Quantitative aspects of 1-norepinephrine induced pathologic changes: a study in normal dogs

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

Szakacs, J.E.; Mehlman, B.

1959-08-01

The effects of constant rate intravenous infusions of norepinephrine were studied in 28 normal dogs, sedated with morphine. The range of dose rates in this experiment was from 0.5 to 15 mcg/min/kg. Blood levels of epinephrine and norepinephrine were determined in 12 animals up to 10 hours during constant rate infusions. The heart rate and blood pressure were recorded in frequent intervals. The reflex bradycardia was reversed in the animals by prolonged infusions of one or more mcg/min/kg of norepinephrine. Tachycardia and arrhythmia were regularly present in the animals that developed myocardial lesions. Death occurred due to cardiac arrest, massivemore » cerebral hemorrhage or pulmonary edema in the animals infused with 10 mcg/min/kg for 1/2 to 3 hours, or 5 mcg/min/kg for 6 hours. Post mortem examination was performed on all animals. The tissue changes were described and correlated with dosage rate and blood catecholamine levels. 17 references, 8 figures.« less

Flies without centrioles.

PubMed

Basto, Renata; Lau, Joyce; Vinogradova, Tatiana; Gardiol, Alejandra; Woods, C Geoffrey; Khodjakov, Alexey; Raff, Jordan W

2006-06-30

Centrioles and centrosomes have an important role in animal cell organization, but it is uncertain to what extent they are essential for animal development. The Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for centriole replication in flies. DSas-4 mutants start to lose centrioles during embryonic development, and, by third-instar larval stages, no centrioles or centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and approximately 30% of the asymmetric divisions of larval neuroblasts are abnormal. Nevertheless, mutant flies develop with near normal timing into morphologically normal adults. These flies, however, have no cilia or flagella and die shortly after birth because their sensory neurons lack cilia. Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development.

A study of the influence of experimentally induced hypothyroidism on antibody production and decay rates

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

Johnstone, Douglas E.; Howland, Joe W.; Michaelson, Solomon

1962-01-01

The effect of hypothyroidism induced by intravenous injections of I 131 on antibody production, the anamnestic response, and on antibody decay rate, compared to normal animals, was studied in 63 rabbits. After initial antigenic stimulation, normal animals reached a higher peak titer on an average of 5 days earlier than hypothyroid animals. Antibody half-life in these animals, as measured by time for antibody concentration to fall 50% from peak titer, was 11.4 days in normal compared to 21.3 days in hypothyroid animals. Following a second antigenic stimulation, normal rabbits reached a peak titer in an average of 6.4 days comparedmore » to 15 days for hypothyroid animals. The half-life for both groups was measured by determining the rate of disappearance of passively infused antibody. The half-life, thus measured, in normals was 2.4 plus or minus 0.2 days and was 8.8 plus or minus 1.9 days for hypothyroid animals. The time required for serum-tissue equilibration of infused antibody in normals was 1.0 plus or minus 0.00 days compared to 2.3 plus or minus 1.5 days in hypothyroid animals.« less

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

EFFECTS OF ENVIRONMENTAL ANTIANDROGENS ON REPRODUCTIVE DEVELOPMENT IN EXPERIMENTAL ANIMALS

EPA Science Inventory

In mammals, the androgens testosterone (T) and dihydrotestosterone (DHT) are critical for normal male reproductive development and function. In humans, drugs that act as androgen receptor (AR) agonists and antagonists or inhibit fetal steroidogenesis can cause pseudohermaphrodi...

Electrocardiogram reference intervals for clinically normal wild-born chimpanzees (Pan troglodytes).

PubMed

Atencia, Rebeca; Revuelta, Luis; Somauroo, John D; Shave, Robert E

2015-08-01

To generate reference intervals for ECG variables in clinically normal chimpanzees (Pan troglodytes). 100 clinically normal (51 young [< 10 years old] and 49 adult [≥ 10 years old]) wild-born chimpanzees. Electrocardiograms collected between 2009 and 2013 at the Tchimpounga Chimpanzee Rehabilitation Centre were assessed to determine heart rate, PR interval, QRS duration, QT interval, QRS axis, P axis, and T axis. Electrocardiographic characteristics for left ventricular hypertrophy (LVH) and morphology of the ST segment, T wave, and QRS complex were identified. Reference intervals for young and old animals were calculated as mean ± 1.96•SD for normally distributed data and as 5th to 95th percentiles for data not normally distributed. Differences between age groups were assessed by use of unpaired Student t tests. RESULTS Reference intervals were generated for young and adult wild-born chimpanzees. Most animals had sinus rhythm with small or normal P wave morphology; 24 of 51 (47%) young chimpanzees and 30 of 49 (61%) adult chimpanzees had evidence of LVH as determined on the basis of criteria for humans. Cardiac disease has been implicated as the major cause of death in captive chimpanzees. Species-specific ECG reference intervals for chimpanzees may aid in the diagnosis and treatment of animals with, or at risk of developing, heart disease. Chimpanzees with ECG characteristics outside of these intervals should be considered for follow-up assessment and regular cardiac monitoring.

Is the ferret a suitable species for studying perinatal brain injury?

PubMed Central

Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E.

2016-01-01

Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies. PMID:26102988

Gaze-stabilizing deficits and latent nystagmus in monkeys with brief, early-onset visual deprivation: eye movement recordings.

PubMed

Tusa, R J; Mustari, M J; Burrows, A F; Fuchs, A F

2001-08-01

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys (Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40-20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.

Silence and Denial in Everyday Life—The Case of Animal Suffering

PubMed Central

Wicks, Deidre

2011-01-01

Simple Summary This paper analyses issues implicit in the question: How is it that decent and compassionate people co-exist in silence about widespread animal suffering? The paper explores the complex process of denial which operates at both a personal and societal level to allow people to ‘not see’ and ‘not know’ about the realities of the lives of animals in our world. The paper argues that silence allows animal suffering to exist and flourish at a historically unprecedented level at this time. It goes on to examine the conditions under which silence can be punctured and acknowledgement and action for animals becomes possible. Abstract How can we make sense of the fact that we live in a world where good people co-exist in silence about widespread animal suffering. How is it that sites of suffering such as laboratories, factory farms, abattoirs and animal transportation are all around us and yet we ‘do not, in a certain sense, know about them’ [1]. This ‘not knowing’ is one of the most difficult barriers for animal activists who must constantly develop new strategies in an attempt to catch public attention and translate it into action. Recent contributions from the ‘sociology of denial’ have elucidated many of the mechanisms involved in ‘not knowing’ in relation to human atrocities and genocide. In this context, ‘denial’ refers to the maintenance of social worlds in which an undesirable situation is unrecognized, ignored or made to seem normal [2]. These include different types of denial: personal, official and cultural, as well as the process of normalization whereby suffering becomes invisible through routinization, tolerance, accommodation, collusion and cover up. Denial and normalization reflect both personal and collective states where suffering is not acknowledged [3]. In this paper, I will examine insights from the sociology of denial and apply them to human denial and normalization of animal suffering. This will include an examination of denial which is both individual and social and the implications of these insights for theory and practice in the human/animal relationship. PMID:26486223

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys.

PubMed

Walton, Mark M G; Mustari, Michael J

2015-08-01

Strabismus is a common disorder, characterized by a chronic misalignment of the eyes and numerous visual and oculomotor abnormalities. For example, saccades are often highly disconjugate. For humans with pattern strabismus, the horizontal and vertical disconjugacies vary with eye position. In monkeys, manipulations that disturb binocular vision during the first several weeks of life result in a chronic strabismus with characteristics that closely match those in human patients. Early onset strabismus is associated with altered binocular sensitivity of neurons in visual cortex. Here we test the hypothesis that brain stem circuits specific to saccadic eye movements are abnormal. We targeted the pontine paramedian reticular formation, a structure that directly projects to the ipsilateral abducens nucleus. In normal animals, neurons in this structure are characterized by a high-frequency burst of spikes associated with ipsiversive saccades. We recorded single-unit activity from 84 neurons from four monkeys (two normal, one exotrope, and one esotrope), while they made saccades to a visual target on a tangent screen. All 24 neurons recorded from the normal animals had preferred directions within 30° of pure horizontal. For the strabismic animals, the distribution of preferred directions was normal on one side of the brain, but highly variable on the other. In fact, 12/60 neurons recorded from the strabismic animals preferred vertical saccades. Many also had unusually weak or strong bursts. These data suggest that the loss of corresponding binocular vision during infancy impairs the development of normal tuning characteristics for saccade-related neurons in brain stem. Copyright © 2015 the American Physiological Society.

Activation of muscle-specific actin genes in Xenopus development by an induction between animal and vegetal cells of a blastula.

PubMed

Gurdon, J B; Fairman, S; Mohun, T J; Brennan, S

1985-07-01

Muscle gene expression is induced a few hours after vegetal cells of a Xenopus blastula are placed in contact with animal cells that normally develop into epidermis and nerve cells. We have used a muscle-specific actin gene probe to determine the timing of gene activation in animal-vegetal conjugates. Muscle actin RNA is first transcribed in a minority of animal cells at a stage equivalent to late gastrula. The time of muscle gene activation is determined by the developmental stage of the responding (animal) cells, and not by the time when cells are first placed in contact. The minimal cell contact time required for induction is between 1 1/2 and 2 1/2 hr, and the minimal time for gene activation after induction is 5-7 hr.

Assessment of hindlimb locomotor strength in spinal cord transected rats through animal-robot contact force.

PubMed

Nessler, Jeff A; Moustafa-Bayoumi, Moustafa; Soto, Dalziel; Duhon, Jessica; Schmitt, Ryan

2011-12-01

Robotic locomotor training devices have gained popularity in recent years, yet little has been reported regarding contact forces experienced by the subject performing automated locomotor training, particularly in animal models of neurological injury. The purpose of this study was to develop a means for acquiring contact forces between a robotic device and a rodent model of spinal cord injury through instrumentation of a robotic gait training device (the rat stepper) with miniature force/torque sensors. Sensors were placed at each interface between the robot arm and animal's hindlimb and underneath the stepping surface of both hindpaws (four sensors total). Twenty four female, Sprague-Dawley rats received mid-thoracic spinal cord transections as neonates and were included in the study. Of these 24 animals, training began for 18 animals at 21 days of age and continued for four weeks at five min/day, five days/week. The remaining six animals were untrained. Animal-robot contact forces were acquired for trained animals weekly and untrained animals every two weeks while stepping in the robotic device with both 60 and 90% of their body weight supported (BWS). Animals that received training significantly increased the number of weight supported steps over the four week training period. Analysis of raw contact forces revealed significant increases in forward swing and ground reaction forces during this time, and multiple aspects of animal-robot contact forces were significantly correlated with weight bearing stepping. However, when contact forces were normalized to animal body weight, these increasing trends were no longer present. Comparison of trained and untrained animals revealed significant differences in normalized ground reaction forces (both horizontal and vertical) and normalized forward swing force. Finally, both forward swing and ground reaction forces were significantly reduced at 90% BWS when compared to the 60% condition. These results suggest that measurement of animal-robot contact forces using the instrumented rat stepper can provide a sensitive and reliable measure of hindlimb locomotor strength and control of flexor and extensor muscle activity in neurologically impaired animals. Additionally, these measures may be useful as a means to quantify training intensity or dose-related functional outcomes of automated training.

The relation between the cell-mediated immunological response and the induction of circulating antibodies to collagen in guinea-pigs.

PubMed Central

Gentner, G J; Adelmann, B C

1976-01-01

Cutaneous delayed hypersensitivity reactions to collagen in guinea-pigs were partially but specifically suppressed if the animals had been pretreated with collagen and Freund's incomplete adjuvant. Such animals responded normally to skin-reactive factor prepared with ovalbumin. Lymphoid cells from animals with normal delayed hypersensitivity to collagen functioned normally in animals with suppressed skin reactivity. Cells from animals with suppressed delayed hypersensitivity were specifically, functionally impaired since they transferred delayed hypersensitivity into neutral recipients efficiently for PPD but not for collagen. Suppression could be induced in Cy-treated animals, and it persisted for at least 143 days. It is concluded that guinea-pigs with depressed delayed hypersensitivity to collagen are functionally impaired with respect to those T cells normally generated by induction of delayed hypersensitivity. PMID:1088420

Visualizing Infrared (IR) Spectroscopy with Computer Animation

NASA Technical Reports Server (NTRS)

Abrams, Charles B.; Fine, Leonard W.

1996-01-01

IR Tutor, an interactive, animated infrared (IR) spectroscopy tutorial has been developed for Macintosh and IBM-compatible computers. Using unique color animation, complicated vibrational modes can be introduced to beginning students. Rules governing the appearance of IR absorption bands become obvious because the vibrational modes can be visualized. Each peak in the IR spectrum is highlighted, and the animation of the corresponding normal mode can be shown. Students can study each spectrum stepwise, or click on any individual peak to see its assignment. Important regions of each spectrum can be expanded and spectra can be overlaid for comparison. An introduction to the theory of IR spectroscopy is included, making the program a complete instructional package. Our own success in using this software for teaching and research in both academic and industrial environments will be described. IR Tutor consists of three sections: (1) The 'Introduction' is a review of basic principles of spectroscopy. (2) 'Theory' begins with the classical model of a simple diatomic molecule and is expanded to include larger molecules by introducing normal modes and group frequencies. (3) 'Interpretation' is the heart of the tutorial. Thirteen IR spectra are analyzed in detail, covering the most important functional groups. This section features color animation of each normal mode, full interactivity, overlay of related spectra, and expansion of important regions. This section can also be used as a reference.

Do we still need to collect stool? Evaluation of visualized fatty acid absorption: experimental studies using rats.

PubMed

Chiba, T; Ohi, R

1998-01-01

Short-gut syndrome is likely to impair enteric fat utilization. This study was undertaken to develop a clinical test of lipid absorption without fecal collection. The absorption of enterally fed radioactive long-chain fatty acid, beta-methyl-p-(123I)-iodophenylpentadecanoic acid was investigated with continuous chyle collection in rats. The changes in excretion and time-dependent biodistribution of radioactivity of the enterally fed agent were assessed in normal control animals. Similarly, sequential urinary excretion and biodistribution were studied along with scintigraphy using sham-operated and short-gut animals. Approximately 64% of the enterally fed radioactivity was recovered in the collected chyle (24 hours). A comparison of normal control, sham-operated, and short-gut animals showed significantly less urinary and greater fecal excretions of radioactivity in short-gut animals. With the use of sequential scintigraphy, the small intestine, whole-body soft tissues, and urinary bladder were well visualized in sham-operated animals, whereas the large intestine and feces were demonstrated earlier in short-gut animals. Our results suggest that enteral feeding of the agent might be feasible for determining lipid absorption from the the dynamic changes of radioactivity in visualized abdominal organs and in urine.

Development and Characterisation of a Human Chronic Skin Wound Cell Line-Towards an Alternative for Animal Experimentation.

PubMed

Caley, Matthew; Wall, Ivan B; Peake, Matthew; Kipling, David; Giles, Peter; Thomas, David W; Stephens, Phil

2018-03-27

Background : Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives : To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results : Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions : These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.

It was a first class start which laid the basis for a promising future: Experience from comparative studies on gravity related behavior in animals and consequences for future experiments

NASA Astrophysics Data System (ADS)

Horn, Eberhard R.

