groups were sedated surreptitiously in the early morning and blood samples were collected. Compared to animals foraging exclusively in the wild, animals that supplemented their diet with the refuse items had two- to threefold elevations in serum insulin concentrations, as well as increased total cholesterol (C), HDL-C, and VLDL+LDL-C levels. No sex differences in physiological measures were observed except in body mass. Elevated serum insulin, and cholesterol and lipoprotein concentrations influence the development of cardiovascular disease and have been shown to be subject to dietary manipulation and exercise under controlled conditions. The present results suggest potentially deleterious effects of a highly accessible, calorically dense food source, and associated reduction of physical activity for baboons living in an otherwise natural environment. Copyright 2002 Wiley-Liss, Inc.

“Resting” CBF in the Epileptic Baboon: Correlation with Ketamine Dose and Interictal Epileptic Discharges

PubMed Central

Szabó, C. Ákos; Narayana, Shalini; Franklin, Crystal; Knape, Koyle D.; Davis, M. Duff; Fox, Peter T.; Leland, M. Michelle; Williams, Jeff T.

2011-01-01

Background Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares “resting” CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Methods Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8–14.6 mg/kg/hr). Three resting H215O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4 mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI = 3.04/2100/785 msec, flip angle=13 degrees). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. Results When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. Conclusions “Resting” CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine’s propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Group decision-making in chacma baboons: leadership, order and communication during movement

PubMed Central

2011-01-01

Background Group coordination is one of the greatest challenges facing animals living in groups. Obligatory trade-offs faced by group members can potentially lead to phenomena at the group level such as the emergence of a leader, consistent structure in the organization of individuals when moving, and the use of visual or acoustic communication. This paper describes the study of collective decision-making at the time of departure (i.e. initiation) for movements of two groups of wild chacma baboons (Papio ursinus). One group was composed of 11 individuals, whilst the other consisted of about 100 individuals. Results Results for both groups showed that adult males initiated more movements even if the leadership was also distributed to adult females and young individuals. Baboons then joined a movement according to a specific order: adult males and adult females were at the front and the back of the group, sub-adults were at the back and juveniles were located in the central part of the progression. In the two groups, vocalisations, especially loud calls, were more frequently emitted just before the initiation of a group movement, but the frequency of these vocalisations did not influence the success of an initiation in any way. Conclusion The emergence of a leadership biased towards male group members might be related to their dominance rank and to the fact that they have the highest nutrient requirements in the group. Loud calls are probably not used as recruitment signals but more as a cue concerning the motivation to move, therefore enhancing coordination between group members. PMID:22014356

Group decision-making in chacma baboons: leadership, order and communication during movement.

PubMed

Sueur, Cédric

2011-10-20

Group coordination is one of the greatest challenges facing animals living in groups. Obligatory trade-offs faced by group members can potentially lead to phenomena at the group level such as the emergence of a leader, consistent structure in the organization of individuals when moving, and the use of visual or acoustic communication. This paper describes the study of collective decision-making at the time of departure (i.e. initiation) for movements of two groups of wild chacma baboons (Papio ursinus). One group was composed of 11 individuals, whilst the other consisted of about 100 individuals. Results for both groups showed that adult males initiated more movements even if the leadership was also distributed to adult females and young individuals. Baboons then joined a movement according to a specific order: adult males and adult females were at the front and the back of the group, sub-adults were at the back and juveniles were located in the central part of the progression. In the two groups, vocalisations, especially loud calls, were more frequently emitted just before the initiation of a group movement, but the frequency of these vocalisations did not influence the success of an initiation in any way. The emergence of a leadership biased towards male group members might be related to their dominance rank and to the fact that they have the highest nutrient requirements in the group. Loud calls are probably not used as recruitment signals but more as a cue concerning the motivation to move, therefore enhancing coordination between group members.

Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons

PubMed Central

Archie, Elizabeth A.; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C.

2014-01-01

Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. ‘social connectedness’) with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes—females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals. PMID:25209936

Explaining sex differences in lifespan in terms of optimal energy allocation in the baboon.

PubMed

King, Annette M; Kirkwood, Thomas B L; Shanley, Daryl P

2017-10-01

We provide a quantitative test of the hypothesis that sex role specialization may account for sex differences in lifespan in baboons if such specialization causes the dependency of fitness upon longevity, and consequently the optimal resolution to an energetic trade-off between somatic maintenance and other physiological functions, to differ between males and females. We present a model in which females provide all offspring care and males compete for access to reproductive females and in which the partitioning of available energy between the competing fitness-enhancing functions of growth, maintenance, and reproduction is modeled as a dynamic behavioral game, with the optimal decision for each individual depending upon his/her state and the behavior of other members of the population. Our model replicates the sexual dimorphism in body size and sex differences in longevity and reproductive scheduling seen in natural populations of baboons. We show that this outcome is generally robust to perturbations in model parameters, an important finding given that the same behavior is seen across multiple populations and species in the wild. This supports the idea that sex differences in longevity result from differences in the value of somatic maintenance relative to other fitness-enhancing functions in keeping with the disposable soma theory. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Effects of 60-Heartz electric and magnetic fields on implanted cardiac pacemakers. Final report. [Hazards of power transmission line frequencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bridges, J.E.; Frazier, M.J.

1979-09-01

The effects of 60-Hz electric and magnetic fields of exta-high voltage (EHV) transmission lines on the performance of implanted cardiac pacemakers were studied by: (1) in vitro bench tests of a total of thirteen cardiac pacemakers; (2) in vivo tests of six implanted cardiac pacemakers in baboons; and (3) non-hazardous skin measurement tests on four humans. Analytical methods were developed to predict the thresholds of body current and electric fields capable of affecting normal pacemaker operation in humans. The field strengths calculated to alter implanted pacemaker performance were compared with the range of maximum electric and magnetic field strengths amore » human would normally encounter under transmission lines of various voltages. Results indicate that the electric field or body current necessary to alter the normal operation of pacemakers is highly dependent on the type of pacemaker and the location of the implanted electrodes. However, cardiologists have not so far detected harmful effects of pacemaker reversion to the asynchronous mode in current types of pacemakers and with present methods of implantation. Such interferences can be eliminated by using advanced pacemakers less sensitive to 60-Hz voltages or by using implantation lead arrangements less sensitive to body current.« less

Periodontitis in pregnancy: clinical and serum antibody observations from a baboon model of ligature-induced disease.

PubMed

Cappelli, D; Steffen, M J; Holt, S C; Ebersole, J L

2009-07-01

Chronic oral infections that elicit host responses leading to periodontal disease are linked with various sequelae of systemic diseases. This report provides seminal information on the clinical and adaptive immunologic characteristics of a baboon model of ligature-induced periodontitis during pregnancy. Female Papio anubis were evaluated for periodontal health at baseline. Ligatures were tied around selected teeth to initiate oral inflammation and periodontitis. Then the animals were bred. At midpregnancy ( approximately 90 days), a clinical evaluation was performed, and additional ligatures were tied on teeth in the contralateral quadrants to maintain progressing periodontitis throughout pregnancy. A final clinical evaluation was done for all experimental teeth after delivery, and ligatures were removed. Serum was collected at all sampling intervals for the determination of antibody levels to a group of 20 oral bacteria. Unligated animals served as controls. At baseline, 16% of animals exhibited minimal plaque and gingival inflammation without periodontal disease. The remaining baboons demonstrated varying levels of inflammation/bleeding, and approximately 20% of the population had periodontal pocketing (>3 mm). Ligated animals expressed increased levels of inflammation and increased probing depths and clinical attachment loss (AL) and could be stratified into multiple subsets postligation based upon changes in clinical parameters at midpregnancy and at delivery. Baboons were categorized into disease susceptibility groups (periodontal disease susceptibility 1 through 4) that described the extent/severity of induced disease during pregnancy. Control animals showed minimal periodontal changes during gestation. Significant differences in serum antibody to multiple oral bacteria were found in animals presenting with periodontitis at baseline and during the 6 months of ligature-induced disease. A significant correlation to antibody to P. gingivalis, which was sustained

First records of talon cusps on baboon maxillary incisors argue for standardizing terminology and prompt a hypothesis of their formation.

PubMed

Heaton, Jason L; Pickering, Travis Rayne

2013-12-01

Dental characters can provide vital clues for understanding intra- and intertaxonomic morphological variation and its underlying genetic and environmental components. However, the unambiguous identification of particular traits and their comparative study is often confounded by lack of consistent terminology in the relevant literature. This difficulty is exacerbated when the etiologies are not completely understood, as is the case with talon cusps. To date, research on talon cusps has focused on modern humans. In many instances, descriptions of talon cusps appear in clinical case studies focusing on their treatment and removal. What is lacking in those discussions, though, is a comparative framework, in which the occurrence of talon cusps in nonhuman primates, and possibly other mammals, is established and understood. Here, we report on a taloned upper central incisor of a wild baboon (Papio hamadryas ursinus) from South Africa. The anomalous incisor of this individual includes an exaggerated accessory cusp diagnosed as a Type II talon. Microcomputed tomographic and radiographic analyses show that the taloned cusp possesses enamel, dentin, and pulp. In addition, we identified an unclassifiable talon cusp on a central maxillary incisor of a baboon skull housed in the Smithsonian Institution's Natural History Museum collection. Our observations of talon cusps on baboon incisors demonstrate that, with regard to this phenomenon, systematic study of nonhuman primates is much needed, along with a consistent use of terminology in the anatomical and anthropological literature. Finally, we present a hypothesis of the formation of talon cusps on mammalian incisors. Copyright © 2013 Wiley Periodicals, Inc.

Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1

PubMed Central

Chen, Shuyuan; Bastarrachea, Raul A; Roberts, Brad J; Voruganti, V Saroja; Frost, Patrice A; Nava-Gonzalez, Edna J; Arriaga-Cazares, Hector E; Chen, Jiaxi; Huang, Pintong; DeFronzo, Ralph A; Comuzzie, Anthony G; Grayburn, Paul A

2014-01-01

Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation or β-cell regeneration. The pancreas, not the liver, is the ideal organ for islet regeneration, because it is the natural milieu for islets. Since islet mass is known to increase during obesity and pregnancy, the concept of stimulating pancreatic islet regeneration in vivo is both rational and physiologic. This paper proposes a novel approach in which non-viral gene therapy is targeted to pancreatic islets using ultrasound targeted microbubble destruction (UTMD) in a non-human primate model (NHP), the baboon. Treated baboons received a gene cocktail comprised of cyclinD2, CDK, and GLP1, which in rats results in robust and durable islet regeneration with normalization of blood glucose, insulin, and C-peptide levels. We were able to generate important preliminary data indicating that gene therapy by UTMD can achieve in vivo normalization of the intravenous (IV) glucose tolerance test (IVGTT) curves in STZ hyperglycemic-induced conscious tethered baboons. Immunohistochemistry clearly demonstrated evidence of islet regeneration and restoration of β-cell mass. PMID:24553120

Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1.

PubMed

Chen, Shuyuan; Bastarrachea, Raul A; Roberts, Brad J; Voruganti, V Saroja; Frost, Patrice A; Nava-Gonzalez, Edna J; Arriaga-Cazares, Hector E; Chen, Jiaxi; Huang, Pintong; DeFronzo, Ralph A; Comuzzie, Anthony G; Grayburn, Paul A

2014-01-01

Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation or β-cell regeneration. The pancreas, not the liver, is the ideal organ for islet regeneration, because it is the natural milieu for islets. Since islet mass is known to increase during obesity and pregnancy, the concept of stimulating pancreatic islet regeneration in vivo is both rational and physiologic. This paper proposes a novel approach in which non-viral gene therapy is targeted to pancreatic islets using ultrasound targeted microbubble destruction (UTMD) in a non-human primate model (NHP), the baboon. Treated baboons received a gene cocktail comprised of cyclinD2, CDK, and GLP1, which in rats results in robust and durable islet regeneration with normalization of blood glucose, insulin, and C-peptide levels. We were able to generate important preliminary data indicating that gene therapy by UTMD can achieve in vivo normalization of the intravenous (IV) glucose tolerance test (IVGTT) curves in STZ hyperglycemic-induced conscious tethered baboons. Immunohistochemistry clearly demonstrated evidence of islet regeneration and restoration of β-cell mass.

Xenotransplantation in immunodeficient mice to study ovarian follicular development in domestic animals.

PubMed

Bols, P E J; Aerts, J M J; Langbeen, A; Goovaerts, I G F; Leroy, J L M R

2010-04-01

Nowadays, in vitro study of follicular dynamics of primordial and primary follicular stages is limited because in vitro culture systems for these follicles are lacking, both in domestic animal species and in human. Therefore, additional insights might be generated by grafting ovarian tissue into immunodeficient mice to study activation and maturation of early follicular stages. A considerable amount of data has already been gathered in laboratory animals and through clinical application of human assisted reproduction technologies where live births were reported recently after the use of (cryopreserved) ovarian grafts. However, given that human preantral follicles are difficult to obtain and that there are many similarities between the bovine and human species with regard to ovarian physiology, the bovine model offers exciting additional prospects and is therefore discussed in more detail. This review will focus on recent developments related to preantral follicle and (repeated) ovarian tissue retrieval and xenotransplantation of (bovine) ovarian tissue strips to immunodeficient mice as a model to study preantral follicular dynamics. Different grafting strategies will be discussed as well as the consequences of this procedure on the viability and dynamic behavior of the grafted tissue and follicles. 2010 Elsevier Inc. All rights reserved.

MicroRNA Expression for Early Prediction of Late Occurring Hematologic Acute Radiation Syndrome in Baboons.

PubMed

Port, Matthias; Herodin, Francis; Valente, Marco; Drouet, Michel; Ullmann, Reinhard; Doucha-Senf, Sven; Lamkowski, Andreas; Majewski, Matthäus; Abend, Michael

2016-01-01

For effective medical management of radiation-exposed persons after a radiological/nuclear event, blood-based screening measures in the first few days that could predict hematologic acute radiation syndrome (HARS) are needed. For HARS severity prediction, we used microRNA (miRNA) expression changes measured on days one and two after irradiation in a baboon model. Eighteen baboons underwent different patterns of partial or total body irradiation, corresponding to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts (BCC) the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. In a two Stage study design we screened 667 miRNAs using a quantitative real-time polymerase chain reaction (qRT-PCR) platform. In Stage II we validated candidates where miRNAs had to show a similar regulation (up- or down-regulated) and a significant 2-fold miRNA expression difference over H0. Seventy-two candidate miRNAs (42 for H1-2 and 30 for H2-3) were forwarded for validation. Forty-two of the H1-2 miRNA candidates from the screening phase entered the validation step and 20 of them showed a statistically significant 2-4 fold up-regulation relative to the unexposed reference (H0). Fifteen of the 30 H2-3 miRNAs were validated in Stage II. All miRNAs appeared 2-3 fold down-regulated over H0 and allowed an almost complete separation of HARS categories; the strongest candidate, miR-342-3p, showed a sustained and 10-fold down-regulation on both days 1 and 2. In summary, our data support the medical decision making of the HARS even within the first two days after exposure where diagnostic tools for early medical decision are required but so far missing. The miRNA species identified and in particular miR-342-3p add to the previously identified mRNAs and complete the portfolio of identified mRNA and miRNA transcripts for HARS prediction and medical management.

Testosterone related to age and life-history stages in male baboons and geladas

PubMed Central

Beehner, Jacinta C.; Gesquiere, Laurence; Seyfarth, Robert M.; Cheney, Dorothy L.; Alberts, Susan C.; Altmann, Jeanne

2013-01-01

Despite significant advances in our knowledge of how testosterone mediates life-history trade-offs, this research has primarily focused on seasonal species. We know comparatively little about the relationship between testosterone and life-history stages for non-seasonally breeding species. Here we examine testosterone profiles across the lifespan of males from three non-seasonally breeding primates: yellow baboons (Papio cynocephalus or P. hamadryas cynocephalus), chacma baboons (Papio ursinus or P. h. ursinus), and geladas (Theropithecus gelada). First, we predict that testosterone profiles will track the reproductive profiles of each taxon across their respective breeding years. Second, we evaluate age-related changes in testosterone to determine whether several life-history transitions are associated with these changes. Subjects include males (>2.5 years) from wild populations of each taxon from whom we had fecal samples for hormone determination. Although testosterone profiles across species were broadly similar, considerable variability was found in the timing of two major changes: (1) the attainment of adult levels of testosterone, and (2) the decline in testosterone after the period of maximum production. Attainment of adult testosterone levels was delayed by one year in chacmas compared with yellows and geladas. With respect to the decline in testosterone, geladas and chacmas exhibited a significant drop after three years of maximum production, while yellows declined so gradually that no significant annual drop was ever detected. For both yellows and chacmas, increases in testosterone production preceded elevations in social dominance rank. We discuss these differences in the context of ecological and behavioral differences exhibited by these taxa. PMID:19712676

Bombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation.

PubMed

Emanuel, R L; Torday, J S; Mu, Q; Asokananthan, N; Sikorski, K A; Sunday, M E

1999-11-01

Previously, we have shown that bombesin-like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [(3)H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or peptides might be implicated in these responses.

GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

PubMed

Watanabe, Hironosuke; Sahara, Hisashi; Nomura, Shunichiro; Tanabe, Tatsu; Ekanayake-Alper, Dilrukshi K; Boyd, Lennan K; Louras, Nathan J; Asfour, Arsenoi; Danton, Makenzie A; Ho, Siu-Hong; Arn, Scott J; Hawley, Robert J; Shimizu, Akira; Nagayasu, Takeshi; Ayares, David; Lorber, Marc I; Sykes, Megan; Sachs, David H; Yamada, Kazuhiko

2018-03-12

Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine. The first 2 XLTx procedures were performed under a non-survival protocol that allowed a 72-hour follow-up of the recipients with general anesthesia, while the remaining 9 underwent a survival protocol with the intention of weaning from ventilation. Lung graft survivals in the 2 non-survival animals were 48 and >72 hours, while survivals in the other 9 were 25 and 28 hours, at 5, 5, 6, 7, >7, 9, and 10 days. One baboon with graft survival >7 days, whose entire lung graft remained well aerated, was euthanized on POD 7 due to malfunction of femoral catheters. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days. All other grafts lacked hCD47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss. To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT-KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of ethanol on the retention of americium-241 in the baboon liver.

PubMed

Cohen, N; Antonelli, R; Lo Sasso, T; Wrenn, M E

1978-01-01

The oral administration of ethyl alcohol enhanced the excretion of 241Am from the liver of a baboon by 2.5 times that of a control animal. After ethanol administration, increases in the total content of 241Am excreted in feces were accompanied by corresponding increases in fecal volumes, although administration of nonalcoholic cathartics would not be expected to produce a similar effect. The effectiveness of ethanol as a decorporating agent may result from its ability to mobilize intracellularly bound 241Am from the liver, thereby making the nuclide more available for metabolic secretory mechanisms occurring via liver-bile-fecal route.

Agricultural expansion as risk to endangered wildlife: Pesticide exposure in wild chimpanzees and baboons displaying facial dysplasia.

PubMed

Krief, Sabrina; Berny, Philippe; Gumisiriza, Francis; Gross, Régine; Demeneix, Barbara; Fini, Jean Baptiste; Chapman, Colin A; Chapman, Lauren J; Seguya, Andrew; Wasswa, John

2017-11-15

Prenatal exposure to environmental endocrine disruptors can affect development and induce irreversible abnormalities in both humans and wildlife. The northern part of Kibale National Park, a mid-altitude rainforest in western Uganda, is largely surrounded by industrial tea plantations and wildlife using this area (Sebitoli) must cope with proximity to human populations and their activities. The chimpanzees and baboons in this area raid crops (primarily maize) in neighboring gardens. Sixteen young individuals of the 66 chimpanzees monitored (25%) exhibit abnormalities including reduced nostrils, cleft lip, limb deformities, reproductive problems and hypopigmentation. Each pathology could have a congenital component, potentially exacerbated by environmental factors. In addition, at least six of 35 photographed baboons from a Sebitoli troop (17%) have similar severe nasal deformities. Our inquiries in villages and tea factories near Sebitoli revealed use of eight pesticides (glyphosate, cypermethrin, profenofos, mancozeb, metalaxyl, dimethoate, chlorpyrifos and 2,4-D amine). Chemical analysis of samples collected from 2014 to 2016 showed that mean levels of pesticides in fresh maize stems and seeds, soils, and river sediments in the vicinity of the chimpanzee territory exceed recommended limits. Notably, excess levels were found for total DDT and its metabolite pp'-DDE and for chlorpyrifos in fresh maize seeds and in fish from Sebitoli. Imidacloprid was detected in coated maize seeds planted at the edge the forest and in fish samples from the Sebitoli area, while no pesticides were detected in fish from central park areas. Since some of these pesticides are thyroid hormone disruptors, we postulate that excessive pesticide use in the Sebitoli area may contribute to facial dysplasia in chimpanzees and baboons through this endocrine pathway. Chimpanzees are considered as endangered by IUCN and besides their intrinsic value and status as closely related to humans, they

Interaction of SR 33557 with skeletal muscle calcium channel blocker receptors in the baboon: characterization of its binding sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sol-Rolland, J.; Joseph, M.; Rinaldi-Carmona, M.

1991-05-01

A procedure for the isolation of primate skeletal microsomal membranes was initiated. Membranes exhibited specific enzymatic markers such as 5'-nucleotidase, Ca{sup 2}{sup +},Mg({sup 2}{sup +})-adenosine triphosphatase and an ATP-dependent calcium uptake. Baboon skeletal microsomes bound specifically with high-affinity potent Ca{sup 2}{sup +} channel blockers such as dihydropyridine, phenylalkylamine and benzothiazepine derivatives. Scatchard analysis of equilibrium binding assays with ({sup 3}H)(+)-PN 200-110, ({sup 3}H)(-)-desmethoxyverapamil (( {sup 3}H)(-)-D888) and ({sup 3}H)-d-cis-dilitiazem were consistent with a single class of binding sites for the three radioligands. The pharmacological profile of SR 33557, an original compound with calcium antagonist properties, was investigated using radioligand bindingmore » studies. SR 33557 totally inhibited the specific binding of the three main classes of Ca{sup 2}{sup +} channel effectors and interacted allosterically with them. In addition, SR 33557 bound with high affinity to a homogeneous population of binding sites in baboon skeletal muscle.« less

A review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a “humanized” tilapia insulin

PubMed Central

Wright, James R; Yang, Hua; Hyrtsenko, Olga; Xu, Bao-You; Yu, Weiming; Pohajdak, Bill

2014-01-01

Most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. Teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called Brockmann bodies which can be inexpensively harvested. When transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. Like porcine islets, when transplanted into euthymic mice, they are rejected in a CD4 T-cell-dependent manner. However, unlike pigs, tilapia are so phylogenetically primitive that their cells do not express α(1,3)Gal and, because tilapia are highly evolved to live in warm stagnant waters nearly devoid of dissolved oxygen, their islet cells are exceedingly resistant to hypoxia, making them ideal for transplantation within encapsulation devices. Encapsulation, especially when combined with co-stimulatory blockade, markedly prolongs tilapia islet xenograft survival in small animal recipients, and a collaborator has shown function in diabetic cynomolgus monkeys. In anticipation of preclinical xenotransplantation studies, we have extensively characterized tilapia islets (morphology, embryologic development, cell biology, peptides, etc.) and their regulation of glucose homeostasis. Because tilapia insulin differs structurally from human insulin by 17 amino acids, we have produced transgenic tilapia whose islets stably express physiological levels of humanized insulin and have now bred these to homozygosity. These transgenic fish can serve as a platform for further development into a cell therapy product for diabetes. PMID:25040337

Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.

PubMed

Hildebrandt, V A; Babischkin, J S; Koos, R D; Pepe, G J; Albrecht, E D

2001-05-01

Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels

Effect of allo- and xenotransplantation of embryonic nervous tissue and umbilical cord blood-derived stem cells on structural and functional state of cerebral cortex of albino rats in posttraumatic period.

PubMed

Ereniev, S I; Semchenko, V V; Sysheva, E V; Bogdashin, I V; Shapovalova, V V; Khizhnyak, A S; Gasanenko, L N

2005-11-01

Comparative study of the structural and functional state of cerebral cortex of adult albino rats after intracerebral allo- and xenotransplantation of embryonic nervous tissue and intravenous injection of umbilical cord blood-derived stem cells at different terms after diffuse-focal cerebral trauma revealed the best cerebroprotective effect on day 7 of posttraumatic period in animals receiving embryonic nervous tissue.

Cumulative early life adversity predicts longevity in wild baboons

PubMed Central

Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

2016-01-01

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

T-Cell-Based Immunosuppressive Therapy Inhibits the Development of Natural Antibodies in Infant Baboons

PubMed Central

Dons, Eefje M.; Montoya, Claudia; Long, Cassandra E.; Hara, Hidetaka; Echeverri, Gabriel J.; Ekser, Burcin; Ezzelarab, Corin; Medellin, Dasha Roa; van der Windt, Dirk J.; Murase, Noriko; Rigatti, Lora H.; Wagner, Robert; Wolf, Roman F.; Ezzelarab, Mohamed; West, Lori J.; Ijzermans, Jan N. M.; Cooper, David K. C.

2013-01-01

Background We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons. Methods Artery patch grafts were implanted in the abdominal aorta in 3-month-old baboons using A/B-incompatible (AB-I) allografts or wild-type pig xenografts (pig). Group 1 (Gp1) (controls, n = 6) received no immunosuppressive therapy (IS) and no graft. Gp2 (n = 2) received an AB-I or pig graft but no IS. Gp3 received AB-I grafts + IS (Gp3A: n = 2) or pig grafts + IS (Gp3B: n = 2). IS consisted of ATG, anti-CD154mAb, and mycophenolate mofetil until age 8 to 12 months. Gp4 (n = 2) received IS only but no graft. Results In Gp1, anti-A/B and cytotoxic anti-pig immunoglobulin-M increased steadily during the first year. Gp2 became sensitized to donor-specific AB-I or pig antigens within 2 weeks. Gp3 and Gp4 infants that received anti-CD154mAb made no or minimal anti-A/B and anti-pig antibodies while receiving IS. Discussion The production of natural anti-A/B and anti-pig antibodies was inhibited by IS with anti-CD154mAb, even in the absence of an allograft or xenograft, suggesting that natural antibodies may not be entirely T-cell independent. These data are in contrast to clinical experience with AB-I allotransplantation in infants, who cease producing only donor-specific antibodies. PMID:22441321

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing.

PubMed

van der Wiel, Marit K H; Doxiadis, Gaby G M; de Groot, N; Otting, N; de Groot, N G; Poirier, N; Blancho, G; Bontrop, R E

2018-02-24

The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.

Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

PubMed Central

RODRIGUEZ, Jesse S.; ZÜRCHER, Nicole R.; KEENAN, Kathryn E.; BARTLETT, Thad Q.; NATHANIELSZ, Peter W.; NIJLAND, Mark J.

2011-01-01

Objective We investigated effects of three weekly courses of fetal betamethasone (βM) exposure on motivation and cognition in juvenile baboon offspring utilizing the Cambridge Neuropsychological Test Automated Battery. Study design Pregnant baboons (Papio sp.) received two injections of saline control (C) or 175 μg/kg βM 24h apart at 0.6, 0.65 and 0.7 gestation. Offspring [Female (FC), n = 7 and Male (MC), n = 6; Female (FβM), n = 7 and Male (MβM), n = 5] were studied at 2.6–3.2 years with a progressive ratio test for motivation, simple discriminations (SD) and reversals (SR) for associative learning and rule change plasticity, and an intra-dimensional/extra-dimensional (IDED) set-shifting test for attention allocation. Results βM exposure decreased motivation in both sexes. In IDED testing, FβM made more errors in the SR [mean difference of errors (FβM minus MβM) = 20.2 ± 9.9; P≤0.05], compound discrimination [mean difference of errors = 36.3 ± 17.4; P≤0.05] and compound reversal [mean difference of errors = 58 ± 23.6; P<0.05] stages as compared to the MβM offspring. Conclusion This central nervous system developmental programming adds growing concerns of long-term effects of repeated fetal synthetic glucocorticoid exposure. In summary, behavioral effects observed show sex specific differences in resilience to multiple fetal βM exposures. PMID:21411054

First Generation Gene Expression Signature for Early Prediction of Late Occurring Hematological Acute Radiation Syndrome in Baboons.

PubMed

Port, M; Herodin, F; Valente, M; Drouet, M; Lamkowski, A; Majewski, M; Abend, M

2016-07-01

We implemented a two-stage study to predict late occurring hematologic acute radiation syndrome (HARS) in a baboon model based on gene expression changes measured in peripheral blood within the first two days after irradiation. Eighteen baboons were irradiated to simulate different patterns of partial-body and total-body exposure, which corresponded to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. Blood samples taken before irradiation served as unexposed control (H0, n = 17). For stage I of this study, a whole genome screen (mRNA microarrays) was performed using a portion of the samples (H0, n = 5; H1-2, n = 4; H2-3, n = 5). For stage II, using the remaining samples and the more sensitive methodology, qRT-PCR, validation was performed on candidate genes that were differentially up- or down-regulated during the first two days after irradiation. Differential gene expression was defined as significant (P < 0.05) and greater than or equal to a twofold difference above a H0 classification. From approximately 20,000 genes, on average 46% appeared to be expressed. On day 1 postirradiation for H2-3, approximately 2-3 times more genes appeared up-regulated (1,418 vs. 550) or down-regulated (1,603 vs. 735) compared to H1-2. This pattern became more pronounced at day 2 while the number of differentially expressed genes decreased. The specific genes showed an enrichment of biological processes coding for immune system processes, natural killer cell activation and immune response (P = 1 × E-06 up to 9 × E-14). Based on the P values, magnitude and sustained differential gene expression over time, we selected 89 candidate genes for validation using qRT-PCR. Ultimately, 22 genes were confirmed for identification of H1-3 classifications and seven genes for identification of H2-3 classifications using qRT-PCR. For H1-3 classifications, most genes were

2D:4D digit ratio is not a biomarker of developmental programming in baboons (Papio hamadryas species).

PubMed

Huber, Hillary F; Li, Cun; Nathanielsz, Peter W

2018-02-01

We hypothesized second-to-fourth hand digit ratio (2D:4D) is a biomarker of developmental programming in 3 baboon groups: intrauterine growth restriction (7 females, 8 males), exposure during fetal life to synthetic glucocorticoids (4 females, 5 males), and controls (66 females, 20 males). 2D:4D was similar between sexes and groups. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variation of hair cortisol concentrations among wild populations of two baboon species (Papio anubis, P. hamadryas) and a population of their natural hybrids.