2000-01-01

The main title was chosen in imitation of the headline of a lecture given by H. S. Wolff at the ESA-Symposium ``Life Odyssey'' in Maastricht/NL (1999) to contrast his pessimistic view of the science output from biological microgravity studies during the past 25 years with an optimistic view of the author who had the opportunity for studies on the gravity sensory systems of developing vertebrates and insects during the space missions STS-55, STS-84, and STS-90, and who was stimulated by this experience to undertake any effort to extend these studies on the International Space Station ISS. We studied compensatory eye and head movements induced by a lateral roll of the animals, and we found that exposure to both microgravity and hypergravity affect their development. Future studies have to consider long-term exposures to altered gravitational conditions to find answers to two questions, the mechanisms of adaptation during exposure, and the degree of residual effects after becoming an adult animal and also after re-entry to IG-conditions. The main hypothesis on the development of animals in space is that a fertilized egg will be converted to a normal adult animal guided by physiological and morphological set-points which represent the genetic program. In case of developmental retardations or accelerations or otherwise occurring deviations from normal structural and physiological development during specific periods of the embryonic and postembryonic life, these genetically defined supervisors activate readaptive mechanisms which direct the developmental processes towards normality, i.e., stability. Thus, an orbit-stabilized organism will be dramatically disturbed after return to Earth. Because this failure will need support to reach neuronal stability, research has also to consider the analysis of mechanisms which are able to overcome these disturbances. This research will open the door to applications because it forms a bridge to human medicine with its analytical research on control procedures over neuropathological mechanisms. .

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

PubMed Central

Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.

2015-01-01

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

Improved animal models for testing gene therapy for atherosclerosis.

PubMed

Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

2014-04-01

Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long-term therapy from vascular endothelium without accelerating atherosclerotic disease.

The influence of surgical transection and anastomosis on the rate of cell proliferation in the colonic epithelium of normal and DMH-treated rats.

PubMed

Barkla, D H; Tutton, P M

1983-10-01

Normal and DMH-treated male rats aged 18-20 weeks underwent surgical transection and anastomosis of the transverse colon. Animals were subsequently killed at intervals of 14, 30 and 72 days. Three hours prior to sacrifice animals were injected with vinblastine sulphate and mitotic indices were subsequently estimated in histological sections. Possible differences between experimental and control groups were tested using a Student's t-test. The results show that the accumulated mitotic indices in normal and DMH-treated colon are statistically similar. The results also show that transection and anastomosis stimulates cell division in both normal and DMH-treated colon and that the increase is of greater amplitude and more prolonged duration in the DMH-treated rats. Carcinomas developed close to the line of anastomosis in DMH-treated but not in control rats. The results support the hypothesis that non-specific injury to hyperplastic colonic epithelium promotes carcinogenesis.

Animal models of human immunodeficiency virus infection. Public Health Service Animal Models Committee.

PubMed

Spertzel, R O

1989-12-01

The search for a model of HIV infection continues. While much of the initial work focussed on animal models of AIDS, more recent efforts have sought animal models of HIV infection in which one or more signs of AIDS may be reproduced. Most initial small animal modelling efforts were negative and many such efforts remain unpublished. In 1988, the Public Health Service (PHS) AIDS Animal Model Committee conducted a survey among PHS agencies to identify published and unpublished data on animal models of HIV. To date, the chimpanzee is the only animal to be reliably infected with HIV albeit without development of signs and symptoms normally associated with human AIDS. One recent study has shown the gibbon to be similarly susceptible to infection with HIV. Mice carrying a chimera of elements of the human immune system have been shown to support the growth of HIV and F1 progeny of transgenic mice containing intact copies of HIV proviral DNA, have developed a disease that resembles some aspects of human AIDS. Rabbits, baboons and rhesus monkeys have also been shown to be infected under certain conditions and/or with selected strains of HIV but again without the development of AIDS symptomatology. This report briefly summarizes published and available unpublished data on these efforts to develop an animal model of HIV infection.

EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

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

Nagareda, C.S.; Kaplan, H.S.

1959-04-01

Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

Enteropathogens identified in dogs entering a Florida animal shelter with normal feces or diarrhea.

PubMed

Tupler, Tiffany; Levy, Julie K; Sabshin, Stephanie J; Tucker, Sylvia J; Greiner, Ellis C; Leutenegger, Christian M

2012-08-01

To determine the frequency of enteropathogens in dogs entering an animal shelter with normal feces or diarrhea. Cross-sectional study. 100 dogs evaluated at an open-admission municipal animal shelter in Florida. Fecal samples were collected within 24 hours after admission from 50 dogs with normal feces and 50 dogs with diarrhea. Feces were tested by fecal flotation, antigen testing, PCR assay, and electron microscopy for selected enteropathogens. 13 enteropathogens were identified. Dogs with diarrhea were significantly more likely to be infected with ≥ 1 enteropathogens (96%) than were dogs with normal feces (78%). Only Clostridium perfringens enterotoxin A gene was significantly more common in dogs with diarrhea (64%) than in dogs with normal feces (40%). Other enteropathogens identified in dogs with and without diarrhea included hookworms (58% and 48%, respectively), Giardia spp (22% and 16%, respectively), canine enteric coronavirus (2% and 18%, respectively), whipworms (12% and 8%, respectively), Cryptosporidium spp (12% and 2%, respectively), ascarids (8% and 8%, respectively), Salmonella spp (2% and 6%, respectively), Cystoisospora spp (2% and 4%, respectively), canine distemper virus (8% and 0%, respectively), Dipylidium caninum (2% and 2%, respectively), canine parvovirus (2% and 2%, respectively), and rotavirus (2% and 0%, respectively). Dogs entered the shelter with a variety of enteropathogens, many of which are pathogenic or zoonotic. Most infections were not associated with diarrhea or any specific dog characteristics, making it difficult to predict the risk of infection for individual animals. Guidelines for preventive measures and empirical treatments that are logistically and financially feasible for use in shelters should be developed for control of the most common and important enteropathogens.

[The ethical aspects of physiological experiment].

PubMed

Al'bertin, S V

2014-01-01

A modern classification of invasive procedures developed according to International Bioethical Principles has been presented. The experimental data convincingly demonstrate that using of noninvasive approaches and techniques give a good opportunity to reduce a number of animals recruited in experiment as well as to keep the normal (not distressful) physiological functions of animals. The data presented stress that development of noninvasive techniques is closely related both to scientific and social aspects of our life, allowing the scientists to provide high validity of experimental data obtained as well as to keep themselves as a human beings.

The cholesteryl octanoate breath test: a new procedure for detection of pancreatic insufficiency in the rat.

PubMed

Mundlos, S; Rhodes, J B; Hofmann, A F

1987-09-01

A breath test for the detection of pancreatic insufficiency was developed and tested in rats. The test features the hydrophobic molecule cholesteryl-1-14C-octanoate, which liberates 14C-octanoic acid when hydrolyzed by carboxyl ester lipase (cholesterol esterase). The 14C-octanoate is absorbed passively and rapidly metabolized to 14CO2, which is excreted in expired air. The compound was administered as an emulsion of cholesteryl octanoate, triglyceride, and lecithin to rats with mild pancreatic insufficiency induced by injecting the pancreatic duct with zein. The animals had exocrine pancreatic hypofunction based on the enzyme content of pancreas at autopsy. Amylase was reduced by 97.1 +/- 1.4%, whereas chymotrypsin was reduced by 73 +/- 14%. The p-aminobenzoic acid test was abnormal at 1 wk (21.68 +/- 8.4%), but become normal at 3 months (72.08 +/- 5.8%) after zein injection. Despite this, the animals gained weight and absorbed fat normally. The 14CO2 excretion rate in the 110-min interval after feeding was significantly reduced to 60% of sham-operated animals. Peak 14CO2 collections 20 min after feeding were reduced by 75 +/- 11%. 14CO2 output was completely normalized by administration of pancreatin prior to the test meal. The results suggest that a sensitive, noninvasive method for detecting deficiency of pancreatic carboxyl ester lipase (cholesterol esterase) secretion in the rat has been developed.

Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

NASA Astrophysics Data System (ADS)

Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

2014-05-01

Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00699b

Animal models of GM2 gangliosidosis: utility and limitations.

PubMed

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.

Animal models of GM2 gangliosidosis: utility and limitations

PubMed Central

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

PubMed

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

I Vivo Quantitative Ultrasound Imaging and Scatter Assessments.

NASA Astrophysics Data System (ADS)

Lu, Zheng Feng

There is evidence that "instrument independent" measurements of ultrasonic scattering properties would provide useful diagnostic information that is not available with conventional ultrasound imaging. This dissertation is a continuing effort to test the above hypothesis and to incorporate quantitative ultrasound methods into clinical examinations for early detection of diffuse liver disease. A well-established reference phantom method was employed to construct quantitative ultrasound images of tissue in vivo. The method was verified by extensive phantom tests. A new method was developed to measure the effective attenuation coefficient of the body wall. The method relates the slope of the difference between the echo signal power spectrum from a uniform region distal to the body wall and the echo signal power spectrum from a reference phantom to the body wall attenuation. The accuracy obtained from phantom tests suggests further studies with animal experiments. Clinically, thirty-five healthy subjects and sixteen patients with diffuse liver disease were studied by these quantitative ultrasound methods. The average attenuation coefficient in normals agreed with previous investigators' results; in vivo backscatter coefficients agreed with the results from normals measured by O'Donnell. Strong discriminating power (p < 0.001) was found for both attenuation and backscatter coefficients between fatty livers and normals; a significant difference (p < 0.01) was observed in the backscatter coefficient but not in the attenuation coefficient between cirrhotic livers and normals. An in vivo animal model of steroid hepatopathy was used to investigate the system sensitivity in detecting early changes in canine liver resulting from corticosteroid administration. The average attenuation coefficient slope increased from 0.7 dB/cm/MHz in controls to 0.82 dB/cm/MHz (at 6 MHz) in treated animals on day 14 into the treatment, and the backscatter coefficient was 26times 10^{ -4}cm^{-1}sr^{-1} in controls compared with 74times 10^{-4}cm^{-1}sr^ {-1} (at 6 MHz) in treated animals. A simplified quantitative approach using video image signals was developed. Results derived both from the r.f. signal analysis and from the video signal analysis are sensitive to the changes in the liver in this animal model.

Dmrt1 is necessary for male sexual development in zebrafish

PubMed Central

Webster, Kaitlyn A.; Schach, Ursula; Ordaz, Angel; Steinfeld, Jocelyn S.; Draper, Bruce W.; Siegfried, Kellee R.

2018-01-01

The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosomes may evolve. PMID:27940159

EFFECTS OF ENVIRONMENTAL ANTIANDROGENS IN EXPERIMENTAL ANIMALS

EPA Science Inventory

In mammals, the androgens testosterone (T) and dihydrotestosterone (DHT) are critical for normal male reproductive development and function. In humans, drugs that act as androgen receptor (AR) agonists and antagonists or inhibit fetal steroidogenesis can cause pseudohermaphrodi...

Normal variation in thermal radiated temperature in cattle: implications for foot-and-mouth disease detection.

PubMed

Gloster, John; Ebert, Katja; Gubbins, Simon; Bashiruddin, John; Paton, David J

2011-11-21

Thermal imagers have been used in a number of disciplines to record animal surface temperatures and as a result detect temperature distributions and abnormalities requiring a particular course of action. Some work, with animals infected with foot-and-mouth disease virus, has suggested that the technique might be used to identify animals in the early stages of disease. In this study, images of 19 healthy cattle have been taken over an extended period to determine hoof and especially coronary band temperatures (a common site for the development of FMD lesions) and eye temperatures (as a surrogate for core body temperature) and to examine how these vary with time and ambient conditions. The results showed that under UK conditions an animal's hoof temperature varied from 10°C to 36°C and was primarily influenced by the ambient temperature and the animal's activity immediately prior to measurement. Eye temperatures were not affected by ambient temperature and are a useful indicator of core body temperature. Given the variation in temperature of the hooves of normal animals under various environmental conditions the use of a single threshold hoof temperature will be at best a modest predictive indicator of early FMD, even if ambient temperature is factored into the evaluation.

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

NASA Technical Reports Server (NTRS)

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Spatial learning and memory is preserved in rats after early development in a microgravity environment.

PubMed

Temple, Meredith D; Kosik, Kenneth S; Steward, Oswald

2002-09-01

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

Spatial learning and memory is preserved in rats after early development in a microgravity environment

NASA Technical Reports Server (NTRS)

Temple, Meredith D.; Kosik, Kenneth S.; Steward, Oswald

2002-01-01

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

PubMed Central

Lindeman, Geoffrey J.; Dagnino, Lina; Gaubatz, Stefan; Xu, Yuhui; Bronson, Roderick T.; Warren, Henry B.; Livingston, David M.

1998-01-01

Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. PMID:9553039

Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept.

PubMed

Prezado, Y; Dos Santos, M; Gonzalez, W; Jouvion, G; Guardiola, C; Heinrich, S; Labiod, D; Juchaux, M; Jourdain, L; Sebrie, C; Pouzoulet, F

2017-12-11

Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to significantly higher doses. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to develop a cost-effective equipment to perform systematic radiobiological studies in view of MBRT. Tumor control for various tumor entities will be addressable as well as studies to unravel the distinct biological mechanisms involved in normal and tumor tissues responses when applying MBRT. With that aim, a series of modifications of a small animal irradiator were performed to make it suitable for MBRT experiments. In addition, the brains of two groups of rats were irradiated. Half of the animals received a standard irradiation, the other half, MBRT. The animals were followed-up for 6.5 months. Substantial brain damage was observed in the group receiving standard RT, in contrast to the MBRT group, where no significant lesions were observed. This work proves the feasibility of the transfer of MBRT outside synchrotron sources towards a small animal irradiator.

Molecular and immunohistochemical analyses of cardiac troponin T during cardiac development in the Mexican axolotl, Ambystoma mexicanum.

PubMed

Zhang, C; Pietras, K M; Sferrazza, G F; Jia, P; Athauda, G; Rueda-de-Leon, E; Rveda-de-Leon, E; Maier, J A; Dube, D K; Lemanski, S L; Lemanski, L F

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for studying heart development because it carries a naturally occurring recessive genetic mutation, designated gene c, for cardiac nonfunction. The double recessive mutants (c/c) fail to form organized myofibrils in the cardiac myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns have been studied in detail and show dramatically decreased expression in the hearts of homozygous mutant embryos. Because of the direct interaction between tropomyosin and troponin T (TnT), and the crucial functions of TnT in the regulation of striated muscle contraction, we have expanded our studies on this animal model to characterize the expression of the TnT gene in cardiac muscle throughout normal axolotl development as well as in mutant axolotls. In addition, we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from axolotl hearts. Confocal microscopy has shown a substantial, but reduced, expression of TnT protein in the mutant hearts when compared to normal during embryonic development. 2006 Wiley-Liss, Inc.

Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation

PubMed Central

Wall, Ivan B.; Peake, Matthew; Kipling, David; Giles, Peter; Thomas, David W.

2018-01-01

Background: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives: To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results: Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions: These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening. PMID:29584680

Animating functional anatomy for the web.

PubMed

Guttmann, G D

2000-04-15

The instructor sometimes has a complex task in explaining the concepts of functional anatomy and embryology to health professional students. However, animations can easily illustrate functional anatomy, clinical procedures, or the developing embryo. Web animation increases the accessibility of this information and makes it much more useful for independent student learning. A modified version of the animation can also be used for patient education. This article defines animation, provides a brief history of animation, discusses the principles of animation, illustrates and evaluates some of the video-editing or movie-making computer software programs, and shows examples of two of the author's animations. These two animations are the inferior alveolar nerve block from the mandibular nerve anesthetics unit and normal temporomandibular joint (TMJ) function from the muscles of the mastication and the TMJ function unit. The software discussed are the industry leaders and have made the job of producing computer-based animations much easier. The programs are Adobe Premiere, Adobe After Effects, Apple QuickTime and Macromedia Flash .