PubMed

Fourie, Nicolaas H; Jolly, Clifford J; Phillips-Conroy, Jane E; Brown, Janine L; Bernstein, Robin M

2015-07-01

Male olive (Papio anubis) and hamadryas (P. hamadryas) baboons have distinctive sociobehavioral and physical characteristics. In the Awash National Park, Ethiopia, a hybrid population at the contact zone between these two species, exhibits heterogeneous sociobehavioral and physical characteristics. The ambiguity of the hybrid social environment and disruption of parental stress genotypes may be sources of physiological stress for hybrids. We examined levels of chronic stress among males of the three populations and tested the prediction that chronic cortisol levels would be higher among the hybrids. Animals were captured, sampled, and released during the wet season, and a hair sample was taken for assay. Cortisol was extracted from 182 hair samples with methanol and quantified by ELISA. We included age, age class, rainfall variation, and species affiliation in models examining variation in hair cortisol levels. Species and age significantly contributed to models explaining variation in hair cortisol. Infant hypercortisolism was observed in all three groups, and a decline in cortisol through juvenile and adolescent stages, with a subsequent rise in adulthood. This rise occurred earliest in hamadryas, corroborating other evidence of the precocious development of hamadryas baboons. As expected, hybrids had significantly elevated hair cortisol compared with olive baboons and hamadryas, irrespective of age, except for very young animals. Infant hypercortisolism was also less pronounced among hybrids. Species differences and age-related differences in cortisol levels suggest a dysregulated cortisol phenotype in hybrids, and possibly reflect some form of hybrid disadvantage. More work will be required to disentangle the effects of genetic factors and the social environment.

Delayed extubation to nasal continuous positive airway pressure in the immature baboon model of bronchopulmonary dysplasia: lung clinical and pathological findings.

PubMed

Thomson, Merran A; Yoder, Bradley A; Winter, Vicki T; Giavedoni, Luis; Chang, Ling Yi; Coalson, Jacqueline J

2006-11-01

Using the 125-day baboon model of bronchopulmonary dysplasia treated with prenatal steroid and exogenous surfactant, we hypothesized that a delay of extubation from low tidal volume positive pressure ventilation to nasal continuous positive airway pressure at 5 days (delayed nasal continuous positive airway pressure group) would not induce more lung injury when compared with baboons aggressively weaned to nasal continuous positive airway pressure at 24 hours (early nasal continuous positive airway pressure group), because both received positive pressure ventilation. After delivery by cesarean section at 125 days (term: 185 days), infants received 2 doses of Curosurf (Chiesi Farmaceutica S.p.A., Parma, Italy) and daily caffeine citrate. The delay in extubation to 5 days resulted in baboons in the delayed nasal continuous positive airway pressure group having a lower arterial to alveolar oxygen ratio, high PaCO2, and worse respiratory function. The animals in the delayed nasal continuous positive airway pressure group exhibited a poor respiratory drive that contributed to more reintubations and time on mechanical ventilation. A few animals in both groups developed necrotizing enterocolitis and/or sepsis, but infectious pneumonias were not documented. Cellular bronchiolitis and peribronchiolar alveolar wall thickening were more frequently seen in the delayed nasal continuous positive airway pressure group. Bronchoalveolar lavage levels of interleukin-6, interleukin-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and growth-regulated oncogene-alpha were significantly increased in the delayed nasal continuous positive airway pressure group. Standard and digital morphometric analyses showed no significant differences in internal surface area and nodal measurements between the groups. Platelet endothelial cell adhesion molecule vascular staining was not significantly different between the 2 nasal continuous positive airway pressure groups

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

PubMed

Boosalis, Michael S; Sangerman, Jose I; White, Gary L; Wolf, Roman F; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H; Li, Biaoru; Pace, Betty S; Nouraie, Mehdi; Faller, Douglas V; Perrine, Susan P

2015-01-01

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice

PubMed Central

Boosalis, Michael S.; Sangerman, Jose I.; White, Gary L.; Wolf, Roman F.; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H.; Li, Biaoru; Pace, Betty S.; Nouraie, Mehdi; Faller, Douglas V.; Perrine, Susan P.

2015-01-01

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies. PMID:26713848

Contrast of Hand Preferences between Communicative Gestures and Non-Communicative Actions in Baboons: Implications for the Origins of Hemispheric Specialization for Language

ERIC Educational Resources Information Center

Meguerditchian, Adrien; Vauclair, Jacques

2009-01-01

Gestural communication is a modality considered in the literature as a candidate for determining the ancestral prerequisites of the emergence of human language. As reported in captive chimpanzees and human children, a study in captive baboons revealed that a communicative gesture elicits stronger degree of right-hand bias than non-communicative…

Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation

PubMed Central

Lavitrano, Marialuisa; Bacci, Maria Laura; Forni, Monica; Lazzereschi, Davide; Di Stefano, Carla; Fioretti, Daniela; Giancotti, Paola; Marfé, Gabriella; Pucci, Loredana; Renzi, Luigina; Wang, Hongjun; Stoppacciaro, Antonella; Stassi, Giorgio; Sargiacomo, Massimo; Sinibaldi, Paola; Turchi, Valeria; Giovannoni, Roberto; Della Casa, Giacinto; Seren, Eraldo; Rossi, Giancarlo

2002-01-01

A large number of hDAF transgenic pigs to be used for xenotransplantation research were generated by using sperm-mediated gene transfer (SMGT). The efficiency of transgenesis obtained with SMGT was much greater than with any other method. In the experiments reported, up to 80% of pigs had the transgene integrated into the genome. Most of the pigs carrying the hDAF gene transcribed it in a stable manner (64%). The great majority of pigs that transcribed the gene expressed the protein (83%). The hDAF gene was transmitted to progeny. Expression was stable and found in caveolae as it is in human cells. The expressed gene was functional based on in vitro experiments performed on peripheral blood mononuclear cells. These results show that our SMGT approach to transgenesis provides an efficient procedure for studies involving large animal models. PMID:12393815

A Pacific Culture among Wild Baboons: Its Emergence and Transmission

PubMed Central

Share, Lisa J

2004-01-01

Reports exist of transmission of culture in nonhuman primates. We examine this in a troop of savanna baboons studied since 1978. During the mid-1980s, half of the males died from tuberculosis; because of circumstances of the outbreak, it was more aggressive males who died, leaving a cohort of atypically unaggressive survivors. A decade later, these behavioral patterns persisted. Males leave their natal troops at adolescence; by the mid-1990s, no males remained who had resided in the troop a decade before. Thus, critically, the troop's unique culture was being adopted by new males joining the troop. We describe (a) features of this culture in the behavior of males, including high rates of grooming and affiliation with females and a “relaxed” dominance hierarchy; (b) physiological measures suggesting less stress among low-ranking males; (c) models explaining transmission of this culture; and (d) data testing these models, centered around treatment of transfer males by resident females. PMID:15094808

Female chacma baboons form strong, equitable, and enduring social bonds

PubMed Central

Beehner, Jacinta C.; Bergman, Thore J.; Crockford, Catherine; Engh, Anne L.; Moscovice, Liza R.; Wittig, Roman M.; Seyfarth, Robert M.; Cheney, Dorothy L.

2010-01-01

Analyses of the pattern of associations, social interactions, coalitions, and aggression among chacma baboons (Papio hamadryas ursinus) in the Okavango Delta of Botswana over a 16-year period indicate that adult females form close, equitable, supportive, and enduring social relationships. They show strong and stable preferences for close kin, particularly their own mothers and daughters. Females also form strong attachments to unrelated females who are close to their own age and who are likely to be paternal half-sisters. Although absolute rates of aggression among kin are as high as rates of aggression among nonkin, females are more tolerant of close relatives than they are of others with whom they have comparable amounts of contact. These findings complement previous work which indicates that the strength of social bonds enhances the fitness of females in this population and support findings about the structure and function of social bonds in other primate groups. PMID:20976293

Cross-Species Withdrawal of MCL1 Facilitates Postpartum Uterine Involution in Both the Mouse and Baboon

PubMed Central

Kyathanahalli, Chandrashekara; Marks, Jason; Nye, Kennedy; Lao, Belinda; Albrecht, Eugene D.; Aberdeen, Graham W.; Nathanielsz, Peter W.; Jeyasuria, Pancharatnam

2013-01-01

A successful postpartum involution permits the postnatal uterus to rapidly regain its prepregnancy function and size to ultimately facilitate an ensuing blastocyst implantation. This study investigates the molecular mechanisms that govern the initiation of the involution process by examining the signaling events that occur as the uterus transitions from the pregnant to postnatal state. Using mouse and baboon uteri, we found a remarkable cross-species conservation at the signal transduction level as the pregnant uterus initiates and progresses through the involution process. This study originated with the observation of elevated levels of caspase-3 activation in both the laboring mouse and baboon uterus, which we found to be apoptotic in nature as evidenced by the concurrent appearance of cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and potential tocolytic role for uterine caspase-3 during pregnancy regulated by increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1 and X-linked inhibitor of apoptosis. In contrast, this study determined that diminished antiapoptotic signaling in the postpartum uterus allowed for both endometrial apoptotic and myometrial autophagic episodes, which we speculate are responsible for the rapid reduction in size of the postpartum uterus. Using our human telomerase immortalized myometrial cell line and the Simian virus-40 immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of antiapoptotic signaling was also an upstream event for both the autophagic and apoptotic processes in the human uterine myocyte and endometrial epithelial cell. PMID:24140717

In vivo distribution of human milk leucocytes after ingestion by newborn baboons.

PubMed Central

Jain, L; Vidyasagar, D; Xanthou, M; Ghai, V; Shimada, S; Blend, M

1989-01-01

The in vivo distribution of enterally administered human milk leucocytes labelled with indium hydroxyquinoline (111In) was studied in premature baboons. The animals were killed at 72 hours of age and tissue samples examined for radioactivity. Maximum activity was found in the luminal contents, and activity in the liver and spleen was higher than in bone marrow, the site where free isotope is normally deposited. These findings suggest that some intact milk leucocytes may cross from the gastrointestinal tract into the neonatal circulation. Also the high activity in gastrointestinal tissue that had been washed several times indicates that leucocytes adhere to mucosa or lie intramurally. We speculate that the presence of leucocytes in the gastrointestinal tract 60 hours after a single breast feed can provide an important defence mechanism against infection. PMID:2774634

Reduced reproductive function in wild baboons (Papio hamadryas anubis) related to natural consumption of the African black plum (Vitex doniana).

PubMed

Higham, James P; Ross, Caroline; Warren, Ymke; Heistermann, Michael; MacLarnon, Ann M

2007-09-01

Several authors have suggested that the consumption of plant compounds may have direct effects on wild primate reproductive biology, but no studies have presented physiological evidence of such effects. Here, for two troops of olive baboons (Papio hamadryas anubis) at Gashaka-Gumti National Park, Nigeria, we show major seasonal increases in levels of fecal progesterone metabolites in females, and provide evidence that this is linked to the consumption of natural plant compounds. Increases in fecal progestogen excretion occurred seasonally in all females, in all reproductive states, including lactation. Detailed feeding data on the study animals showed that only one food species is consumed by both troops at the time of observed progestogen peaks, and at no other times of the year: the African black plum, Vitex doniana. Laboratory tests demonstrated the presence of high concentrations of progestogen-like compounds in V. doniana. Together with published findings linking the consumption of a related Vitex species (Vitex agnus castus) to increased progestogen levels in humans, our data suggest that natural consumption of V. doniana was a likely cause of the observed increases in progestogens. Levels of progestogen excretion in the study baboons during periods of V. doniana consumption are higher than those found during pregnancy, and prevent the expression of the sexual swelling, which is associated with ovulatory activity. As consortship and copulatory activity in baboons occur almost exclusively in the presence of a sexual swelling, V. doniana appears to act on cycling females as both a physiological contraceptive (simulating pregnancy in a similar way to some forms of the human contraceptive pill) and a social contraceptive (preventing sexual swelling, thus reducing association and copulation with males). The negative effects of V. doniana on reproduction may be counter-balanced by the wide-range of medicinal properties attributed to plants in this genus. This is

Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

PubMed

Staley, J K; Van Dyck, C H; Tan, P Z; Al Tikriti, M; Ramsby, Q; Klump, H; Ng, C; Garg, P; Soufer, R; Baldwin, R M; Innis, R B

2001-04-01

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

Germ cell survival and differentiation after xenotransplantation of testis tissue from three endangered species: Iberian lynx (Lynx pardinus), Cuvier's gazelle (Gazella cuvieri) and Mohor gazelle (G. dama mhorr).

PubMed

Arregui, Lucía; Dobrinski, Ina; Roldan, Eduardo R S

2014-01-01

The use of assisted reproductive techniques for endangered species is a major goal for conservation. One of these techniques, testis tissue xenografting, allows for the development of spermatozoa from animals that die before reaching sexual maturity. To assess the potential use of this technique with endangered species, testis tissue from six Iberian lynxes (one fetus, two perinatal cubs, two 6-month-old and one 2-year-old lynx), two Cuvier's gazelle fetuses and one 8-month-old Mohor gazelle were transplanted ectopically into nude mice. Tissue from the lynx fetus, perinatal cubs and 2-year-old donors degenerated, whereas spermatogonia were present in 15% of seminiferous tubules more than 70 weeks after grafting in transplanted testis tissue from 6-month-old donors. Seminal vesicle weights (indicative of testosterone production) increased over time in mice transplanted with tissue from 6-month-old lynxes. Progression of spermatogenesis was observed in xenografts from gazelles and was donor age dependent. Tissue from Cuvier's gazelle fetuses contained spermatocytes 40 weeks after grafting. Finally, round spermatids were found 28 weeks after transplantation in grafts from the 8-month-old Mohor gazelle. This is the first time that xenotransplantation of testicular tissue has been performed with an endangered felid and the first successful xenotransplantation in an endangered species. Our results open important options for the preservation of biological diversity.

The processing of positional information in a two-item sequence limits the emergence of symmetry in baboons (Papio papio), but not in humans (Homo sapiens).

PubMed

Fagot, Joël; Malassis, Raphaelle; Medam, Tiphaine

2018-03-01

When trained to associate Stimulus A to Stimulus B, humans can derive the untrained symmetrical B to A relation while nonhuman animals have much more difficulties. Urcuioli (2008, Journal of the Experimental Analysis of Behavior, 90, 257--282; 2015, Conductal, 3, 4--25) proposed that the apparent difficulty of animals in symmetry testing reflects their double encoding of the information on the stimuli (identity and relation) and their positional (i.e., spatial and temporal/ordinal) characteristics. This comparative study tested the emergence of symmetry in humans and baboons in a task in which the position of the stimuli was manipulated independently of their relation. Humans and baboons initially learned to associate pairs of visual shapes on a touch screen in a specific order. Three pairs of (A-B, C-D, and E-F) stimuli were used in training. After training, the two species were tested with the B-A, F-C, and E-D pairs. The B-A pairs preserved the association initially learned with A-B but reversed the positional information relative to training. The F-C pair neither preserved the association nor the positional information of the training pairs, and positional information were the only cues preserved in the E-D pair. Humans showed a response time advantage for B-A, suggesting symmetry, but also for E-D, suggesting that they also process positional information. In baboons, the advantage was found only for E-D, suggesting that they only process positional information. These results confirm that the processing of stimulus pairs differ between nonhuman animals to humans.

Effects of exercise and excitement on mesenteric and renal dynamics in conscious, unrestrained baboons

NASA Technical Reports Server (NTRS)

Vatner, S. F.

1978-01-01

Radiotelemetry was used to measure arterial pressure and mesenteric and renal blood flows from nine unrestrained, conscious baboons during periods of rest, moderate exercise, and extreme excitement. A description of the experiments hardware is presented, including artificial depressants phenylcyclidine hydrochloride, 0.5-1.0 mg/kg, and pentobarbital sodium, 15 mg/kg, and an ultrasonic telemetry flow meter. Results showed rising heart rate and arterial pressure coupled with a reduction of mesenteric and renal flows as the level of exercise was increased. These findings are compared with mesenteric and renal flows somewhat above control level, but relatively stable heart rate and arterial pressure, postprandially. Attention is given to a quantitative analysis of the experimental results.

Disrupted dispersal and its genetic consequences: Comparing protected and threatened baboon populations (Papio papio) in West Africa.

PubMed

Ferreira da Silva, Maria Joana; Kopp, Gisela H; Casanova, Catarina; Godinho, Raquel; Minhós, Tânia; Sá, Rui; Zinner, Dietmar; Bruford, Michael W

2018-01-01

Dispersal is a demographic process that can potentially counterbalance the negative impacts of anthropogenic habitat fragmentation. However, mechanisms of dispersal may become modified in populations living in human-dominated habitats. Here, we investigated dispersal in Guinea baboons (Papio papio) in areas with contrasting levels of anthropogenic fragmentation, as a case study. Using molecular data, we compared the direction and extent of sex-biased gene flow in two baboon populations: from Guinea-Bissau (GB, fragmented distribution, human-dominated habitat) and Senegal (SEN, continuous distribution, protected area). Individual-based Bayesian clustering, spatial autocorrelation, assignment tests and migrant identification suggested female-mediated gene flow at a large spatial scale for GB with evidence of contact between genetically differentiated males at one locality, which could be interpreted as male-mediated gene flow in southern GB. Gene flow was also found to be female-biased in SEN for a smaller scale. However, in the southwest coastal part of GB, at the same geographic scale as SEN, no sex-biased dispersal was detected and a modest or recent restriction in GB female dispersal seems to have occurred. This population-specific variation in dispersal is attributed to behavioural responses to human activity in GB. Our study highlights the importance of considering the genetic consequences of disrupted dispersal patterns as an additional impact of anthropogenic habitat fragmentation and is potentially relevant to the conservation of many species inhabiting human-dominated environments.

Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott

Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques.more » These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.« less

Behavioral Effects and Pharmacokinetics of (±)-3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) after Intragastric Administration to Baboons

PubMed Central

Goodwin, Amy K.; Mueller, Melanie; Shell, Courtney D.; Ricaurte, George A.

2013-01-01

(±)-3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32–7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N = 4). Effects of MDMA on food-maintained responding were assessed over a 20-hour period, whereas untrained behaviors and fine-motor coordination were characterized every 30 minutes until 3 hours postadministration. Levels of MDMA and metabolites in plasma were measured in the same animals (n = 3) after dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-hour period, and systematic behavioral observations revealed increased frequency of bruxism as the dose of MDMA was increased. Drug blood level determinations showed no MDMA after the lower doses of MDMA tested (0.32–1.0 mg/kg) and modest levels after higher MDMA doses (3.2–7.8 mg/kg). High levels of 3,4-dihydroxymethamphetamine (HHMA) were detected after all doses of MDMA, suggesting extensive first-pass metabolism of MDMA in the baboon. The present results demonstrate that MDMA administered via an intragastric catheter produced behavioral effects that have also been reported in humans. Similar to humans, blood levels of MDMA after oral administration may not be predictive of the behavioral effects of MDMA. Metabolites, particularly HHMA, may play a significant role in the behavioral effects of MDMA. PMID:23516331

Behavioral effects and pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) after intragastric administration to baboons.

PubMed

Goodwin, Amy K; Mueller, Melanie; Shell, Courtney D; Ricaurte, George A; Ator, Nancy A

2013-06-01

(±)-3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32-7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N = 4). Effects of MDMA on food-maintained responding were assessed over a 20-hour period, whereas untrained behaviors and fine-motor coordination were characterized every 30 minutes until 3 hours postadministration. Levels of MDMA and metabolites in plasma were measured in the same animals (n = 3) after dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-hour period, and systematic behavioral observations revealed increased frequency of bruxism as the dose of MDMA was increased. Drug blood level determinations showed no MDMA after the lower doses of MDMA tested (0.32-1.0 mg/kg) and modest levels after higher MDMA doses (3.2-7.8 mg/kg). High levels of 3,4-dihydroxymethamphetamine (HHMA) were detected after all doses of MDMA, suggesting extensive first-pass metabolism of MDMA in the baboon. The present results demonstrate that MDMA administered via an intragastric catheter produced behavioral effects that have also been reported in humans. Similar to humans, blood levels of MDMA after oral administration may not be predictive of the behavioral effects of MDMA. Metabolites, particularly HHMA, may play a significant role in the behavioral effects of MDMA.

Tooth Size Variation Related to Age in Amboseli Baboons

PubMed Central

Galbany, Jordi; Dotras, Laia; Alberts, Susan C.; Pérez-Pérez, Alejandro

2011-01-01

We measured the molar size from a single population of wild baboons from Amboseli (Kenya), both females (n = 57) and males (n = 50). All the females were of known age; the males represented a mix of known-age individuals (n = 31) and individuals with ages estimated to within 2 years (n = 19). The results showed a significant reduction in the mesiodistal length of teeth in both sexes as a function of age. Overall patterns of age-related change in tooth size did not change whether we included or excluded the individuals of estimated age, but patterns of statistical significance changed as a result of changed sample sizes. Our results demonstrate that tooth length is directly related to age due to interproximal wearing caused by M2 and M3 compression loads. Dental studies in primates, including both fossil and extant species, are mostly based on specimens obtained from osteological collections of varying origins, for which the age at death of each individual in the sample is not known. Researchers should take into account the phenomenon of interproximal attrition leading to reduced tooth size when measuring tooth length for ondontometric purposes. PMID:21325862

Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons ( Papio anubis) With Experimentally-Induced Disease.

PubMed

Nothnick, Warren B; Falcone, Tommaso; Joshi, Niraj; Fazleabas, Asgerally T; Graham, Amanda

2017-08-01

We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.

Prostaglandin control of renal circulation in the unanesthetized dog and baboon

NASA Technical Reports Server (NTRS)

Swain, J. A.; Vatner, S. F.; Heyndrickx, G. R.; Boettcher, D. H.

1975-01-01

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow and an elevation of renal vascular resistance. Meclofenamate, 4 mg/kg, reduced renal flow and increased renal vascular resistance in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed. Methoxamine and angiotensin II infused in graded doses induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor part in the control of renal circulation at rest, but they are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons1

PubMed Central

Pantham, Priyadarshini; Rosario, Fredrick J.; Weintraub, Susan T.; Nathanielsz, Peter W.; Powell, Theresa L.; Li, Cun; Jansson, Thomas

2016-01-01

Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P < 0.05) in MNR fetuses compared to controls. In this primate model of IUGR, placental MVM system A amino acid transporter activity is decreased prior to the onset of reduction in the fetal growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced

Recurrent patterning in the daily foraging routes of hamadryas baboons (Papio hamadryas): spatial memory in large-scale versus small-scale space.

PubMed

Schreier, Amy L; Grove, Matt

2014-05-01

The benefits of spatial memory for foraging animals can be assessed on two distinct spatial scales: small-scale space (travel within patches) and large-scale space (travel between patches). While the patches themselves may be distributed at low density, within patches resources are likely densely distributed. We propose, therefore, that spatial memory for recalling the particular locations of previously visited feeding sites will be more advantageous during between-patch movement, where it may reduce the distances traveled by animals that possess this ability compared to those that must rely on random search. We address this hypothesis by employing descriptive statistics and spectral analyses to characterize the daily foraging routes of a band of wild hamadryas baboons in Filoha, Ethiopia. The baboons slept on two main cliffs--the Filoha cliff and the Wasaro cliff--and daily travel began and ended on a cliff; thus four daily travel routes exist: Filoha-Filoha, Filoha-Wasaro, Wasaro-Wasaro, Wasaro-Filoha. We use newly developed partial sum methods and distribution-fitting analyses to distinguish periods of area-restricted search from more extensive movements. The results indicate a single peak in travel activity in the Filoha-Filoha and Wasaro-Filoha routes, three peaks of travel activity in the Filoha-Wasaro routes, and two peaks in the Wasaro-Wasaro routes; and are consistent with on-the-ground observations of foraging and ranging behavior of the baboons. In each of the four daily travel routes the "tipping points" identified by the partial sum analyses indicate transitions between travel in small- versus large-scale space. The correspondence between the quantitative analyses and the field observations suggest great utility for using these types of analyses to examine primate travel patterns and especially in distinguishing between movement in small versus large-scale space. Only the distribution-fitting analyses are inconsistent with the field observations, which

Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions.

PubMed

Salmon, Adam B; Dorigatti, Jonathan; Huber, Hillary F; Li, Cun; Nathanielsz, Peter W

2018-05-25

Compelling data exist for programming of chronic later-life diseases and longevity by perinatal developmental programming challenges. Understanding mechanisms by which life course health trajectory and longevity are set is fundamental to understanding aging. Appropriate approaches are needed to determine programming effects on cellular function. We have developed a baboon model in which control mothers eat ad libitum while a second group eat 70% of the global diet fed controls, leading to male and female offspring intrauterine growth restriction (IUGR). We have shown that IUGR suffer from acceleration of several age-related physiological declines. Here, we report on a skin-derived fibroblast model with potential relevance for mechanistic studies on how IUGR impacts aging. Fibroblasts were cultured from the skin biopsies taken from adult baboons from control and IUGR cohorts. IUGR-derived fibroblasts grew in culture less well than controls and those derived from male, but not female, IUGR baboons had a significant reduction in maximum respiration rate compared to control-derived fibroblasts. We also show that relative levels of several mitochondrial protein subunits, including NDUFB8 and cytochrome c oxidase subunit IV, were reduced in IUGR-derived fibroblasts even after serial passaging in culture. The lower levels of electron transport system components provide potential mechanisms for accelerated life course aging in the setting of programmed IUGR. This observation fits with the greater sensitivity of males compared with females to many, but not all, outcomes in response to programming challenges. These approaches will be powerful in the determination of programming-aging interactions.

Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

PubMed

Kim, Sei Eun; Lee, Seul Yi; Blanco, Cynthia L; Kim, Jun Hee

2014-08-20

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse. Copyright © 2014 the authors 0270-6474/14/3411399-06$15.00/0.

Patterns of gastro-intestinal parasites and commensals as an index of population and ecosystem health: the case of sympatric western chimpanzees (Pan troglodytes verus) and guinea baboons (Papio hamadryas papio) at Fongoli, Senegal.

PubMed

Howells, Michaela E; Pruetz, Jill; Gillespie, Thomas R

2011-02-01

The exponential decline of great apes over the past 50 years has resulted in an urgent need for data to inform population viability assessment and conservation strategies. Health monitoring of remaining ape populations is an important component of this process. In support of this effort, we examined endoparasitic and commensal prevalence and richness as proxies of population health for western chimpanzees (Pan troglodytes verus) and sympatric guinea baboons (Papio hamadryas papio) at Fongoli, Senegal, a site dominated by woodland-savanna at the northwestern extent of chimpanzees' geographic range. The small population size and extreme environmental pressures experienced by Fongoli chimpanzees make them particularly sensitive to the potential impact of pathogens. One hundred thirty-two chimpanzee and seventeen baboon fecal samples were processed using sodium nitrate floatation and fecal sedimentation to isolate helminth eggs, larvae, and protozoal cysts. Six nematodes (Physaloptera sp., Ascaris sp., Stronglyloides fuelleborni, Trichuris sp., an unidentified hookworm, and an unidentified larvated nematode), one cestode (Bertiella sp.), and five protozoans (Iodamoeba buetschlii, Entamoeba coli, Troglodytella abrassarti, Troglocorys cava, and an unidentified ciliate) were detected in chimpanzee fecal samples. Four nematodes (Necator sp., S. fuelleborni, Trichuris sp., and an unidentified hookworm sp.), two trematodes (Shistosoma mansoni and an unidentified fluke), and six protozoans (Entamoeba histolytica/dispar, E. coli, Chilomastix mesnili, Balantidium coli, T. abrassarti, and T. cava) were detected in baboon fecal samples. The low prevalence of pathogenic parasite species and high prevalence of symbiotic protozoa in Fongoli chimpanzees are indicative of good overall population health. However, the high prevalence of pathogenic parasites in baboons, who may serve as transport hosts, highlight the need for ongoing pathogen surveillance of the Fongoli chimpanzee

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons.

PubMed

Pantham, Priyadarshini; Rosario, Fredrick J; Weintraub, Susan T; Nathanielsz, Peter W; Powell, Theresa L; Li, Cun; Jansson, Thomas

2016-11-01

Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P < 0.05) in MNR fetuses compared to controls. In this primate model of IUGR, placental MVM system A amino acid transporter activity is decreased prior to the onset of reduction in the fetal growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced

Soft tissue around three different implant types after 1.5 years of functional loading without oral hygiene: a preliminary study in baboons.

PubMed

Watzak, Georg; Zechner, Werner; Tangl, Stefan; Vasak, Christoph; Donath, Karl; Watzek, Georg

2006-04-01

The purpose of this study was to determine the peri-implant soft tissue dimension (PSD) and peri-implant bone level (BL) of dental implants with different designs and surface modifications after functional loading without oral hygiene. Three types of dental implants were placed in the posterior jaws of adult baboons, three of the same design per quadrant, and fitted with fixed partial dentures. After 1.5 years of functional loading and plaque accumulation, all implants showed severe peri-implant mucositis and comparatively high BL. A histomorphometric evaluation of the sulcus depth (SD), the dimension of the junctional epithelium (JE) and the connective tissue contact (CTC) resulted in no significant differences between the three implant designs, neither in the maxilla nor in the mandible (P>0.05). The sum of SD, JE and CTC forming the PSD was nearly the same in the maxilla (commercially pure titanium, CpTi: 3.5 mm 2.9/4.1 confidence interval (CI); titanium plasma sprayed (TPS): 3.5 mm 2.9/4.2 CI; sand blasted acid-etched (GBAE): 3.2 mm 2.7/3.9 CI) and in the mandible (CpTi: 3.2 mm 2.6/3.8 CI; TPS: 3.2 mm 2.6/3.8 CI; GBAE: 3.2 mm 2.7/3.9 CI; P>0.05). There was no difference in BL around the three implant designs (maxilla: CpTi: 0.9 mm 0.5/1.6 CI; TPS: 0.9 mm 0.5/1.5CI; GBAE: 0.9 mm 0.5/1.6 CI; mandible: CpTi: 0.8 mm 0.5/1.2 CI; TPS: 0.6 mm 0.4/0.9 CI; GBAE: 0.7 mm 0.5/1.1 CI; P>0.05). Overall, the data presented did not show any significant differences in peri-implant soft tissue conditions in baboons. Moreover, plaque accumulation and propagation of peri-implant mucositis after 1.5 years of functional loading was not influenced by implant design and surface modifications in baboons.

Experimental acute thrombotic stroke in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.

1986-11-01

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9more » cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8.« less

A novel ex-vivo porcine renal xenotransplantation model using a pulsatile machine preservation system.

PubMed

Guarrera, James V; Stone, Jonathan; Tulipan, Jacob; Jhang, Jeffrey; Arrington, Ben; Boykin, Jason; Markowitz, Glen; Ratner, Lloyd E

2011-01-01

Animal models to investigate pathophysiology and xenotransplantation require complex techniques and significant animal utilization. The aim of the study was to develop a reliable ex-vivo technique to test xenotransplant interventions. Miniature Swine being utilized for a nonsurvival study acted as donor animals. Kidneys were flushed and rapidly explanted and chilled to 4°C. Kidneys were assigned to be the control (CK) (n=3) and the mate were used as a Xenograft Kidneys (XK) (n=3). Kidneys were perfused on separate Waters RM 3 perfusion devices. Perfusion temperature was 35-37°C and pressure was 100-110/60-70 mmHg at 60 pulses per minute. CKs were reperfused with autologous blood collected at the time of organ procurement. XKs were reperfused using freshly donated whole human blood. Physical characteristics, urine output were recorded. Core needle biopsies were obtained and examined by a blinded pathologist for evidence of antibody mediated rejection. XK kidneys demonstrated homogenous reperfusion which rapidly became patchy at 5-7 minutes. XK kidneys had become complete black and thrombosed by 60-70 minutes. XK biopsies demonstrated peritubular capillaritis. CK kidneys demonstrated homogenous reperfusion and urine production. H&E stain of CKs only demonstrated nonspecific inflammation. Our ex-vivo porcine xenotransplant model shows early promise as a tool for studying Xeno- associated hyperacute rejection. This technique saves resources and animal utilization.

Increased aggressive and affiliative display behavior in intrauterine growth restricted (IUGR) baboons

PubMed Central

Huber, Hillary F; Ford, Susan M; Bartlett, Thad Q; Nathanielsz, Peter W

2016-01-01

Background We hypothesized intrauterine growth restricted offspring (IUGR) demonstrate higher rates of aggression and higher dominance ranks than control (CTR) offspring with normal weight at term; if aggressive behavior is advantageous during resource scarcity, developmental programming may lead to an association between aggression and IUGR. Methods We studied 22 group-housed baboons (ages 3-5 years). CTR (male n=8, female n=5) mothers ate ad libitum. IUGR (male n=4, female n=5) mothers were fed 70% feed eaten by CTR mothers during pregnancy and lactation. Results IUGR showed higher rates of aggressive displays (p<0.01) and friendly displays (p<0.02). Dominance ranks and physical aggression rates did not differ between groups. Conclusions High rates of IUGR aggressive display might reflect developmental programming of behavioral phenotypes enhancing fitness. Friendly displays may reflect reconciliation. Potential mechanisms include neurodevelopment and learning. Exploration of IUGR as a risk factor for behavioral patterns is important for developing diagnostic and therapeutic strategies. PMID:25891005

Isolation and characterization of new strains of cholesterol-reducing bacteria from baboons.

PubMed

Brinkley, A W; Gottesman, A R; Mott, G E

1982-01-01

We isolated and characterized nine new strains of cholesterol-reducing bacteria from feces and intestinal contents of baboons. Cholesterol-brain agar was used for the primary isolation, and subsequent biochemical tests were done in a lecithin-cholesterol broth containing plasmenylethanolamine and various substrates. All strains had similar colony and cell morphology, hydrolyzed the beta-glucosides esculin and amygdalin, metabolized pyruvate, and produced acetate and acetoin. Unlike previously reported strains, the nine new strains did not require cholesterol and an alkenyl ether lipid (e.g., plasmalogen) for growth; however, only two strains reduced cholesterol in the absence of the plasmalogen. These two strains also produced succinate as an end product. Carbohydrate fermentation was variable; some strains produced weak acid (pH 5.5 to 6.0) from only a few carbohydrates, whereas other strains produced strong acid reactions (pH less than or equal to 5.5) from a wide variety of carbohydrates.

Trade-off between fertility and predation risk drives a geometric sequence in the pattern of group sizes in baboons.

PubMed

Dunbar, R I M; MacCarron, Padraig; Robertson, Cole

2018-03-01

Group-living offers both benefits (protection against predators, access to resources) and costs (increased ecological competition, the impact of group size on fertility). Here, we use cluster analysis to detect natural patternings in a comprehensive sample of baboon groups, and identify a geometric sequence with peaks at approximately 20, 40, 80 and 160. We suggest (i) that these form a set of demographic oscillators that set habitat-specific limits to group size and (ii) that the oscillator arises from a trade-off between female fertility and predation risk. © 2018 The Authors.

Real-time assessment of encapsulated neonatal porcine islets prior to clinical xenotransplantation.

PubMed

Kitzmann, Jennifer P; Law, Lee; Shome, Avik; Muzina, Marija; Elliott, Robert B; Mueller, Kate R; Schuurman, Henk-Jan; Papas, Klearchos K

2012-01-01

Porcine islet transplantation is emerging as an attractive option for the treatment of patients with type 1 diabetes, with the possibility of providing islets of higher and more consistent quality and in larger volumes than available from human pancreata. The use of encapsulated neonatal porcine islets (ENPI) is appealing because it can address islet supply limitations while reducing the need for anti-rejection therapy. Pre-transplant characterization of ENPI viability and potency is an essential component of the production process. We applied the validated assay for oxygen consumption rate normalized for DNA content (OCR/DNA) to characterize ENPI viability. ENPI of low viscosity and high m alginate were prepared according to standard methods and characterized at various culture time points up to 5 weeks. The OCR/DNA (nmol/min·mgDNA ± SEM) of ENPI (235 ± 10, n = 9) was comparable to that of free NPI (255 ± 14, n = 13). After encapsulation, NPI OCR/DNA was sustained over a culture period of up to 5 weeks. The average OCR/DNA of ENPI cultured longer than 9 days was higher than that of freshly encapsulated NPI. This is the first characterization of ENPI by a validated and more sensitive method for product viability. The NPI encapsulation process does not compromise viability as measured by OCR/DNA, and ENPI can be cultured for up to 5 weeks with maintenance of viability. ENPI meet or exceed current adult porcine islet product release criteria (established at the University of Minnesota) for preclinical xenotransplantation in terms of OCR/DNA. © 2012 John Wiley & Sons A/S.

DNA-polymerase induced by Herpesvirus papio (HVP) in cells of lymphoblastoid cultures derived from lymphomatous baboons. Report V.

PubMed

Djachenko, A G; Lapin, B A

1981-01-01

A new DNA-polymerase was found in the cells of suspension lymphoblastoid cultures which produce lymphotropic baboon herpesvirus (HVP). This enzyme was isolated in a partially purified form. Some of its properties vary from those of other cellular DNA-polymerases. HVP-induced DNA-polymerase has a molecule weight of 160,000 and sedimentation coefficient of about 8 S. The enzyme is resistant to high salt concentration and N-ethylmaleimide, but it is very sensitive to phosphonoacetate. It effectively copies "activated" DNA and synthetic deoxyribohomopolymers. Attempts to reveal the DNA-polymerase activity in HVP virions were unsuccessful.

Pig kidney transplantation in baboons: anti-Gal(alpha)1-3Gal IgM alone is associated with acute humoral xenograft rejection and disseminated intravascular coagulation.

PubMed

Bühler, L; Yamada, K; Kitamura, H; Alwayn, I P; Basker, M; Appel, J Z; Colvin, R B; White-Scharf, M E; Sachs, D H; Robson, S C; Awwad, M; Cooper, D K

2001-12-15

Kidneys harvested from miniature swine or pigs transgenic for human decay-accelerating factor (hDAF) were transplanted into baboons receiving an anti-CD154 monoclonal antibody (mAb) and either a whole body irradiation (WBI)- or cyclophosphamide (CPP)-based immunosuppressive regimen. Group 1 baboons (n=3) underwent induction therapy with WBI and thymic irradiation, pretransplantation antithymocyte globulin, and immunoadsorption of anti-Gal(alpha)1-3Gal (Gal) antibody (Ab). After transplantation of a miniature swine kidney, maintenance therapy comprised cobra venom factor, mycophenolate mofetil, and an anti-CD154 mAb (for 14-28 days). In group 2 (n=2), WBI was replaced by CPP in the induction protocol. Group 3 (n=3) animals received the group 2 regimen, but underwent transplantation with hDAF pig kidneys. Group 1 and 2 animals developed features of disseminated intravascular coagulation (DIC), with reductions of fibrinogen and platelets and increases of prothrombin time, partial thromboplastin time, and fibrin split products. Graft survival was for 6-13 days. Histology showed mild acute humoral xenograft rejection (AHXR) of the kidneys, but severe rejection of the ureters. Group 3 animals developed features of DIC in two of three cases during the fourth week, with AHXR in the third case. Graft survival was for 28 (n=1) or 29 (n=2) days. Histology of day 15 biopsy specimens showed minimal focal mononuclear cellular infiltrates, with predominantly CD3+ cells. By days 28 and 29, kidneys showed mild-to-moderate features of AHXR. In all groups, the humoral response was manifest by reappearance of anti-Gal IgM below baseline level, with no or low return of anti-Gal IgG. All excised kidneys showed IgM deposition, but no complement and no or minimal IgG deposition. No baboon showed a rebound of anti-Gal Ab immediately after excision of the graft, and anti-Gal Ab increased over pretransplantation levels only when anti-CD154 mAb was discontinued. DIC was observed with WBI- or

Delayed revascularization of islets after transplantation by IL-6 blockade in pig to non-human primate islet xenotransplantation model.

PubMed

Min, Byoung-Hoon; Shin, Jun-Seop; Kim, Jong-Min; Kang, Seong-Jun; Kim, Hyun-Je; Yoon, Il-Hee; Park, Su-Kyoung; Choi, Ji-Won; Lee, Min-Suk; Park, Chung-Gyu

2018-01-01

Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model. Also, the endothelial cell origin in a new vessel of the transplanted pig islets was determined. Pig islets were isolated from designated pathogen-free (DPF) SNU miniature pigs and transplanted via portal vein into five streptozotocin-induced diabetic monkeys. One group (n = 2, basal group) was treated with anti-thymoglobulin (ATG), anti-CD40 antibody (2C10R4), sirolimus, and tacrolimus, and the other group was additionally given tocilizumab on top of basal immunosuppression (n = 3, Tocilizumab group). To confirm IL-6 blocking effect, C-reactive protein (CRP) levels and serum IL-6 concentration were measured. Scheduled biopsy of the margin of the posterior segment right lobe inferior of the liver was performed at 3 weeks after transplantation to assess the degree of revascularization of the transplanted islets. Immunohistochemical staining using anti-insulin, anti-CD31 antibodies, and lectin IB4 was conducted to find the origin of endothelial cells in the islet graft. CRP significantly increased at 1~2 days after transplantation in Basal group, but not in Tocilizumab group, and higher serum IL-6 concentration was measured in latter group, showing the biological potency of tocilizumab. In Basal group, well-developed endothelial cells were observed on the peri- and intraislet area, whereas the number of CD31 + cells in the intraislet space was significantly reduced in Tocilizumab group. Finally, new endothelial

Prematurity disrupts glomeruli development, whereas prematurity and hyperglycemia lead to altered nephron maturation and increased oxidative stress in newborn baboons.

PubMed

Callaway, Danielle A; McGill-Vargas, Lisa L; Quinn, Amy; Jordan, Jasmine L; Winter, Lauryn A; Anzueto, Diana; Dick, Edward J; Blanco, Cynthia L

2018-03-01

BackgroundPremature birth occurs when nephrogenesis is incomplete and has been linked to increased renal pathologies in the adult. Metabolic factors complicating preterm birth may have additional consequences for kidney development. Here, we evaluated the effects of prematurity and hyperglycemia on nephrogenesis in premature baboons when compared with those in term animals.MethodsBaboons were delivered prematurely (67% gestation; n=9) or at term (n=7) and survived for 2-4 weeks. Preterm animals were classified by glucose control during the first 5 days of life: normoglycemic (PtN; serum glucose 50-100 mg/dl, n=6) and hyperglycemic (PtH; serum glucose 150-250 mg/dl, n=3). Kidneys were assessed histologically for glomeruli relative area, maturity, size, and overall morphology. Kidney lysates were evaluated for oxidative damage with 4-hydroxynonenal (4-HNE) antibody.ResultsHistological examination revealed decreased glomeruli relative area (P<0.05), fewer glomerular generations (P<0.01), and increased renal corpuscle area (P<0.001) in preterm compared with those in term animals. Numbers of apoptotic glomeruli were similar between groups. PtH kidneys exhibited reduced nephrogenic zone width (P<0.0001), increased numbers of mature glomeruli (P<0.05), and increased 4-HNE staining compared with those in PtN kidneys.ConclusionPrematurity interrupts normal kidney development, independent of glomerular cell apoptosis. When prematurity is complicated by hyperglycemia; kidney development shifts toward accelerated maturation and increased oxidative stress.

Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice

PubMed Central

Papin, James F.; Verardi, Paulo H.; Jones, Leslie A.; Monge-Navarro, Francisco; Brault, Aaron C.; Holbrook, Michael R.; Worthy, Melissa N.; Freiberg, Alexander N.; Yilma, Tilahun D.

2011-01-01

Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF. PMID:21873194

Cardiac catheterization

MedlinePlus

Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

Evaluation of Biodistribution and Safety of Adenovirus Vectors Containing Group B Fibers after Intravenous Injection into Baboons

PubMed Central

NI, SHAOHENG; BERNT, KATHRIN; GAGGAR, ANUJ; LI, ZONG-YI; KIEM, HANS-PETER; LIEBER, ANDRÉ

2005-01-01

Vectors containing group B adenovirus (Ad) fibers are able to efficiently transduce gene therapy targets that are refractory to infection with standard Ad serotype 5 (Ad5) vectors, including malignant tumor cells, hematopoietic stem cells, and dendritic cells. Preliminary studies in mice indicate that, after intravenous injection, B-group fiber-containing Ads do not efficiently transduce most organs and cause less acute toxicity than Ad5 vectors. However, biodistribution and safety studies in mice are of limited value because the mouse analog of the B-group Ad receptor, CD46, is expressed only in the testis, whereas in humans, CD46 is expressed on all nucleated cells. Unlike mice, baboons have CD46 expression patterns and levels that closely mimic those in humans. We conducted a biodistribution and toxicity study of group B Ad fiber-containing vectors in baboons. Animals received phosphate-buffered saline, Ad5-bGal (a first-generation Ad5 vector), or B-group fiber-containing Ads (Ad5/35-bGal and Ad5/11-bGal) at a dose of 2 × 1012 VP/kg, and vector biodistribution and safety was analyzed over 3 days. The amount of Ad5/35-bGal and Ad5/11-bGal vector genomes was in most tissues one to three orders of magnitude below that of Ad5. Significant Ad5/35- and Ad5/11-mediated transgene (β-galactosidase) expression was seen only in the marginal zone of splenic follicles. Compared with the animal that received Ad5-bGal, all animals injected with B-group fiber-containing Ad vectors had lower elevations in serum proinflammatory cytokine levels. Gross and histopathology were normal in animals that received B-group Ad fiber-containing Ads, in contrast to the Ad5-infused animal, which showed widespread endothelial damage and inflammation. In a further study, a chimeric Ad5/35 vector carrying proapoptotic TRAIL and Ad E1A genes under tumor-specific regulation was well tolerated in a 30-day toxicity study. No major clinical, serologic, or pathologic abnormalities were noticed in

Transesophageal echocardiographic evaluation of baboons during microgravity induced by parabolic flight

NASA Technical Reports Server (NTRS)

Vernalis, Marina N.; Latham, Ricky D.; Fanton, John W.; Geffney, F. Andrew

1993-01-01

Transthoracic echocardiography (TTE) is a feasible method to noninvasively examine cardiac anatomy during parabolic flight. However, transducer placement on the chest wall is very difficult to maintain during transition to microgravity. In addition, TTE requires the use of low frequency transponders which limit resolution. Transesophical echocardiography (TEE) is an established imaging technique which obtains echocardiographic information from the esophagus. It is a safe procedure and provides higher quality images of cardiac structure than obtained with TTE. This study is designed to determine whether TEE was feasible to perform during parabolic flight and to determine whether acute central volume responses occur in acute transition to zero gravity by direct visualization of the cardiac chambers.

Effect of sumatriptan on cerebral blood flow in the baboon model.

PubMed

Oliver, D W; Dormehl, I C; Hugo, N

1994-08-01

Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.

[Chronic surplus of Japanese cardiac surgeon--ideal nurse practitioner for cardiac surgery, cardiac surgeon's attitude toward the future].

PubMed

Ikegami, Hirohisa

2014-03-01

It is chronically surplus of doctors in the world of cardiac surgery. There are too many cardiac surgeons because cardiac surgery requires a large amount of manpower resources to provide adequate medical services. Many Japanese cardiac surgeons do not have enough opportunity to perform cardiac surgery operations, and many Japanese cardiac surgery residents do not have enough opportunity to learn cardiac surgery operations. There are physician assistants and nurse practitioners in the US. Because they provide a part of medical care to cardiac surgery patients, American cardiac surgeons can focus more energy on operative procedures. Introduction of cardiac surgery specialized nurse practitioner is essential to deliver a high quality medical service as well as to solve chronic problems that Japanese cardiac surgery has had for a long time.

Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biegon, A.; Biegon, A.; Kim, S.-W.

Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largestmore » reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.« less

Assessment of buprenorphine, carprofen, and their combination for postoperative analgesia in olive baboons (Papio anubis).

PubMed

Allison, Sarah O; Halliday, Lisa C; French, Jeffrey A; Novikov, Dmitri D; Fortman, Jeffrey D

2007-05-01

This study compared the efficacy of buprenorphine, carprofen, and a combination of the 2 analgesics in female baboons. Physiologic and behavioral parameters were assessed at baseline and postoperatively for 6 d by use of continuous noninvasive physiologic monitoring and twice-daily videotaping. Prior to surgery, all animals received a pre-emptive dose of either 0.01 mg/kg buprenorphine intramuscularly, 2.2 mg/kg carprofen intramuscularly, or a combination of 0.01 mg/kg buprenorphine and 2.2 mg/kg carprofen intramuscularly. All animals in the carprofen (n = 4) and buprenorphine+carprofen (n = 4) treatment groups appeared to have sufficient analgesia. Three of 4 animals in the buprenorphine group had adequate analgesia. The fourth animal had an elevated heart rate and spent less time standing during the postoperative period. In this study, the use of carprofen or a combination of carprofen plus buprenorphine provided more reliable postoperative analgesia than buprenorphine alone.

Cardiac catheterization - discharge

MedlinePlus

Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary artery disease - cardiac catheterization ...

Cardiac Trauma.

PubMed

Gosavi, Sucheta; Tyroch, Alan H; Mukherjee, Debabrata

2016-11-01

Cardiac trauma is a leading cause of death in the United States and occurs mostly due to motor vehicle accidents. Blunt cardiac trauma and penetrating chest injuries are most common, and both can lead to aortic injuries. Timely diagnosis and early management are the key to improve mortality. Cardiac computed tomography and cardiac ultrasound are the 2 most important diagnostic modalities. Mortality related to cardiac trauma remains high despite improvement in diagnosis and management.

Effect of immobilization on the EEG of the baboon. Comparison with telemetry results from unrestricted animals

NASA Technical Reports Server (NTRS)

Bert, J.; Collomb, H.

1980-01-01

The EEG of the baboon was studied under two very different sets of conditions: 37 were totally immobolized while 12 were studied in their free movements with 4 channel telemetry. For the immobilzed, 3 stages were described: (1) activation, record desynchronized; (2) rest with 13-15 cm/sec rhythm, like the human alpha rhythm stage but with eyes open or closed; (3)relaxation with a decrease in 13-15 rhythm and the appearance of 5-7 cm/sec theta waves, eyelids closed, animal apparently sleeping. For the free animals the rest stage appeared when the animal's attention was not directed anywhere and there was no relaxation stage. It is concluded that the EEG pattern of the immobilized animal that was described as the "relaxation" stage really represents a special functional state which one must distinguish clearly from the physiological stages of sleep.

Ancestral genomic duplication of the insulin gene in tilapia: An analysis of possible implications for clinical islet xenotransplantation using donor islets from transgenic tilapia expressing a humanized insulin gene.

PubMed

Hrytsenko, Olga; Pohajdak, Bill; Wright, James R

2016-07-03

Tilapia, a teleost fish, have multiple large anatomically discrete islets which are easy to harvest, and when transplanted into diabetic murine recipients, provide normoglycemia and mammalian-like glucose tolerance profiles. Tilapia insulin differs structurally from human insulin which could preclude their use as islet donors for xenotransplantation. Therefore, we produced transgenic tilapia with islets expressing a humanized insulin gene. It is now known that fish genomes may possess an ancestral duplication and so tilapia may have a second insulin gene. Therefore, we cloned, sequenced, and characterized the tilapia insulin 2 transcript and found that its expression is negligible in islets, is not islet-specific, and would not likely need to be silenced in our transgenic fish.

Ancestral genomic duplication of the insulin gene in tilapia: An analysis of possible implications for clinical islet xenotransplantation using donor islets from transgenic tilapia expressing a humanized insulin gene

PubMed Central

Hrytsenko, Olga; Pohajdak, Bill; Wright, James R.

2016-01-01

ABSTRACT Tilapia, a teleost fish, have multiple large anatomically discrete islets which are easy to harvest, and when transplanted into diabetic murine recipients, provide normoglycemia and mammalian-like glucose tolerance profiles. Tilapia insulin differs structurally from human insulin which could preclude their use as islet donors for xenotransplantation. Therefore, we produced transgenic tilapia with islets expressing a humanized insulin gene. It is now known that fish genomes may possess an ancestral duplication and so tilapia may have a second insulin gene. Therefore, we cloned, sequenced, and characterized the tilapia insulin 2 transcript and found that its expression is negligible in islets, is not islet-specific, and would not likely need to be silenced in our transgenic fish. PMID:27222321

Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity.

PubMed

Maloyan, Alina; Muralimanoharan, Sribalasubashini; Huffman, Steven; Cox, Laura A; Nathanielsz, Peter W; Myatt, Leslie; Nijland, Mark J

2013-10-01

Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.

The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town - with reference to : the operation. A human cardiac transplant : an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town.

PubMed

Brink, J G; Hassoulas, J

2009-01-01

Christiaan (Chris) Barnard was born in 1922 and qualified in medicine at the University of Cape Town in 1946. Following surgical training in South Africa and the USA, Barnard established a successful open-heart surgery programme at Groote Schuur Hospital and the University of Cape Town in 1958. In 1967, he led the team that performed the world's first human-to-human heart transplant. The article describing this remarkable achievement was published in the South African Medical Journal just three weeks after the event and is one of the most cited articles in the cardiovascular field. In the lay media as well, this first transplant remains the most publicised event in world medical history. Although the first heart transplant patient survived only 18 days, four of Groote Schuur Hospital's first 10 patients survived for more than one year, two living for 13 and 23 years, respectively. This relative success amid many failures worldwide did much to generate guarded optimism that heart transplantation would eventually become a viable therapeutic option. This first heart transplant and subsequent ongoing research in cardiac transplantation at the University of Cape Town and in a few other dedicated centres over the subsequent 15 years laid the foundation for heart transplantation to become a well-established form of therapy for end-stage cardiac disease. During this period from 1968 to 1983, Chris Barnard and his team continued to make major contributions to organ transplantation, notably the development of the heterotopic ( 'piggy-back') heart transplants; advancing the concept of brain death, organ donation and other related ethical issues; better preservation and protection of the donor heart (including hypothermic perfusion storage of the heart; studies on the haemodynamic and metabolic effects of brain death; and even early attempts at xenotransplantation.

Assessment of Buprenorphine, Carprofen, and Their Combination for Postoperative Analgesia in Olive Baboons (Papio anubis)

PubMed Central

Allison, Sarah O; Halliday, Lisa C; French, Jeffrey A; Novikov, Dmitri D; Fortman, Jeffrey D

2010-01-01

This study compared the efficacy of buprenorphine, carprofen, and a combination of the 2 analgesics in female baboons. Physiologic and behavioral parameters were assessed at baseline and postoperatively for 6 d by use of continuous noninvasive physiologic monitoring and twice-daily videotaping. Prior to surgery, all animals received a pre-emptive dose of either 0.01 mg/kg buprenorphine intramuscularly, 2.2 mg/kg carprofen intramuscularly, or a combination of 0.01 mg/kg buprenorphine and 2.2 mg/kg carprofen intramuscularly. All animals in the carprofen (n = 4) and buprenorphine+carprofen (n = 4) treatment groups appeared to have sufficient analgesia. Three of 4 animals in the buprenorphine group had adequate analgesia. The fourth animal had an elevated heart rate and spent less time standing during the postoperative period. In this study, the use of carprofen or a combination of carprofen plus buprenorphine provided more reliable postoperative analgesia than buprenorphine alone. PMID:17487949

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis.

PubMed

Wu, Mei-Ping; Zhang, Yi-Shuai; Xu, Xiangbin; Zhou, Qian; Li, Jian-Dong; Yan, Chen

2017-04-01

Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling.

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

PubMed Central

Wu, Mei-ping; Zhang, Yi-shuai; Xu, Xiangbin; Zhou, Qian

2017-01-01

Purpose Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Methods Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. Results We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Conclusions Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling. PMID:28321644

The origin of bipedality as the result of a developmental by-product: The case study of the olive baboon (Papio anubis).

PubMed

Druelle, François; Aerts, Peter; Berillon, Gilles

2017-12-01

In this paper, we point to the importance of considering infancy in the emergence of new locomotor modes during evolution, and particularly when considering bipedal walking. Indeed, because infant primates commonly exhibit a more diverse posturo-locomotor repertoire than adults, the developmental processes of locomotion represent an important source of variation upon which natural selection may act. We have had the opportunity to follow the development of locomotion in captive individuals of a committed quadrupedal primate, the olive baboon (Papio anubis). We observed six infants at two different stages of their development. In total, we were able to analyze the temporal parameters of 65 bipedal steps, as well as their behavioral components. Our results show that while the basic temporal aspects of the bipedal walking gait (i.e., duty factor, dimensionless frequency, and hind lag) do not change during development, the baboon is able to significantly improve the coordination pattern between hind limbs. This probably influences the bout duration of spontaneous bipedal walking. During the same developmental stage, the interlimb coordination in quadrupedal walking is improved and the proportion of quadrupedal behaviors increases significantly. Therefore, the quadrupedal pattern of primates does not impede the developmental acquisition of bipedal behaviors. This may suggest that the same basic mechanism is responsible for controlling bipedal and quadrupedal locomotion, i.e., that in non-human primates, the neural networks for quadrupedal locomotion are also employed to perform (occasional) bipedal walking. In this context, a secondary locomotor mode (e.g., bipedalism) experienced during infancy as a by-product of locomotor development may lead to evolutionary novelties when under appropriate selective pressures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence of a Vocalic Proto-System in the Baboon (Papio papio) Suggests Pre-Hominin Speech Precursors

PubMed Central

Boë, Louis-Jean; Berthommier, Frédéric; Legou, Thierry; Captier, Guillaume; Kemp, Caralyn; Sawallis, Thomas R.; Becker, Yannick; Rey, Arnaud; Fagot, Joël

2017-01-01

Language is a distinguishing characteristic of our species, and the course of its evolution is one of the hardest problems in science. It has long been generally considered that human speech requires a low larynx, and that the high larynx of nonhuman primates should preclude their producing the vowel systems universally found in human language. Examining the vocalizations through acoustic analyses, tongue anatomy, and modeling of acoustic potential, we found that baboons (Papio papio) produce sounds sharing the F1/F2 formant structure of the human [ɨ æ ɑ ɔ u] vowels, and that similarly with humans those vocalic qualities are organized as a system on two acoustic-anatomic axes. This confirms that hominoids can produce contrasting vowel qualities despite a high larynx. It suggests that spoken languages evolved from ancient articulatory skills already present in our last common ancestor with Cercopithecoidea, about 25 MYA. PMID:28076426

Cardiac Biomarkers: a Focus on Cardiac Regeneration

PubMed Central

Forough, Reza; Scarcello, Catherine; Perkins, Matthew

2011-01-01

Historically, biomarkers have been used in two major ways to maintain and improve better health status: first, for diagnostic purposes, and second, as specific targets to treat various diseases. A new era in treatment and even cure for the some diseases using reprograming of somatic cells is about to be born. In this approach, scientists are successfully taking human skin cells (previously considered terminally-differentiated cells) and re-programming them into functional cardiac myocytes and other cell types in vitro. A cell reprograming approach for treatment of cardiovascular diseases will revolutionize the field of medicine and significantly expand the human lifetime. Availability of a comprehensive catalogue for cardiac biomarkers is necessary for developing cell reprograming modalities to treat cardiac diseases, as well as for determining the progress of reprogrammed cells as they become cardiac cells. In this review, we present a comprehensive survey of the cardiac biomarkers currently known. PMID:23074366

Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

PubMed

Marshall, P E; Goldsmith, P C

1980-07-14

The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

PubMed Central

Havill, L.M.; Allen, M.R.; Bredbenner, T.L.; Burr, D.B.; Nicolella, D.P.; Turner, C.H.; Warren, D.M.; Mahaney, M.C.

2010-01-01

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2=0.58), toughness (h2=0.64), and BV/TV (h2=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures. PMID:19900599

First report on Aonchotheca annulosa Dujardin, 1845 (Nematoda, Capillariidae) in a Hamadryas baboon (Papio hamadryas) from a zoo in northern Turkey.

PubMed

Umur, Sinasi; Moravec, Frantiśek; Gurler, Ali; Bolukbas, Cenk; Acici, Mustafa

2012-12-01

A dead male Hamadryas baboon, Papio hamadryas, from a zoo in Samsun in northern Turkey was submitted for necropsy examination. Standard techniques were performed for necropsy and for parasitic identification. A total of 14 nematodes were recovered from the small intestine. All nematodes were identified as Aonchotheca annulosa. This nematode is most often reported from murid rodents under natural conditions. To date, little is known about the occurrence of A. annulosa in monkeys, with the exception of a single report in a capuchin monkey. This is the first record of A. annulosa from P. hamadryas. © 2012 John Wiley & Sons A/S.