Characterization of beta-cell function of pancreatic islets isolated from bank voles developing glucose intolerance/diabetes: an animal model showing features of both type 1 and type 2 diabetes mellitus, and a possible role of the Ljungan virus.

PubMed

Blixt, Martin; Niklasson, Bo; Sandler, Stellan

2007-01-01

Bank voles (Clethrionomys glareolus) kept in captivity develop diabetes mellitus to a significant extent. Also in wild bank voles, elevated blood glucose has been observed. A newly isolated picornavirus named Ljungan virus (LV) has been found in the pancreas of these bank voles. Moreover, LV infection in combination with environmental factors may cause glucose intolerance/diabetes (GINT/D) in normal mice. The aim of the present study was to investigate the functional characteristics of pancreatic islets, isolated from bank voles, bred in the laboratory but considered LV infected. About 20% of all males and females were classified as GINT/D following a glucose tolerance test. Of these animals the majority had become diabetic by 20 weeks of age, with a tendency towards an earlier onset in the males. GINT/D animals had increased serum insulin levels. Islets were tested on the day of isolation (day 0) and after 1 week of culture for their insulin content and their capacity to synthesize (pro)insulin, secrete insulin and metabolize glucose. Functional differences could be observed between normal and GINT/D animals as well as between genders. An elevated basal insulin secretion was observed on day 0 indicating beta-cell dysfunction among islets isolated from diabetic males. In vitro culture could reverse some functional changes. The increased serum insulin level and the increased basal islet insulin secretion may suggest that the animals had developed a type 2 diabetes-like condition. It is likely that the putative stress imposed in the laboratory, maybe in combination with LV infection, can lead to an increased functional demand on the beta-cells.

Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

PubMed

Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

1985-06-01

To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.

PubMed

Ošiņa, Kristīne; Rostoka, Evita; Isajevs, Sergejs; Sokolovska, Jelizaveta; Sjakste, Tatjana; Sjakste, Nikolajs

2016-11-01

Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein expression, while AV-153 (0.5 mg/kg) administration decreased it. AV-153 increased the expression of Parp1 gene in the kidneys of both intact and diabetic animals. Expression of H2afx mRNA and γH2AX histone protein, a marker of DNA breakage, was not changed in diabetic animals, but AV-153 up-regulated the expression of the gene without any impact on the protein expression. Development of DM was followed by a significant increase in iNOS enzyme expression, while AV-153 down-regulated the enzyme expression up to normal levels. iNos gene expression was also found to be increased in diabetic animals, but unlike the protein, the expression of mRNA was found to be enhanced by AV-153 administration. Expression of both eNOS protein and eNos gene in the kidneys was down-regulated, and the administration of AV-153 normalized the expression level. The effects of the compound in the kidneys of diabetic animals appear to be beneficial, as a trend for the normalization of expression of NO synthases is observed. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats

PubMed Central

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D.; Planer, David; Ben-Dov, Iddo Z.; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-01-01

Aims Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Methods and results Sprague–Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks (‘diet group’). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet (‘low-phosphate group’, n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor κB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. Conclusion We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies. PMID:18390899

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

PubMed

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D; Planer, David; Ben-Dov, Iddo Z; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-08-01

Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies.

[Growth suppression of transplantable tumors in experimental animals given soya proteins].

PubMed

Kireev, G V; Asserova, Iu Iu; Iusupova, A A; Koloiarova, I E; Ibragimov, F A

2006-01-01

The development of a malignant process and antitumor treatment leads to the occurrence of a variety of complications. It is expedient to use biological regulators of natural origin to eliminate the side effect of chemical drugs and to improve the outcomes of antitumor therapy. The antitumor effect of soya proteins and their influence on antibody formation and oxidative processes in the sera of tumor-bearing animals were investigated. Soya proteins are shown to retard the development of a tumorous process, modulate the therapeutic effect of 5-fluorouracil, enhance antibody formation, and normalize serum oxidative processes.

Improved Methods for Electroacupuncture and Electromyographic Recordings in Normal and Parkinsonian Rhesus Monkeys

PubMed Central

Zhao, Feng; Fan, Xiaotong; Grondin, Richard; Edwards, Ramsey; Forman, Eric; Moorehead, Jennifer; Gerhardt, Greg; Wang, Xiaomin; Zhang, Zhiming

2010-01-01

Although acupuncture has been widely and routinely used in healthcare in the USA, its use has been based more on empirical observation than on scientific knowledge. Therefore, there is a great need for better understanding the underlying mechanism(s) of action. A great body of evidence supports that nonhuman primates are a candidate for studying human diseases. However, the use of nonhuman primates in neurophysiological, neuroimaging and neurochemical studies is extremely challenging, especially under fully conscious, alert conditions. In the present study, we developed a protocol for safely performing acupuncture, electro-acupuncture (EA) and electromyography (EMG) in both normal nonhuman primates and animals with parkinsonian-like symptoms. Four normal and four hemiparkinsonian middle-aged rhesus monkeys were extensively trained, behaviorally monitored, and received both EA and EMG for several months. The results demonstrated that (1) all rhesus monkeys used in the study could be trained for procedures including EA and EMG; (2) all animals tolerated the procedures involving needle/electrode insertion; (3) EA procedures used in the study did not adversely alter the animal’s locomotor activities; rather, MPTP-treated animals showed a significant improvement in movement speed; and (4) EMG detected significant differences in muscle activity between the arms with and without MPTP-induced rigidity. Our results support that rhesus monkeys can be used as an experimental animal model to study EA and that EMG has the potential to be used to objectively assess the effects of antiparkinsonian therapies. The results also indicate that animals, especially those with parkinsonian-like symptoms, could benefit from long-term EA stimulations. PMID:20654649

Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus.

PubMed

Derjuga, Anna; Gourley, Tania S; Holm, Teresa M; Heng, Henry H Q; Shivdasani, Ramesh A; Ahmed, Rafi; Andrews, Nancy C; Blank, Volker

2004-04-01

Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.

Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?

PubMed

Mychasiuk, Richelle; Metz, Gerlinde A S

2016-11-01

Adolescence is defined as the gradual period of transition between childhood and adulthood that is characterized by significant brain maturation, growth spurts, sexual maturation, and heightened social interaction. Although originally believed to be a uniquely human aspect of development, rodent and non-human primates demonstrate maturational patterns that distinctly support an adolescent stage. As epigenetic processes are essential for development and differentiation, but also transpire in mature cells in response to environmental influences, they are an important aspect of adolescent brain maturation. The purpose of this review article was to examine epigenetic programming in animal models of brain maturation during adolescence. The discussion focuses on animal models to examine three main concepts; epigenetic processes involved in normal adolescent brain maturation, the influence of fetal programming on adolescent brain development and the epigenome, and finally, postnatal experiences such as exercise and drugs that modify epigenetic processes important for adolescent brain maturation. This corollary emphasizes the utility of animal models to further our understanding of complex processes such as epigenetic regulation and brain development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Animal models of ocular angiogenesis: from development to pathologies.

PubMed

Liu, Chi-Hsiu; Wang, Zhongxiao; Sun, Ye; Chen, Jing

2017-11-01

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies. © FASEB.

[The thyroid gland in emotional and pain stress].

PubMed

Akhmetov, I Z

1987-01-01

The reaction of wild rodent thyroid gland on emotional and painful stress appearing as a result of animal's catching has been studied. The thyroid activity has been shown to raise considerably during the primary stage of stress reaction. Later on the function of the gland normalizes in animals without trauma and in traumatized animals it becomes weaker. The complete normalization of the thyroid function in traumatized animals coincides with osteal regeneration according to time.

Establishment and characterization of a normal melanocyte cell line derived from pig skin.

PubMed

Julé, Sophia; Bossé, Philippe; Egidy, Giorgia; Panthier, Jean-Jacques

2003-08-01

Several minipig strains develop spontaneous malignant melanoma. As a first step toward the analysis of genes involved in the tumoral progression of melanoma in these animal models, we developed culture conditions for pig melanocytes whereby melanocytes from normal epidermis can be isolated directly onto mitotically inactivated keratinocytes in Eagle's minimal essential medium supplemented with fetal calf serum, tetradecanoyl phorbol acetate (TPA) and cholera toxin. We also derived an immortal line of pigmented melanocytes from the epidermis of a healthy Meishan pig. This cell line, designated PigMel, retains differentiation function in culture, dependence on TPA and cholera toxin and a diploid chromosome number. PigMel melanocytes exhibit morphological and molecular characteristics common to normal mammalian skin melanocytes.

THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY.

EPA Science Inventory

The role of apoptosis in neurodegeneration in developing animals and in adults has become increasingly apparent in the past ten years. Normal apoptosis occurs in the CNS from the embryonic stage through senescence, with different cells in each region of the nervous system having ...

Aging of Cloned Animals: A Mini-Review.

PubMed

Burgstaller, Jörg Patrick; Brem, Gottfried

2017-01-01

The number of species for which somatic cell nuclear transfer (SCNT) protocols are established is still increasing. Due to the high number of cloned farm, companion, and sport animals, the topic of animal cloning never ceases to be of public interest. Numerous studies cover the health status of SCNT-derived animals, but very few cover the effects of SCNT on aging. However, only cloned animals that reach the full extent of the species-specific lifespan, doing so with only the normal age-related afflictions and diseases, would prove that SCNT can produce completely healthy offspring. Here, we review the available literature and own data to answer the question whether the aging process of cloned animals is qualitatively different from normal animals. We focus on 4 main factors that were proposed to influence aging in these animals: epigenetic (dys)regulation, accumulation of damaged macromolecules, shortened telomeres, and (nuclear donor-derived) age-related DNA damage. We find that at least some cloned animals can reach the species-specific maximum age with a performance that matches that of normal animals. However, for most species, only anecdotal evidence of cloned animals reaching high age is available. We therefore encourage reports on the aging of cloned animals to make further analysis on the performance of SCNT possible. © 2016 S. Karger AG, Basel.

The dual-specificity protein phosphatase DUSP9/MKP-4 is essential for placental function but is not required for normal embryonic development.

PubMed

Christie, Graham R; Williams, David J; Macisaac, Fiona; Dickinson, Robin J; Rosewell, Ian; Keyse, Stephen M

2005-09-01

To elucidate the physiological role(s) of DUSP9 (dual-specificity phosphatase 9), also known as MKP-4 (mitogen-activated protein kinase [MAPK] phosphatase 4), the gene was deleted in mice. Crossing male chimeras with wild-type females resulted in heterozygous (DUSP9(+/-)) females. However, when these animals were crossed with wild-type (DUSP9(+/y)) males none of the progeny carried the targeted DUSP9 allele, indicating that both female heterozygous and male null (DUSP9(-/y)) animals die in utero. The DUSP9 gene is on the X chromosome, and this pattern of embryonic lethality is consistent with the selective inactivation of the paternal X chromosome in the extraembryonic tissues of the mouse, suggesting that DUSP9/MKP4 performs an essential function during placental development. Examination of embryos between 8 and 10.5 days postcoitum confirmed that lethality was due to a failure of labyrinth development, and this correlates exactly with the normal expression pattern of DUSP9/MKP-4 in the trophoblast giant cells and labyrinth of the placenta. Finally, when the placental defect was rescued, male null (DUSP9(-/y)) embryos developed to term, appeared normal, and were fertile. Our results indicate that DUSP9/MKP-4 is essential for placental organogenesis but is otherwise dispensable for mammalian embryonic development and highlights the critical role of dual-specificity MAPK phosphatases in the regulation of developmental outcomes in vertebrates.

Companion Animal Death.

PubMed

Reisbig, Allison M J; Hafen, McArthur; Siqueira Drake, Adryanna A; Girard, Destiny; Breunig, Zachary B

2017-06-01

Human-animal relationships are increasingly incorporated into families as a normal part of family life. Despite this, relationships with animals are often viewed as inferior to human relationships. This becomes problematic during times of loss and grief when members of a grieving companion animal owner's support system do not understand the salience of the relationship with the animal. Veterinary and other helping professionals need basic information about the experience of companion animal loss in order to help support and normalize the experiences of grieving companion animal owners. The present study qualitatively describes human-animal relationships and the subsequent loss and coping experienced by owners of beloved companion animals. Comparison with human and other types of loss and factors unique to companion animal loss are discussed, and practical applications for veterinary and other helping professionals are provided.

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

PubMed Central

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM+/−) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM+/− cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage. PMID:12119422

The case from animal studies for balanced binocular treatment strategies for human amblyopia.

PubMed

Mitchell, Donald E; Duffy, Kevin R

2014-03-01

Although amblyopia typically manifests itself as a monocular condition, its origin has long been linked to unbalanced neural signals from the two eyes during early postnatal development, a view confirmed by studies conducted on animal models in the last 50 years. Despite recognition of its binocular origin, treatment of amblyopia continues to be dominated by a period of patching of the non-amblyopic eye that necessarily hinders binocular co-operation. This review summarizes evidence from three lines of investigation conducted on an animal model of deprivation amblyopia to support the thesis that treatment of amblyopia should instead focus upon procedures that promote and enhance binocular co-operation. First, experiments with mixed daily visual experience in which episodes of abnormal visual input were pitted against normal binocular exposure revealed that short exposures of the latter offset much longer periods of abnormal input to allow normal development of visual acuity in both eyes. Second, experiments on the use of part-time patching revealed that purposeful introduction of episodes of binocular vision each day could be very beneficial. Periods of binocular exposure that represented 30-50% of the daily visual exposure included with daily occlusion of the non-amblyopic could allow recovery of normal vision in the amblyopic eye. Third, very recent experiments demonstrate that a short 10 day period of total darkness can promote very fast and complete recovery of visual acuity in the amblyopic eye of kittens and may represent an example of a class of artificial environments that have similar beneficial effects. Finally, an approach is described to allow timing of events in kitten and human visual system development to be scaled to optimize the ages for therapeutic interventions. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.

PubMed

Garelli, Andres; Gontijo, Alisson M; Miguela, Veronica; Caparros, Esther; Dominguez, Maria

2012-05-04

Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginal discs autonomously activate DILP8, a Drosophila insulin-like peptide, to communicate abnormal growth and postpone maturation. DILP8 delays metamorphosis by inhibiting ecdysone biosynthesis, slowing growth in the imaginal discs, and generating normal-sized animals. Loss of dilp8 yields asymmetric individuals with an unusually large variation in size and a more varied time of maturation. Thus, DILP8 is a fundamental element of the hitherto ill-defined machinery governing the plasticity that ensures developmental stability and robustness.

Ablation of TrkB expression in RGS9-2 cells leads to hyperphagic obesity★

PubMed Central

Liao, Guey-Ying; Li, Yuqing; Xu, Baoji

2013-01-01

Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB (tropomyosin receptor kinase B), are widely expressed in the brain where they regulate a wide variety of biological processes, including energy homeostasis. However, the specific population(s) of TrkB-expressing neurons through which BDNF governs energy homeostasis remain(s) to be determined. Using the Cre-loxP recombination system, we deleted the mouse TrkB gene in RGS9-2-expressing cells. In this mouse mutant, TrkB expression was abolished in several hypothalamic nuclei, including arcuate nucleus, dorsomedial hypothalamus, and lateral hypothalamus. TrkB expression was also abolished in a small number of cells in other brain regions, including the cerebral cortex and striatum. The mutant animals developed hyperphagic obesity with normal energy expenditure. Despite hyperglycemia under fed conditions, these animals exhibited normal fasting blood glucose levels and normal glucose tolerance. These results suggest that BDNF regulates energy homeostasis in part through TrkB-expressing neurons in the hypothalamus. PMID:24327964

Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content.

PubMed

Showalter, Brent L; Beckstein, Jesse C; Martin, John T; Beattie, Elizabeth E; Espinoza Orías, Alejandro A; Schaer, Thomas P; Vresilovic, Edward J; Elliott, Dawn M

2012-07-01

Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these with the human disc. To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar discs, and cow, rat, and mouse caudal discs. Collagen content was measured and normalized by dry weight for the same discs except the rat and the mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human discs. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Disc torsion mechanics are comparable with human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented are useful for selecting and interpreting results for animal disc models. Structural organization of the fiber angle may explain the differences that were noted between species after geometric normalization.

Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content

PubMed Central

Showalter, Brent L.; Beckstein, Jesse C.; Martin, John T.; Beattie, Elizabeth E.; Orías, Alejandro A. Espinoza; Schaer, Thomas P.; Vresilovic, Edward J.; Elliott, Dawn M.

2012-01-01

Study Design Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these to the human disc. Objective To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. Summary of Background Data There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Methods Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar, and cow, rat, and mouse caudal. Collagen content was measured and normalized by dry weight for the same discs except the rat and mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Results Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Conclusion Disc torsion mechanics are comparable to human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented is useful for selecting and interpreting results for animal models of the disc. Structural composition of the disc, such as initial fiber angle, may explain the differences that were noted between species after geometric normalization. PMID:22333953

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A

PubMed Central

PORADA, C. D.; SANADA, C.; LONG, C. R.; WOOD, J. A.; DESAI, J.; FREDERICK, N.; MILLSAP, L.; BORMANN, C.; MENGES, S. L.; HANNA, C.; FLORES-FOXWORTH, G.; SHIN, T.; WESTHUSIN, M. E.; LIU, W.; GLIMP, H.; ZANJANI, E. D.; LOZIER, J. N.; PLISKA, V.; STRANZINGER, G.; JOERG, H.; KRAEMER, D. C.; ALMEIDA-PORADA, G.

2010-01-01

Summary Background Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives To re-establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non-existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame-shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients. PMID:19943872

Multimedia Materials for Language and Literacy Learning.

ERIC Educational Resources Information Center

Hallett, Terry L.

1999-01-01

Introduces educators to inexpensive, commercially-available CD-ROM software that combines speech, text, graphics, sound, video, animation, and special effects that may be incorporated into classroom activities for both normally developing and language learning disabled children. Discusses three types of multimedia CD-ROM products: (1) virtual…

40 CFR 132.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... lipid) of a substance's lipid-normalized concentration in tissue of an aquatic organism to its organic... develop neoplasms, in animals or humans. The classification of carcinogens is discussed in section II.A of... Species Act. Existing Great Lakes discharger is any building, structure, facility, or installation from...

40 CFR 132.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... lipid) of a substance's lipid-normalized concentration in tissue of an aquatic organism to its organic... develop neoplasms, in animals or humans. The classification of carcinogens is discussed in section II.A of... Species Act. Existing Great Lakes discharger is any building, structure, facility, or installation from...

Environmental enrichment normalizes hippocampal timing coding in a malformed hippocampus.

PubMed

Hernan, Amanda E; Mahoney, J Matthew; Curry, Willie; Richard, Greg; Lucas, Marcella M; Massey, Andrew; Holmes, Gregory L; Scott, Rod C

2018-01-01

Neurodevelopmental insults leading to malformations of cortical development (MCD) are a common cause of psychiatric disorders, learning impairments and epilepsy. In the methylazoxymethanol (MAM) model of MCDs, animals have impairments in spatial cognition that, remarkably, are improved by post-weaning environmental enrichment (EE). To establish how EE impacts network-level mechanisms of spatial cognition, hippocampal in vivo single unit recordings were performed in freely moving animals in an open arena. We took a generalized linear modeling approach to extract fine spike timing (FST) characteristics and related these to place cell fidelity used as a surrogate of spatial cognition. We find that MAM disrupts FST and place-modulated rate coding in hippocampal CA1 and that EE improves many FST parameters towards normal. Moreover, FST parameters predict spatial coherence of neurons, suggesting that mechanisms determining altered FST are responsible for impaired cognition in MCDs. This suggests that FST parameters could represent a therapeutic target to improve cognition even in the context of a brain that develops with a structural abnormality.

Detection of early changes in lung cell cytology by flow-systems analysis techniques. [Rats

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

Steinkamp, J.A.; Wilson, J.S.; Svitra, Z.V.

1980-03-01

Ongoing experiments designed to develop automated flow-analysis methods for assaying damage to pulmonary lavage cells in experimental animals exposed by inhalation to environmental pollutants are summarized. Pulmonary macrophages were characterized on their ability to phagocytize polystyrene latex fluorescent spheres. Lung cells consisting primarily of macrophages and leukocytes were analyzed for fluorescence (phagocytosis of spheres) and size using flow cytometric methods. Studies also concentrated on combining phagocytosis with other cellular parameters (DNA content, cell viability, and B-glucuronidase activity). As baseline studies are completed in normal animals, experimental animals will be exposed to gaseous and particulate environmental pollutants. (ERB

Mouse Model for Human Arginase Deficiency

PubMed Central

Iyer, Ramaswamy K.; Yoo, Paul K.; Kern, Rita M.; Rozengurt, Nora; Tsoa, Rosemarie; O'Brien, William E.; Yu, Hong; Grody, Wayne W.; Cederbaum, Stephen D.

2002-01-01

Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a disorder characterized by progressive mental impairment, growth retardation, and spasticity and punctuated by sometimes fatal episodes of hyperammonemia. We constructed a knockout mouse strain carrying a nonfunctional AI gene by homologous recombination. Arginase AI knockout mice completely lacked liver arginase (AI) activity, exhibited severe symptoms of hyperammonemia, and died between postnatal days 10 and 14. During hyperammonemic crisis, plasma ammonia levels of these mice increased >10-fold compared to those for normal animals. Livers of AI-deficient animals showed hepatocyte abnormalities, including cell swelling and inclusions. Plasma amino acid analysis showed the mean arginine level in knockouts to be approximately fourfold greater than that for the wild type and threefold greater than that for heterozygotes; the mean proline level was approximately one-third and the ornithine level was one-half of the proline and ornithine levels, respectively, for wild-type or heterozygote mice—understandable biochemical consequences of arginase deficiency. Glutamic acid, citrulline, and histidine levels were about 1.5-fold higher than those seen in the phenotypically normal animals. Concentrations of the branched-chain amino acids valine, isoleucine, and leucine were 0.4 to 0.5 times the concentrations seen in phenotypically normal animals. In summary, the AI-deficient mouse duplicates several pathobiological aspects of the human condition and should prove to be a useful model for further study of the disease mechanism(s) and to explore treatment options, such as pharmaceutical administration of sodium phenylbutyrate and/or ornithine and development of gene therapy protocols. PMID:12052859

NASA Workshop on Animal Gravity-Sensing Systems

NASA Technical Reports Server (NTRS)

Corcoran, M. L. (Editor)

1986-01-01

The opportunity for space flight has brought about the need for well-planned research programs that recognize the significance of space flight as a scientific research tool for advancing knowledge of life on Earth, and that utilize each flight opportunity to its fullest. For the first time in history, gravity can be almost completely eliminated. Thus, studies can be undertaken that will help to elucidate the importance of gravity to the normal functioning of living organisms, and to determine the effects microgravity may have on an organism. This workshop was convened to organize a plan for space research on animal gravity-sensing systems and the role that gravity plays in the development and normal functioning of these systems. Scientists working in the field of animal gravity-sensing systems use a wide variety of organisms in their research. The workshop presentations dealt with topics which ranged from the indirect gravity receptor of the water flea, Daphnia (whose antennal setae apparently act as current-sensing receptors as the animal moves up and down in water), through specialized statocyst structures found in jellyfish and gastropods, to the more complex vestibular systems that are characteristic of amphibians, avians, and mammals.

Complete life cycle of the canid tapeworm, Echinococcus multilocularis, in laboratory rodents.

PubMed

Kamiya, M; Sato, H

1990-12-01

Mongolian gerbils, Meriones unguiculatus, when treated at intervals of 2-6 days with prednisolone tertiary butyl acetate, sustained infection with adult Echinococcus multilocularis in the small intestine, with the tapeworm exhibiting normal strobilation and egg production as in the natural canid host. Host age is critical for the survival of the tapeworm in normal gerbils; parasites survive for only 2 days in 20-wk-old animals, 4 days in 4-wk-old animals, but at least 7 days in 3-wk-old animals. The host age dependence in parasite recovery between days 28-37 postinfection was not affected by treatment from around the day of infection. Starting the treatment before infection (on day -17 relative to infection) remarkably improved the tapeworm's survival within the intestine of older animals. Eggs produced in this rodent model system 28 days postinfection were infective to rodents such as Mongolian gerbils and gray red-backed voles, Clethrionomys rufocanus bedfordiae, by oral or intraperitoneal inoculation. The E. multilocularis/Mongolian gerbil system can replace the natural canid hosts as a new way to obtain infective eggs and to analyze host-parasite interactions. The development of an alternative definitive host for zoonotic tapeworms may accelerate experimentation in this field.

The transcription factor Nfix is essential for normal brain development.

PubMed

Campbell, Christine E; Piper, Michael; Plachez, Céline; Yeh, Yu-Ting; Baizer, Joan S; Osinski, Jason M; Litwack, E David; Richards, Linda J; Gronostajski, Richard M

2008-05-13

The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nfic-deficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice. Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals. These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

Variability of hair coat and skin traits as related to adaptation in Criollo Limonero cattle.

PubMed

Landaeta-Hernández, Antonio; Zambrano-Nava, Sunny; Hernández-Fonseca, Juan P; Godoy, Rosario; Calles, Marcos; Iragorri, José L; Añez, Lauderys; Polanco, Miguel; Montero-Urdaneta, Merilio; Olson, Tim

2011-03-01

The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

Animal production systems in the industrialised world.

PubMed

Sørensen, J T; Edwards, S; Noordhuizen, J; Gunnarsson, S

2006-08-01

The production of food from animal origin is relatively stable in the industrialised world. However, animal production systems are changing dramatically with respect to location, herd size and specialisation. Increased pressure from a critical public is moving animal-based production towards systems such as organic production and loose-housing systems which allow the animals to better express normal behaviour. The focus on food safety promotes systems with a high degree of biosecurity, often associated with an increase in herd size and self-containment. The globalisation of agricultural trade and increased competition also favours an increase in herd size and specialisation. These trends also lead to regions with livestock-dense areas, giving rise to environmental concerns. Therefore, good farming practice regulations and systems to provide a higher level of transparency, such as quality risk management programmes, are being developed.

Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease

PubMed Central

Jobe, Alan H.

2015-01-01

Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD. PMID:26301222

Estrogens and development

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

McLachlan, J.A.; Newbold, R.R.

1987-11-01

The normal development of the genital organs of mammals, including humans, is under hormonal control. A role for the female sex hormone estrogen in this process is still unclear. However, exposure of experimental animals or humans to the potent exogenous estrogen, diethylstilbestrol (DES), results in persistent differentiation effects. Since many chemicals in the environment are weakly estrogenic, the possibility of hormonally altered differentiation must be considered.

Protective Role of Eosinophils and TNFa after Ozone Inhalation.

PubMed

Fryer, Allison D; Jacoby, David B; Wicher, Sarah A

2017-03-01

Exposure to ozone induces deleterious responses in the airways that include shortness of breath, inflammation, and bronchoconstriction. People with asthma have increased airway sensitivity to ozone and other irritants. Dr. Allison Fryer and colleagues addressed how exposure to ozone affects the immune and physiological responses in guinea pigs. Guinea pigs are considered a useful animal model for studies of respiratory and physiological responses in humans; their response to airborne allergens is similar to that in humans and shares some features of allergic asthma. Fryer and colleagues had previously observed that within 24 hours of exposure, ozone not only induced bronchoconstriction but also stimulated the production of new cells in the bone marrow, where all white blood cells develop. As a result of ozone exposure, increased numbers of newly synthesized white blood cells, particularly eosinophils, moved into the blood and lungs. The central hypothesis of the current study was that newly synthesized eosinophils recruited to the lungs 3 days after ozone exposure were beneficial to the animals because they reduced ozoneinduced bronchoconstriction. The investigators also hypothesized that the beneficial effect seen in normal (nonsensitized) animals was lost in animals that had been injected with an allergen, ovalbumin (sensitized). They also planned to explore the effects of inhibitors of certain cytokines (cellsignaling molecules). Immune responses in sensitized animals are dominated by a Th2 pattern, which is characterized by the synthesis of cytokines (interleukin [IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+ T lymphocytes and the cells they activate (predominantly eosinophils, and B lymphocytes that switch to making immunoglobulin E [IgE]). Thus, sensitized animals were used as a model of allergic humans, whose immune responses tend to be dominated by IgE. Fryer and colleagues exposed normal and sensitized (allergic) guinea pigs to 2 ppm ozone or filtered air for 4 hours and measured changes in cell numbers and airway responses 1 or 3 days later. They counted the numbers of eosinophils and other white blood cells (macrophages, neutrophils, and lymphocytes) in bone marrow, blood, and bronchoalveolar lung lavage fluid. The investigators also measured important physiological responses, including bronchoconstriction. Some animals were pretreated with etanercept and monoclonal anti-IL-5, which block tumor necrosis factor-a (TNFa) and IL-5, respectively. TNFa and IL-5 blockers have been used to treat patients with asthma. A key feature of the study was a technique to distinguish which white blood cells were synthesized after exposure from those that already existed, by injecting animals with bromodeoxyuridine (BrdU). BrdU is a thymidine analogue that is incorporated into the DNA of dividing cells, serving as a marker of newly produced cells. Therefore, a snapshot can be obtained of the proportion of newly synthesized (BrdU-positive) versus pre-existing (BrdU-negative) cell types. 1. Allergic and normal animals differed in the time course of bronchoconstriction and changes in cell types after ozone exposure. In normal animals, bronchoconstriction increased substantially at day 1 but decreased by day 3 after ozone exposure. In contrast, in allergic animals bronchoconstriction remained high at day 3. Ozone also increased the percentage of newly formed, BrdU2 positive eosinophils in the bone marrow and lungs of normal but not allergic animals. 2. Pretreatment with the TNFa blocker etanercept had complex effects, which differed between normal and allergic animals. In normal animals, etanercept decreased ozone-induced new synthesis of eosinophils in the bone marrow and blocked eosinophil migration to the lung; it also increased bronchoconstriction at day 3 (relative to day 1 without etanercept). In allergic animals, etanercept had no effect on any cell type in the bone marrow or lung after exposure to ozone and did not change bronchoconstriction compared with allergic animals not treated with etanercept. Etanercept tended to increase the numbers of blood monocytes and lymphocytes in air- and ozone-exposed normal and allergic animals at day 3, but had no effect on eosinophils in blood at this time point. This was one of the few statistically significant findings in the blood of exposed animals in the study. 3. Anti-IL-5 reduced bronchoconstriction at day 3 after exposure of allergic animals to ozone. In contrast, bronchoconstriction was greatly increased in normal animals treated with anti-IL-5. Fryer and colleagues explored the airway and cellular responses in guinea pigs exposed to ozone. The HEI Review Committee, which conducted an independent review of the study, agreed that the findings supported the authors’ hypothesis (1) that exposure to ozone stimulates production of eosinophils in bone marrow, (2) that these newly formed eosinophils migrate to the lungs, and (3) that those eosinophils play a delayed but potentially beneficial role in reducing ozone-induced inflammation in the airways of healthy normal animals, but not in allergen-sensitized animals. The Committee also agreed that guinea pigs were a good model for studying responses to an allergen, because a major subtype of asthma (the high Th2 or allergic type) is associated with high levels of eosinophils in the blood. A novel finding was that the TNFa blocker etanercept decreased ozone-induced formation of eosinophils in the bone marrow and blocked eosinophil migration to the lung in normal animals. However, because injecting etanercept had little effect on eosinophils and did not decrease bronchoconstriction in allergic guinea pigs, the potential for treating patients with allergic asthma with TNFa blockers is uncertain. This is consistent with the poor performance of TNFa blockers in clinical studies of asthma treatment. Blocking the cytokine IL-5 with an anti-IL-5 antibody substantially decreased bronchoconstriction in sensitized animals. This suggests that therapies targeting IL-5 and eosinophils would be promising in at least some types of asthma. The Committee expressed caution toward experiments with cytokine blockers, both in animal models and humans, because such blockers are often not specific to a particular cell type and may differ at different sites in the body. Without further detailed confirmation of the effects of the blockers, interpreting these experiments can be challenging. The Committee concluded that the study by Fryer and colleagues raises several intriguing directions for future research, including exploring ways in which newly formed eosinophils differ from pre-existing ones, and how such findings apply to humans with allergy or asthma.