A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging.

PubMed

Yang, Shanshan; Gerow, Kenneth G; Huber, Hillary F; Considine, McKenna M; Li, Cun; Mattern, Vicki; Comuzzie, Anthony G; Ford, Stephen P; Nathanielsz, Peter W

2017-05-09

Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.

Effects of GABAergic modulators on food and cocaine self-administration in baboons.

PubMed

Weerts, Elise M; Froestl, Wolfgang; Griffiths, Roland R

2005-12-12

Drugs that indirectly alter dopaminergic systems may alter the reinforcing effects of cocaine. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has extensive neural connections in mesolimbic regions that appear to modulate dopamine. The current study evaluated the effects of GABA(B) receptor agonists baclofen and CGP44532, the benzodiazepine agonist alprazolam, and the GABA reuptake inhibitor tiagabine on lever responding maintained by low dose cocaine injections (0.032 mg/kg) or by food pellet (1 g) delivery in baboons. The benzodiazepine antagonist flumazenil was tested as a negative control. Cocaine or food was available under a fixed ratio (FR 10) schedule of reinforcement during daily 2-h sessions. During baseline conditions, cocaine and pellets maintained similar numbers of reinforcers per session. Baclofen, CGP44532 and tiagabine dose-dependently reduced the number of cocaine injections, where as the benzodiazepine antagonist flumazenil did not. Baclofen, CGP44532 and tiagabine also produced dose-related decreases in food-maintained behavior. In contrast, the benzodiazepine agonist alprazolam, which positively modulates GABA(A) receptors via the benzodiazepine site, produced decreases in cocaine self-injection, but not food-maintained behavior. Thus, the effects of alprazolam were specific for cocaine-maintained behavior, where as the effects of baclofen and CGP44532 were not.

Changes in gene expression associated with reproductive maturation in wild female baboons.

PubMed

Babbitt, Courtney C; Tung, Jenny; Wray, Gregory A; Alberts, Susan C

2012-01-01

Changes in gene expression during development play an important role in shaping morphological and behavioral differences, including between humans and nonhuman primates. Although many of the most striking developmental changes occur during early development, reproductive maturation represents another critical window in primate life history. However, this process is difficult to study at the molecular level in natural primate populations. Here, we took advantage of ovarian samples made available through an unusual episode of human-wildlife conflict to identify genes that are important in this process. Specifically, we used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in the ovarian tissue of juvenile and adult female baboons from Amboseli National Park, Kenya. We combined this information with prior evidence of selection occurring on two primate lineages (human and chimpanzee). We found that in cases in which genes were both differentially expressed over the course of ovarian maturation and also linked to lineage-specific selection this selective signature was much more likely to occur in regulatory regions than in coding regions. These results suggest that adaptive change in the development of the primate ovary may be largely driven at the mechanistic level by selection on gene regulation, potentially in relationship to the physiology or timing of female reproductive maturation.

Changes in Gene Expression Associated with Reproductive Maturation in Wild Female Baboons

PubMed Central

Babbitt, Courtney C.; Tung, Jenny; Wray, Gregory A.; Alberts, Susan C.

2012-01-01

Changes in gene expression during development play an important role in shaping morphological and behavioral differences, including between humans and nonhuman primates. Although many of the most striking developmental changes occur during early development, reproductive maturation represents another critical window in primate life history. However, this process is difficult to study at the molecular level in natural primate populations. Here, we took advantage of ovarian samples made available through an unusual episode of human–wildlife conflict to identify genes that are important in this process. Specifically, we used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in the ovarian tissue of juvenile and adult female baboons from Amboseli National Park, Kenya. We combined this information with prior evidence of selection occurring on two primate lineages (human and chimpanzee). We found that in cases in which genes were both differentially expressed over the course of ovarian maturation and also linked to lineage-specific selection this selective signature was much more likely to occur in regulatory regions than in coding regions. These results suggest that adaptive change in the development of the primate ovary may be largely driven at the mechanistic level by selection on gene regulation, potentially in relationship to the physiology or timing of female reproductive maturation. PMID:22155733

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitorymore » effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.« less

Living cardiac patch: the elixir for cardiac regeneration.

PubMed

Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

Initial Efficacy of a Cardiac Rehabilitation Transition Program: Cardiac TRUST

PubMed Central

Zullo, Melissa; Boxer, Rebecca; Moore, Shirley M.

2012-01-01

Patients recovering from cardiac events are increasingly using postacute care, such as home health care and skilled nursing facility services. The purpose of this pilot study was to test the initial efficacy, feasibility, and safety of a specially designed postacute care transitional rehabilitation intervention for cardiac patients. Cardiac Transitional Rehabilitation Using Self- Management Techniques (Cardiac TRUST) is a family-focused intervention that includes progressive low-intensity walking and education in self-management skills to facilitate recovery following a cardiac event. Using a randomized two-group design, exercise self-efficacy, steps walked, and participation in an outpatient cardiac rehabilitation program were compared in a sample of 38 older adults; 17 who received the Cardiac TRUST program and 21 who received usual care only. At discharge from postacute care, the intervention group had a trend for higher levels of self-efficacy for exercise outcomes (X=39.1, SD=7.4) than the usual care group (X=34.5; SD=7.0) (t-test 1.9, p=.06). During the 6 weeks following discharge, compared with the usual care group, the intervention group had more attendance in out-patient cardiac rehabilitation (33% compared to 11.8%, F=7.1, p=.03) and a trend toward more steps walked during the first week (X=1,307, SD=652 compared to X=782, SD=544, t-test 1.8, p=.07). The feasibility of the intervention was better for the home health participants than for those in the skilled nursing facility and there were no safety concerns. The provision of cardiac-focused rehabilitation during postacute care has the potential to bridge the gap in transitional services from hospitalization to outpatient cardiac rehabilitation for these patients at high risk for future cardiac events. Further evidence of the efficacy of Cardiac TRUST is warranted. PMID:22084960

Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons

PubMed Central

Morral, Núria; O’Neal, Wanda; Rice, Karen; Leland, Michele; Kaplan, Johanne; Piedra, Pedro A.; Zhou, Heshan; Parks, Robin J.; Velji, Rizwan; Aguilar-Córdova, Estuardo; Wadsworth, Samuel; Graham, Frank L.; Kochanek, Stefan; Carey, K. Dee; Beaudet, Arthur L.

1999-01-01

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human α1-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3–5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes. PMID:10536005

A comparative study of working memory: immediate serial spatial recall in baboons (Papio papio) and humans.

PubMed

Fagot, Joël; De Lillo, Carlo

2011-12-01

Two experiments assessed if non-human primates can be meaningfully compared to humans in a non-verbal test of serial recall. A procedure was used that was derived from variations of the Corsi test, designed to test the effects of sequence structure and movement path length in humans. Two baboons were tested in Experiment 1. The monkeys showed several attributes of human serial recall. These included an easier recall of sequences with a shorter number of items and of sequences characterized by a shorter path length when the number of items was kept constant. However, the accuracy and speed of processing did not indicate that the monkeys were able to benefit from the spatiotemporal structure of sequences. Humans tested in Experiment 2 showed a quantitatively longer memory span, and, in contrast with monkeys, benefitted from sequence structure. The results are discussed in relation to differences in how human and non-human primates segment complex visual patterns. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK-6577 in baboons.

PubMed

Zheng, Ming-Qiang; Lin, Shu-Fei; Holden, Daniel; Naganawa, Mika; Ropchan, Jim R; Najafzaden, Soheila; Kapinos, Michael; Tabriz, Mike; Carson, Richard E; Hamill, Terence G; Huang, Yiyun

2016-03-01

Glycine transporter type-1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [(11) C]GSK931145, and [(18) F]MK-6577, in baboons. Two baboons were imaged with [(11) C]GSK931145 and [(18) F]MK-6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [(11) C]GSK931145 and [(18) F]MK-6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ∼ 30% of parent at 30 min post-injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [(18) F]MK-6577 displayed higher uptake and faster kinetics than [(11) C]GSK931145. Time activity curves were well described by the two-tissue compartment model. Regional volume of distribution (VT ) values were higher for [(18) F]MK-6577 than [(11) C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of VT estimates between tracers indicated higher specific binding for [(18) F]MK-6577 than [(11) C]GSK931145, consistent with higher regional binding potential (BPND ) values of [(18) F]MK-6577 calculated using VT from the baseline scans and non-displaceable distribution volume (VND ) derived from blocking studies. [(18) F]MK-6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [(11) C]GSK931145. © 2016 Wiley Periodicals, Inc.

Comparative anatomy of the pelvic vessels in the bearded capuchin (Sapajus libidinosus) and baboons, apes and modern humans.

PubMed

Aversi-Ferreira, Roqueline A G M F; de Souza Vieira, Vanessa; Tomaz, Carlos; Aversi-Ferreira, Tales Alexandre

2014-01-01

Cebus/Sapajus has shown high cognitive and manipulatory behaviour as well as intermittent bipedalism. Although the function of the muscles and bones of this genus has been widely investigated, the arterial system that supports these tissues has not been studied in much detail, and a full description of the blood vessels of the pelvis is still missing. Therefore, we studied the vessels of the pelvis of Sapajus libidinosus in terms of their origin, distribution and muscle irrigation and compared them with those of other primates available in the literature. In general, the distribution pattern and origin of arteries in the pelvis of the bearded capuchin are more similar to those of baboons compared to other primates. This similarity may be because both have a tail, a similar body shape and use, preferentially, quadrupedal movement. 2014 S. Karger AG, Basel

Cardiac function and cognition in older community-dwelling cardiac patients.

PubMed

Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

2017-11-01

Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

Patterns of wounding in hamadryas baboons (Papio hamadryas) in North American zoos.

PubMed

Wiley, Jodi N; Leeds, Austin; Carpenter, Kamisha D; Kendall, Corinne J

2018-03-01

In North American zoos, hamadryas baboons (Papio hamadryas) have traditionally been housed as single one-male units (single male groups). In recent years, efforts have been made to house hamadryas in groups composed of multiple one-male units (multi-male groups) to more closely mirror their natural social structure, in addition to all-male or bachelor groups to manage surplus males. Given that the majority of social conflict in hamadryas occurs between males during the acquisition and defense of females, it was thought that managing hamadryas in these multi-male groups would result in increased rates of wounding. To assess this, incidences of wounding were recorded over one year across seven zoos (10 social groups, 59 individuals). Overall, we found no difference in wounding rates between group types, or by sex, and group type. These data provide evidence that managing hamadryas in multi-male and bachelor groups is an effective husbandry practice that does not negatively impact the welfare of the individuals, in addition to providing a more species-appropriate social setting for hamadryas in zoos. As the management of hamadryas in multi-male and bachelor groups continues and expands, additional research will be needed to understand what factors contribute to optimal cohesion, and welfare of groups and if wounding rates change as group size continues to increase. © 2018 Wiley Periodicals, Inc.

Characterizing cardiac arrest in children undergoing cardiac surgery: A single-center study.

PubMed

Gupta, Punkaj; Wilcox, Andrew; Noel, Tommy R; Gossett, Jeffrey M; Rockett, Stephanie R; Eble, Brian K; Rettiganti, Mallikarjuna

2017-02-01

To characterize cardiac arrest in children undergoing cardiac surgery using single-center data from the Society of Thoracic Surgeons and Pediatric Advanced Life Support Utstein-Style Guidelines. Patients aged 18 years or less having a cardiac arrest for 1 minute or more during the same hospital stay as heart operation qualified for inclusion (2002-2014). Patients having a cardiac arrest both before or after heart operation were included. Heart operations were classified on the basis of the first cardiovascular operation of each hospital admission (the index operation). The primary outcome was survival to hospital discharge. A total of 3437 children undergoing at least 1 heart operation were included. Overall rate of cardiac arrest among these patients was 4.5% (n = 154) with survival to hospital discharge of 84 patients (66.6%). Presurgery cardiac arrest was noted among 28 patients, with survival of 21 patients (75%). Among the 126 patients with postsurgery cardiac arrest, survival was noted among 84 patients (66.6%). Regardless of surgical case complexity, the median days between heart operation and cardiac arrest, duration of cardiac arrest, and survival after cardiac arrest were similar. The independent risk factors associated with improved chances of survival included shorter duration of cardiac arrest (odds ratio, 1.12; 95% confidence interval, 1.05-1.20; P = .01) and use of defibrillator (odds ratio, 4.51; 95% confidence interval, 1.08-18.87; P = .03). This single-center study demonstrates that characterizing cardiac arrest in children undergoing cardiac surgery using definitions from 2 societies helps to increase data granularity and understand the relationship between cardiac arrest and heart operation in a better way. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Acoustic features of male baboon loud calls: Influences of context, age, and individuality

NASA Astrophysics Data System (ADS)

Fischer, Julia; Hammerschmidt, Kurt; Cheney, Dorothy L.; Seyfarth, Robert M.

2002-03-01

The acoustic structure of loud calls (``wahoos'') recorded from free-ranging male baboons (Papio cynocephalus ursinus) in the Moremi Game Reserve, Botswana, was examined for differences between and within contexts, using calls given in response to predators (alarm wahoos), during male contests (contest wahoos), and when a male had become separated from the group (contact wahoos). Calls were recorded from adolescent, subadult, and adult males. In addition, male alarm calls were compared with those recorded from females. Despite their superficial acoustic similarity, the analysis revealed a number of significant differences between alarm, contest, and contact wahoos. Contest wahoos are given at a much higher rate, exhibit lower frequency characteristics, have a longer ``hoo'' duration, and a relatively louder ``hoo'' portion than alarm wahoos. Contact wahoos are acoustically similar to contest wahoos, but are given at a much lower rate. Both alarm and contest wahoos also exhibit significant differences among individuals. Some of the acoustic features that vary in relation to age and sex presumably reflect differences in body size, whereas others are possibly related to male stamina and endurance. The finding that calls serving markedly different functions constitute variants of the same general call type suggests that the vocal production in nonhuman primates is evolutionarily constrained.

Radiosynthesis and bioimaging of the tuberculosis chemotherapeutics isoniazid, rifampicin and pyrazinamide in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, L.; Hooker, J.; Liu, L.

2010-03-03

The front-line tuberculosis (TB) chemotherapeutics isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) have been labeled with carbon-11 and the biodistribution of each labeled drug has been determined in baboons using positron emission tomography (PET). Each radiosynthesis and formulation has been accomplished in 1 h, using [{sup 11}C]CH{sub 3}I to label RIF and [{sup 11}C]HCN to label INH and PZA. Following iv administration, INH, PZA, RIF, and/or their radiolabeled metabolites clear rapidly from many tissues; however, INH, PZA, and/or their radiolabeled metabolites accumulate in the bladder while RIF and/or its radiolabeled metabolites accumulates in the liver and gall bladder, consistent withmore » the known routes of excretion of the drugs. In addition, the biodistribution data demonstrate that the ability of the three drugs and their radiolabeled metabolites to cross the blood-brain barrier decreases in the order PZA > INH > RIF, although in all cases the estimated drug concentrations are greater than the minimum inhibitory concentration (MIC) values for inhibiting bacterial growth of Mycobacterium tuberculosis (MTB). The pharmacokinetic (PK) and drug distribution data have important implications for treatment of disseminated TB in the brain and pave the way for imaging the distribution of the pathogen in vivo.« less

Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadroy, Y.; Hanson, S.R.; Harker, L.A.

1991-02-15

To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi the authors evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function. When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generatedmore » platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins. Thrombus formation was quantified by measurements of {sup 111}In-labeled platelet and {sup 125}I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device. These finding suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented. This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated.« less

Social environment influences the relationship between genotype and gene expression in wild baboons

PubMed Central

Runcie, Daniel E.; Wiedmann, Ralph T.; Archie, Elizabeth A.; Altmann, Jeanne; Wray, Gregory A.; Alberts, Susan C.; Tung, Jenny

2013-01-01

Variation in the social environment can have profound effects on survival and reproduction in wild social mammals. However, we know little about the degree to which these effects are influenced by genetic differences among individuals, and conversely, the degree to which social environmental variation mediates genetic reaction norms. To better understand these relationships, we investigated the potential for dominance rank, social connectedness and group size to modify the effects of genetic variation on gene expression in the wild baboons of the Amboseli basin. We found evidence for a number of gene–environment interactions (GEIs) associated with variation in the social environment, encompassing social environments experienced in adulthood as well as persistent effects of early life social environment. Social connectedness, maternal dominance rank and group size all interacted with genotype to influence gene expression in at least one sex, and either in early life or in adulthood. These results suggest that social and behavioural variation, akin to other factors such as age and sex, can impact the genotype–phenotype relationship. We conclude that GEIs mediated by the social environment are important in the evolution and maintenance of individual differences in wild social mammals, including individual differences in responses to social stressors. PMID:23569293

Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration

PubMed Central

O’Meara, Caitlin C.; Wamstad, Joseph A.; Gladstone, Rachel; Fomovsky, Gregory M.; Butty, Vincent L.; Shrikumar, Avanti; Gannon, Joseph; Boyer, Laurie A.; Lee, Richard T.

2014-01-01

Rationale Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. PMID:25477501

In vitro dissolution of uranium oxide by baboon alveolar macrophages.

PubMed Central

Poncy, J L; Metivier, H; Dhilly, M; Verry, M; Masse, R

1992-01-01

In vitro cellular dissolution tests for insoluble forms of uranium oxide are technically difficult with conventional methodology using adherent alveolar macrophages. The limited number of cells per flask and the slow dissolution rate in a large volume of nutritive medium are obvious restricting factors. Macrophages in suspension cannot be substituted because they represent different and poorly reproducible functional subtypes with regard to activation and enzyme secretion. Preliminary results on the dissolution of uranium oxide using immobilized alveolar macrophages are promising because large numbers of highly functional macrophages can be cultured in a limited volume. Cells were obtained by bronchoalveolar lavages performed on baboons (Papio papio) and then immobilized after the phagocytosis of uranium octoxide (U3O8) particles in alginate beads linked with Ca2+. The dissolution rate expressed as percentage of initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold increase in the dissolution rate was observed when the same number of particles was immobilized without macrophages. These results, obtained in vitro, suggest that the U3O8 preparation investigated should be assigned to inhalation class Y as recommended by the International Commission on Radiological Protection. Future experiments are intended to clarify this preliminary work and to examine the dissolution characteristics of other particles such as uranium dioxide. It is recommended that the dissolution rate should be measured over an interval of 3 weeks, which is compatible with the survival time of immobilized cells in culture and may reveal transformation states occurring with aging of the particles. PMID:1396447

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Cardiac registers: the adult cardiac surgery register.

PubMed

Bridgewater, Ben

2010-09-01

AIMS OF THE SCTS ADULT CARDIAC SURGERY DATABASE: To measure the quality of care of adult cardiac surgery in GB and Ireland and provide information for quality improvement and research. Feedback of structured data to hospitals, publication of named hospital and surgeon mortality data, publication of benchmarked activity and risk adjusted clinical outcomes through intermittent comprehensive database reports, annual screening of all hospital and individual surgeon risk adjusted mortality rates by the professional society. All NHS hospitals in England, Scotland and Wales with input from some private providers and hospitals in Ireland. 1994-ongoing. Consecutive patients, unconsented. Current number of records: 400000. Adult cardiac surgery operations excluding cardiac transplantation and ventricular assist devices. 129 fields covering demographic factors, pre-operative risk factors, operative details and post-operative in-hospital outcomes. Entry onto local software systems by direct key board entry or subsequent transcription from paper records, with subsequent electronic upload to the central cardiac audit database. Non-financial incentives at hospital level. Local validation processes exist in the hospitals. There is currently no external data validation process. All cause mortality is obtained through linkage with Office for National Statistics. No other linkages exist at present. Available for research and audit by application to the SCTS database committee at http://www.scts.org.

Alternative routes to the leader male role in a multi-level society: follower vs. solitary male strategies and outcomes in hamadryas baboons.

PubMed

Pines, Mathew; Saunders, Julian; Swedell, Larissa

2011-07-01

The nested one-male units (OMUs) of the hamadryas baboon are part of a complex social system in which "leader" males achieve near exclusive mating access by forcibly herding females into permanent consortships. Within this multi-level social system (troops, bands, clans and OMUs) are two types of prereproductive males--the follower and solitary male--whose different trajectories converge on the leader role. Here we compare OMU formation strategies of followers, who associate with a particular OMU and may have social access to females, with those of solitary males, who move freely within the band and do not associate regularly with OMUs. Data were derived from 42 OMU formations (16 by followers and 26 by solitary males) occurring over 8 years in a hamadryas baboon band at the Filoha site in Ethiopia. "Initial units" (IUs) with sexually immature females (IU strategy) were formed by 44% of followers and 46% of solitary males. The remaining followers took over mature females when their leader was deposed (challenge strategy) or disappeared (opportunistic strategy), or via a seemingly peaceful transfer (inheritance strategy). Solitary males took over mature females from other clans and bands, but mainly from old, injured or vanished leaders within their clan (via both the challenge and opportunistic strategies). Former followers of an OMU were more successful at taking over females from those OMUs than any other category of male. Despite this advantage enjoyed by ex-follower leaders, ex-solitary leaders were equally capable of increasing their OMU size at a comparable rate in their first 2 years as a leader. These results demonstrate the potential for males to employ both multiple roles (follower vs. solitary male) and multiple routes (IU, inheritance, challenge, opportunistic) to acquire females and become a leader male in a mating system characterized by female defense polygyny in a competitive arena. © 2011 Wiley-Liss, Inc.

Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

PubMed

Sairaku, Akinori; Yoshida, Yukihiko; Nakano, Yukiko; Hirayama, Haruo; Maeda, Mayuho; Hashimoto, Haruki; Kihara, Yasuki

2017-05-01

Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Preservation of primordial follicles from lions by slow freezing and xenotransplantation of ovarian cortex into an immunodeficient mouse.

PubMed

Wiedemann, C; Hribal, R; Ringleb, J; Bertelsen, M F; Rasmusen, K; Andersen, C Y; Kristensen, S G; Jewgenow, K

2012-12-01

Assisted reproductive technology (ART) is considered an important tool in the conservation of endangered species, but often the most limiting factor of ART is the availability of mature oocytes. The aim of the present study was to investigate the feasibility of preserving female germ cells from ovaries of female lions (Panthera leo). Good quality cumulus-oocyte complexes (COCs) were isolated and subjected to in vitro maturation (IVM). In addition, ovarian cortex was obtained and cut into pieces for culture and cryopreservation by slow freezing. The survival of ovarian follicles was assessed by histology. Frozen-thawed samples of ovarian cortex samples were xenotransplanted under the skin of ovariectomized immunodeficient mouse for 28 days. Overall, 178 intact COCs were obtained from 13 lions, but only 28.1% were matured in vitro indicating insufficient IVM conditions. In contrast, almost all follicles within the ovarian cortex survived culture when the original sample was from a young healthy lion collected immediately after euthanasia. Within the xenotransplants, the number of primordial follicles decreased after 28 days by 20%, but the relation between primordial and growing follicles changed in favour of follicular growth. Female gamete rescue from valuable felids may be performed by slow freeze cryopreservation of ovarian cortex. Although the IVM protocol for lions is not yet optimized, mature oocytes may be obtained after long-term xenotransplantation and IVM and could potentially represent one way of salvage of endangered felid species in the future. © 2012 Blackwell Verlag GmbH.

Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming

PubMed Central

Spitler, Kathryn M.; Ponce, Jessica M.; Oudit, Gavin Y.; Hall, Duane D.

2017-01-01

The mediator complex, a multisubunit nuclear complex, plays an integral role in regulating gene expression by acting as a bridge between transcription factors and RNA polymerase II. Genetic deletion of mediator subunit 1 (Med1) results in embryonic lethality, due in large part to impaired cardiac development. We first established that Med1 is dynamically expressed in cardiac development and disease, with marked upregulation of Med1 in both human and murine failing hearts. To determine if Med1 deficiency protects against cardiac stress, we generated two cardiac-specific Med1 knockout mouse models in which Med1 is conditionally deleted (Med1cKO mice) or inducibly deleted in adult mice (Med1cKO-MCM mice). In both models, cardiac deletion of Med1 resulted in early lethality accompanied by pronounced changes in cardiac function, including left ventricular dilation, decreased ejection fraction, and pathological structural remodeling. We next defined how Med1 deficiency alters the cardiac transcriptional profile using RNA-sequencing analysis. Med1cKO mice demonstrated significant dysregulation of genes related to cardiac metabolism, in particular genes that are coordinated by the transcription factors Pgc1α, Pparα, and Errα. Consistent with the roles of these transcription factors in regulation of mitochondrial genes, we observed significant alterations in mitochondrial size, mitochondrial gene expression, complex activity, and electron transport chain expression under Med1 deficiency. Taken together, these data identify Med1 as an important regulator of vital cardiac gene expression and maintenance of normal heart function. NEW & NOTEWORTHY Disruption of transcriptional gene expression is a hallmark of dilated cardiomyopathy; however, its etiology is not well understood. Cardiac-specific deletion of the transcriptional coactivator mediator subunit 1 (Med1) results in dilated cardiomyopathy, decreased cardiac function, and lethality. Med1 deletion disrupted cardiac

Epidemiology and Outcomes After In-Hospital Cardiac Arrest After Pediatric Cardiac Surgery

PubMed Central

Gupta, Punkaj; Jacobs, Jeffrey P.; Pasquali, Sara K.; Hill, Kevin D.; Gaynor, J. William; O’Brien, Sean M.; He, Max; Sheng, Shubin; Schexnayder, Stephen M.; Berg, Robert A.; Nadkarni, Vinay M.; Imamura, Michiaki; Jacobs, Marshall L.

2014-01-01

Background Multicenter data regarding cardiac arrest in children undergoing heart operations are limited. We describe epidemiology and outcomes associated with postoperative cardiac arrest in a large multiinstitutional cohort. Methods Patients younger than 18 years in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2007 through 2012) were included. Patient factors, operative characteristics, and outcomes were described for patients with and without postoperative cardiac arrest. Multivariable models were used to evaluate the association of center volume with cardiac arrest rate and mortality after cardiac arrest, adjusting for patient and procedural factors. Results Of 70,270 patients (97 centers), 1,843 (2.6%) had postoperative cardiac arrest. Younger age, lower weight, and presence of preoperative morbidities (all p < 0.0001) were associated with cardiac arrest. Arrest rate increased with procedural complexity across common benchmark operations, ranging from 0.7% (ventricular septal defect repair) to 12.7% (Norwood operation). Cardiac arrest was associated with significant mortality risk across procedures, ranging from 15.4% to 62.3% (all p < 0.0001). In multivariable analysis, arrest rate was not associated with center volume (odds ratio, 1.06; 95% confidence interval, 0.71 to 1.57 in low- versus high-volume centers). However, mortality after cardiac arrest was higher in low-volume centers (odds ratio, 2.00; 95% confidence interval, 1.52 to 2.63). This association was present for both high- and low-complexity operations. Conclusions Cardiac arrest carries a significant mortality risk across the stratum of procedural complexity. Although arrest rates are not associated with center volume, lower-volume centers have increased mortality after cardiac arrest. Further study of mechanisms to prevent cardiac arrest and to reduce mortality in those with an arrest is warranted. PMID:25443018

One-male units and clans in a colony of hamadryas baboons (Papio hamadryas hamadryas): effect of male number and clan cohesion on feeding success.

PubMed

Colmenares, Fernando; Esteban, Marta M; Zaragoza, Félix

2006-01-01

In the multilevel societies of hamadryas baboons, adult males can be attached to single one-male units (OMUs) or to clans containing several such OMUs. This paper examines the effect of male number and rivalry between males within a clan on their ability to compete for access to a clumped food resource. The data come from a study of a multilevel colony of hamadryas baboons (Papio hamadryas hamadryas) housed at the Madrid Zoo. The colony consisted of 12 harem-holding males and 40 sexually mature females, and was organized into five single OMUs and two clans (containing three and four OMUs, respectively). The top-ranking male of one of the clans was removed and later reintroduced, so the study involved an analysis of the composition of clans and OMUs and of the males' use of the feeding area across three study periods: preseparation, separation, and reintroduction. The findings reported indicate that both males and females derived clear advantages in the context of contest competition for access to clumped food if they were members of clans, because the males and females from large clans had a feeding advantage over those from smaller clans and single OMUs. Furthermore, rivalry among males within the clan reduced their ability to compete for food against males outside their clan. This paper provides empirical evidence for one of the potential advantages that hamadryas males may enjoy if they are attached to clans, and also provides empirical support for the general hypothesis that a large number of males in a group may provide fitness-related benefits to the group members, provided they are able to cooperate with each other. 2006 Wiley-Liss, Inc.

Cardiac rehabilitation

MedlinePlus

... page: //medlineplus.gov/ency/patientinstructions/000791.htm Cardiac rehabilitation To use the sharing features on this page, please enable JavaScript. Cardiac rehabilitation (rehab) is a program that helps you live ...

Cumulative Burden of Myocardial Dysfunction in Cardiac Amyloidosis Assessed Using Four-Chamber Cardiac Strain.

PubMed

Kado, Yuichiro; Obokata, Masaru; Nagata, Yasufumi; Ishizu, Tomoko; Addetia, Karima; Aonuma, Kazutaka; Kurabayashi, Masahiko; Lang, Roberto M; Takeuchi, Masaaki; Otsuji, Yutaka

2016-11-01

The aim of this study was to test the hypothesis that prognosis in patients with cardiac amyloidosis is closely coupled with amyloid burden in all four cardiac chambers. The goal was to evaluate longitudinal strain (LS) in each cardiac chamber and to determine whether LS in specific cardiac chambers is preferentially associated with prognosis over conventional two-dimensional echocardiographic parameters in patients with cardiac amyloidosis. Patients with two phenotypes of left ventricular (LV) hypertrophy (cardiac amyloidosis in 55 patients and nonobstructive hypertrophic cardiomyopathy in 40 patients) and 55 healthy subjects were retrospectively enrolled for the simultaneous assessment of LS of all four cardiac chambers in the apical four-chamber view. Patients with cardiac amyloidosis were followed up to record major adverse cardiovascular events, including cardiac death, heart transplantation, nonfatal myocardial infarction, ventricular tachyarrhythmia, and exacerbation of heart failure requiring hospitalization. LS in each chamber was significantly depressed in patients with both LV hypertrophy phenotypes compared with healthy subjects. Right atrial LS was significantly lower in patients with cardiac amyloidosis than those with nonobstructive hypertrophic cardiomyopathy after adjusting for LV ejection fraction and LV mass index. During a median follow-up period of 10 months, major adverse cardiovascular events developed in 22 patients with cardiac amyloidosis. Four-chamber LS were significantly associated with major adverse cardiovascular events, with incremental value over traditional echocardiographic parameters. Cardiac amyloidosis involves all cardiac chambers, and thus, chamber-specific strain analysis may be useful to assess the total cumulative burden of cardiac dysfunction. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Applying the termination of resuscitation rules to out-of-hospital cardiac arrests of both cardiac and non-cardiac etiologies: a prospective cohort study.