Diet-induced loss of cyclic ovarian function at normal body weight in a rodent model for bulimia nervosa.

PubMed

Leigh, A J; Stock, M J; Lacey, J H; Wilson, C A

1998-03-01

A bulimic rat model was used to test whether type and frequency of food intake mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce an effect on glycoprotein (LH) structure, or affect both processes and if so, to determine whether any such effects were acute, or persisted after return to normal eating patterns. Voluntary hyperphagia was induced by offering female rats a varied and palatable choice of human food items--the 'cafeteria diet'. There were four groups: control (normal chow), obese (continuous cafeteria diet), post-obese (cafeteria diet, then fasted to reduce weight to that of controls) and binge (cafeteria alternated with normal diet every few days). Animals were maintained on these diets for 60 days (phase I). They were then given a GnRH challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of the animals in each group were killed for assessment of effects on their reproductive organs. The remaining animals were returned to normal diets and kept for a further 40 days, when the GnRH challenge was repeated and the animals were killed 24 h later (phase II). All animals on the cafeteria diet in phase I exhibited significant disruption of oestrous cyclicity irrespective of body weight. LH released in response to the first GnRH challenge showed a prolonged half-life, and/or increased rate of secretion in the obese and post-obese groups but in the binge group the secretory/clearance properties resembled those of control animals. After the second GnRH challenge at the end of phase II, however, the LH of the binge group appeared to have different secretory or clearance characteristics, whereas that of the previously obese animals had returned to normal. These data show ovarian cyclicity was disrupted by hyperphagia and irregular eating, even at normal body weight. Relating ovarian function to pituitary output in terms of LH, the effects of the continuous cafeteria diet did not appear to persist in the animals that returned to normal diets, but in the binge group the effect, presumably of the diet manipulation, was manifested after return to a normal eating pattern. This finding suggests that irregular eating habits may exert a direct (and acute) effect on the ovary, but that effects on the pituitary (and LH glycoforms) take longer to be expressed, explaining many features of bulimia nervosa.

The development of Wilms tumor: from WT1 and microRNA to animal models.

PubMed

Tian, Fang; Yourek, Gregory; Shi, Xiaolei; Yang, Yili

2014-08-01

Wilms tumor recapitulates the development of the kidney and represents a unique opportunity to understand the relationship between normal and tumor development. This has been illustrated by the findings that mutations of Wnt/β-catenin pathway-related WT1, β-catenin, and WTX together account for about one-third of Wilms tumor cases. While intense efforts are being made to explore the genetic basis of the other two-thirds of tumor cases, it is worth noting that, epigenetic changes, particularly the loss of imprinting of the DNA region encoding the major fetal growth factor IGF2, which results in its biallelic over-expression, are closely associated with the development of many Wilms tumors. Recent investigations also revealed that mutations of Drosha and Dicer, the RNases required for miRNA generation, and Dis3L2, the 3'-5' exonuclease that normally degrades miRNAs and mRNAs, could cause predisposition to Wilms tumors, demonstrating that miRNA can play a pivotal role in Wilms tumor development. Interestingly, Lin28, a direct target of miRNA let-7 and potent regulator of stem cell self-renewal and differentiation, is significantly elevated in some Wilms tumors, and enforced expression of Lin28 during kidney development could induce Wilms tumor. With the success in establishing mice nephroblastoma models through over-expressing IGF2 and deleting WT1, and advances in understanding the ENU-induced rat model, we are now able to explore the molecular and cellular mechanisms induced by these genetic, epigenetic, and miRNA alterations in animal models to understand the development of Wilms tumor. These animal models may also serve as valuable systems to assess new treatment targets and strategies for Wilms tumor. Copyright © 2014 Elsevier B.V. All rights reserved.

New Concepts in the Pathogenesis, Diagnosis and Control of Diseases Caused by the Bovine Viral Diarrhea Virus

PubMed Central

Radostits, Otto M.; Littlejohns, Ian R.

1988-01-01

The new information on the pathogenesis and epidemiology of mucosal disease of cattle is reviewed. It is now known that clinical mucosal disease occurs only in cattle which were infected with a pestivirus in early gestation and were born with persistent viral infection and specific immunotolerance. These animals may be clinically normal at birth but may develop fatal mucosal disease, perhaps following superinfection with another pestivirus, usually between 6 and 24 months of age. They may also remain clinically normal indefinitely and breed successfully. The progeny from persistently infected females will similarly be persistently viremic, and maternal families of such animals may be established. Congenital defects may occur when infection of the fetus occurs in mid-gestation. Although fetuses may be infected in utero in late gestation, the infections do not persist, the fetuses develop antibodies, and they appear to suffer no ill-effects. Postnatal infection can result in subclinical disease (bovine viral diarrhea) with a normal immune response; the virus may also be responsible for enhanced susceptibility to other infections, diarrhea in newborn calves, and reproductive failure. Prevention of the economically important diseases caused by the virus is dependent upon the identification and elimination of persistently viremic animals, which are reservoirs of infection, and the vaccination of immunocompetent females at least three weeks before breeding. However, because of serotypic differences between strains, there is some doubt whether vaccination will reliably provide protection against the transplacental fetal infections that are important in the pathogenesis of this disease. There is no substantial evidence to warrant the vaccination of feedlot cattle. PMID:17423063

Spontaneous occurrence of a potentially night blinding disorder in guinea pigs.

PubMed

Racine, Julie; Behn, Darren; Simard, Eric; Lachapelle, Pierre

2003-07-01

Several hereditary retinal disorders such as retinitis pigmentosa and congenital stationary night blindness compromise, sometimes exclusively, the activity of the rod pathway. Unfortunately, there are few animal models of these disorders that could help us better understand the pathophysiological processes involved. The purpose of this report is to present a pedigree of guinea pigs where, as a result of a consanguineous mating and subsequent selective breeding, we developed a new and naturally occurring animal model of a rod disorder. Analysis of the retinal function with the electroretinogram reveals that the threshold for rod-mediated electroretinograms (ERGs) is significantly increased by more than 2 log-units compared to that of normal guinea pigs. Furthermore, in response to a suprathreshold stimulus, also delivered under scotopic condition, which yield a mixed cone-rod response in normal guinea pigs, the ERG waveform in our mutant guinea pigs is almost identical (amplitude and timing of a- and b-waves) to that evoked in photopic condition. The above would thus suggest either a structural (abnormal development or absence) or a functional deficiency of the rod photoreceptors. We believe that our pedigree possibly represents a new animal model of a night blinding disorder, and that this condition is inherited as anautosomal recessive trait in the guinea pig population.

Animals in a bacterial world, a new imperative for the life sciences

PubMed Central

McFall-Ngai, Margaret; Hadfield, Michael G.; Bosch, Thomas C. G.; Carey, Hannah V.; Domazet-Lošo, Tomislav; Douglas, Angela E.; Dubilier, Nicole; Eberl, Gerard; Fukami, Tadashi; Gilbert, Scott F.; Hentschel, Ute; King, Nicole; Kjelleberg, Staffan; Knoll, Andrew H.; Kremer, Natacha; Mazmanian, Sarkis K.; Metcalf, Jessica L.; Nealson, Kenneth; Pierce, Naomi E.; Rawls, John F.; Reid, Ann; Ruby, Edward G.; Rumpho, Mary; Sanders, Jon G.; Tautz, Diethard; Wernegreen, Jennifer J.

2013-01-01

In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbioses, is fundamentally altering our understanding of animal biology. Specifically, we highlight recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction. As answers to these fundamental questions emerge, all biologists will be challenged to broaden their appreciation of these interactions and to include investigations of the relationships between and among bacteria and their animal partners as we seek a better understanding of the natural world. PMID:23391737

IT-25DEVELOPMENTALLY REGULATED ANTIGENS FOR IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES

PubMed Central

Pham, Christina; Flores, Catherine; Pei, Yanxin; Wechsler-Reya, Robert; Mitchell, Duane

2014-01-01

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy presents a promising alternative by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Emerging evidence from integrated genomic studies has suggested MB variants arise from deregulation of pathways affecting proliferation of progenitor cell populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and can be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.

Bone development in laboratory mammals used in developmental toxicity studies.

PubMed

DeSesso, John M; Scialli, Anthony R

2018-06-19

Evaluation of the skeleton in laboratory animals is a standard component of developmental toxicology testing. Standard methods of performing the evaluation have been established, and modification of the evaluation using imaging technologies is under development. The embryology of the rodent, rabbit, and primate skeleton has been characterized in detail and summarized herein. The rich literature on variations and malformations in skeletal development that can occur in the offspring of normal animals and animals exposed to test articles in toxicology studies is reviewed. These perturbations of skeletal development include ossification delays, alterations in number, shape, and size of ossification centers, and alterations in numbers of ribs and vertebrae. Because the skeleton is undergoing developmental changes at the time fetuses are evaluated in most study designs, transient delays in development can produce apparent findings of abnormal skeletal structure. The determination of whether a finding represents a permanent change in embryo development with adverse consequences for the organism is important in study interpretation. Knowledge of embryological processes and schedules can assist in interpretation of skeletal findings. © 2018 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

PubMed Central

Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

Animal Enclosure Module (AEM)

NASA Technical Reports Server (NTRS)

1998-01-01

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

Neural image analysis in the process of quality assessment: domestic pig oocytes

NASA Astrophysics Data System (ADS)

Boniecki, P.; Przybył, J.; Kuzimska, T.; Mueller, W.; Raba, B.; Lewicki, A.; Przybył, K.; Zaborowicz, M.; Koszela, K.

2014-04-01

The questions related to quality classification of animal oocytes are explored by numerous scientific and research centres. This research is important, particularly in the context of improving the breeding value of farm animals. The methods leading to the stimulation of normal development of a larger number of fertilised animal oocytes in extracorporeal conditions are of special importance. Growing interest in the techniques of supported reproduction resulted in searching for new, increasingly effective methods for quality assessment of mammalian gametes and embryos. Progress in the production of in vitro animal embryos in fact depends on proper classification of obtained oocytes. The aim of this paper was the development of an original method for quality assessment of oocytes, performed on the basis of their graphical presentation in the form of microscopic digital images. The classification process was implemented on the basis of the information coded in the form of microphotographic pictures of the oocytes of domestic pig, using the modern methods of neural image analysis.

Animal Models for Dysphagia Studies: What Have We Learnt So Far.

PubMed

German, Rebecca Z; Crompton, A W; Gould, Francois D H; Thexton, Allan J

2017-02-01

Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes.

Animal Models for Dysphagia Studies: What have we learnt so far

PubMed Central

German, Rebecca Z.; Crompton, A.W.; Gould, Francois D. H.; Thexton, Allan J.

2017-01-01

Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes. PMID:28132098

The use of a whole animal biophotonic model as a screen for the angiogenic potential of estrogenic compounds

USDA-ARS?s Scientific Manuscript database

Vascular endothelial growth factor (VEGF) is essential for normal vascular growth and development during wound repair. VEGF is estrogen responsive and capable of regulating its own receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). Several agricultural pesticides (e.g., methoxychlor)...

Ancient Dietary Wisdom for Tomorrow's Children.

ERIC Educational Resources Information Center

Fallon, Sally

1997-01-01

A review of Dr. Weston Price's work on the nutritional practices of "primitive" peoples and their subsequent levels of physical development shows that animal fats and cholesterol are not villains but vital factors in the diet, necessary for normal growth, proper functioning of the brain and nervous system, protection from disease, and…

Bilateral phacoemulsification in an orangutan (Pongo pygmaeus).

PubMed

Montiani-Ferreira, Fabiano; Lima, Leandro; Bacellar, Marianna; D'Otaviano Vilani, Ricardo G; Fedullo, José Daniel; Lange, Rogério R

2010-09-01

A 14-year-old, female, captive-born orangutan (Pongo pygmaeus) developed bilateral cataracts. Ultrasonography, electroretinography and cataract correction using phacoemulsification were performed bilaterally. This case report aims to describe the ophthalmic procedures performed in this animal critically endangered of extinction. The surgery successfully restored vision and normal activity to the patient.

Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease

PubMed Central

Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.

2014-01-01

Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD. PMID:24911162

Animal studies on growth and development.

PubMed

Lerchl, Alexander

2011-12-01

Despite the fact that no plausible biological mechanism has yet been identified how electromagnetic fields below recommended exposure limits could negatively affect health of animals or humans, many experiments have been performed in various animal species, mainly mice and rats, to investigate the possible effects on growth and development. While older studies often suffered from sub-optimal exposure conditions, recent investigations, using sophisticated exposure devices and thus preventing thermal effects, have been performed without these limitations. In principle, two types of studies can be addressed: those which have investigated the carcinogenic or co-carcinogenic effects of exposure in developing animals, and those which have been done in developing animals without the focus on carcinogenic or co-carcinogenic effects. In both areas, the vast majority of publications did not show adverse effects. The largest study so far has been done in normal mice which have been chronically exposed to UMTS signals up to 1.3 W/kg SAR, thus 16 times higher than the whole-body exposure limit for humans. Even after four generations, no systematic or dose-dependent alterations in development or fertility could be found, supporting the view that negative effects on humans are very unlikely. Ongoing experiments in our laboratory investigate the effects of head-only exposure in rats (up to 10 W/kg local SAR) which are exposed from 14 days of age daily for 2 h. A battery of behavioral tests is performed in young, adult, and pre-senile animals. The results will help to clarify possible effects of exposure on brain development. Copyright © 2011 Elsevier Ltd. All rights reserved.

How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets.