PubMed

Kashiura, Masahiro; Hamabe, Yuichi; Akashi, Akiko; Sakurai, Atsushi; Tahara, Yoshio; Yonemoto, Naohiro; Nagao, Ken; Yaguchi, Arino; Morimura, Naoto

2016-03-01

The 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation recommend Basic Life Support (BLS) and Advanced Life Support (ALS) rules for termination of resuscitation (TOR). However, it is unclear whether the TOR rules are valid for out-of-hospital cardiac arrests (OHCAs) of both cardiac and non-cardiac etiologies. In this study, we validated the TOR rules for OHCA resulting from both etiologies. This was a prospective multicenter observational study of OHCA patients transported to 67 emergency hospitals between January 2012 and March 2013 in the Kanto region of Japan. We calculated the specificity and positive predictive value (PPV) for neurologically unfavorable outcomes at one month in patients with OHCA of cardiac and non-cardiac etiologies. Of 11,505 eligible cases, 6,138 and 5,367 cases were of cardiac and non-cardiac etiology, respectively. BLS was performed on 2,818 and 2,606 patients with OHCA of cardiac and non-cardiac etiology, respectively. ALS was performed on 3,320 and 2,761 patients with OHCA of cardiac and non-cardiac etiology, respectively. The diagnostic accuracy of the TOR rules for predicting unfavorable outcomes in patients with OHCA of cardiac etiology who received BLS included a specificity of 0.985 (95% confidence interval [CI]: 0.956-0.997) and a PPV of 0.999 (95% CI: 0.996-1.000). In patients with OHCA from cardiac etiologies who received ALS, the TOR rules had a specificity of 0.963 (95% CI: 0.896-0.992) and a PPV of 0.997 (95% CI: 0.991-0.999). In patients with OHCA from non-cardiac etiologies who received BLS, the specificity was 0.915 (95% CI: 0.796-0.976) and PPV was 0.998 (95% CI: 0.995-0.999). For patients with OHCA from non-cardiac etiologies who received ALS, the specificity was 0.833 (95% CI: 0.586-0.964) and PPV was 0.996 (95% CI: 0.988-0.999). Both TOR rules have high specificity and PPV in patients with OHCA from cardiac etiologies. For patients with OHCA from non-cardiac etiologies, the rules had a high

Cardiac arrest

MedlinePlus

... it does not necessarily cause death. Sometimes a heart attack can trigger a cardiac arrest, however. Cardiac arrest is caused by a problem with the heart's electrical system, such as: Ventricular fibrillation (VF) . When ...

Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture, Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio)

PubMed Central

Atkinson, Elizabeth G.; Rogers, Jeffrey; Mahaney, Michael C.; Cox, Laura A.; Cheverud, James M.

2015-01-01

Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical–cortical connectivity, and gyrification’s potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution. PMID:25873632

Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative Cardiac Risk Assessments.

PubMed

Liu, Jason B; Liu, Yaoming; Cohen, Mark E; Ko, Clifford Y; Sweitzer, Bobbie J

2018-02-01

Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk. Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation. Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17). A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations.

A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

PubMed

Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

2015-12-02

Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. Copyright © 2015, American Association for the Advancement of Science.

A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

PubMed Central

Nguyen, Annalee W.; Wagner, Ellen K.; Laber, Joshua R.; Goodfield, Laura L.; Smallridge, William E.; Harvill, Eric T.; Papin, James F.; Wolf, Roman F.; Padlan, Eduardo A.; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A.

2016-01-01

In spite of wide-spread vaccination, pertussis rates are rising in industrialized countries and remain high world-wide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. Here, we humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human IgG1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the B. pertussis-induced rise in white blood cell count and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated but not control animals experienced a blunted rise in white blood cell count and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

[Cardiac Anaesthesia: Anaesthesiological Management].

PubMed

Renner, Jochen; Bein, Berthold; Broch, Ole

2018-05-01

The anaesthesiological management of patients scheduled for cardiac surgery has been refined distinctively over the last decade due to different reasons. The continuing growth of the elderly patient population and the increasing number of combined cardiac surgery procedures in octogenarians on the one hand are one aspect. The rapid development of minimally invasive cardiac surgery and the enhancements in mechanical, artificial heart assist devices on the other hand can be seen as additional decisive factors. All of these innovations in the field of cardiac surgery implicate further enhancements regarding the anaesthesiological management. This review article addresses the following subareas of cardiac anaesthesia: significance of pharmacological myocardial protection, anaesthetic management during cardiopulmonary bypass, importance of "Enhanced Recovery After Cardiac Surgery"-protocols as well as innovations in the field of minimally invasive cardiac surgery like transcatheter aortic valve implantation. Georg Thieme Verlag KG Stuttgart · New York.

Norlestrin-induced pseudopregnancy in the baboon. Effects on blood coagulation and endocrine glands during attempted production of Sheehan's syndrome.

PubMed

Klaus, H; Rao, P S; Gaston, L W; Russfield, A B

1975-02-15

Production of Sheehan's syndrome was attempted. As it was not possible to obtain pregnant baboons initially, pseudopregnancy was induced with norlestrin, 2.k mg., for 3 and 4 months, respectively. Sheehan's syndrome was not produced with massive hypovolemic shock but failure to obtain true pregnancy has given serendipitous information on the long-term action of norlestrin on the pituitary and its target organs. Unusual abundance of prolactin acidophils and decrease of growth hormone acidophils was found. Further studies will be necessary to show the possible significance of these findings. As fibrin degradation products did not appear in the serum, we can make no inference about the necessity of intravascular coagulation for the production of Sheehan's phenomenon. Finally one animal became pregnant. Sheehan's phenomenon was not produced in her despite induction of intrapartum hypovolemic shock. Histologic findings in her pituitary resemble those of the pseudopregnant animals.

Cardiac Endothelial Cell Transcriptome.

PubMed

Lother, Achim; Bergemann, Stella; Deng, Lisa; Moser, Martin; Bode, Christoph; Hein, Lutz

2018-03-01

Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the Meox2 / Tcf15, Fabp4 , and Cd36 signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis. The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation. © 2018 American Heart Association, Inc.

Association between dental caries and out-of-hospital cardiac arrests of cardiac origin in Japan.

PubMed

Suematsu, Yasunori; Miura, Shin-Ichiro; Zhang, Bo; Uehara, Yoshinari; Ogawa, Masahiro; Yonemoto, Naohiro; Nonogi, Hiroshi; Nagao, Ken; Kimura, Takeshi; Saku, Keijiro

2016-04-01

Oral infection contributes to atherosclerosis and coronary heart disease. We hypothesized that dental caries may be associated with out-of-hospital cardiac arrests (OHCA) of cardiac origin, but not non-cardiac origin. We compared the age-adjusted incidence of OHCA (785,591 cases of OHCA: 55.4% of cardiac origin and 44.6% of non-cardiac origin) to the age-adjusted prevalence of dental caries between 2005 and 2011 in the 47 prefectures of Japan. In both the total population and males over 65 years, the number of cases of dental caries was significantly associated with the number of OHCA of total and cardiac origin from 2005 to 2011, but not those of non-cardiac origin. In the total population, the age-adjusted prevalence of dental caries was not significantly associated with the age-adjusted incidence of OHCA (total OHCA: r correlation coefficient=0.22, p=0.14; OHCA of cardiac origin: r=0.25, p=0.09; OHCA of non-cardiac origin: r=-0.002, p=0.99). Among male patients over 65 years, the age-adjusted prevalence of dental caries was significantly associated with OHCA of total and cardiac origin, but not non-cardiac origin (total OHCA: r=0.47, p<0.001; OHCA of cardiac origin: r=0.37, p=0.01; OHCA of non-cardiac origin: r=0.28, p=0.054). While oral hygiene is important in all age groups, it may be particularly associated with OHCAs of cardiac origin in males over 65 years. Copyright © 2015. Published by Elsevier Ltd.

Cardiac Metastasis from Invasive Thymoma Via the Superior Vena Cava: Cardiac MRI Findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dursun, Memduh, E-mail: memduhdursun@yahoo.com; Sarvar, Sadik; Cekrezi, Bledi

2008-07-15

Cardiac tumors are rare, and metastatic deposits are more common than primary cardiac tumors. We present cardiac magnetic resonance imaging (MRI) findings of a 50-year-old woman with invasive thymoma. Cardiac MRI revealed a heterogeneous, lobulated anterior mediastinal mass invading the superior vena cava and extending to the right atrium. In cine images there was no invasion to the right atrial wall.

Transthyretin Cardiac Amyloidosis.

PubMed

Mankad, Anit K; Shah, Keyur B

2017-08-24

Transthyretin (TTR)-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive, hypertrophic heart disease and may go undiagnosed. Transthyretin-derived amyloidosis accounts for 18% of all cases of cardiac amyloidosis. Thus, the study's purpose is to provide a comprehensive review of transthyretin cardiac amyloidosis. Wild-type transthyretin (ATTRwt) protein causes cardiac amyloidosis sporadically, with 25 to 36% of the population older than 80 years of age are at risk to develop a slowly progressive, infiltrative amyloid cardiomyopathy secondary to ATTRwt. In contrast, hereditary amyloidosis (ATTRm) is an autosomal dominant inherited disease associated with more than 100 point mutations in the transthyretin gene and has a tendency to affect the heart and nervous system. Up to 4% of African-Americans carry the Val122Ile mutation in the transthyretin gene, the most prevalent cause of hereditary cardiac amyloidosis in the USA. Identifying transthyretin cardiac amyloidosis requires increased awareness of the prevalence, signs and symptoms, and diagnostic tools available for discrimination of this progressive form of cardiomyopathy associated with left ventricular hypertrophy. While there are no FDA-approved medical treatments, investigation is underway on agents to reduce circulating mutated transthyretin.

Cardiac rhabdomyosarcoma

PubMed Central

Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

2001-01-01

Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical staining confirmed cardiac rhabdomyosarcoma with metastatic spread to the lungs. Difficulty in diagnosing and treating cardiac tumours is discussed. PMID:20428274

Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

PubMed

Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

2016-08-01

Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy. Copyright © 2016 American Federation for Medical Research.

[Cardiac failure in endocrine diseases].

PubMed

Hashizume, K

1993-05-01

Several endocrine diseases show the symptoms of cardiac failure. Among them, patients with acromegaly show a specific cardiomyopathy which results in a severe left-sided cardiac failure. Hypoparathyroidism also induces cardiac failure, which is resulted from hypocalcemia and low levels of serum parathyroid hormone. In the cases of hypothyroidism, the patients with myxedemal coma show a severe cardiac failure, which is characterized by disturbance of central nervous system, renal function, and cardiac function. In the patients with thyroid crisis (storm), the cardiac failure comes from the great reduction of cardiac output with dehydration. The reduction of circulation volume, observed in the patients with pheochromocytoma easily induces cardiac failure (shock) just after the removal of adrenal tumor. In patients with malignant carcinoid syndrome, right-sided ventricular failure which may be occurred through the actions of biogenic amines is observed.

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis.

PubMed

Treibel, Thomas A; Bandula, Steve; Fontana, Marianna; White, Steven K; Gilbertson, Janet A; Herrey, Anna S; Gillmore, Julian D; Punwani, Shonit; Hawkins, Philip N; Taylor, Stuart A; Moon, James C

2015-01-01

Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis

PubMed Central

Treibel, Thomas A.; Bandula, Steve; Fontana, Marianna; White, Steven K.; Gilbertson, Janet A.; Herrey, Anna S.; Gillmore, Julian D.; Punwani, Shonit; Hawkins, Philip N.; Taylor, Stuart A.; Moon, James C.

2015-01-01

Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Conclusion Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. PMID:26209459

Cardiac Autonomic Balance vs. Cardiac Regulatory Capacity

PubMed Central

Berntson, Gary G.; Norman, Greg J.; Hawkley, Louise C.; Cacioppo, John T.

2013-01-01

The concept of autonomic balance views autonomic states along a bipolar continuum from sympathetic (S) to parasympathetic (P) dominance, whereas regulatory capacity models emphasize overall autonomic flexibility as a marker of the capacity for regulation. These two concepts were evaluated for their utility in characterizing patterns of autonomic control. Measures of P (high frequency heart rate variability, HF) and S (pre-ejection period, PEP) cardiac control were obtained. A measure of cardiac autonomic balance (CAB) was derived as the difference in the normalized P index minus the S index, and a measure of cardiac autonomic regulation (CAR) was derived as the normalized P index plus the S index. Results reveal that CAR, but not CAB, was a significant predictor of the prior occurrence of a myocardial infarction, net of demographic and other variables, whereas CAB, but not CAR, was a significant predictor of concurrent diabetes. PMID:18282204

Effect of body mass distribution on the ontogeny of positional behaviors in non-human primates: Longitudinal follow-up of infant captive olive baboons (Papio anubis).

PubMed

Druelle, François; Aerts, Peter; Berillon, Gilles

2016-11-01

The diversity of primates' positional capabilities is unique among mammals. Indeed, they exhibit a daily repertoire composed of various locomotor and postural modes that may be linked to their particular morphological pattern. Because ontogeny undergoes parallel behavioral and morphological modifications, it may be useful to investigate the biomechanical consequences of the changing body shape. We, therefore, collected accurate quantitative and longitudinal data on positional behaviors, body mass distribution patterns, activities, and environment on a sample of six infant olive baboons, Papio anubis. These baboons are kept at the Primatology Station of the CNRS, France, where they live within the same social group. Individual behaviors were quantified using the focal sampling method. The body mass distribution was estimated according to a geometric model based on direct external measurements. Multivariate analysis enabled us to analyze the interactions between the data. Our results show that body mass distribution changes together with the ontogenetic changes in positional behaviors. At an early age, individuals have distally heavy segment masses in the limbs and an important fraction of the behavioral repertoire involves efficient grasping abilities. At the end of infancy, the same individuals have relatively more mass in proximal segments of the limbs and the proportion of quadrupedal walking is significantly higher while other climbing and suspensory behaviors decreased substantially. The present study experimentally confirms the association between body mass distribution and the positional repertoire of primates. These relationships, when interpreted in the context of basic biomechanical concepts, may improve our understanding of primate locomotion. We discuss further the implications of these functional relationships when modeling the evolutionary pathway of primates. Am. J. Primatol. 78:1201-1221, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

Cardiac conduction system

MedlinePlus Videos and Cool Tools

... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system's electrical activity in the heart.

Continuous cardiac output measurement - Aspects of Doppler frequency analysis

NASA Technical Reports Server (NTRS)

Mackay, R. S.; Hechtman, H. B.

1975-01-01

From the suprasternal notch blood flow velocity in the aorta can be measured non-invasively by a Doppler probe. Integration over systole after frequency analysis gives a measure of stroke volume if a separate diameter observation is incorporated. Frequency analysis by a zero crossing counter or by a set of parallel phaselock loops was less effective than a set of bandpass filters. Observations on dogs, baboons and humans before and after exercise or surgery suggest the indications to be useful. Application to judging heart failure by the effect of introducing a volume load is indicated. Changes in output also are measured in freely moving subjects.

Association between a Hospital’s Rate of Cardiac Arrest Incidence and Cardiac Arrest Survival

PubMed Central

Chen, Lena M.; Nallamothu, Brahmajee K.; Spertus, John A.; Li, Yan; Chan, Paul S.

2014-01-01

Context National efforts to measure hospital performance for cardiac arrest have focused on case survival, with the hope of improving survival after cardiac arrest. However, it is plausible that hospitals with high case-survival rates do a poor job of preventing cardiac arrests in the first place. Objective To describe the association between inpatient cardiac arrest incidence and survival rates. Design, Setting, and Patients Within a large, national registry, we identified hospitals with at least 50 adult in-hospital cardiac arrest cases between January 1, 2000 and November 30, 2009. We used multivariable hierarchical regression to evaluate the correlation between a hospital’s cardiac arrest incidence rate and its case-survival rate after adjusting for patient and hospital characteristics. Main Outcome Measure The correlation between a hospital’s incidence rate and case-survival rate for cardiac arrest. Results Of 102,153 cases at 358 hospitals, the median hospital cardiac arrest incidence rate was 4.02 per 1000 admissions (IQR: 2.95 to 5.65 per 1000 admissions), and the median hospital case-survival rate was 18.8% (IQR: 14.5% to 22.6%). In crude analyses, hospitals with higher case-survival rates also had lower cardiac arrest incidence (correlation of -0.16; P=0.003). This relationship persisted after adjusting for patient characteristics (correlation of -0.15; P=0.004). After adjusting for potential mediators of this relationship (i.e., hospital characteristics), the relationship between incidence and case-survival was attenuated (correlation of -0.07; P=0.18). The one modifiable hospital factor that most attenuated this relationship was a hospital’s nurse-to-bed ratio (correlation of -0.12; P=0.03). Conclusions Hospitals with exceptional rates of survival for in-hospital cardiac arrest are also better at preventing cardiac arrests, even after adjusting for patient case-mix. This relationship is partially mediated by measured hospital attributes

Brucella papionis sp. nov., isolated from baboons (Papio spp.)

PubMed Central

Davison, Nicholas; Cloeckaert, Axel; Al Dahouk, Sascha; Zygmunt, Michel S.; Brew, Simon D.; Perrett, Lorraine L.; Koylass, Mark S.; Vergnaud, Gilles; Quance, Christine; Scholz, Holger C.; Dick, Edward J.; Hubbard, Gene; Schlabritz-Loutsevitch, Natalia E.

2014-01-01

Two Gram-negative, non-motile, non-spore-forming coccoid bacteria (strains F8/08-60T and F8/08-61) isolated from clinical specimens obtained from baboons (Papio spp.) that had delivered stillborn offspring were subjected to a polyphasic taxonomic study. On the basis of 16S rRNA gene sequence similarities, both strains, which possessed identical sequences, were assigned to the genus Brucella. This placement was confirmed by extended multilocus sequence analysis (MLSA), where both strains possessed identical sequences, and whole-genome sequencing of a representative isolate. All of the above analyses suggested that the two strains represent a novel lineage within the genus Brucella. The strains also possessed a unique profile when subjected to the phenotyping approach classically used to separate species of the genus Brucella, reacting only with Brucella A monospecific antiserum, being sensitive to the dyes thionin and fuchsin, being lysed by bacteriophage Wb, Bk2 and Fi phage at routine test dilution (RTD) but only partially sensitive to bacteriophage Tb, and with no requirement for CO2 and no production of H2S but strong urease activity. Biochemical profiling revealed a pattern of enzyme activity and metabolic capabilities distinct from existing species of the genus Brucella. Molecular analysis of the omp2 locus genes showed that both strains had a novel combination of two highly similar omp2b gene copies. The two strains shared a unique fingerprint profile of the multiple-copy Brucella-specific element IS711. Like MLSA, a multilocus variable number of tandem repeat analysis (MLVA) showed that the isolates clustered together very closely, but represent a distinct group within the genus Brucella. Isolates F8/08-60T and F8/08-61 could be distinguished clearly from all known species of the genus Brucellaand their biovars by both phenotypic and molecular properties. Therefore, by applying the species concept for the genus Brucellasuggested by the ICSP Subcommittee on

Measuring fecal testosterone in females and fecal estrogens in males: comparison of RIA and LC/MS/MS methods for wild baboons (Papio cynocephalus)

PubMed Central

Gesquiere, Laurence R.; Ziegler, Toni E.; Chen, Patricia A.; Epstein, Katherine A.; Alberts, Susan C.; Altmann, Jeanne

2014-01-01

The development of non-invasive methods, particularly fecal determination, has made possible the assessment of hormone concentrations in wild animal populations. However, measuring fecal metabolites needs careful validation for each species and for each sex. We investigated whether radioimmunoassays (RIAs) previously used to measure fecal testosterone (fT) in male baboons and fecal estrogens (fE) in female baboons were well suited to measure these hormones in the opposite sex. We compared fE and fT concentrations determined by RIA to those measured by liquid chromatography combined with triple quadropole mass spectrometry (LC/MS/MS), a highly specific method. Additionally, we conducted a biological validation to assure that the measurements of fecal concentrations reflected physiological levels of the hormone of interest. Several tests produced expected results that led us to conclude that our RIAs can reliably measure fT and fE in both sexes, and that within-sex comparisons of these measures are valid: (i) fTRIA were significantly correlated to fTLC/MS/MS for both sexes; (ii) fTRIA were higher in adult than in immature males; (iii) fTRIA were higher in pregnant than non-pregnant females; (iv) fERIA were correlated with 17β-estradiol (fE2) and with estrone (fE1) determined by LC/MS/MS in pregnant females; (v) fERIA were significantly correlated with fE2 in non-pregnant females and nearly significantly correlated in males; (vi) fERIA were higher in adult males than in immature males. fERIA were higher in females than in males, as predicted, but unexpectedly, fTRIA were higher in females than in males, suggesting a difference in steroid metabolism in the two sexes; consequently, we conclude that while within-sex comparisons are valid, fTRIA should not be used for intersexual comparisons. Our results should open the field to important additional studies, as to date the roles of testosterone in females and estrogens in males have been little investigated. PMID

Pregnancy as a cardiac stress model

PubMed Central

Chung, Eunhee; Leinwand, Leslie A.

2014-01-01

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

About Cardiac Arrest

MedlinePlus

... Options for Heart Failure Living With HF and Advanced HF High Blood Pressure ... Updated:Mar 10,2017 What is cardiac arrest? Cardiac arrest is the abrupt loss of heart function in a person who may or may not ...

Marketing cardiac CT programs.

PubMed

Scott, Jason

2010-01-01

There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

Cardiac Fibroblast: The Renaissance Cell

PubMed Central

Souders, Colby A.; Bowers, Stephanie L.K.; Baudino, Troy A.

2012-01-01

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. While a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart. PMID:19959782

Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kan, Lijuan; Thayer, Patrick; Fan, Huimin

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increasedmore » expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.« less

Sacral neuromodulation and cardiac pacemakers.

PubMed

Roth, Ted M

2010-08-01

Potential for cross-talk between cardiac pacemakers and sacral neuromodulation remains speculative. We present a case series of patients with cardiac pacemakers who underwent staged Interstim (Medtronic, Minneapolis, MN) implantation and patients who had pulse generator implantation who later required cardiac pacemakers. No cross-talk was demonstrated in either group. Sacral neuromodulation appears to be safe in the setting of cardiac pacemakers without cardioversion/defibrillation technology.

Cardiac perioperative complications in noncardiac surgery.

PubMed

Radovanović, Dragana; Kolak, Radmila; Stokić, Aleksandar; Radovanović, Zoran; Jovanović, Gordana

2008-01-01

Anesthesiologists are confronted with an increasing population of patients undergoing noncardiac surgery who are at risk for cardiac complications in the perioperative period. Perioperative cardiac complications are responsible for significant mortality and morbidity. The aim of the present study was to determine the incidence of perioperative (operative and postoperative) cardiac complications and correlations between the incidence of perioperative cardiac complications and type of surgical procedure, age, presence of concurrent deseases. A total of 100 patients with cardiac diseases undergoing noncardiac surgery were included in the prospective study (Group A 50 patients undergoing intraperitoneal surgery and Group B 50 patients undergoing breast and thyroid surgery). The patients were followed up during the perioperative period and after surgery until leaving hospital to assess the occurrence of cardiac events. Cardiac complications (systemic arterial hypertension, systemic arterial hypotension, abnormalities of cardiac conduction and cardiac rhythm, perioperative myocardial ischemia and acute myocardial infarction) occurred in 64% of the patients. One of the 100 patients (1%) had postoperative myocardial infarction which was fatal. Systemic arterial hypertension occured in 57% of patients intraoperatively and 33% postoperatively, abnormalities of cardiac rhythm in 31% of patients intraoperatively and 17% postoperatively, perioperative myocardial ischemia in 23% of patients intraoperatively and 11% of postoperatively. The most often cardiac complications were systemic arterial hypertension, abnormalities of cardiac rhythm and perioperative mvocardial ischemia. Factors independently associated with the incidence of cardiac complications included the type of surgical procedure, advanced age, duration of anaesthesia and surgery, abnormal preoperative electrocardiogram, abnormal preoperative chest radiography and diabetes.

Asymmetries in the individual distinctiveness and maternal recognition of infant contact calls and distress screams in baboons

PubMed Central

Rendall, Drew; Notman, Hugh; Owren, Michael J.

2009-01-01

A key component of nonhuman primate vocal communication is the production and recognition of clear cues to social identity that function in the management of these species’ individualistic social relationships. However, it remains unclear how ubiquitous such identity cues are across call types and age-sex classes and what the underlying vocal production mechanisms responsible might be. This study focused on two structurally distinct call types produced by infant baboons in contexts that place a similar functional premium on communicating clear cues to caller identity: (1) contact calls produced when physically separated from, and attempting to relocate, mothers and (2) distress screams produced when aggressively attacked by other group members. Acoustic analyses and field experiments were conducted to examine individual differentiation in single vocalizations of each type and to test mothers’ ability to recognize infant calls. Both call types showed statistically significant individual differentiation, but the magnitude of the differentiation was substantially higher in contact calls. Mothers readily discriminated own-offspring contact calls from those of familiar but unrelated infants, but did not do so when it came to distress screams. Several possible explanations for these asymmetries in call differentiation and recognition are considered. PMID:19275336

Hybrid options for treating cardiac disease.

PubMed

Umakanthan, Ramanan; Leacche, Marzia; Zhao, David X; Gallion, Anna H; Mishra, Prabodh C; Byrne, John G

2011-01-01

The options for treating heart disease have greatly expanded during the course of the last 2 1/2 decades with the advent of hybrid technology. The hybrid option for treating cardiac disease implies using the technology of both interventional cardiology and cardiac surgery to treat cardiac disease. This rapidly developing technology has given rise to new and creative techniques to treat cardiac disease involving coronary artery disease, coronary artery disease and cardiac valve disease, and atrial fibrillation. It has also led to the establishment of new procedural suites called hybrid operating rooms that facilitate the integration of technologies of interventional cardiology catheterization laboratories with those of cardiac surgery operating rooms. The development of hybrid options for treating cardiac disease has also greatly augmented teamwork and collaboration between interventional cardiologists and cardiac surgeons. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiac differentiation of cardiosphere-derived cells in scaffolds mimicking morphology of the cardiac extracellular matrix.

PubMed

Xu, Yanyi; Patnaik, Sourav; Guo, Xiaolei; Li, Zhenqing; Lo, Wilson; Butler, Ryan; Claude, Andrew; Liu, Zhenguo; Zhang, Ge; Liao, Jun; Anderson, Peter M; Guan, Jianjun

2014-08-01

Stem cell therapy has the potential to regenerate heart tissue after myocardial infarction (MI). The regeneration is dependent upon cardiac differentiation of the delivered stem cells. We hypothesized that timing of the stem cell delivery determines the extent of cardiac differentiation as cell differentiation is dependent on matrix properties such as biomechanics, structure and morphology, and these properties in cardiac extracellular matrix (ECM) continuously vary with time after MI. In order to elucidate the relationship between ECM properties and cardiac differentiation, we created an in vitro model based on ECM-mimicking fibers and a type of cardiac progenitor cell, cardiosphere-derived cells (CDCs). A simultaneous fiber electrospinning and cell electrospraying technique was utilized to fabricate constructs. By blending a highly soft hydrogel with a relatively stiff polyurethane and modulating fabrication parameters, tissue constructs with similar cell adhesion property but different global modulus, single fiber modulus, fiber density and fiber alignment were achieved. The CDCs remained alive within the constructs during a 1week culture period. CDC cardiac differentiation was dependent on the scaffold modulus, fiber volume fraction and fiber alignment. Two constructs with relatively low scaffold modulus, ∼50-60kPa, most significantly directed the CDC differentiation into mature cardiomyocytes as evidenced by gene expressions of cardiac troponin T (cTnT), calcium channel (CACNA1c) and cardiac myosin heavy chain (MYH6), and protein expressions of cardiac troponin I (cTnI) and connexin 43 (CX43). Of these two low-modulus constructs, the extent of differentiation was greater for lower fiber alignment and higher fiber volume fraction. These results suggest that cardiac ECM properties may have an effect on cardiac differentiation of delivered stem cells. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cardiac rhythm management devices

PubMed

Stevenson, Irene; Voskoboinik, Alex

2018-05-01

The last decade has seen ongoing evolution and use of cardiac rhythm management devices, including pacemakers, cardiac resynchronisation therapy, implantable cardioverter defibrillators and loop recorders. General practitioners are increasingly involved in follow-up and management of patients with these devices. The aim of this article is to provide an overview of different cardiac rhythm management devices, including their role, implant procedure, post-procedural care, potential complications and follow‑up. We also include practical advice for patients regarding driving, exercise, sexual intimacy and precautions with regards to electromagnetic interference. Cardiac rhythm management devices perform many functions, including bradycardia pacing, monitoring for arrhythmias, cardiac resynchronisation for heart failure, defibrillation and anti-tachycardia pacing for tachyarrhythmias. Concerns regarding potential device-related complications should be discussed with the implanting physician. In the post-implant period, patients with cardiac rhythm management devices can expect to lead normal, active lives. However, caution must occasionally be exercised in certain situations, such as near appliances with electromagnetic interference. Future innovations will move away from transvenous leads to leadless designs with combinations of different components on a 'modular' basis according to the function required.

Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis

PubMed Central

Warfel, Jason M.; Zimmerman, Lindsey I.

2015-01-01

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection. PMID:26561389

Cardiac Dysautonomia in Huntington's Disease.

PubMed

Abildtrup, Mads; Shattock, Michael

2013-01-01

Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

PubMed

Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

2016-08-04

Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We

Diagnostic value of quantitative assessment of cardiac 18F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis.

PubMed

Lebasnier, Adrien; Legallois, Damien; Bienvenu, Boris; Bergot, Emmanuel; Desmonts, Cédric; Zalcman, Gérard; Agostini, Denis; Manrique, Alain

2018-06-01

The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18 F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min -1 )/global Ki (min -1 ) was determined using a validated software (Carimas ® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18 F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. Our results suggest that quantitative analysis of cardiac dynamic 18 F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

Maternal cardiac metabolism in pregnancy

PubMed Central

Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

Ethical Issues in Cardiac Surgery

PubMed Central

Kavarana, Minoo N.; Sade, Robert M.

2012-01-01

While ethical behavior has always been part of cardiac surgical practice, ethical deliberation has only recently become an important component of cardiac surgical practice. Issues such as informed consent, conflict of interest, and professional self-regulation, among many others, have increasingly attracted the attention of cardiac surgeons. This review covers several broad topics of interest to cardiac surgeons and cardiologists, and treats several other topics more briefly. There is much uncertainty about what the future holds for cardiac surgical practice, research, and culture, and we discuss the background of ethical issues to serve as a platform for envisioning what is to come. PMID:22642634

Biomechanics of Early Cardiac Development

PubMed Central

Goenezen, Sevan; Rennie, Monique Y.

2012-01-01

Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming. PMID:22760547

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee.

PubMed

González-Alvarez, Rafael; Garza-Rodríguez, María de Lourdes; Delgado-Enciso, Iván; Treviño-Alvarado, Víctor Manuel; Canales-Del-Castillo, Ricardo; Martínez-De-Villarreal, Laura Elia; Lugo-Trampe, Ángel; Tejero, María Elizabeth; Schlabritz-Loutsevitch, Natalia E; Rocha-Pizaña, María Del Refugio; Cole, Shelley A; Reséndez-Pérez, Diana; Moises-Alvarez, Mario; Comuzzie, Anthony G; Barrera-Saldaña, Hugo Alberto; Garza-Guajardo, Raquel; Barboza-Quintana, Oralia; Rodríguez-Sánchez, Irám Pablo

2015-06-12

Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Cardiac Arrest Resuscitation.

PubMed

Guyette, Francis X; Reynolds, Joshua C; Frisch, Adam

2015-08-01

Cardiac arrest is a dynamic disease that tests the multitasking and leadership abilities of emergency physicians. Providers must simultaneously manage the logistics of resuscitation while searching for the cause of cardiac arrest. The astute clinician will also realize that he or she is orchestrating only one portion of a larger series of events, each of which directly affects patient outcomes. Resuscitation science is rapidly evolving, and emergency providers must be familiar with the latest evidence and controversies surrounding resuscitative techniques. This article reviews evidence, discusses controversies, and offers strategies to provide quality cardiac arrest resuscitation. Copyright © 2015 Elsevier Inc. All rights reserved.

The frequency of anesthesia-related cardiac arrests in patients with congenital heart disease undergoing cardiac surgery.

PubMed

Odegard, Kirsten C; DiNardo, James A; Kussman, Barry D; Shukla, Avinash; Harrington, James; Casta, Al; McGowan, Francis X; Hickey, Paul R; Bacha, Emile A; Thiagarajan, Ravi R; Laussen, Peter C

2007-08-01

The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center. Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related. There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist. The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.

Mesenchymal-endothelial-transition contributes to cardiac neovascularization

PubMed Central

Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

2014-01-01

Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

Survival and surgical outcomes of cardiac cancer of the remnant stomach in comparison with primary cardiac cancer

PubMed Central

2014-01-01

Background Although cardiac cancer of the remnant stomach and primary cardiac cancer both occur in the same position, their clinical characteristics and outcomes have not been compared previously. The objective of this study was designed to evaluate the prognosis of cardiac cancer of the remnant stomach in comparison with primary cardiac cancer. Methods In this retrospective comparative study, clinical data and prognosis were compared in 48 patients with cardiac cancer of the remnant stomach and 96 patients with primary cardiac cancer who underwent radical resection from January 1995 to June 2007. Clinicopathologic characteristics, survival times, mortality, and complications were analyzed. Results The 5-year survival rate was significantly higher in patients with primary cardiac cancer than in those with cardiac cancer of the remnant stomach (28.4% vs. 16.7%, P = 0.035). Serosal invasion, lymph node metastasis and tumor location were independent prognostic factors for survival. Subgroup analysis, however, showed similar survival rates in patients with primary cardiac cancer and cardiac cancer of the remnant stomach without serosal invasion (25.0% vs. 43.8%, P = 0.214) and without lymph node metastasis (25.0% vs. 38.8%, P = 0.255), as well as similar complication rates (20.8% vs. 11.5%, P = 0.138). Conclusion Although the survival rates after radical resection in patients with cardiac cancer of the remnant stomach were poorer than in those with primary cardiac cancer, they were similar in survival rates when patients without serosal invasion or lymph node metastasis. Therefore, early detection is an important way to improve overall survival in cardiac cancer of the remnant stomach. PMID:24468299

Automatic segmentation and quantification of the cardiac structures from non-contrast-enhanced cardiac CT scans

NASA Astrophysics Data System (ADS)

Shahzad, Rahil; Bos, Daniel; Budde, Ricardo P. J.; Pellikaan, Karlijn; Niessen, Wiro J.; van der Lugt, Aad; van Walsum, Theo

2017-05-01

Early structural changes to the heart, including the chambers and the coronary arteries, provide important information on pre-clinical heart disease like cardiac failure. Currently, contrast-enhanced cardiac computed tomography angiography (CCTA) is the preferred modality for the visualization of the cardiac chambers and the coronaries. In clinical practice not every patient undergoes a CCTA scan; many patients receive only a non-contrast-enhanced calcium scoring CT scan (CTCS), which has less radiation dose and does not require the administration of contrast agent. Quantifying cardiac structures in such images is challenging, as they lack the contrast present in CCTA scans. Such quantification would however be relevant, as it enables population based studies with only a CTCS scan. The purpose of this work is therefore to investigate the feasibility of automatic segmentation and quantification of cardiac structures viz whole heart, left atrium, left ventricle, right atrium, right ventricle and aortic root from CTCS scans. A fully automatic multi-atlas-based segmentation approach is used to segment the cardiac structures. Results show that the segmentation overlap between the automatic method and that of the reference standard have a Dice similarity coefficient of 0.91 on average for the cardiac chambers. The mean surface-to-surface distance error over all the cardiac structures is 1.4+/- 1.7 mm. The automatically obtained cardiac chamber volumes using the CTCS scans have an excellent correlation when compared to the volumes in corresponding CCTA scans, a Pearson correlation coefficient (R) of 0.95 is obtained. Our fully automatic method enables large-scale assessment of cardiac structures on non-contrast-enhanced CT scans.

Behavioural processes in social context: female abductions, male herding and female grooming in hamadryas baboons.

PubMed

Polo, Pablo; Colmenares, Fernando

2012-06-01

The formation of bonds between strangers is an event that occurs routinely in many social animals, including humans, and, as social bonds in general, they affect the individuals' welfare and biological fitness. The present study was motivated by an interest in the behavioural processes that drive bond formation in a social context of hostility, in which the incumbent partners vary greatly in physical power and reproductive interests, a situation in which individuals of many group-living species find themselves often throughout their lives. We focused on the quantitative analysis of female abductions via male aggressive herding in a nonhuman primate, the hamadryas baboon, in which intersexual bonds are known to be strong. We tested three hypotheses informed by sexual conflict/sexual coercion theory (male herding-as-conditioning and female grooming-as-appeasement) and by socioecological theory (unit size and female competition). The results supported the predictions: males resorted to coercive tactics (aggressive herding) with abducted females, and abducted females elevated the amount of grooming directed at their new unit males; in fact, they escaped from the otherwise negative effect of unit size on female-to-male grooming. These findings reveal that conflicts of interest are natural ingredients underpinning social bonds and that resorting to coercive aggression may be an option especially when partners differ greatly in their physical power. Copyright © 2012 Elsevier B.V. All rights reserved.

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction.

PubMed

Lang, Hongmei; Xiang, Yang; Ai, Zhihua; You, Zhiqing; Jin, Xiaolan; Wan, Yong; Yang, Yongjian

2018-04-20

Excessive salt intake and left ventricular hypertrophy (LVH) are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3) plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction. © 2018 The Author(s). Published by S. Karger AG, Basel.

Cardiac Emergencies in Neurosurgical Patients

PubMed Central

Petropolis, Andrea; Cappellani, Ronald B.

2015-01-01

Perioperative safety concerns are a major area of interest in recent years. Severe cardiac perturbation such as cardiac arrest is one of the most dreaded complications in the intraoperative period; however, little is known about the management of these events in the patients undergoing elective neurosurgery. This special group needs further attention, as it is often neither feasible nor appropriate to apply conventional advanced cardiac life support algorithms in patients undergoing neurosurgery. Factors such as neurosurgical procedure and positioning can also have a significant effect on the occurrence of cardiac arrest. Therefore, the aim of this paper is to describe the various causes and management of cardiac emergencies with special reference to cardiac arrest during elective neurosurgical procedures, including discussion of position-related factors and resuscitative considerations in these situations. This will help to formulate possible guidelines for management of such events. PMID:25692145

Cardiac rehabilitation after myocardial infarction.

PubMed

Contractor, Aashish S

2011-12-01

Cardiac rehabilitation/secondary prevention programs are recognized as integral to the comprehensive care of patients with coronary heart disease (CHD), and as such are recommended as useful and effective (Class I) by the American Heart Association and the American College of Cardiology in the treatment of patients with CHD. The term cardiac rehabilitation refers to coordinated, multifaceted interventions designed to optimize a cardiac patient's physical, psychological, and social functioning, in addition to stabilizing, slowing, or even reversing the progression of the underlying atherosclerotic processes, thereby reducing morbidity and mortality. Cardiac rehabilitation, aims at returning the patient back to normal functioning in a safe and effective manner and to enhance the psychosocial and vocational state of the patient. The program involves education, exercise, risk factor modification and counselling. A meta-analysis based on a review of 48 randomized trials that compared outcomes of exercise-based rehabilitation with usual medical care, showed a reduction of 20% in total mortality and 26% in cardiac mortality rates, with exercise-based rehabilitation compared with usual medical care. Risk stratification helps identify patients who are at increased risk for exercise-related cardiovascular events and who may require more intensive cardiac monitoring in addition to the medical supervision provided for all cardiac rehabilitation program participants. During exercise, the patients' ECG is continuously monitored through telemetry, which serves to optimize the exercise prescription and enhance safety. The safety of cardiac rehabilitation exercise programs is well established, and the occurrence of major cardiovascular events during supervised exercise is extremely low. As hospital stays decrease, cardiac rehabilitation is assuming an increasingly important role in secondary prevention. In contrast with its growing importance internationally, there are very few

Analysis of left atrial respiratory and cardiac motion for cardiac ablation therapy

NASA Astrophysics Data System (ADS)

Rettmann, M. E.; Holmes, D. R.; Johnson, S. B.; Lehmann, H. I.; Robb, R. A.; Packer, D. L.

2015-03-01

Cardiac ablation therapy is often guided by models built from preoperative computed tomography (CT) or magnetic resonance imaging (MRI) scans. One of the challenges in guiding a procedure from a preoperative model is properly synching the preoperative models with cardiac and respiratory motion through computational motion models. In this paper, we describe a methodology for evaluating cardiac and respiratory motion in the left atrium and pulmonary veins of a beating canine heart. Cardiac catheters were used to place metal clips within and near the pulmonary veins and left atrial appendage under fluoroscopic and ultrasound guidance and a contrast-enhanced, 64-slice multidetector CT scan was collected with the clips in place. Each clip was segmented from the CT scan at each of the five phases of the cardiac cycle at both end-inspiration and end-expiration. The centroid of each segmented clip was computed and used to evaluate both cardiac and respiratory motion of the left atrium. A total of three canine studies were completed, with 4 clips analyzed in the first study, 5 clips in the second study, and 2 clips in the third study. Mean respiratory displacement was 0.2+/-1.8 mm in the medial/lateral direction, 4.7+/-4.4 mm in the anterior/posterior direction (moving anterior on inspiration), and 9.0+/-5.0 mm superior/inferior (moving inferior with inspiration). At end inspiration, the mean left atrial cardiac motion at the clip locations was 1.5+/-1.3 mm in the medial/lateral direction, and 2.1+/-2.0 mm in the anterior/posterior and 1.3+/-1.2 mm superior/inferior directions. At end expiration, the mean left atrial cardiac motion at the clip locations was 2.0+/-1.5mm in the medial/lateral direction, 3.0+/-1.8mm in the anterior/posterior direction, and 1.5+/-1.5 mm in the superior/inferior directions.

Xenotransplantation

MedlinePlus

... Consumer Affairs Office of Communication, Outreach and Development Food and Drug Administration 10903 New ... Providers (Biologics) Industry (Biologics) About the Center for Biologics Evaluation and ...

Nuclear cardiac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

Discovery and progress of direct cardiac reprogramming.

PubMed

Kojima, Hidenori; Ieda, Masaki

2017-06-01

Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

Cardiac-CT and Cardiac-MR examinations cost analysis, based on data of four Italian Centers.

PubMed

Centonze, Maurizio; Lorenzin, Giuseppe; Francesconi, Andrea; Cademartiri, Filippo; Casagranda, Giulia; Fusaro, Michele; Ligabue, Guido; Zanetti, Giovanna; Spanti, Demetrio; De Cobelli, Francesco

2016-01-01

To establish the appropriate number of Cardiac-CT and Cardio-MR examinations, to determine an economically justified and sustainable investment in these two technologies, for an exclusive cardiologic use. From July 2013 to July 2014, through a survey in four different Italian Departments of Radiology, data on the costs of Cardiac-CT and Cardiac-MR examinations were collected. For the evaluation of the costs of examinations, it was used an analytical accounting system, considering only the direct costs (consumables, health personnel work time, equipment amortization/maintenance) and other costs (utilities, services, etc.). Indirect costs (general costs) were not assessed. It was made a simulation, assuming an exclusive use of the CT and MR equipments for Cardiac-CT and Cardiac-MR examinations, calculating the annual number necessary to arrive at the Break Even Point (BEP: the point at which cost or expenses and revenue are equal). On the basis of the CT costs, in order to reach the BEP, performing only Cardiac-CT examinations, an average of 2641-2752 examinations/year is needed. The annual time commitment of the Medical Professional to ensure the number of examinations to reach the BEP is 2625-2750 h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent Cardiac-CT Italian Registry, in the period January-June 2011, reports a number of examinations of 3455 patients in 47 different Centers, distributed throughout the whole national territory. With regard to MR, in order to reach the BEP, performing only Cardiac-MR examinations, an average of 2435-3123 examinations/year is needed. The annual time commitment of the Medical Professional to ensure the number of examinations to reach the BEP is 2437-3125 h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent Cardiac-MR Italian Registry reports a number of examinations of 3776 patients in 40 Centers, distributed throughout the whole national territory. This research has

Isolated, broad-based apical diverticulum: cardiac magnetic resonance is a "terminator" of cardiac imaging modality for the evaluation of cardiac apex.

PubMed

Ahn, Hyo-Suk; Kim, Hyung-Kwan; Park, Eun-Ah; Lee, Whal; Park, Jae-Hyung; Sohn, Dae-Won

2013-10-01

In spite of the frequent involvement of many cardiac diseases, it is difficult to evaluate the left ventricular apex in detail with transthoracic echocardiography, a first-line imaging modality in cardiovascular diseases, because the apex is very closely located at the echocardiographic probe. Cardiac magnetic resonance enables us to evaluate the cardiac apex without any limitation to the image acquisition. We here present a case regarding a broad-based apical diverticulum, which was initially confused with apical aneurysm.

Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a blunt cardiac injury: A case report.

PubMed

Ishida, Kenichiro; Kinoshita, Yoshihiro; Iwasa, Nobutaka; Nakae, Masaro; Sakaki, Masayuki; Ieki, Yohei; Takahashi, Kyosuke; Shimahara, Yumiko; Sogabe, Taku; Shimono, Keiichiro; Noborio, Mitsuhiro; Sadamitsu, Daikai

2017-01-01

Traumatic blunt cardiac injuries have a high mortality rate, and prompt diagnosis and treatment can be lifesaving in cardiac tamponade. A 62-year-old man was transferred to the emergency department after a motor vehicle accident. He was hemodynamically unstable. A focused assessment with sonography in trauma (FAST) showed pericardial fluid with right ventricular collapse consistent with cardiac tamponade in the subxiphoid view. He collapsed despite a subxiphoid pericardiotomy. Owing to the ongoing hemodynamic instability, we performed a left anterolateral thoracotomy. Direct incision of the pericardium showed blood and clots within the pericardial space, indicating hemopericardium. The heart stroke and hemodynamic status recovered on removing the clot. Although the physical findings of cardiac tamponade are not always apparent in life-threatening acute cardiac tamponade after blunt trauma, FAST is a reliable tool for diagnosing and following cardiac tamponade. A median sternotomy is a standard approach for evaluating cardiac injury in hemodynamically stable patients with or without cardiopulmonary bypass. However, a left anterior thoracotomy was the fastest, simplest life-saving procedure considering the need for open-chest cardiac massage given our patient's life-threatening condition. A prompt diagnosis using FAST and treatment can be lifesaving in traumatic acute cardiac tamponade. A pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac decompression in acute traumatic cardiac tamponade in cases of ineffective drainage due to clot formation within the pericardial space. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cardiac torsion and electromagnetic fields: the cardiac bioinformation hypothesis.

PubMed

Burleson, Katharine O; Schwartz, Gary E

2005-01-01

Although in physiology the heart is often referred to as a simple piston pump, there are in fact two additional features that are integral to cardiac physiology and function. First, the heart as it contracts in systole, also rotates and produces torsion due to the structure of the myocardium. Second, the heart produces a significant electromagnetic field with each contraction due to the coordinated depolarization of myocytes producing a current flow. Unlike the electrocardiogram, the magnetic field is not limited to volume conduction and extends outside the body. The therapeutic potential for interaction of this cardioelectromagnetic field both within and outside the body is largely unexplored. It is our hypothesis that the heart functions as a generator of bioinformation that is central to normative functioning of body. The source of this bioinformation is based on: (1) vortex blood flow in the left ventricle; (2) a cardiac electromagnetic field and both; (3) heart sounds; and (4) pulse pressure which produce frequency and amplitude information. Thus, there is a multidimensional role for the heart in physiology and biopsychosocial dynamics. Recognition of these cardiac properties may result in significant implications for new therapies for cardiovascular disease based on increasing cardiac energy efficiency (coherence) and bioinformation from the cardioelectromagnetic field. Research studies to test this hypothesis are suggested.

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

PubMed Central

Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571

Assessment of cardiac risk before non-cardiac surgery: brain natriuretic peptide in 1590 patients.

PubMed

Dernellis, J; Panaretou, M

2006-11-01

To evaluate the predictive value of brain natriuretic peptide (BNP) for assessment of cardiac risk before non-cardiac surgery. Consecutively treated patients (947 men, 643 women) whose BNP was measured before non-cardiac surgery were studied. Clinical and ECG variables were evaluated to identify predictors of postoperative cardiac events. Events occurred in 6% of patients: 21 cardiac deaths, 20 non-fatal myocardial infarctions, 41 episodes of pulmonary oedema and 14 patients with ventricular tachycardia. All of these patients had raised plasma BNP concentrations (best cut-off point 189 pg/ml). The only independent predictor of postoperative events was BNP (odds ratio 34.52, 95% confidence interval (CI) 17.08 to 68.62, p < 0.0001). Clinical variables of Goldman's multifactorial index identified 18% of patients in class I, 40% in class II, 24% in class III and 18% in class IV preoperatively; postoperative event rates were 2%, 3%, 7% and 14%, respectively. BNP identified 60% of patients as having zero risk (BNP 0-100 pg/ml), 22% low risk (101-200 pg/ml), 14% intermediate risk (201-300 pg/ml) and 4% high risk (> 300 pg/ml); postoperative event rates were 0%, 5%, 12% and 81%, respectively. In this population of patients evaluated before non-cardiac surgery, BNP is an independent predictor of postoperative cardiac events. BNP > 189 pg/ml identified patients at highest risk.

Plasma cardiac troponin I concentration and cardiac death in cats with hypertrophic cardiomyopathy.

PubMed

Borgeat, K; Sherwood, K; Payne, J R; Luis Fuentes, V; Connolly, D J

2014-01-01

The use of cardiac biomarkers to assist in the diagnosis of occult and symptomatic hypertrophic cardiomyopathy (HCM) in cats has been established. There is limited data describing their prognostic utility in cats with HCM. Circulating concentrations of N-terminal B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) predict cardiac death in cats with HCM. Forty-one cats diagnosed with HCM at a veterinary teaching hospital, between February 2010 and May 2011. Prospective investigational study. Plasma samples were collected from cats diagnosed with HCM and concentrations of NTproBNP and cTnI were analyzed at a commercial laboratory. Echocardiographic measurements from the day of blood sampling were recorded. Long-term outcome data were obtained. Associations with time to cardiac death were analyzed using Cox proportional hazards models. When controlling for the presence/absence of heart failure and echocardiographic measures of left atrial size and function, cTnI > 0.7 ng/mL was independently associated with time to cardiac death. In univariable analysis, NTproBNP > 250 pmol/L was associated with cardiac death (P = .023), but this did not remain significant (P = .951) when controlling for the effect of clinical signs or left atrial size/function. Plasma concentration of cTnI (cutoff >0.7 ng/mL) is a predictor of cardiac death in cats with HCM that is independent of the presence of heart failure or left atrial dilatation. Copyright © 2014 by the American College of Veterinary Internal Medicine.

The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac Sarcoidosis.

PubMed

Stanton, Kelly M; Ganigara, Madhusudan; Corte, Peter; Celermajer, David S; McGuire, Mark A; Torzillo, Paul J; Corte, Tamera J; Puranik, Rajesh

2017-11-01

Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25% of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is made in only 5% of cases. Current diagnostic algorithms are complex and lack sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to detect myocardial involvement in sarcoidosis. The aim of this study is to determine the prevalence and clinical significance of late gadolinium enhancement (LGE) on CMR in patients with sarcoidosis. Consecutive patients with biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for cardiac sarcoidosis. Medical records were correlated with CMR. Forty-six patients were evaluated. Late gadolinium enhancement was present in 22%, indicating myocardial involvement, and 70% had corresponding hyper-intense T2 signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7% of overall left ventricular (LV) mass and most commonly located in the basal to mid septum. There was no association between LGE and cardiovascular symptoms or pulmonary stage. Eighty per cent of patients with LGE did not fulfill conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was associated with clinically significant arrhythmia (p<0.01) and a lower LVEF (p=0.04). Using CMR, we identified a higher prevalence of cardiac sarcoidosis than previously reported clinical studies, a prevalence which is more consistent with autopsy data. The presence of LGE was highly correlated with clinically significant arrhythmias and lower LVEF. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Current perspectives on cardiac amyloidosis

PubMed Central

Guan, Jian; Mishra, Shikha; Falk, Rodney H.

2012-01-01

Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed “cardiac amyloidosis” or “amyloid cardiomyopathy.” Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis. PMID:22058156

Cardiac misconceptions in healthcare workers.

PubMed

Angus, Neil; Patience, Fiona; Maclean, Elizabeth; Corrigall, Helen; Bradbury, Ian; Thompson, David R; Atherton, Iain; Leslie, Stephen J

2012-12-01

Cardiac misconceptions are common and may have a detrimental effect on patients. Such misconceptions may be introduced or reinforced by vague and inconsistent advice from healthcare staff and can adversely affect health outcomes. To assess whether level of cardiac misconceptions significantly differs between groups of healthcare staff based on occupation. The 22-item York cardiac beliefs questionnaire (YCBQ) was administered to a convenience sample of healthcare staff (n = 263) in direct contact with cardiac patients. Data was also collected on the occupation of healthcare staff and years worked. Medical staff had the lowest mean score (17.5, CI 15.6-19.4), indicating fewest misconceptions, and unqualified healthcare workers had the highest mean score (32.1, CI 28.4-35.7). Analysis by ANOVA indicated differences between staff groups to be statistically significant (F = 17.66, p < 0.001). Length of time worked was found to be significantly associated with cardiac misconception score (Pearson's r = - 0.243, p < 0.001). Further analysis demonstrated that significant differences between mean group scores remained when years worked was defined as a covariate, F = 15.68, p < 0.001). There is significant variability in cardiac misconceptions in different groups of healthcare staff. Education to correct cardiac misconceptions should be particularly targeted at unqualified healthcare staff. The importance of maintaining appropriate ratios of qualified to unqualified healthcare staff in the care of cardiac patients is supported by this study.

Cardiac sarcoidosis: challenges in clinical practice.

PubMed

Bakker, Anne L; Grutters, Jan C; Keijsers, Ruth G; Post, Martijn C

2017-09-01

To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging.

PubMed

Lamare, F; Le Maitre, A; Dawood, M; Schäfers, K P; Fernandez, P; Rimoldi, O E; Visvikis, D

2014-07-01

Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were observed in the performance of the

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamare, F., E-mail: frederic.lamare@chu-bordeaux.fr; Fernandez, P.; CNRS, INCIA, UMR 5287, F-33400 Talence

Purpose: Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET)more » acquisitions. Methods: A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Results: Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were

Brucella papionis sp. nov., isolated from baboons (Papio spp.).

PubMed

Whatmore, Adrian M; Davison, Nicholas; Cloeckaert, Axel; Al Dahouk, Sascha; Zygmunt, Michel S; Brew, Simon D; Perrett, Lorraine L; Koylass, Mark S; Vergnaud, Gilles; Quance, Christine; Scholz, Holger C; Dick, Edward J; Hubbard, Gene; Schlabritz-Loutsevitch, Natalia E

2014-12-01

Two Gram-negative, non-motile, non-spore-forming coccoid bacteria (strains F8/08-60(T) and F8/08-61) isolated from clinical specimens obtained from baboons (Papio spp.) that had delivered stillborn offspring were subjected to a polyphasic taxonomic study. On the basis of 16S rRNA gene sequence similarities, both strains, which possessed identical sequences, were assigned to the genus Brucella. This placement was confirmed by extended multilocus sequence analysis (MLSA), where both strains possessed identical sequences, and whole-genome sequencing of a representative isolate. All of the above analyses suggested that the two strains represent a novel lineage within the genus Brucella. The strains also possessed a unique profile when subjected to the phenotyping approach classically used to separate species of the genus Brucella, reacting only with Brucella A monospecific antiserum, being sensitive to the dyes thionin and fuchsin, being lysed by bacteriophage Wb, Bk2 and Fi phage at routine test dilution (RTD) but only partially sensitive to bacteriophage Tb, and with no requirement for CO2 and no production of H2S but strong urease activity. Biochemical profiling revealed a pattern of enzyme activity and metabolic capabilities distinct from existing species of the genus Brucella. Molecular analysis of the omp2 locus genes showed that both strains had a novel combination of two highly similar omp2b gene copies. The two strains shared a unique fingerprint profile of the multiple-copy Brucella-specific element IS711. Like MLSA, a multilocus variable number of tandem repeat analysis (MLVA) showed that the isolates clustered together very closely, but represent a distinct group within the genus Brucella. Isolates F8/08-60(T) and F8/08-61 could be distinguished clearly from all known species of the genus Brucella and their biovars by both phenotypic and molecular properties. Therefore, by applying the species concept for the genus Brucella suggested by the ICSP

Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

PubMed Central

He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

2014-01-01

Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

Challenges in Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

2010-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

Non-Cardiac Chest Pain

MedlinePlus

... Home / Digestive Health Topic / Non-cardiac Chest Pain Non-cardiac Chest Pain Basics Overview and Symptoms What ... at a reduced dose such as Omeprazole (or equivalent PPI medication ) 20 mg twice daily about 40 ...

Boosters and barriers for direct cardiac reprogramming.

PubMed

Talkhabi, Mahmood; Zonooz, Elmira Rezaei; Baharvand, Hossein

2017-06-01

Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs. As a result, numerous combinations of cardiac TFs exist for direct cardiac reprogramming of mouse and human fibroblasts. However, the efficiency of direct cardiac reprogramming remains low. Recently, a number of cellular and molecular mechanisms have been identified to increase the efficiency of direct cardiac reprogramming and the quality of iCMs. For example, microgrooved substrate, cardiogenic growth factors [VEGF, FGF, BMP4 and Activin A], and an appropriate stoichiometry of TFs boost the direct cardiac reprogramming. On the other hand, serum, TGFβ signaling, activators of epithelial to mesenchymal transition, and some epigenetic factors (Bmi1 and Ezh2) are barriers for direct cardiac reprogramming. Manipulating these mechanisms by the application of boosters and removing barriers can increase the efficiency of direct cardiac reprogramming and possibly make iCMs reliable for cell-based therapy or other potential applications. In this review, we summarize the latest trends in cardiac TF- or miRNA-based direct cardiac reprogramming and comprehensively discuses all molecular and cellular boosters and barriers affecting direct cardiac reprogramming. Copyright © 2017 Elsevier Inc. All rights reserved.

Seroprevalence of Zika Virus in Wild African Green Monkeys and Baboons.

PubMed

Buechler, Connor R; Bailey, Adam L; Weiler, Andrea M; Barry, Gabrielle L; Breitbach, Meghan E; Stewart, Laurel M; Jasinska, Anna J; Freimer, Nelson B; Apetrei, Cristian; Phillips-Conroy, Jane E; Jolly, Clifford J; Rogers, Jeffrey; Friedrich, Thomas C; O'Connor, David H

2017-01-01

Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive "sentinel" macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying

Investigation following resuscitated cardiac arrest.

PubMed

Skinner, Jonathan R

2013-01-01

Roughly two thirds of resuscitated cardiac arrests in children and youth are due to inherited heart diseases. The most commonly implicated are the cardiac ion channelopathies long QT syndrome, CPVT (catecholaminergic polymorphic ventricular tachycardia) and Brugada syndrome. Diagnosis is pivotal to further management of the child if he/she survives, and also to other family members who may be at risk. Thorough investigation of the cardiac arrest survivor is essential to either identify or exclude inherited heart disease. If standard cardiac investigation does not reveal a diagnosis, pharmacological provocation tests are needed to unmask electrocardiographic signs of disease, even if, due to severe brain injury, it is planned ultimately to allow a natural death. Examples are the ajmaline/flecainide challenge for Brugada syndrome and epinephrine for CPVT. A supportive, informative and sympathetic approach to the family is essential. An arrhythmia specialist and a cardiac genetic service should be involved early, with storage of DNA and cardiac/genetic investigation of the family. This review proposes a diagnostic algorithm-based approach to the investigation of this increasingly common clinical scenario.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

PubMed

Cesana, Francesca; Avalli, Leonello; Garatti, Laura; Coppo, Anna; Righetti, Stefano; Calchera, Ivan; Scanziani, Elisabetta; Cozzolino, Paolo; Malafronte, Cristina; Mauro, Andrea; Soffici, Federica; Sulmina, Endrit; Bozzon, Veronica; Maggioni, Elena; Foti, Giuseppe; Achilli, Felice

2017-10-01

Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection

The Influence of Cardiac Risk Factor Burden on Cardiac Stress Test Outcomes.