PubMed

Vanden Hole, Charlotte; Goyens, Jana; Prims, Sara; Fransen, Erik; Ayuso Hernando, Miriam; Van Cruchten, Steven; Aerts, Peter; Van Ginneken, Chris

2017-08-01

Locomotion is one of the most important ecological functions in animals. Precocial animals, such as pigs, are capable of independent locomotion shortly after birth. This raises the question whether coordinated movement patterns and the underlying muscular control in these animals is fully innate or whether there still exists a rapid maturation. We addressed this question by studying gait development in neonatal pigs through the analysis of spatio-temporal gait characteristics during locomotion at self-selected speed. To this end, we made video recordings of piglets walking along a corridor at several time points (from 0 h to 96 h). After digitization of the footfalls, we analysed self-selected speed and spatio-temporal characteristics (e.g. stride and step lengths, stride frequency and duty factor) to study dynamic similarity, intralimb coordination and interlimb coordination. To assess the variability of the gait pattern, left-right asymmetry was studied. To distinguish neuromotor maturation from effects caused by growth, both absolute and normalized data (according to the dynamic similarity concept) were included in the analysis. All normalized spatio-temporal variables reached stable values within 4 h of birth, with most of them showing little change after the age of 2 h. Most asymmetry indices showed stable values, hovering around 10%, within 8 h of birth. These results indicate that coordinated movement patterns are not entirely innate, but that a rapid neuromotor maturation, potentially also the result of the rearrangement or recombination of existing motor modules, takes place in these precocial animals. © 2017. Published by The Company of Biologists Ltd.

Establishment of Normal Gut Microbiota Is Compromised under Excessive Hygiene Conditions

PubMed Central

Schmidt, Bettina; Mulder, Imke E.; Musk, Corran C.; Aminov, Rustam I.; Lewis, Marie; Stokes, Christopher R.; Bailey, Mick; Prosser, James I.; Gill, Bhupinder P.; Pluske, John R.; Kelly, Denise

2011-01-01

Background Early gut colonization events are purported to have a major impact on the incidence of infectious, inflammatory and autoimmune diseases in later life. Hence, factors which influence this process may have important implications for both human and animal health. Previously, we demonstrated strong influences of early-life environment on gut microbiota composition in adult pigs. Here, we sought to further investigate the impact of limiting microbial exposure during early life on the development of the pig gut microbiota. Methodology/Principal Findings Outdoor- and indoor-reared animals, exposed to the microbiota in their natural rearing environment for the first two days of life, were transferred to an isolator facility and adult gut microbial diversity was analyzed by 16S rRNA gene sequencing. From a total of 2,196 high-quality 16S rRNA gene sequences, 440 phylotypes were identified in the outdoor group and 431 phylotypes in the indoor group. The majority of clones were assigned to the four phyla Firmicutes (67.5% of all sequences), Proteobacteria (17.7%), Bacteroidetes (13.5%) and to a lesser extent, Actinobacteria (0.1%). Although the initial maternal and environmental microbial inoculum of isolator-reared animals was identical to that of their naturally-reared littermates, the microbial succession and stabilization events reported previously in naturally-reared outdoor animals did not occur. In contrast, the gut microbiota of isolator-reared animals remained highly diverse containing a large number of distinct phylotypes. Conclusions/Significance The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene. PMID:22164261

High-Throughput Fluorescence-Based Isolation of Live C. elegans Larvae

PubMed Central

Fernandez, Anita G.; Bargmann, Bastiaan O. R.; Mis, Emily K.; Edgley, Mark. L.; Birnbaum, Kenneth D.; Piano, Fabio

2017-01-01

For the nematode Caenorhabditis elegans, automated selection of animals of specific genotypes from a mixed pool has become essential for genetic interaction or chemical screens. To date, such selection has been accomplished using specialized instruments. However, access to such dedicated equipment is not common. Here we describe live animal fluorescence-activated cell sorting (laFACS), a protocol for automatic selection of live L1 animals using a standard FACS. We show that a FACS can be used for the precise identification of GFP-expressing and non-GFP-expressing sub-populations and can accomplish high-speed sorting of live animals. We have routinely collected 100,000 or more homozygotes from a mixed starting population within two hours and with greater than ninety-nine percent purity. The sorted animals continue to develop normally, making this protocol ideally suited for the isolation of terminal mutants for use in genetic interaction or chemical genetic screens. PMID:22814389

What Do Animal Studies Tell Us about the Mechanism of Myopia-Protection by Light?

PubMed

Norton, Thomas T

2016-09-01

: Human studies have provided strong evidence that exposure to time outdoors is protective against the onset of myopia. A causal factor may be that the light levels outdoors (30,000-130,000 lux) are much higher than light levels indoors (typically less than 500 lux). Studies using animal models have found that normal animals exposed to low illuminance levels (50 lux) can develop myopia. The myopia and axial elongation, produced in animals by monocular form deprivation, is reduced by light levels in the 15,000 to 25,000 range. Myopia induced with a negative-power lens seems less affected, perhaps because the lens provides a powerful target for the emmetropization mechanism. Animal studies suggest that raising the light levels may have their effect by increasing retinal dopamine activity, probably via the D2 receptor pathway, altering gene expression in the retina and reducing the signals that produce axial elongation.

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

PubMed Central

2011-01-01

Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

Behavioural Adaptation to diminished Gravity in Fish - a Parabolic Aircraft Flight Study

NASA Astrophysics Data System (ADS)

Forster, A.; Anken, R.; Hilbig, R.

During the micro gravity phases in the course of parabolic aircraft flights PFs some fish of a given batch were frequently shown to exhibit sensorimotor disorders in terms of revealing so-called looping responses LR or spinning movements SM both forms of motion sickness a kinetosis In order to gain some insights into the time-course of the behavioural adaptation towards diminished gravity in total 272 larval cichlid fish Oreochromis mossambicus were subjected to PFs and their respective behaviour was monitored With the onset of the first parabola P1 15 9 of the animals revealed a kinetotic behaviour whereas kinetoses were shown in 6 5 1 5 and 1 of the animals in P5 P10 and P15 With P20 the animals had adapted completely 0 swimming kinetotically Since the relative decrease of kinetotic animals was especially prominent from P5 to P10 a detailed analysis of the behaviour was undertaken Regarding SM a ratio of 2 9 in P5 decreased to 0 5 in P10 Virtually all individuals showing a SM in P5 had regained a normal behaviour with P10 The SM animals in P10 had all exhibited a normal swimming behaviour in P5 The ratio of LR-fish also decreased from P5 3 6 to P10 1 0 In contrast to the findings regarding SM numerous LM specimens did not regain a normal postural control and only very few animals behaving normally in P5 began to sport a LM behaviour by P10 Summarizing most kinetotic animals rapidly adapted to diminished gravity but few individual fish who swam normally at the beginning of the flights may loose sensorimotor control

Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states.

PubMed

Bee, L A; Dickenson, A H

2007-07-13

Complex networks of pathways project from various structures in the brain to modulate spinal processing of sensory input in a top-down fashion. The rostral ventromedial medulla (RVM) in the brainstem is one major final common output of this endogenous modulatory system and is involved in the relay of sensory information between the spinal cord and brain. The net output of descending neurons that exert inhibitory and facilitatory effects will determine whether neuronal activity in the spinal cord is increased or decreased. By pharmacologically blocking RVM activity with the local anesthetic lignocaine, and then measuring evoked responses of dorsal horn neurons to a range of applied peripheral stimuli, our aim was to determine the prevailing descending influence operating in normal anesthetized animals and animals with experimental neuropathic pain. The injection of 0.8 microl 2% lignocaine into the RVM caused a reduction in deep dorsal horn neuronal responses to electrical and natural stimuli in 64% of normal animals and in 81% of spinal-nerve-ligated (SNL) animals. In normal animals, responses to noxious input were predominantly reduced, while in SNL animals, reductions in spinal cord activity induced by intra-RVM lignocaine further included responses to non-noxious stimuli. This suggests that in terms of activity at least, if not number, descending facilitations are the predominant RVM influence that impacts the spinal cord in normal animals. Moreover, the increase in the proportion of neurons showing a post-lignocaine reduction in dorsal horn activity in SNL rats suggests that the strength of these facilitatory influences increases after neuropathy. This predominant inhibitory spinal effect following the injection of lignocaine into the RVM may be due to blockade of facilitatory On cells.

Estrogen Deprivation in Primate Pregnancy Leads to Insulin Resistance in Offspring

PubMed Central

Maniu, Adina; Aberdeen, Graham W.; Lynch, Terrie J.; Nadler, Jerry L.; Kim, Soon OK; Quon, Michael J.; Pepe, Gerald J.; Albrecht, Eugene D.

2016-01-01

This study tested the hypothesis that estrogen programs mechanisms within the primate fetus that promote insulin sensitivity and glucose homeostasis in offspring. Glucose tolerance tests were performed longitudinally in prepubertal offspring of baboons untreated or treated on days 100 to 165/175 of gestation (term is 184 days) with the aromatase inhibitor letrozole which decreased fetal estradiol levels by 95%. Basal plasma insulin levels were over 2-fold greater in offspring delivered to letrozole-treated than untreated animals. Moreover, the peak 1 min, average of the 1, 3 and 5 min, and area under the curve blood glucose and plasma insulin levels after an iv bolus of glucose were greater (P<0.05 and P<0.01, respectively) in offspring deprived of estrogen in utero than in untreated animals and partially or completely restored in letrozole plus estradiol-treated baboons. The value for the homeostasis model assessment of insulin resistance was 2.5-fold greater (P<0.02) and quantitative insulin sensitivity check index lower (P<0.01) in offspring of letrozole-treated versus untreated animals and returned to almost normal in letrozole plus estradiol-treated animals. The exaggerated rise in glucose and insulin levels after glucose challenge in baboon offspring deprived of estrogen in utero indicates that pancreatic beta cells had the capacity to secrete insulin, but that peripheral glucose uptake and/or metabolism were impaired, indicative of insulin resistance and glucose intolerance. We propose that estrogen normally programs mechanisms in utero within the developing primate fetus that lead to insulin sensitivity, normal glucose tolerance and the capacity to metabolize glucose after birth. PMID:27207093

Bright light induces choroidal thickening in chickens.

PubMed

Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

2013-11-01

Bright light is a potent inhibitor of myopia development in animal models. Because development of refractive errors has been linked to changes in choroidal thickness, we have studied in chickens whether bright light may exert its effects on myopia also through changes in choroidal thickness. Three-day-old chickens were exposed to "bright light" (15,000 lux; n = 14) from 10 AM to 4 PM but kept under "normal light" (500 lux) during the remaining time of the light phase for 5 days (total duration of light phase 8 AM to 6 PM). A control group (n = 14) was kept under normal light during the entire light phase. Choroidal thickness was measured in alert, hand-held animals with optical coherence tomography at 10 AM, 4 PM, and 8 PM every day. Complete data sets were available for 12 chicks in bright light group and nine in normal light group. The striking inter-individual variability in choroidal thickness (coefficient of variance: 23%) made it necessary to normalize changes to the individual baseline thickness of the choroid. During the 6 hours of exposure to bright light, choroidal thickness decreased by -5.2 ± 4.0% (mean ± SEM). By contrast, in the group kept under normal light, choroidal thickness increased by +15.4 ± 4.7% (difference between both groups p = 0.003). After an additional 4 hours, choroidal thickness increased also in the "bright light group" by +17.8 ± 3.5%, while there was little further change (+0.6 ± 4.0%) in the "normal light group" (difference p = 0.004). Finally, the choroid was thicker in the "bright light group" (+7.6 ± 26.0%) than in the "normal light group" (day 5: -18.6 ± 26.9%; difference p = 0.036). Bright light stimulates choroidal thickening in chickens, although the response is smaller than with experimentally imposed myopic defocus, and it occurs with some time delay. It nevertheless suggests that choroidal thickening is also involved in myopia inhibition by bright light.

Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene.

PubMed Central

Maroulakou, I G; Anver, M; Garrett, L; Green, J E

1994-01-01

A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. Female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands. Images PMID:7972041

A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart.

PubMed

Schleich, Jean-Marc; Dillenseger, Jean-Louis; Houyel, Lucile; Almange, Claude; Anderson, Robert H

2009-01-01

Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three-dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning.

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

PubMed Central

Hudoklin, Samo; Zupančič, Daša; Makovec, Darko; Kreft, Mateja Erdani; Romih, Rok

2013-01-01

Background Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed fat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells. PMID:24143099

Reduced noise susceptibility in littermate offspring from heterozygous animals of the German waltzing guinea pig.

PubMed

Skjönsberg, Åsa; Mannström, Paula

2015-07-08

The German waltzing guinea pig is a spontaneously mutated strain with severe auditory and vestibular impairment caused by a so far unknown genetic mutation. The animals are born deaf and show a circling behavior. The heterozygote animals of this guinea pig strain have functionally normal hearing and balance. However, these animals have, in earlier studies, shown an increased resistance to noise compared with normal wild-type guinea pigs. In the present study, we explored the functional hearing with auditory brainstem response thresholds before and at different time points after noise exposure. Symptom-free littermates from heterozygote couples of the German waltzing guinea pigs were exclusively used for the study, which, after the hearing test, were sent back for breeding to confirm their genotype (i.e. heterozygote or normal). The aim of this paper was to ascertain that the previously shown reduced susceptibility to noise trauma in the heterozygote animals of the German waltzing guinea pig was also evident when littermates were used as control animals. The findings are important for further analysis of the heterozygote animals of this strain and for future investigations of the underlying mechanisms behind the diverse susceptibility to exposures of loud sound.

Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters.

PubMed

Mateo, Rosa I; Xiao, Shu-Yuan; Travassos da Rosa, Amelia P A; Lei, Hao; Guzman, Hilda; Lu, Liang; Tesh, Robert B

2007-11-01

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.

The long term immunological response of swine after two exposures to a salmon thrombin and fibrinogen hemostatic bandage

PubMed Central

Rothwell, Stephen W.; Settle, Timothy; Wallace, Shannon; Dorsey, Jennifer; Simpson, David; Bowman, James R.; Janmey, Paul; Sawyer, Evelyn

2014-01-01

Experimental salmon thrombin/fibrinogen dressings have been shown to provide effective hemostasis in severe hemorrhage situations. The hypothesis for this study was that swine would still remain healthy without coagulopathy six months after exposure to salmon thrombin/fibrinogen dressings. Initial exposure was by insertion of the salmon dressing into the peritoneal cavity. Three months after the initial exposure, the same animals were subjected to two full thickness dermal wounds on the dorsal surface. One wound was bandaged with the salmon thrombin/fibrinogen bandage and the other wound was dressed with a standard bandage. The animals were monitored for an additional three months. Blood was drawn every 14 days over the six months for immunological and coagulation function analysis. All of the animals (8 pigs) remained healthy during the six month period and the dermal wounds healed without incidence. Lymph nodes and spleen showed signs of normal immune response and Western blots showed development of antibodies against salmon fibrinogen, but none of the animals made antibodies that recognized any species of thrombin. Coagulation parameters (fibrinogen concentration, thrombin time, PT and aPTT) and hematological parameters remained normal over the course of the study when compared to initial values of the subject swine. PMID:20705479

Phenotypic Correction of Hemophilia A in Sheep by Postnatal Intraperitoneal Transplantation of FVIII-Expressing MSC

PubMed Central

Porada, Christopher D.; Sanada, Chad; Kuo, Chung-Jung; Colletti, Evan; Mandeville, Walter; Hasenau, John; Zanjani, Esmail D.; Moot, Robert; Doering, Christopher; Spencer, H. Trent; Almeida-Porada, Graça

2011-01-01

We recently re-established a line of sheep that accurately mimics the clinical symptoms and genetics of severe hemophilia A (HA). Herein, we tested a novel, non-ablative transplant therapy in 2 pediatric HA animals. Paternal mesenchymal stem cells (MSC) were transduced with a porcine FVIII-encoding lentivector, and transplanted via the intraperitoneal route, without preconditioning. At the time of transplantation, these animals had received multiple hFVIII treatments for various spontaneous bleeds, and had developed debilitating hemarthroses which produced severe defects in posture and gait. Transplantation of transduced MSC resolved all existent hemarthroses, and spontaneous bleeds ceased. Damaged joints recovered fully; the animals regained normal posture and gait and resumed normal activity. Despite achieving factor-independence, a sharp rise in pre-existent Bethesda titers occurred following transplantation, decreasing the effectiveness and duration of therapy. Post-mortem examination revealed widespread engraftment, with MSC present within the lung, liver, intestine, and thymus, but particularly within joints affected at the time of transplantation, suggesting MSC homed to sites of ongoing injury/inflammation to release FVIII, explaining the dramatic improvement in hemarthrotic joints. In summary, this novel, non-ablative MSC transplantation was straightforward, safe, and converted life-threatening, debilitating HA to a moderate phenotype in a large animal model. PMID:21906573

Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization.