PubMed

Schrock, Jon W; Li, Morgan; Orazulike, Chidubem; Emerman, Charles L

2011-06-01

Chest pain is the most common admission diagnosis for observation unit patients. These patients often undergo cardiac stress testing to further risk stratify for coronary artery disease (CAD). The decision of whom to stress is currently based on clinical judgment. We sought to determine the influence of cardiac risk factor burden on cardiac stress test outcome for patients tested from an observation unit, inpatient or outpatient setting. We performed a retrospective observational cohort study for all patients undergoing stress testing in our institution from June 2006 through July 2007. Cardiac risk factors were collected at the time of stress testing. Risk factors were evaluated in a summative fashion using multivariate regression adjusting for age and known coronary artery disease. The model was tested for goodness of fit and collinearity and the c statistic was calculated using the receiver operating curve. A total of 4026 subjects were included for analysis of which 22% had known CAD. The rates of positive outcome were 89 (12.0%), 95 (12.6%), and 343 (16.9%) for the OU, outpatients, and hospitalized patients respectively. While the odds of a positive test outcome increased for additional cardiac risk factors, ROC curve analysis indicates that simply adding the number of risk factors does not add significant diagnostic value. Hospitalized patients were more likely to have a positive stress test, OR 1.41 (1.10 - 1.81). Our study does not support basing the decision to perform a stress test on the number of cardiac risk factors.

Cardiac Arrhythmias in Experimental Syncope

DTIC Science & Technology

1958-11-01

cardiac toward respiratory alkalosis . Regardless of arriythmias by stress procedures. It follows these two extremes in the assumed change in that previous...frequently induced by respiratory maneuvers without syncope. Intravenous aidministration of atropine appatently prevented recurrence of cardiac...arrhythmia induced by respiratory maneuvers. Significant cardiac arrhythmia was also noted in simple orthostatic syncope. Loss of consciousness presents a

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following

Trends in Cardiac Pacemaker Batteries

PubMed Central

Mallela, Venkateswara Sarma; Ilankumaran, V; Rao, N.Srinivasa

2004-01-01

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future. PMID:16943934

Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model.

PubMed

Borra, Ronald Jh; Cho, Hoon-Sung; Bowen, Spencer L; Attenberger, Ulrike; Arabasz, Grae; Catana, Ciprian; Josephson, Lee; Rosen, Bruce R; Guimaraes, Alexander R; Hooker, Jacob M

2015-12-01

Simultaneous PET/MR imaging depends on MR-derived attenuation maps (mu-maps) for accurate attenuation correction of PET data. Currently, these maps are derived from gradient-echo-based MR sequences, which are sensitive to susceptibility changes. Iron oxide magnetic nanoparticles have been used in the measurement of blood volume, tumor microvasculature, tumor-associated macrophages, and characterizing lymph nodes. Our aim in this study was to assess whether the susceptibility effects associated with iron oxide nanoparticles can potentially affect measured (18)F-FDG PET standardized uptake values (SUV) through effects on MR-derived attenuation maps. The study protocol was approved by the Institutional Animal Care and Use Committee. Using a Siemens Biograph mMR PET/MR scanner, we evaluated the effects of increasing concentrations of ferumoxytol and ferumoxytol aggregates on MR-derived mu-maps using an agarose phantom. In addition, we performed a baboon experiment evaluating the effects of a single i.v. ferumoxytol dose (10 mg/kg) on the liver, spleen, and pancreas (18)F-FDG SUV at baseline (ferumoxytol-naïve), within the first hour and at 1, 3, 5, and 11 weeks. Phantom experiments showed mu-map artifacts starting at ferumoxytol aggregate concentrations of 10 to 20 mg/kg. The in vivo baboon data demonstrated a 53% decrease of observed (18)F-FDG SUV compared to baseline within the first hour in the liver, persisting at least 11 weeks. A single ferumoxytol dose can affect measured SUV for at least 3 months, which should be taken into account when administrating ferumoxytol in patients needing sequential PET/MR scans. Advances in knowledge 1. Ferumoxytol aggregates, but not ferumoxytol alone, produce significant artifacts in MR-derived attenuation correction maps at approximate clinical dose levels of 10 mg/kg. 2. When performing simultaneous whole-body (18)F-FDG PET/MR, a single dose of ferumoxytol can result in observed SUV decreases up to 53%, depending on the

Cardiac radiology: centenary review.

PubMed

de Roos, Albert; Higgins, Charles B

2014-11-01

During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

The effect of excluding juveniles on apparent adult olive baboons (Papio anubis) social networks

PubMed Central

Fedurek, Piotr; Lehmann, Julia

2017-01-01

In recent years there has been much interest in investigating the social structure of group living animals using social network analysis. Many studies so far have focused on the social networks of adults, often excluding younger, immature group members. This potentially may lead to a biased view of group social structure as multiple recent studies have shown that younger group members can significantly contribute to group structure. As proof of the concept, we address this issue by investigating social network structure with and without juveniles in wild olive baboons (Papio anubis) at Gashaka Gumti National Park, Nigeria. Two social networks including all independently moving individuals (i.e., excluding dependent juveniles) were created based on aggressive and grooming behaviour. We used knockout simulations based on the random removal of individuals from the network in order to investigate to what extent the exclusion of juveniles affects the resulting network structure and our interpretation of age-sex specific social roles. We found that juvenile social patterns differed from those of adults and that the exclusion of juveniles from the network significantly altered the resulting overall network structure. Moreover, the removal of juveniles from the network affected individuals in specific age-sex classes differently: for example, including juveniles in the grooming network increased network centrality of adult females while decreasing centrality of adult males. These results suggest that excluding juveniles from the analysis may not only result in a distorted picture of the overall social structure but also may mask some of the social roles of individuals belonging to different age-sex classes. PMID:28323851

The effect of excluding juveniles on apparent adult olive baboons (Papio anubis) social networks.

PubMed

Fedurek, Piotr; Lehmann, Julia

2017-01-01

In recent years there has been much interest in investigating the social structure of group living animals using social network analysis. Many studies so far have focused on the social networks of adults, often excluding younger, immature group members. This potentially may lead to a biased view of group social structure as multiple recent studies have shown that younger group members can significantly contribute to group structure. As proof of the concept, we address this issue by investigating social network structure with and without juveniles in wild olive baboons (Papio anubis) at Gashaka Gumti National Park, Nigeria. Two social networks including all independently moving individuals (i.e., excluding dependent juveniles) were created based on aggressive and grooming behaviour. We used knockout simulations based on the random removal of individuals from the network in order to investigate to what extent the exclusion of juveniles affects the resulting network structure and our interpretation of age-sex specific social roles. We found that juvenile social patterns differed from those of adults and that the exclusion of juveniles from the network significantly altered the resulting overall network structure. Moreover, the removal of juveniles from the network affected individuals in specific age-sex classes differently: for example, including juveniles in the grooming network increased network centrality of adult females while decreasing centrality of adult males. These results suggest that excluding juveniles from the analysis may not only result in a distorted picture of the overall social structure but also may mask some of the social roles of individuals belonging to different age-sex classes.

[A new variant of the simian T-lymphotropic retrovirus type I (STLV-IF) in the Sukhumi colony of hamadryas baboons].

PubMed

Chikobaeva, M G; Schatzl, H; Rose, D; Bush, U; Iakovleva, L A; Deinhardt, F; Helm, K; Lapin, B A

1993-01-01

Polymerase chain reaction (PCR) was developed for the detection of simian T-lymphotropic virus type 1 (STLV-1) infection of P. hamadryas and direct sequencing using oligo-nucleotide primer pairs specific for the tax and env regions of the related human T-lymphotropic virus type 1 (HTLV-1). Excellent specificity was shown in the detection of STLV-1 provirus in infected baboons by PCR using HTLV-1-derived primers. The nucleotide sequences of env 467bp and tax 159bp of the proviral genome (env position 5700-6137, tax position 7373-7498 HTLV-1, according to Seiki et al., 1983) derived from STLV-1-infected P. hamadryas were analysed using PCR and direct sequencing techniques. Two STLV-1 isolates from different sources (Sukhumi main-SuTLV-1 and forest stocks-STLV-1F) were compared. Two variants of STLV-1 among P. hamadryas with different level of homology to HTLV-1 were wound (83.8% and 95.2%, respectively). A possible role of nucleotide changes in env and tax sequenced fragments and oncogenicity of STLV-1 variants is discussed.

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

PubMed

Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

[Cardiac cachexia].

PubMed

Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

2006-05-01

Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

du Toit, D.F.; Heydenrych, J.J.; Smit, B.

1985-04-01

The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/ kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversiblemore » bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 x 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 x 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 x 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 x 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients.« less

Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability

PubMed Central

Nijland, Mark J; Mitsuya, Kozoh; Li, Cun; Ford, Stephen; McDonald, Thomas J; Nathanielsz, Peter W; Cox, Laura A

2010-01-01

Decreased maternal nutrient availability during pregnancy induces compensatory fetal metabolic and endocrine responses. Knowledge of cellular changes involved is critical to understanding normal and abnormal development. Several studies in rodents and sheep report increased fetal plasma cortisol and associated increased gluconeogenesis in response to maternal nutrient reduction (MNR) but observations in primates are lacking. We determined MNR effects on fetal liver phosphoenolpyruvate carboxykinase 1 (protein, PEPCK1; gene, PCK1 orthologous/homologous human chromosomal region 20q13.31) at 0.9 gestation (G). Female baboon social groups were fed ad libitum (control, CTR) or 70% CTR (MNR) from 0.16 to 0.9G when fetuses were delivered by caesarean section under general anaesthesia. Plasma cortisol was elevated in fetuses of MNR mothers (P < 0.05). Immunoreactive PEPCK1 protein was located around the liver lobule central vein and was low in CTR fetuses but rose to 63% of adult levels in MNR fetuses. PCK1 mRNA measured by QRT-PCR increased in MNR (2.3-fold; P < 0.05) while the 25% rise in protein by Western blot analysis was not significant. PCK1 promoter methylation analysis using bisulfite sequencing was significantly reduced in six out of nine CpG-dinucleotides evaluated in MNR compared with CTR liver samples. In conclusion, these are the first data from a fetal non-human primate indicating hypomethylation of the PCK1 promoter in the liver following moderate maternal nutrient reduction. PMID:20176628

Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons.

PubMed

Kumar, Rajesh; Nyakundi, Ruth; Kariuki, Thomas; Ozwara, Hastings; Nyamongo, Onkoba; Mlambo, Godfree; Ellefsen, Barry; Hannaman, Drew; Kumar, Nirbhay

2013-06-28

Plasmodium falciparum Pfs25 antigen, expressed on the surface of zygotes and ookinetes, is one of the leading targets for the development of a malaria transmission-blocking vaccine (TBV). Our laboratory has been evaluating DNA plasmid based Pfs25 vaccine in mice and non-human primates. Previously, we established that in vivo electroporation (EP) delivery is an effective method to improve the immunogenicity of DNA vaccine encoding Pfs25 in mice. In order to optimize the in vivo EP procedure and test for its efficacy in more clinically relevant larger animal models, we employed in vivo EP to evaluate the immune response and protective efficacy of Pfs25 encoding DNA vaccine in nonhuman primates (olive baboons, Papio anubis). The results showed that at a dose of 2.5mg DNA vaccine, antibody responses were significantly enhanced with EP as compared to without EP resulting in effective transmission blocking efficiency. Similar immunogenicity enhancing effect of EP was also observed with lower doses (0.5mg and 1mg) of DNA plasmids. Further, final boosting with a single dose of recombinant Pfs25 protein resulted in dramatically enhanced antibody titers and significantly increased functional transmission blocking efficiency. Our study suggests priming with DNA vaccine via EP along with protein boost regimen as an effective method to elicit potent immunogenicity of malaria DNA vaccines in nonhuman primates and provides the basis for further evaluation in human volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Targeted Nuclear Imaging Probes for Cardiac Amyloidosis.

PubMed

Bravo, Paco E; Dorbala, Sharmila

2017-07-01

The aim of the present manuscript is to review the latest advancements of radionuclide molecular imaging in the diagnosis and prognosis of individuals with cardiac amyloidosis. 99m Technetium labeled bone tracer scintigraphy had been known to image cardiac amyloidosis, since the 1980s; over the past decade, bone scintigraphy has been revived specifically to diagnose transthyretin cardiac amyloidosis. 18 F labeled and 11 C labeled amyloid binding radiotracers developed for imaging Alzheimer's disease, have been repurposed since 2013, to image light chain and transthyretin cardiac amyloidosis. 99m Technetium bone scintigraphy for transthyretin cardiac amyloidosis, and amyloid binding targeted PET imaging for light chain and transthyretin cardiac amyloidosis, are emerging as highly accurate methods. Targeted radionuclide imaging may soon replace endomyocardial biopsy in the evaluation of patients with suspected cardiac amyloidosis. Further research is warranted on the role of targeted imaging to quantify cardiac amyloidosis and to guide therapy.

Local Xenotransplantation of Bone Marrow Derived Mast Cells (BMMCs) Improves Functional Recovery of Transected Sciatic Nerve in Cat: A Novel Approach in Cell Therapy.

PubMed

Mohammadi, Rahim; Anousheh, Dana; Alaei, Mohammad-Hazhir; Nikpasand, Amin; Rostami, Hawdam; Shahrooz, Rasoul

2018-04-01

To determine the effects of bone marrow derived mast cells (BMMCs) on functional recovery of transected sciatic nerve in animal model of cat. A 20-mm sciatic nerve defect was bridged using a silicone nerve guide filled with BMMCs in BMMC group. In Sham-surgery group (SHAM), the sciatic nerve was only exposed and manipulated. In control group (SILOCONE) the gap was repaired with a silicone nerve guide and both ends were sealed using sterile Vaseline to avoid leakage and the nerve guide was filled with 100 μL of phosphate-buffered saline alone. In cell treated group ([SILOCONE/BMMC) the nerve guide was filled with 100 μL BMMCs (2× 106 cells/100 μL). The regenerated nerve fibers were studied, biomechanically, histologically and immunohiscochemically 6 months later. Biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to control group ( p <0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in control group ( p <0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in control group. BMMCs xenotransplantation could be considered as a readily accessible source of cells that could improve recovery of transected sciatic nerve.

Using Cardiac Biomarkers in Veterinary Practice.

PubMed

Oyama, Mark A

2015-09-01

Blood-based assays for various cardiac biomarkers can assist in the diagnosis of heart disease in dogs and cats. The two most common markers are cardiac troponin-I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in differentiating cardiac from noncardiac causes of respiratory signs and detection of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac biomarker testing can help assess the risk of morbidity and mortality in animals with heart disease. Usage of cardiac biomarker testing in clinical practice relies on proper patient selection, correct interpretation of test results, and incorporation of biomarker testing into existing diagnostic methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Using cardiac biomarkers in veterinary practice.

PubMed

Oyama, Mark A

2013-11-01

Blood-based assays for various cardiac biomarkers can assist in the diagnosis of heart disease in dogs and cats. The two most common markers are cardiac troponin-I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in differentiating cardiac from noncardiac causes of respiratory signs and detection of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac biomarker testing can help assess the risk of morbidity and mortality in animals with heart disease. Usage of cardiac biomarker testing in clinical practice relies on proper patient selection, correct interpretation of test results, and incorporation of biomarker testing into existing diagnostic methods. Copyright © 2013 Elsevier Inc. All rights reserved.

Imaging in blunt cardiac injury: Computed tomographic findings in cardiac contusion and associated injuries.

PubMed

Hammer, Mark M; Raptis, Demetrios A; Cummings, Kristopher W; Mellnick, Vincent M; Bhalla, Sanjeev; Schuerer, Douglas J; Raptis, Constantine A

2016-05-01

Blunt cardiac injury (BCI) may manifest as cardiac contusion or, more rarely, as pericardial or myocardial rupture. Computed tomography (CT) is performed in the vast majority of blunt trauma patients, but the imaging features of cardiac contusion are not well described. To evaluate CT findings and associated injuries in patients with clinically diagnosed BCI. We identified 42 patients with blunt cardiac injury from our institution's electronic medical record. Clinical parameters, echocardiography results, and laboratory tests were recorded. Two blinded reviewers analyzed chest CTs performed in these patients for myocardial hypoenhancement and associated injuries. CT findings of severe thoracic trauma are commonly present in patients with severe BCI; 82% of patients with ECG, cardiac enzyme, and echocardiographic evidence of BCI had abnormalities of the heart or pericardium on CT; 73% had anterior rib fractures, and 64% had pulmonary contusions. Sternal fractures were only seen in 36% of such patients. However, myocardial hypoenhancement on CT is poorly sensitive for those patients with cardiac contusion: 0% of right ventricular contusions and 22% of left ventricular contusions seen on echocardiography were identified on CT. CT signs of severe thoracic trauma are frequently present in patients with severe BCI and should be regarded as indirect evidence of potential BCI. Direct CT findings of myocardial contusion, i.e. myocardial hypoenhancement, are poorly sensitive and should not be used as a screening tool. However, some left ventricular contusions can be seen on CT, and these patients could undergo echocardiography or cardiac MRI to evaluate for wall motion abnormalities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiac changes in anorexia nervosa.

PubMed

Spaulding-Barclay, Michael A; Stern, Jessica; Mehler, Philip S

2016-04-01

Introduction Anorexia nervosa is an eating disorder, which is associated with many different medical complications as a result of the weight loss and malnutrition that characterise this illness. It has the highest mortality rate of any psychiatric disorder. A large portion of deaths are attributable to the cardiac abnormalities that ensue as a result of the malnutrition associated with anorexia nervosa. In this review, the cardiac complications of anorexia nervosa will be discussed. A comprehensive literature review on cardiac changes in anorexia nervosa was carried out. There are structural, functional, and rhythm-type changes that occur in patients with anorexia nervosa. These become progressively significant as ongoing weight loss occurs. Cardiac changes are inherent to anorexia nervosa and they become more life-threatening and serious as the anorexia nervosa becomes increasingly severe. Weight restoration and attention to these cardiac changes are crucial for a successful treatment outcome.

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

PubMed Central

Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG

Cardiac neuronal hierarchy in health and disease.

PubMed

Armour, J Andrew

2004-08-01

The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

Cardiac pathologic findings reveal a high rate of sudden cardiac death of undetermined etiology in younger women.

PubMed

Chugh, Sumeet S; Chung, Kiyon; Zheng, Zhi-Jie; John, Benjamin; Titus, Jack L

2003-10-01

Between 1989 and 1998 there was a 21% increase in estimated sudden cardiac death among US women aged 35 to 44 years. In contrast, the sudden cardiac death rate in age-matched men showed a decreasing trend (-2.8%). Due to under-representation of younger adults in published autopsy series, etiologies of sudden cardiac death merit further investigation. We reviewed autopsy and detailed cardiac pathologic findings in younger women (age 35-44 years) from a 270-patient, 13-year (1984-1996) autopsy series of sudden cardiac death, and performed comparisons with findings in age-matched men. Women aged 35 to 44 years constituted 32% of all women in the series compared to men, who constituted 24% of total men (P =.004 vs women). A presumptive cause of sudden cardiac death could not be determined in 13 women (50%). Among women, 6 cases (22%) had significant coronary artery disease. Findings in others included coronary artery anomalies (n = 3), myocarditis (n = 2), hypertrophic cardiomyopathy (n = 1), coronary artery dissection (n = 1) and accessory pathway (n = 1). In younger men, a presumptive cause of sudden cardiac death remained undetermined in only 24% (P =.025 vs younger women), and coronary artery disease accounted for 40% of cases. In younger women, despite autopsy and detailed cardiac pathologic examination, an attributable cause of sudden cardiac death was not determined in 50% of cases; a 2-fold increase compared to men of the same age. Given the dynamic and multifactorial nature of sudden cardiac death, comprehensive population-based investigations are likely to be necessary to further investigate this unexpected sex-based disparity.

Home-Based Cardiac Rehabilitation.

ERIC Educational Resources Information Center

Fardy, Paul S.

1987-01-01

Although cardiac rehabilitation has become increasingly popular, only 15 percent of eligible candidates participate in supervised and monitored programs. This article reviews alternative home-based cardiac rehabilitation, discussing types of activities, monitoring, diet, motivation, and coordination with traditional program staff. (Author/MT)

Cardiac DPP-4 inhibition by saxagliptin ameliorates isoproterenol-induced myocardial remodeling and cardiac diastolic dysfunction in rats.

PubMed

Ikeda, Junichi; Kimoto, Naoya; Kitayama, Tetsuya; Kunori, Shunji

2016-09-01

Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17.5 mg/kg via drinking water) for 2 weeks. In situ cardiac DPP-4 activity was measured by a colorimetric assay. Cardiac gene expressions were examined and an echocardiographic analysis was performed. Saxagliptin treatment significantly inhibited in situ cardiac DPP-4 activity and suppressed isoproterenol-induced myocardial remodeling and the expression of related genes without altering the blood glucose levels. Saxagliptin also significantly ameliorated cardiac diastolic dysfunction in isoproterenol-treated rats. In conclusion, the inhibition of DPP-4 activity in cardiac tissue by saxagliptin was associated with suppression of myocardial remodeling and cardiac diastolic dysfunction independently of its glucose-lowering action in isoproterenol-treated rats. Cardiac DPP-4 activity may contribute to myocardial remodeling in the development of heart failure. Copyright © 2016 Kyowa Hakko Kirin Co.,Ltd. Production and hosting by Elsevier B.V. All rights reserved.

Cardiac-specific ablation of glutaredoxin 3 leads to cardiac hypertrophy and heart failure

USDA-ARS?s Scientific Manuscript database

Experimental and clinical investigations have demonstrated that reactive oxygen species (ROS) production is increased during cardiac hypertrophy and heart failure. Excess ROS can directly impair cardiac contraction through modification of Ca2+ handling proteins or activate multiple effectors and sig...

Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.

PubMed

Dassanayaka, Sujith; Zheng, Yuting; Gibb, Andrew A; Cummins, Timothy D; McNally, Lindsey A; Brittian, Kenneth R; Jagatheesan, Ganapathy; Audam, Timothy N; Long, Bethany W; Brainard, Robert E; Jones, Steven P; Hill, Bradford G

2018-06-01

Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Copyright © 2018. Published by Elsevier B.V.

[Primary cardiac lymphoma: a case report].

PubMed

Parato, Vito Maurizio; Muscente, Francesca; Scarano, Michele

2017-01-01

Primary cardiac lymphomas are rare entities (1.3% of all primary cardiac tumors) of difficult clinical identification. We report a case of a primitive cardiac lymphoma in a 35-year-old immunocompetent patient, presenting with signs and symptoms of cardiac tamponade. Echocardiography revealed a lateral atrioventricular mass associated with large pericardial effusion. After pericardiocentesis, surgical excision was performed. Chemotherapy regimens were administered according to established protocols and were effective in inducing complete remission at 6 months.

Myocardial Dysfunction and Shock after Cardiac Arrest

PubMed Central

Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

Myocardial Dysfunction and Shock after Cardiac Arrest.

PubMed

Jentzer, Jacob C; Chonde, Meshe D; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.

Cardiac integrins the ties that bind.

PubMed

Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

1998-01-01

An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

Cardiac fluid dynamics meets deformation imaging.

PubMed

Dal Ferro, Matteo; Stolfo, Davide; De Paris, Valerio; Lesizza, Pierluigi; Korcova, Renata; Collia, Dario; Tonti, Giovanni; Sinagra, Gianfranco; Pedrizzetti, Gianni

2018-02-20

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.

42 CFR 410.49 - Cardiac rehabilitation program and intensive cardiac rehabilitation program: Conditions of coverage.

Code of Federal Regulations, 2011 CFR

2011-10-01

... prescribed exercise, cardiac risk factor modification, psychosocial assessment, and outcomes assessment... rehabilitation items and services are furnished. (ii) Cardiac risk factor modification, including education...

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

PubMed Central

Thapa, Dharendra; Shepherd, Danielle L.

2014-01-01

Cardiac tissue contains discrete pools of mitochondria that are characterized by their subcellular spatial arrangement. Subsarcolemmal mitochondria (SSM) exist below the cell membrane, interfibrillar mitochondria (IFM) reside in rows between the myofibrils, and perinuclear mitochondria are situated at the nuclear poles. Microstructural imaging of heart tissue coupled with the development of differential isolation techniques designed to sequentially separate spatially distinct mitochondrial subpopulations have revealed differences in morphological features including shape, absolute size, and internal cristae arrangement. These findings have been complemented by functional studies indicating differences in biochemical parameters and, potentially, functional roles for the ATP generated, based upon subcellular location. Consequently, mitochondrial subpopulations appear to be influenced differently during cardiac pathologies including ischemia/reperfusion, heart failure, aging, exercise, and diabetes mellitus. These influences may be the result of specific structural and functional disparities between mitochondrial subpopulations such that the stress elicited by a given cardiac insult differentially impacts subcellular locales and the mitochondria contained within. The goal of this review is to highlight some of the inherent structural and functional differences that exist between spatially distinct cardiac mitochondrial subpopulations as well as provide an overview of the differential impact of various cardiac pathologies on spatially distinct mitochondrial subpopulations. As an outcome, we will instill a basis for incorporating subcellular spatial location when evaluating the impact of cardiac pathologies on the mitochondrion. Incorporation of subcellular spatial location may offer the greatest potential for delineating the influence of cardiac pathology on this critical organelle. PMID:24778166

Assessing acute coronary syndrome patients' cardiac-related beliefs, motivation and mood over time to predict non-attendance at cardiac rehabilitation.

PubMed

Herber, Oliver R; Jones, Martyn C; Smith, Karen; Johnston, Derek W

2012-12-01

This research protocol describes and justifies a study to assess patients' cardiac-related beliefs (i.e. illness representations, knowledge/misconceptions, cardiac treatment beliefs), motivation and mood over time to predict non-attendance at a cardiac rehabilitation programme by measuring weekly/monthly changes in these key variables. Heart disease is the UK's leading cause of death. Evidence from meta-analyses suggests that cardiac rehabilitation facilitates recovery following acute cardiac events. However, 30-60% of patients do not attend cardiac rehabilitation. There is some evidence from questionnaire studies that a range of potentially modifiable psychological variables including patients' cardiac-related beliefs, motivation and mood may influence attendance. Mixed-methods. In this study, during 2012-2013, electronic diary data will be gathered weekly/monthly from 240 patients with acute coronary syndrome from discharge from hospital until completion of the cardiac rehabilitation programme. This will identify changes and interactions between key variables over time and their power to predict non-attendance at cardiac rehabilitation. Data will be analysed to examine the relationship between patients' illness perceptions, cardiac treatment beliefs, knowledge/misconceptions, mood and non-attendance of the cardiac rehabilitation programme. The qualitative component (face-to-face interviews) seeks to explore why patients decide not to attend, not complete or complete the cardiac rehabilitation programme. The identification of robust predictors of (non-)attendance is important for the design and delivery of interventions aimed at optimizing cardiac rehabilitation uptake. Funding for the study was granted in February 2011 by the Scottish Government Chief Scientist Office (CZH/4/650). © 2012 Blackwell Publishing Ltd.

Traumatic Tricuspid Regurgitation Following Cardiac Massage

PubMed Central

Na, Sungwon; Nam, Sang Beom; Lee, Yong Kyung; Oh, Young Jun

2007-01-01

We report a 66-yr-old male patient who developed tricuspid regurgitation secondary to internal cardiac massage. After uneventful off-pump coronary artery bypass surgery, the subject experienced cardiac arrest in the intensive care unit. External cardiac massage was initiated and internal cardiac massage was performed eventually. A transesophageal echocardiography revealed avulsion of the anterior papillary muscle and chordae to the anterior leaflet after successful cardiopulmonary resuscitation. Emergency repair of the papillary muscle was performed under cardiopulmonary bypass. PMID:17728519

The cardiac sonography workforce in New Zealand.

PubMed

Buckley, Belinda; White, Steve; Poppe, Katrina; Whalley, Gillian

2013-05-01

Introduction : The aim of this paper is to investigate the cardiac sonography workforce characteristics and registration requirements in New Zealand (NZ), with a comparison to similar workforces internationally. Methods : The Survey of Clinical Echocardiography in New Zealand 2 (SCANZ2) audit was performed in December 2010. All of NZ's public-funded District Health Board (DHB) centers providing echocardiography services responded to questions relating to staff, equipment, procedure types and patient statistics. The Medical Radiation Technologists Board (MRTB), Clinical Physiologists Registration Board (CPRB) and Australian Sonographers Association Registry (ASAR) websites were reviewed in March 2012 for registered sonographers with a cardiac scope of practice. The cardiac sonography workforces in Australia, the UK, the USA and Canada were investigated for comparison. Results : There are 84 cardiac sonographers (60.3 full-time equivalent) working in DHBs: 71% from a cardiac technical background; 40% have post-graduate qualifications; a further 17% are undertaking post-graduate qualifications; and 59 cardiac sonographers have registration with professional bodies in NZ and/or Australia. Cardiac sonographers in NZ do not undergo compulsory registration, but other sonographers in NZ have compulsory registration with the MRTB. Sonographers are predominantly not licensed internationally. Discussion : Disparity exists between registration of cardiac and non-cardiac sonographers in NZ. Many cardiac sonographers have voluntary registration but few are registered with the MRTB. Reasons for this include professional alignment, educational qualifications and representation. International trends show increased pressure from governments and professional bodies to regulate sonographers. Conclusion : This study provides a snapshot of the cardiac sonography workforce in NZ for the first time.