PubMed

Zhou, Qinghua; Li, Haimin; Li, Hanzeng; Nakagawa, Akihisa; Lin, Jason L J; Lee, Eui-Seung; Harry, Brian L; Skeen-Gaar, Riley Robert; Suehiro, Yuji; William, Donna; Mitani, Shohei; Yuan, Hanna S; Kang, Byung-Ho; Xue, Ding

2016-07-22

Mitochondria are inherited maternally in most animals, but the mechanisms of selective paternal mitochondrial elimination (PME) are unknown. While examining fertilization in Caenorhabditis elegans, we observed that paternal mitochondria rapidly lose their inner membrane integrity. CPS-6, a mitochondrial endonuclease G, serves as a paternal mitochondrial factor that is critical for PME. We found that CPS-6 relocates from the intermembrane space of paternal mitochondria to the matrix after fertilization to degrade mitochondrial DNA. It acts with maternal autophagy and proteasome machineries to promote PME. Loss of cps-6 delays breakdown of mitochondrial inner membranes, autophagosome enclosure of paternal mitochondria, and PME. Delayed removal of paternal mitochondria causes increased embryonic lethality, demonstrating that PME is important for normal animal development. Thus, CPS-6 functions as a paternal mitochondrial degradation factor during animal development. Copyright © 2016, American Association for the Advancement of Science.

Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats.

PubMed

Griffel, M I; Astiz, M E; Rackow, E C; Weil, M H

1990-01-01

We studied the effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis in peritonitis and shock in rats. Sepsis was induced by cecal ligation and perforation. After tracheostomy, rats were randomized to spontaneous breathing (S) or mechanical ventilation with paralysis (V). Five animals were studied in each group. The V animals were paralyzed with pancuronium bromide to eliminate respiratory effort. Mechanical ventilation consisted of controlled ventilation using a rodent respirator with periodic adjustment of minute ventilation to maintain PaCO2 and pH within normal range. Arterial and central venous blood gases and thermodilution cardiac output were measured at baseline before abdominal surgery, and sequentially at 0.5, 3.5, and 6 h after surgery. At 6 h, cardiac output was 193 +/- 30 ml/kg.min in S animals and 199 +/- 32 ml/kg.min in V animals (NS). The central venous oxygen saturation was 27.4 +/- 4.7% in S animals and 30.0 +/- 6.4% in V animals (NS). Systemic oxygen extraction was 70 +/- 5% in S animals and 67 +/- 6% in V animals (NS). Arterial lactate was 2.4 +/- 0.4 mmol/L in S animals and 2.2 +/- 0.5 mmol/L in V animals (NS). The S animals developed lethal hypotension at 6.6 +/- 0.4 h compared to 6.8 +/- 0.4 h in V animals (NS). These data suggest that mechanical ventilation does not decrease systemic oxygen extraction or ameliorate the development of lactic acidosis during septic shock.

50 CFR 14.107 - Conveyance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... sufficient air for it to breathe normally. Primary enclosures shall be positioned in a cargo space in such a manner that each animal has access to sufficient air for normal breathing. (d) The interior of an animal...

THE EFFECTS OF IONIZING RADIATIONS ON THE DEVELOPING ANIMAL WITH SPECIAL REFERENCE TO THE NERVOUS SYSTEM. Progress Report and Application of Renewal of Atomic Energy Commission Contract AT(30-1)-1454

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

Hicks, S.P.

1960-06-01

Findings are summarized from studies on the effects of radiation on the development of the nervous system in mammals. Radiation has been proven to be a useful tool for experimental mammalian embryology in studies of normal brain development as well as in studies of abnormalities of brain development. Manuscripts are included of papers accepted for publication. (C.H.)

Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

PubMed

Soderstrom, Ken; Gilbert, Marcoita T

2013-03-19

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Infectious nature of Clostridium spiroforme-mediated rabbit enterotoxaemia.

PubMed

Carman, R J; Borriello, S P

1984-09-01

Newly weaned rabbits had diarrhoea only if they were infected with Clostridium spiroforme. In adult rabbits exposure to both clindamycin and C. spiroforme was necessary to induce disease. All diseased animals harboured C. spiroforme and its toxin. Adult rabbits given a course of clindamycin survived when held in a protected environment as did those challenged with C. spiroforme alone. At necropsy none of these apparently healthy animals showed signs of diarrhoea or caecitis. These findings suggest that, in the development of enterotoxaemia, weaning or clindamycin treatment and infection with C. spiroforme are separate events and that disease follows infection with this organism from the environment, as opposed to overgrowth by undetectable levels of C. spiroforme resident in the gut. Our data indicate that C. spiroforme is not a normal component of the rabbit gut flora and that the normal bowel ecology of the adult must be disrupted before C. spiroforme will colonize.

Normal anatomy and histology of the adult zebrafish.

PubMed

Menke, Aswin L; Spitsbergen, Jan M; Wolterbeek, Andre P M; Woutersen, Ruud A

2011-08-01

The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.

Early detection of melanoma with the combined use of acoustic microscopy, infrared reflectance and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Karagiannis, Georgios T.; Grivas, Ioannis; Tsingotjidou, Anastasia; Apostolidis, Georgios K.; Grigoriadou, Ifigeneia; Dori, I.; Poulatsidou, Kyriaki-Nefeli; Doumas, Argyrios; Wesarg, Stefan; Georgoulias, Panagiotis

2015-03-01

Malignant melanoma is a form of skin cancer, with increasing incidence worldwide. Early diagnosis is crucial for the prognosis and treatment of the disease. The objective of this study is to develop a novel animal model of melanoma and apply a combination of the non-invasive imaging techniques acoustic microscopy, infrared (IR) and Raman spectroscopies, for the detection of developing tumors. Acoustic microscopy provides information about the 3D structure of the tumor, whereas, both spectroscopic modalities give qualitative insight of biochemical changes during melanoma development. In order to efficiently set up the final devices, propagation of ultrasonic and electromagnetic waves in normal skin and melanoma simulated structures was performed. Synthetic and grape-extracted melanin (simulated tumors), endermally injected, were scanned and compared to normal skin. For both cases acoustic microscopy with central operating frequencies of 110MHz and 175MHz were used, resulting to the tomographic imaging of the simulated tumor, while with the spectroscopic modalities IR and Raman differences among spectra of normal and melanin- injected sites were identified in skin depth. Subsequently, growth of actual tumors in an animal melanoma model, with the use of human malignant melanoma cells was achieved. Acoustic microscopy and IR and Raman spectroscopies were also applied. The development of tumors at different time points was displayed using acoustic microscopy. Moreover, the changes of the IR and Raman spectra were studied between the melanoma tumors and adjacent healthy skin. The most significant changes between healthy skin and the melanoma area were observed in the range of 900-1800cm-1 and 350-2000cm-1, respectively.

Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

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

Green, J.E.; Maroulakou, I.G.; Anver, M.

Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy.more » Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.« less

Mammary Tumor Development: Stromal-Epithelial Interactions in Oncogenesis.

DTIC Science & Technology

1996-09-01

differentiation, prolif- erative preneoplastic lesions, or invasive adenocarcinomas , depending on the promoter con- struct used and the animal’s age when...Zn). Virgin RSV-SGF transgenic mice showed marked preneoplastic MG ductal proliferation by 6 mo. By 8 mo., 1/3 had developed adenocarcinoma . Virgin...fat pRSGF Constitutively expressed Highly abnormal. None Normal Observed at 8 1/3 of mice show months of age invasive secretory adenocarcinoma SGF

The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.

PubMed

Clarke, G; Grenham, S; Scully, P; Fitzgerald, P; Moloney, R D; Shanahan, F; Dinan, T G; Cryan, J F

2013-06-01

Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclinical tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonised control animals. Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonisation of the GF animals post weaning is insufficient to reverse the CNS neurochemical consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addition, reduced anxiety in GF animals is also normalised following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochemical, but not behavioural, profile is resistant to restoration of a normal gut flora in later life.

Electron microscopic quantification of collagen fibril diameters in the rabbit medial collateral ligament: a baseline for comparison.

PubMed

Frank, C; Bray, D; Rademaker, A; Chrusch, C; Sabiston, P; Bodie, D; Rangayyan, R

1989-01-01

To establish a normal baseline for comparison, thirty-one thousand collagen fibril diameters were measured in calibrated transmission electron (TEM) photomicrographs of normal rabbit medial collateral ligaments (MCL's). A new automated method of quantitation was used to compare statistically fibril minimum diameter distributions in one midsubstance location in both MCL's from six animals at 3 months of age (immature) and three animals at 10 months of age (mature). Pooled results demonstrate that rabbit MCL's have statistically different (p less than 0.001) mean minimum diameters at these two ages. Interanimal differences in mean fibril minimum diameters were also significant (p less than 0.001) and varied by 20% to 25% in both mature and immature animals. Finally, there were significant differences (p less than 0.001) in mean diameters and distributions from side-to-side in all animals. These mean left-to-right differences were less than 10% in all mature animals but as much as 62% in some immature animals. Statistical analysis of these data demonstrate that animal-to-animal comparisons using these protocols require a large number of animals with appropriate numbers of fibrils being measured to detect small intergroup differences. With experiments which compare left to right ligaments, far fewer animals are required to detect similarly small differences. These results demonstrate the necessity for rigorous control of sampling, an extensive normal baseline and statistically confirmed experimental designs in any TEM comparisons of collagen fibril diameters.

[Regulatory mechanism for lncRNAs in skeletal muscle development and progress on its research in domestic animals].

PubMed

Zhou, Rui; Wang, Yi Xin; Long, Ke Ren; Jiang, An An; Jin, Long

2018-04-20

Skeletal muscle is an essential tissue to maintain the normal functions of an organism. It is also closely associated with important economic performance, such as carcass weight, of domestic animals. In recent years, studies using high-throughput sequencing techniques have identified numerous long non-coding RNAs (lncRNAs) with myogenic functions involved in regulation of gene expression at multiple levels, including epigenetic, transcriptional and post-transcriptional regulation. These lncRNAs target myogenic factors, which participate in all processes of skeletal muscle development, including proliferation, migration and differentiation of skeletal muscle stem cells, proliferation, differentiation and fusion of myocytes, muscle hypertrophy and conversion of muscle fiber types. In this review, we summarize the functional roles of lncRNAs in regulation of myogenesis in humans and mice, describe the methods for the analysis of lncRNA function, discuss the progress of lncRNA research in domestic animals, and highlight the current problems and challenges in lncRNA research on livestock production. We hope to provide a useful reference for research on lncRNA in domestic animals, thereby further identifying the molecular regulatory mechanisms in skeletal muscle growth and development.

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

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.

9 CFR 313.2 - Handling of livestock.

Code of Federal Regulations, 2010 CFR

2010-01-01

... minimum of excitement and discomfort to the animals. Livestock shall not be forced to move faster than a normal walking speed. (b) Electric prods, canvas slappers, or other implements employed to drive animals... livestock and other animals unable to move. (1) Disabled animals and other animals unable to move shall be...

Mycoplasma and associated bacteria isolated from ovine pink-eye.

PubMed

Langford, E V

1971-01-01

A mycoplasma was recovered from the untreated conjunctival membranes of nine sheep affected by Pink-eye. It was neither isolated from the conjunctiva of treated animals which were affected nor from the conjunctiva of normal animals either in contact or not in contact with affected animals. Bacteria found on normal conjunctival membranes were Neisseria ovis, Escherichia coli, Staphylococcus epidermididis, Streptococcus and Bacillus spp. Bacteria found in clinical cases of Pink-eye were N. ovis, E. coli, a Streptococcus and Pseudomonas spp.

Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat.

PubMed

Zaid, Siti Sarah Mohamad; Othman, Shatrah; Kassim, Normadiah M

2014-12-17

To investigate the potential protective effects of Tualang honey against the toxicity effects induced by Bisphenol A (BPA) on pubertal development of ovaries. This study was conducted on pre-pubertal female Sprague Dawley rats. Animals were divided into four groups (n = 8 in each group). Group I was administered with vehicle 0.2 ml of corn oil (Sigma-Aldrich, USA) using oral gavage daily for six weeks; these animals served as negative control (CO group), Group II was administered with BPA suspended in corn oil at 10 mg/kg body weight and served as positive control (PC group), Group III was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of BPA at 10 mg/kg (TH group) while Group IV was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of corn oil (THC group). Body weight of all animals were monitored weekly. The BPA-exposed animals exhibited disruption of their estrus cycle, while those animals treated with BPA together with Tualang honey, exhibited an improvement in percentage of normal estrous cycle. Their ovaries had lower numbers of atretic follicles compared to the PC group but higher than the CO group. Tualang honey has a potential role in reducing BPA-induced ovarian toxicity by reducing the morphological abnormalities of the ovarian follicles and improving the normal estrous cycle.

Modulation of cytotoxic T lymphocyte, natural killer cell, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by Vernonia cinerea L. and vernolide-A in BALB/c mice via enhanced production of cytokines IL-2 and IFN-γ.

PubMed

Pratheeshkumar, Poyil; Kuttan, Girija

2012-02-01

Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.

Bovine protoporphyria: documentation of autosomal recessive inheritance and comparison with the human disease through measurement of heme synthase activity.

PubMed Central

Bloomer, J R; Morton, K O; Reuter, R J; Ruth, G R

1982-01-01

Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin fibroblasts and whole liver homogenates from animals with protoporphyria, their unaffected parents, and normal cattle in order to examine the mode of inheritance and compare it with human protoporphyria. The mean activity (+/- SEM) in fibroblasts from the three groups was 2.0 +/- 0.4, 47 +/- 12, and 149 +/- 10 pmol heme formed/mg protein per hr, respectively, consistent with autosomal recessive inheritance. Similarly, the levels of heme synthase activity in livers of the parents were intermediate to those of normal animals and of animals with protoporphyria. When compared with normal human fibroblasts and liver, the specific activity of heme synthase in normal bovine tissue was significantly higher. These studies indicate that manifestations of protoporphyria do not occur in cattle unless the animal is homozygous for the gene defect, whereas in humans, the heterozygous condition is sufficient. This is probably because the specific activity of heme synthase in cells of heterozygous animals is not reduced to a level that significantly alters heme metabolism. PMID:7072720

Induction of abnormal respiratory sounds by capsaicin in rats previously infected with Bordetella pertussis.