The cardiac sonography workforce in New Zealand

PubMed Central

White, Steve; Poppe, Katrina; Whalley, Gillian

2015-01-01

Abstract Introduction: The aim of this paper is to investigate the cardiac sonography workforce characteristics and registration requirements in New Zealand (NZ), with a comparison to similar workforces internationally. Methods: The Survey of Clinical Echocardiography in New Zealand 2 (SCANZ2) audit was performed in December 2010. All of NZ's public‐funded District Health Board (DHB) centers providing echocardiography services responded to questions relating to staff, equipment, procedure types and patient statistics. The Medical Radiation Technologists Board (MRTB), Clinical Physiologists Registration Board (CPRB) and Australian Sonographers Association Registry (ASAR) websites were reviewed in March 2012 for registered sonographers with a cardiac scope of practice. The cardiac sonography workforces in Australia, the UK, the USA and Canada were investigated for comparison. Results: There are 84 cardiac sonographers (60.3 full‐time equivalent) working in DHBs: 71% from a cardiac technical background; 40% have post‐graduate qualifications; a further 17% are undertaking post‐graduate qualifications; and 59 cardiac sonographers have registration with professional bodies in NZ and/or Australia. Cardiac sonographers in NZ do not undergo compulsory registration, but other sonographers in NZ have compulsory registration with the MRTB. Sonographers are predominantly not licensed internationally. Discussion: Disparity exists between registration of cardiac and non‐cardiac sonographers in NZ. Many cardiac sonographers have voluntary registration but few are registered with the MRTB. Reasons for this include professional alignment, educational qualifications and representation. International trends show increased pressure from governments and professional bodies to regulate sonographers. Conclusion: This study provides a snapshot of the cardiac sonography workforce in NZ for the first time. PMID:28191178

Cardiac Catheterization (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cardiac Catheterization KidsHealth / For Kids / Cardiac Catheterization Print en español Cateterización cardíaca What ...

Cardiac Rehabilitation Online Pilot: Extending Reach of Cardiac Rehabilitation.

PubMed

Higgins, Rosemary O; Rogerson, Michelle; Murphy, Barbara M; Navaratnam, Hema; Butler, Michael V; Barker, Lauren; Turner, Alyna; Lefkovits, Jeffrey; Jackson, Alun C

While cardiac rehabilitation (CR) is recommended for all patients after an acute cardiac event, limitations exist in reach. The purpose of the current study was to develop and pilot a flexible online CR program based on self-management principles "Help Yourself Online." The program was designed as an alternative to group-based CR as well as to complement traditional CR. The program was based on existing self-management resources developed previously by the Heart Research Centre. Twenty-one patients admitted to Cabrini Health for an acute cardiac event were recruited to test the program. The program was evaluated using qualitative and quantitative methods. Quantitative results demonstrated that patients believed the program would assist them in their self-management. Qualitative evaluation, using focus group and interview methods with 15 patients, showed that patients perceived the online CR approach to be a useful instrument for self-management. Broader implications of the data include the acceptability of the intervention, timing of intervention delivery, and patients' desire for additional online community support.

Motivational factors of adherence to cardiac rehabilitation.

PubMed

Shahsavari, Hooman; Shahriari, Mohsen; Alimohammadi, Nasrollah

2012-05-01

Main suggested theories about patients' adherence to treatment regimens recognize the importance of motivation in positive changes in behaviors. Since cardiac diseases are chronic and common, cardiac rehabilitation as an effective prevention program is crucial in management of these diseases. There is always concern about the patients' adherence to cardiac rehabilitation. The aim of this study was to describe the motivational factors affecting the patients' participation and compliance to cardiac rehabilitation by recognizing and understanding the nature of patients' experiences. The participants were selected among the patients with cardiac diseases who were referred to cardiac rehabilitation in Isfahan Cardiovascular Research Center, Iran. The purposive sampling method was used and data saturation achieved after 8 semi-structured interviews. The three main concepts obtained from this study are "beliefs", "supporters" and "group cohesion". In cardiac rehabilitation programs, emphasis on motivational factors affects the patient's adherence. It is suggested that in cardiac rehabilitation programs more attention should be paid to patients' beliefs, the role of patients' supporters and the role of group-based rehabilitation.

Cardiac Limited Ultrasound Examination Techniques to Augment the Bedside Cardiac Physical Examination.

PubMed

Kimura, Bruce J; Shaw, David J; Amundson, Stan A; Phan, James N; Blanchard, Daniel G; DeMaria, Anthony N

2015-09-01

The current practice of physical diagnosis is dependent on physician skills and biases, inductive reasoning, and time efficiency. Although the clinical utility of echocardiography is well known, few data exist on how to integrate 2-dimensional screening "quick-look" ultrasound applications into a novel, modernized cardiac physical examination. We discuss the evidence basis behind ultrasound "signs" pertinent to the cardiovascular system and elemental in synthesis of bedside diagnoses and propose the application of a brief cardiac limited ultrasound examination based on these signs. An ultrasound-augmented cardiac physical examination can be taught in traditional medical education and has the potential to improve bedside diagnosis and patient care. © 2015 by the American Institute of Ultrasound in Medicine.

Integrative Cardiac Health Project (ICHP)

DTIC Science & Technology

2017-04-01

AWARD NUMBER: W81XWH-16-2-0007 TITLE: Integrative Cardiac Health Project (ICHP) PRINCIPAL INVESTIGATOR: COL (Ret) Marina N. Vernalis, MC, USA...2017 4. TITLE AND SUBTITLE Integrative Cardiac Health Project (ICHP) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-2-0007 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The Integrative Cardiac Health Project (ICHP) aims to lead the way in Cardiovascular Disease (CVD

Cardiac surgery outcomes.

PubMed

Halpin, Linda S; Barnett, Scott D; Beachy, Jim

2003-01-01

Accrediting organizations and payers are demanding valid and reliable data that demonstrate the value of services. Federal agencies, healthcare industry groups, and healthcare watchdog groups are increasing the demand for public access to outcomes data. A new and growing outcomes dynamic is the information requested by prospective patients in an increasingly consumer-oriented business. Patients demand outcomes, and resources are developing to meet these demands. Physicians are increasingly confronted with requests for information about their mortality and morbidity rates, malpractice suits, and disciplinary actions received. For example, in Virginia, prospective patients have access to data provided by the nonprofit group Virginia Health Information. After numerous resolutions by the Virginia Senate since 1999, the prospective Virginia medical consumer now has access to several annual publications: Virginia Hospitals: A Consumer's Guide, 1999 Annual Report and Strategic Plan Update, and the 1999 Industry Report: Virginia Hospitals and Nursing Facilities. Consumers have access to cardiac outcomes data stratified by hospital, gender, and cardiac service line (cardiac surgery, noninvasive cardiology, and invasive cardiology). This is particularly relevant to IHI because Virginia Health Information specifically targets cardiac care. IHI has a sizable investment in cardiovascular outcomes and has found outcomes measurement and research are key to providing quality care. IHI's goal is to move from an outcomes management model to a disease management model. The hope is to incorporate all aspects of the patient's continuum of care, from preoperative and diagnostic services through cardiac interventions to postoperative rehabilitation. Furthermore, every step along the way will be supported with functional status and quality of life assessments. Although these goals are ambitious and expensive, the return on investment is high.

Crisis management during anaesthesia: cardiac arrest.

PubMed

Runciman, W B; Morris, R W; Watterson, L M; Williamson, J A; Paix, A D

2005-06-01

Cardiac arrest attributable to anaesthesia occurs at the rate of between 0.5 and 1 case per 10 000 cases, tends to have a different profile to that of cardiac arrest occurring elsewhere, and has an in-hospital mortality of 20%. However, as individual practitioners encounter cardiac arrest rarely, the rapidity with which the diagnosis is made and the consistency of appropriate management varies considerably. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a sub-algorithm for cardiac arrest, in the management of cardiac arrest occurring in association with anaesthesia. The potential performance of this structured approach for each the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 129 reports of cardiac arrest associated with anaesthesia among the first 4000 AIMS incident reports. Identified aetiological factors were grouped into five categories: (1) anaesthetic technique (11 cases with this category alone; 32 with this and one or more of the other categories, representing 25% of all 129 cardiac arrests); (2) drug related (16; 32, 25%); (3) associated with surgical procedure (9; 29, 22%); (4) associated with pre-existing medical or surgical disease (30; 82, 64%); (5) unknown (8; 14, 11%). The "real life" presentation and management of cardiac arrest in association with anaesthesia differs substantially from that detailed in general published guidelines. Cardiac rhythms at the time were sinus bradycardia (23%); asystole (22%); tachycardia/ventricular tachycardia/ventricular fibrillation (14%); and normal (7%), with a further third unknown. Details of treatment were recorded in 110 reports; modalities employed included cardiac compression (72%); adrenaline (61%); 100% oxygen (58%); atropine (38%); intravenous fluids (25%), and electrical defibrillation (17%). There

Extracorporeal cardiopulmonary resuscitation for blunt cardiac rupture.

PubMed

Kudo, Shunsuke; Tanaka, Keiji; Okada, Kunihiko; Takemura, Takahiro

2017-11-01

Extracorporeal cardiopulmonary resuscitation (ECPR) followed by operating room sternotomy, rather than resuscitative thoracotomy, might be life-saving for patients with blunt cardiac rupture and cardiac arrest who do not have multiple severe traumatic injuries. A 49-year-old man was injured in a vehicle crash and transferred to the emergency department. On admission, he was hemodynamically stable, but a plain chest radiograph revealed a widened mediastinum, and echocardiography revealed hemopericardium. A computed tomography scan revealed hemopericardium and mediastinal hematoma, without other severe traumatic injuries. However, the patient's pulse was lost soon after he was transferred to the intensive care unit, and cardiopulmonary resuscitation was initiated. We initiated ECPR using femorofemoral veno-arterial extracorporeal membrane oxygenation (ECMO) with heparin administration, which achieved hemodynamic stability. He was transferred to the operating room for sternotomy and cardiac repair. Right ventricular rupture and pericardial sac laceration were identified intraoperatively, and cardiac repair was performed. After repairing the cardiac rupture, the cardiac output recovered spontaneously, and ECMO was discontinued intraoperatively. The patient recovered fully and was discharged from the hospital on postoperative day 7. In this patient, ECPR rapidly restored brain perfusion and provided enough time to perform operating room sternotomy, allowing for good surgical exposure of the heart. Moreover, open cardiac massage was unnecessary. ECPR with sternotomy and cardiac repair is advisable for patients with blunt cardiac rupture and cardiac arrest who do not have severe multiple traumatic injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiological characteristics of sudden cardiac arrest in schools.

PubMed

Nishiuchi, Tatsuya; Hayashino, Yasuaki; Iwami, Taku; Kitamura, Tetsuhisa; Nishiyama, Chika; Kajino, Kentaro; Nitta, Masahiko; Hayashi, Yasuyuki; Hiraide, Atsushi

2014-08-01

The present study aimed to clarify the incidence and outcomes of sudden cardiac arrests in schools and the clinically relevant characteristics of individuals who experienced sudden cardiac arrests. We obtained data on sudden cardiac arrests that occurred in schools between January 1, 2005 and December 31, 2009 from the database of the Utstein Osaka Project, a population-based observational study on out-of-hospital cardiac arrests in Osaka, Japan. The data were analyzed to show the epidemiological features of sudden cardiac arrests in schools in conjunction with prehospital documentation. In total, 44 cases were registered as sudden cardiac arrests in schools during the study period. Of these, 34 cases had nontraumatic cardiac arrests. Twenty-one cases (62%) had pre-existing cardiac diseases and/or collapsed during physical exercise. Twenty-three cases (68%) presented with ventricular fibrillation or pulseless ventricular tachycardia, with cases of survival 1 month after cardiac arrest and those having favourable neurological outcome (Cerebral Performance Category 1 or 2) being 12 (52%) and 10 (43%), respectively. The incidence of sudden cardiac arrests in students was 0.23 per 100,000 persons per year, ranging from 0.08 in junior high school to 0.64 in high school. The incidence of sudden cardiac arrests in school faculty and staff was 0.51 per 100,000 persons per year, a rate approximately 2 times of that observed in the students. Although sudden cardiac arrests in schools is rare, they majorly occurred in individuals with cardiac diseases and/or during physical exercise and presented as ventricular fibrillation or pulseless ventricular tachycardia observed initially as cardiac arrhythmia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Takotsubo cardiomyopathy associated with cardiac arrest following cardiac surgery: new variants of an unusual syndrome.

PubMed

Vernick, William J; Hargrove, W Clark; Augoustides, John G; Horak, Jiri

2010-11-01

Takotsubo cardiomyopathy is increasingly being recognized in the perioperative period. To date, there have been only three previous cases involving cardiac surgery reported and this represents the fourth case. The precise mechanism remains elusive, and there is no definitive management strategy. It appears that the syndromes course in cardiac surgical patients is self-limited. This syndrome must now be considered in the differential diagnosis of postcardiotomy cardiac failure. © 2010 Wiley Periodicals, Inc.

Caring for women undergoing cardiac ablation.

PubMed

Keegan, Beryl

2008-09-01

Radiofrequency cardiac ablation (RFCA) has become the treatment of choice for many cardiac arrhythmias that have not responded to medication. Complications of cardiac ablation include bleeding, thrombosis, pericardial tamponade, and stroke. Many complications are procedure specific, and several complications can be avoided with appropriate nursing care. Quality patient outcomes begin with competent nursing care. Therefore it is vital for a patient undergoing a percutaneous cardiac ablation procedure to receive supportive care and pre- and post-interventional patient education. This article discusses the nursing care of women undergoing RFCA.

Mesenchymal stem cells and cardiac repair

PubMed Central

Nesselmann, Catharina; Ma, Nan; Bieback, Karen; Wagner, Wolfgang; Ho, Anthony; Konttinen, Yrjö T; Zhang, Hao; Hinescu, Mihail E; Steinhoff, Gustav

2008-01-01

Accumulating clinical and experimental evidence indicates that mesenchymal stem cells (MSCs) are promising cell types in the treatment of cardiac dysfunction. They may trigger production of reparative growth factors, replace damaged cells and create an environment that favours endogenous cardiac repair. However, identifying mechanisms which regulate the role of MSCs in cardiac repair is still at work. To achieve the maximal clinical benefits, ex vivo manipulation can further enhance MSC therapeutic potential. This review focuses on the mechanism of MSCs in cardiac repair, with emphasis on ex vivo manipulation. PMID:18684237

Mathematical Models of Cardiac Pacemaking Function

NASA Astrophysics Data System (ADS)

Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

2013-10-01

Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Cardiac mechanics: Physiological, clinical, and mathematical considerations

NASA Technical Reports Server (NTRS)

Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

1974-01-01

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

CARDIAC-LIKE OSCILLATION IN LIVER STEM CELLS INDUCE THEIR ACQUISITION OF CARDIAC PHENOTYPE

EPA Science Inventory

We examined in a cardiac microenvironment the plasticity of a liver stem cell line (WB F344) generated from a cloned, single, non-parenchymal epithelial cell from a normal adult male rat. Our previous studies suggested that WB F344 cells acquire a cardiac phenotype in the absenc...

Cardiac macrophages promote diastolic dysfunction.

PubMed

Hulsmans, Maarten; Sager, Hendrik B; Roh, Jason D; Valero-Muñoz, María; Houstis, Nicholas E; Iwamoto, Yoshiko; Sun, Yuan; Wilson, Richard M; Wojtkiewicz, Gregory; Tricot, Benoit; Osborne, Michael T; Hung, Judy; Vinegoni, Claudio; Naxerova, Kamila; Sosnovik, David E; Zile, Michael R; Bradshaw, Amy D; Liao, Ronglih; Tawakol, Ahmed; Weissleder, Ralph; Rosenzweig, Anthony; Swirski, Filip K; Sam, Flora; Nahrendorf, Matthias

2018-02-05

Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic 18 F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction. © 2018 Hulsmans et al.

The role of autophagy in cardiac hypertrophy

PubMed Central

Li, Lanfang; Xu, Jin; He, Lu; Peng, Lijun; Zhong, Qiaoqing; Chen, Linxi; Jiang, Zhisheng

2016-01-01

Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy. PMID:27084518

Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

PubMed Central

2009-01-01

Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays) representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration) in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level. PMID:20003209

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

PubMed Central

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Conflict management by hamadryas baboons (Papio hamadryas hamadryas) during crowding: a tension-reduction strategy.

PubMed

Judge, P G; Griffaton, N S; Fincke, A M

2006-10-01

Primates change a variety of behavioral responses during short-term exposure to crowding. Under crowded conditions, rates of aggression, submissive behavior, and affiliative behavior may increase or decrease. Different patterns of change among these three categories of response have been interpreted as various coping "strategies" for managing the increased risk of conflict under crowded conditions. Grooming is of particular interest because this behavior is known to have a calming influence on the recipient and could be used to manage conflict under tense situations. A captive group of nine hamadryas baboons (Papio hamadryas hamadryas) composed of two harems was observed under short-term crowding to determine whether this species adopts conflict-management strategies similar to those described in other primates. The aggression, submission, affiliation, and displacement activities of the six adults in the group (two males and four females) were recorded, and behaviors in their small indoor quarters was compared with baseline behaviors in the outdoor section of their enclosure, which had over 10 times more space. Repeated-measures analysis of variance (ANOVA) was used to compare behavioral rates during crowding with baseline rates recorded immediately after crowding and during matched controls collected at the same time of day as the crowding sessions. Aggression and submission rates did not change significantly across conditions. Huddling together and proximity increased during crowding, and females increased grooming of their harem male during crowding. Displacement activities (e.g., pacing and self-grooming) increased during crowding, but scratching, an indicator of anxiety in primates, did not. The pattern of behavior exhibited by this group conforms to an active "tension-reduction" strategy in which animals successfully reduce the higher risk of aggression during crowding.

The Endometrial Response to Chorionic Gonadotropin Is Blunted in a Baboon Model of Endometriosis

PubMed Central

Sherwin, J. R. A.; Hastings, J. M.; Jackson, K. S.; Mavrogianis, P. A.; Sharkey, A. M.; Fazleabas, A. T.

2010-01-01

Endometriosis-associated infertility has a multifactorial etiology. We tested the hypothesis that the endometrial response to the early embryonic signal, human chorionic gonadotropin (hCG), alters over time in a nonhuman primate model of endometriosis. Animals with experimental or spontaneous endometriosis were treated with hCG (30 IU/d), from d 6 after ovulation for 5 d, via an oviductal cannula. Microarray analysis of endometrial transcripts from baboons treated with hCG at 3 and 6 months of disease (n = 6) identified 22 and 165 genes, respectively, whose levels differed more than 2-fold compared with disease-free (DF) animals treated with hCG (P < 0.01). Quantitative RT-PCR confirmed abnormal responses of known hCG-regulated genes. APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG were up-regulated by hCG in animals with endometriosis. In contrast, the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry demonstrated dysregulation of C3 and superoxide dismutase 2 proteins. We demonstrate that this abnormal response to hCG persists for up to 15 months after disease induction and that the nature of the abnormal response changes as the disease progresses. Immunohistochemistry showed that this aberrant gene expression was not a consequence of altered LH/choriogonadotropin receptor distribution in the endometrium of animals with endometriosis. We have shown that endometriosis induces complex changes in the response of eutopic endometrium to hCG, which may prevent the acquisition of the full endometrial molecular repertoire necessary for decidualization and tolerance of the fetal allograft. This may in part explain endometriosis-associated implantation failure. PMID:20668030

Neurologic Complications After Cardiac Transplant.

PubMed

Öcal, Ruhsen; Kibaroğlu, Seda; Derle, Eda; Tanoğlu, Ceyda; Camkıran, Aynur; Pirat, Arash; Can, Ufuk; Sezgin, Atilla

2016-06-15

Cardiac transplant is the best available therapy for patients with end-stage heart failure. Neurologic complications occur at a rate of 30% to 70% in patients undergoing cardiac transplant, and they affect mortality and morbidity of these patients. Risk factors for neurologic complications include immunosuppressive medication toxicity, infections, brain lesions, and metabolic disorders. The aim of our study was to determine the incidence of neurologic complications in adult patients undergoing cardiac transplant. We retrospectively evaluated the medical records of 70 patients who underwent cardiac transplant between 2004 and April 2016. We recorded the demographic data, neurologic symptoms, neurologic examination findings, laboratory test results, brain imaging study results, and treatments received of the patients. Of the 70 patients enrolled, 55 were male and 15 were female patients. The age range was 18 to 63 years, and the mean age was 42.4 years. Twelve patients had encephalopathy, 4 had neuropathic pain, 3 had tremor, 2 had ischemic cerebrovascular accident, 7 had posterior reversible encephalopathy syndrome, and 1 had drop foot. Encephalopathy usually developed secondary to other neurologic disorders. The incidence of neurologic complications in adult patients undergoing cardiac transplant was 30%. Neurologic complications are common after cardiac transplant. We observed an incidence of 30% for neurologic complications in our clinic, with encephalopathy being the most common complication. Encephalopathy most commonly developed secondary to posterior reversible encephalopathy syndrome.

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.

PubMed

Kanaan, Georges N; Ichim, Bianca; Gharibeh, Lara; Maharsy, Wael; Patten, David A; Xuan, Jian Ying; Reunov, Arkadiy; Marshall, Philip; Veinot, John; Menzies, Keir; Nemer, Mona; Harper, Mary-Ellen

2018-04-01

Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

PubMed Central

Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

2014-01-01

Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

Cardiac myxoma in pregnancy: a comprehensive review

PubMed Central

Yuan, Shi-Min

2015-01-01

Objective Cardiac myxoma in pregnancy is rare and the clinical characteristics of this entity have been insufficiently elucidated. This article aims to describe the treatment options and the risk factors responsible for the maternal and feto-neonatal prognoses. Methods A comprehensive search of the literature of cardiac myxoma in pregnancy was conducted and 44 articles with 51 patients were included in the present review. Results Transthoracic echocardiography was the most common diagnostic tool for the diagnosis of cardiac myxoma during pregnancy. Cardiac myxoma resection was performed in 95.9% (47/49); while no surgical resection was performed in 4.1% (2/49) patients (P=0.000). More patients had an isolated cardiac myxoma resection in comparison to those with a concurrent or staged additional cardiac operation [87.2% (41/47) vs. 12.8% (6/47), P=0.000]. A voluntary termination of the pregnancy was done in 7 (13.7%) cases. In the remaining 31 (60.8%) pregnant patients, cesarean section was the most common delivery mode representing 61.3% and vaginal delivery was more common accounting for 19.4%. Cardiac surgery was performed in the first, second and third trimester in 5 (13.9%), 14 (38.9%) and 17 (47.2%) patients, respectively. No patients died. In the delivery group, 20 (76.9%) neonates were event-free survivals, 4 (15.4%) were complicated and 2 (7.7%) died. Neonatal prognoses did not differ between the delivery modes, treatment options, timing of cardiac surgery and sequence of cardiac myxoma resection in relation to delivery. Conclusion The diagnosis of cardiac myxoma in pregnancy is important. Surgical treatment of cardiac myxoma in the pregnant patients has brought about favorable maternal and feto-neonatal outcomes in the delivery group, which might be attributable to the shorter operation duration and non-emergency nature of the surgical intervention. Proper timing of cardiac surgery and improved cardiopulmonary bypass conditions may result in even better

Assessing Cardiac Metabolism

PubMed Central

Taegtmeyer, Heinrich; Young, Martin E.; Lopaschuk, Gary D.; Abel, E. Dale; Brunengraber, Henri; Darley-Usmar, Victor; Des Rosiers, Christine; Gerszten, Robert; Glatz, Jan F.; Griffin, Julian L.; Gropler, Robert J.; Holzhuetter, Hermann-Georg; Kizer, Jorge R.; Lewandowski, E. Douglas; Malloy, Craig R.; Neubauer, Stefan; Peterson, Linda R.; Portman, Michael A.; Recchia, Fabio A.; Van Eyk, Jennifer E.; Wang, Thomas J.

2016-01-01

In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart’s needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on “Assessing Cardiac Metabolism” seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity. PMID:27012580

Cardiac anatomy and physiology: a review.

PubMed

Gavaghan, M

1998-04-01

This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy

PubMed Central

Wood, John C.; Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Nelson, Marvin D.; Coates, Thomas D.; Pollack, Harvey; Moats, Rex

2010-01-01

Background Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results Twelve gerbils underwent iron dextran loading (200 mg · kg−1 · wk−1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. Conclusions MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans. PMID:16027257

Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit.

PubMed

Nolan, Jerry P; Soar, Jasmeet; Smith, Gary B; Gwinnutt, Carl; Parrott, Francesca; Power, Sarah; Harrison, David A; Nixon, Edel; Rowan, Kathryn

2014-08-01

To report the incidence, characteristics and outcome of adult in-hospital cardiac arrest in the United Kingdom (UK) National Cardiac Arrest Audit database. A prospectively defined analysis of the UK National Cardiac Arrest Audit (NCAA) database. 144 acute hospitals contributed data relating to 22,628 patients aged 16 years or over receiving chest compressions and/or defibrillation and attended by a hospital-based resuscitation team in response to a 2222 call. The main outcome measures were incidence of adult in-hospital cardiac arrest and survival to hospital discharge. The overall incidence of adult in-hospital cardiac arrest was 1.6 per 1000 hospital admissions with a median across hospitals of 1.5 (interquartile range 1.2-2.2). Incidence varied seasonally, peaking in winter. Overall unadjusted survival to hospital discharge was 18.4%. The presenting rhythm was shockable (ventricular fibrillation or pulseless ventricular tachycardia) in 16.9% and non-shockable (asystole or pulseless electrical activity) in 72.3%; rates of survival to hospital discharge associated with these rhythms were 49.0% and 10.5%, respectively, but varied substantially across hospitals. These first results from the NCAA database describing the current incidence and outcome of adult in-hospital cardiac arrest in UK hospitals will serve as a benchmark from which to assess the future impact of changes in service delivery, organisation and treatment for in-hospital cardiac arrest. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cardiac T1 Imaging

PubMed Central

Jerosch-Herold, Michael; Kwong, Raymond Y.

2014-01-01

T1 mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extra-cellular volume (expansion), and most recently cardiomyocyte hypertrophy. The MRI pulse sequence techniques developed for these applications have had to address at least two important considerations for cardiac applications: measure magnetization inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T1 values, and, secondly, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T1 mapping for assessment of diffuse fibrosis, or myocardial edema show that these techniques enrich the capabilities of MRI for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities. PMID:24509619

Cardiac troponins--Translational biomarkers in cardiology: Theory and practice of cardiac troponin high-sensitivity assays.

PubMed

Adamcova, Michaela; Popelova-Lencova, Olga; Jirkovsky, Eduard; Simko, Fedor; Gersl, Vladimir; Sterba, Martin

2016-01-01

Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the efficacy/safety ratio of novel cardioprotective strategies in clinical settings. cTns can detect myocardial injury not only in a wide spectrum of laboratory animals in experimental studies in vivo, but also in isolated heart models or cardiomyocytes in vitro. The crucial issue regarding the cross-species usage of cardiac troponin investigation remains the choice of cardiac troponin testing. This review summarizes the recent proteomic data on aminoacid sequences of cTnT and cTnI in various species, as well as selected analytical characteristics of human cardiac troponin high-sensitivity assays. Due to the highly phylogenetically conserved structure of troponins, the same bioindicator can be investigated using the same method in both clinical and experimental cardiology, thus contributing to a better understanding of the pathogenesis of cardiac diseases as well as to increased effectiveness of troponin use in clinical practice. Measuring cardiac troponins using commercially available human high-sensitivity cardiac troponin tests with convenient antibodies selected on the basis of adequate proteomic knowledge can solve many issues which would otherwise be difficult to address in clinical settings for various ethical and practical reasons. Our survey could help elaborate the practical guidelines for optimizing the choice of cTns assay in cardiology. © 2016 International Union of Biochemistry and Molecular Biology.

[Rhythm disorders and cardiac crypto-malformations].

PubMed

Davy, J M; Raczka, F; Cung, T T; Combes, N; Bortone, A; Gaty, D

2005-12-01

Faced with a cardiac arrhythmia occuring in an apparently healthy heart, it is necessary to perform an anatomical investigation to detect any unsuspected anomalies. Congenital cardiopathy must certainly be excluded, as this is often responsible for rhythm disorders and/or cardiac conduction defects. Similarly, any acquired conditions, cardiomyopathy, or cardiac tumour must be sought. However, the possibility should always be considered of a minimal congenital malformation, which could be repsonsible for: any type of cardiac arrhythmia: rhythm disorder or conduction defect at the atrial, junctional or ventricular level, with a benign or serious prognosis. Unexpected therapeutic difficulties during radiofrequency ablation procedures or at implantation of pacemakers or defibrillators. Together with rhythm studies, the investigation of choice is high quality imaging, either the classic left or right angiography or the more modern cardiac CT or intracardiac mapping.

The associations between psychological distress and healthcare use in patients with non-cardiac chest pain: does a history of cardiac disease matter?

PubMed

Mourad, Ghassan; Jaarsma, Tiny; Strömberg, Anna; Svensson, Erland; Johansson, Peter

2018-06-05

Psychological distress such as somatization, fear of body sensations, cardiac anxiety and depressive symptoms is common among patients with non-cardiac chest pain, and this may lead to increased healthcare use. However, the relationships between the psychological distress variables and healthcare use, and the differences in relation to history of cardiac disease in these patients has not been studied earlier. Therefore, our aim was to explore and model the associations between different variables of psychological distress (i.e. somatization, fear of body sensations, cardiac anxiety, and depressive symptoms) and healthcare use in patients with non-cardiac chest pain in relation to history of cardiac disease. In total, 552 patients with non-cardiac chest pain (mean age 64 years, 51% women) responded to the Patient Health Questionnaire-15, Body Sensations Questionnaire, Cardiac Anxiety Questionnaire, Patient Health Questionnaire-9 and one question regarding number of healthcare visits. The relationships between the psychological distress variables and healthcare visits were analysed using Structural Equation Modeling in two models representing patients with or without history of cardiac disease. A total of 34% of the patients had previous cardiac disease. These patients were older, more males, and reported more comorbidities, psychological distress and healthcare visits. In both models, no direct association between depressive symptoms and healthcare use was found. However, depressive symptoms had an indirect effect on healthcare use, which was mediated by somatization, fear of body sensations, and cardiac anxiety, and this effect was significantly stronger in patients with history of cardiac disease. Additionally, all the direct and indirect effects between depressive symptoms, somatization, fear of body sensations, cardiac anxiety, and healthcare use were significantly stronger in patients with history of cardiac disease. In patients with non-cardiac chest pain, in