PubMed

Parton, R; Hall, E; Wardlaw, A C

1998-02-01

Sprague Dawley rats, previously infected with Phase-I Bordetella pertussis, developed more severe abnormal respiratory sounds than normal animals, but not coughing, when exposed to aerosolized capsaicin, one of several cough-inducing agents tested. Stethoscope examination suggested that greater production of pulmonary mucus might be occurring after capsaicin challenge of the infected animals, compared to the uninfected controls. Rats of three other strains gave characteristically different responses from the Sprague Dawleys. The administration of capsaicin to B. pertussis-infected rats may provide useful insights into the pathophysiology of excess mucus secretion in human pertussis.

Platelet participation in the pathogenesis of dermonecrosis induced by Loxosceles gaucho venom.

PubMed

Tavares, F L; Peichoto, M E; Marcelino, J R; Barbaro, K C; Cirillo, M C; Santoro, M L; Sano-Martins, I S

2016-06-01

Loxosceles gaucho spider venom induces in vitro platelet activation and marked thrombocytopenia in rabbits. Herein, we investigated the involvement of platelets in the development of the dermonecrosis induced by L. gaucho venom, using thrombocytopenic rabbits as a model. L. gaucho venom evoked a drop in platelet and neutrophil counts 4 h after venom injection. Ecchymotic areas at the site of venom inoculation were noticed as soon as 4 h in thrombocytopenic animals but not in animals with initial normal platelet counts. After 5 days, areas of scars in thrombocytopenic animals were also larger, evidencing the marked development of lesions in the condition of thrombocytopenia. Histologically, local hemorrhage, collagen fiber disorganization, and edema were more severe in thrombocytopenic animals. Leukocyte infiltration, predominantly due to polymorphonuclears, was observed in the presence or not of thrombocytopenia. Thrombus formation was demonstrated by immunohistochemistry at the microvasculature, and it occurred even under marked thrombocytopenia. Taken together, platelets have an important role in minimizing not only the hemorrhagic phenomena but also the inflammatory and wound-healing processes, suggesting that cutaneous loxoscelism may be aggravated under thrombocytopenic conditions. © The Author(s) 2015.

Aposymbiotic culture of the sepiolid squid Euprymna scolopes: role of the symbiotic bacterium Vibrio fischeri in host animal growth, development, and light organ morphogenesis.

PubMed

Claes, M F; Dunlap, P V

2000-02-15

The sepiolid squid Euprymna scolopes forms a bioluminescent mutualism with the luminous bacterium Vibrio fischeri, harboring V. fischeri cells in a complex ventral light organ and using the bacterial light in predator avoidance. To characterize the contribution of V. fischeri to the growth and development of E. scolopes and to define the long-term effects of bacterial colonization on light organ morphogenesis, we developed a mariculture system for the culture of E. scolopes from hatching to adulthood, employing artificial seawater, lighting that mimicked that of the natural environment, and provision of prey sized to match the developmental stage of E. scolopes. Animals colonized by V. fischeri and animals cultured in the absence of V. fischeri (aposymbiotic) grew and survived equally well, developed similarly, and reached sexual maturity at a similar age. Development of the light organ accessory tissues (lens, reflectors, and ink sac) was similar in colonized and aposymbiotic animals with no obvious morphometric or histological differences. Colonization by V. fischeri influenced regression of the ciliated epithelial appendages (CEAs), the long-term growth of the light organ epithelial tubules, and the appearance of the cells composing the ciliated ducts, which exhibit characteristics of secretory tissue. In certain cases, aposymbiotic animals retained the CEAs in a partially regressed state and remained competent to initiate symbiosis with V. fischeri into adulthood. In other cases, the CEAs regressed fully in aposymbiotic animals, and these animals were not colonizable. The results demonstrate that V. fischeri is not required for normal growth and development of the animal or for development of the accessory light organ tissues and that morphogenesis of only those tissues coming in contact with the bacteria (CEAs, ciliated ducts, and light organ epithelium) is altered by bacterial colonization of the light organ. Therefore, V. fischeri apparently makes no major metabolic contribution to E. scolopes beyond light production, and post-embryonic development of the light organ is essentially symbiont independent. J. Exp. Zool. 286:280-296, 2000. Copyright 2000 Wiley-Liss, Inc.

Endoreplication and polyploidy: insights into development and disease

PubMed Central

Fox, Donald T.; Duronio, Robert J.

2013-01-01

Polyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that control the generation of polyploidy and have recently begun to provide clues to its physiological function. These studies demonstrate that cellular polyploidy plays important roles during normal development and also contributes to human disease, particularly cancer. PMID:23222436

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cervids. 55.3 Section 55.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that... owner must not be greater than the normal fee for similar services provided by commercial entities. The...

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2014 CFR

2014-01-01

... cervids. 55.3 Section 55.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that... owner must not be greater than the normal fee for similar services provided by commercial entities. The...

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2012 CFR

2012-01-01

... cervids. 55.3 Section 55.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that... owner must not be greater than the normal fee for similar services provided by commercial entities. The...

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2013 CFR

2013-01-01

... cervids. 55.3 Section 55.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that... owner must not be greater than the normal fee for similar services provided by commercial entities. The...

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2011 CFR

2011-01-01

... cervids. 55.3 Section 55.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that... owner must not be greater than the normal fee for similar services provided by commercial entities. The...

Longitudinal assessment of retinal structure and function reveals a rod-cone degeneration in a guinea pig model initially presented as night blind.

PubMed

Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

2011-08-01

We have previously reported a naturally occurring retinopathy in a population of guinea pigs, where the affected animals presented a defect of the rod-mediated vision. The purpose of this study was to investigate if the mutants were affected with a stationary or degenerative retinopathy and to identify the cellular origin of this unique disorder. Electroretinogram (ERG) [postnatal day 1 (P1) to P450], light (LM) and electron microscopy (EM) [P5, P150, P450], and immunohistochemistry [P30, P150, P450] were evaluated from normal and mutant animals. Irrespective of age, the scotopic ERGs of mutants could only be evoked by bright flashes, and the resulting ERGs were of photopic waveform. Interestingly, the amplitude of the cone and the rod/cone a-waves was always of smaller amplitude in mutants, but this difference tended to decrease with age. In contrast, the b-waves were of larger amplitude than normal in photopic ERGs obtained prior to age 25 (days) and prior to age 10 for rod/cone ERGs. LM revealed, in mutants, an absence of the outer segment layer (OSL) with a reduction in the outer nuclear layer (ONL) thickness. EM disclosed the presence of cone outer segment (OS) while no rod OS could be evidenced. Immunohistochemistry revealed the presence of rhodopsin, both cone opsins as well as normal synaptophysin immunoreactivity. Finally, neither the retinal structure nor the function in the mutants achieved normal development. Results suggest that mutant animals are suffering from a degenerative retinal disorder that affects the structure and function of rods and cones.

Horses Helping Children Grow

ERIC Educational Resources Information Center

Graham, Louise B.; Lindsey, Allison

2017-01-01

A review of Animal-Assisted Therapy and related terms such as "Animal-Assisted Activities" is presented as an introduction to the exploration of additional equine applications with children. Animal-Assisted Therapy has been studied, but Animal-Assisted Activities with children facing normal developmental struggles has not received much…

Intra-Abdominal Hypertension Causes Bacterial Growth in Lungs: An Animal Study

PubMed Central

Papakrivou, Eleni; Manoulakas, Efstratios; Mitroudi, Magda; Tepetes, Konstantinos; Papazoglou, Konstantinos; Zakynthinos, Epaminondas

2017-01-01

To study the effect of intra-abdominal hypertension (IAH) on the frequency of pneumonia with an experimental study, thirteen Sprague-Dawley rats were included. Eight out of thirteen animals were randomly assigned to receive 10 ml of benzalkonium chloride 0.2% (megacolon group) and five animals received 10 ml NaCl 0.9% (controls). Animals were anaesthetized by intramuscular delivery of ketamine. The incidence of positivity for bacteria lung tissue cultures and mesenteric lymph node cultures was assessed at the 21st day after animals' sacrification, or before in case of death. All megacolon group animals presented progressive increase of the abdomen and increased IAP (≥10 mmHg) whereas the frequency of their evacuations was almost eliminated. Controls presented normal evacuations, no sign of abdominal distention, and normal IAP. In megacolon group animals, there was evidence of significant amount of bacteria in lung cultures. In contrast, no bacteria were found in control animals. PMID:28357400

Gonadal and Sex Differentiation Abnormalities of Dogs and Cats

PubMed Central

Meyers-Wallen, V.N.

2012-01-01

The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health. PMID:22005097

[The effect of long-term hyperbarism on pregnant guinea pigs and their progeny].

PubMed

Sviderskaia, G E; Dmitrieva, L E

1991-01-01

The effect of hyperbarism has been investigated on 1-3-, 4-5- and 8-10-week pregnant rats and their offsprings. It was found that the mortality rate of pregnant rats is two times higher after hyperbaric exposures than in control animals. The animals exhibit the highest sensitivity at a stage of 8-10 weeks. Hyperbaric conditions significantly affect offsprings. Only 53% of newborn puppies were found to be normal, whereas 35% were born dead and 12% revealed various abnormalities. The highest sensitivity was observed during organogenesis (4-5 weeks), the mortality rate during this period reached 70%. The body mass in newborn puppies was significantly lower than in control animals. The most significant retardation in the development was observed in animals which were subjected to the effect of hyperbarism at the 4-5-th week of intrauterine life.

A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

PubMed

Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

2015-08-01

Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Wireless inertial measurement of head kinematics in freely-moving rats

PubMed Central

Pasquet, Matthieu O.; Tihy, Matthieu; Gourgeon, Aurélie; Pompili, Marco N.; Godsil, Bill P.; Léna, Clément; Dugué, Guillaume P.

2016-01-01

While miniature inertial sensors offer a promising means for precisely detecting, quantifying and classifying animal behaviors, versatile inertial sensing devices adapted for small, freely-moving laboratory animals are still lacking. We developed a standalone and cost-effective platform for performing high-rate wireless inertial measurements of head movements in rats. Our system is designed to enable real-time bidirectional communication between the headborne inertial sensing device and third party systems, which can be used for precise data timestamping and low-latency motion-triggered applications. We illustrate the usefulness of our system in diverse experimental situations. We show that our system can be used for precisely quantifying motor responses evoked by external stimuli, for characterizing head kinematics during normal behavior and for monitoring head posture under normal and pathological conditions obtained using unilateral vestibular lesions. We also introduce and validate a novel method for automatically quantifying behavioral freezing during Pavlovian fear conditioning experiments, which offers superior performance in terms of precision, temporal resolution and efficiency. Thus, this system precisely acquires movement information in freely-moving animals, and can enable objective and quantitative behavioral scoring methods in a wide variety of experimental situations. PMID:27767085

Pain Relief in Nonhuman Primate Models of Arthritis.

PubMed

Vierboom, Michel P M; Breedveld, Elia; Keehnen, Merei; Klomp, Rianne; Bakker, Jaco

2017-01-01

Animal models of rheumatoid arthritis are important in the elucidation of etiopathogenic mechanisms of the disease and for the development of promising new therapies. Species specificity of new biological compounds and their mode of action preclude safety and efficacy testing in rodent models of disease. Nonhuman primates (NHP) can fill this niche and provide the only relevant model. Over the last two decades models of collagen-induced arthritis (CIA) were developed in the rhesus monkey and the common marmoset. However, NHP are higher-order animals and complex sentient beings. So especially in models where pain is an intricate part of the disease, analgesia needs to be addressed because of ethical considerations. In our model, a morphine-based pain relief was used that does not interfere with the normal development of disease allowing us to evaluate important mechanistic aspects of the arthritis.

Familial male pseudohermaphroditism and testicular descent in the racoon dog (Nyctereutes).

PubMed

Fentener van Vlissingen, J M; Blankenstein, M A; Thijssen, J H; Colenbrander, B; Verbruggen, A J; Wensing, C J

1988-12-01

Sexual differentiation was investigated in familial male pseudohermaphroditism in Nyctereutes procyonoides (Canidae). In intersex males, development of external genital organs and prostate glandular tissue was severely disturbed; Wolffian (mesonephric) duct derivatives developed prepubertally but were absent in some adults. Müllerian (paramesonephric) duct regression was complete. Testicular descent was undisturbed. Male/female sex differences in plasma testosterone, 5 alpha-dihydrotestosterone, and luteinizing hormone concentrations were present. Intersex plasma hormone concentrations were within the normal male range. The concentration of androgen receptors in pubic skin was similar in male, female, and intersex animals and no significant differences in affinity for the ligand were detected. It was concluded that in intersex animals androgen-dependent virilisation was deficient despite the presence of androgens and androgen receptors and that this condition had not affected gubernaculum development and testicular descent.

Chronic In Vivo Testing of the Penn State Infant Ventricular Assist Device

PubMed Central

Weiss, William J.; Carney, Elizabeth L.; Clark, J. Brian; Peterson, Rebecca; Cooper, Timothy K.; Nifong, Thomas P.; Siedlecki, Christopher A; Hicks, Dennis; Doxtater, Bradley; Lukic, Branka; Yeager, Eric; Reibson, John; Cysyk, Joshua; Rosenberg, Gerson; Pierce, William S.

2011-01-01

The Penn State Infant Ventricular Assist Device is a 12-14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute (NHLBI) Pediatric Circulatory Support program. In this report we describe the 7 most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 +/- 4.1 kg. The goal of 4-6 weeks survival was achieved in 5 of 7 studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into 2 protocol groups: the first based on a target activated partial thromboplastin time of 1.5 to 2 times normal, and a second group using a target thromboelastography R-time of 2 times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal, and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals, and are encouraging given the extremely low levels of anticoagulation in the second group. PMID:22157073

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

PubMed Central

Flavell, D. J.; Goepel, J.; Wilson, A. P.; Potter, C. W.

1979-01-01

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis. Images Fig. 2 Fig. 3a, b Fig. 3c, d PMID:92328

Magnetoacoustic imaging of human liver tumor with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Cressman, Erik; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

The development of colon innervation in trisomy 16 mice and Hirschsprungs disease

PubMed Central

Li, Ji Cheng; Mi, Kai Hong; Zhou, Ji Lin; Busch, LC; Kuhnel, W

2001-01-01

AIM: To study the colon innervation of trisomy 16 mouse, an animal model for Down’s syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS: Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS: Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5 mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was evealed in the stenosed segment of HD colon. CONCLUSION: Trisomy 16 mice could serve as an animal model for Hirschsprung’s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency. PMID:11819726

A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart

PubMed Central

Schleich, Jean-Marc; Dillenseger, Jean-Louis; Houyel, Lucile; Almange, Claude; Anderson, Robert H.

2009-01-01

Background Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. Methods We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and paediatric cardiology. This has permitted the preparation of three-dimensional (3-D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. Results We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. Conclusion We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning. PMID:19363807

The cell biology of aging.

PubMed

Hayflick, L

1979-07-01

Cultured normal human and animal cells are predestinued to undergo irreversible functional decrements that mimick age changes in the whole organism. When normal human embryonic fibroblasts are cultured in vitro, 50 +/- 10 population doublings occur. This maximum potential is diminished in cells derived from older donors and appears to be inversely proportional to their age. The 50 population doubling limit can account for all cells produced during a lifetime. The limitation on doubling potential of cultured normal cells is also expressed in vivo when serial transplants are made. There may be a direct correlation between the mean maximum life spans of several species and the population doubling potential of their cultured cells. A plethora of functional decrements occur in cultured normal cells as they approach their maximum division capability. Many of these decrements are similar to those occurring in intact animals as they age. We have concluded that these functional decrements expressed in vitro, rather than cessation of cell division, are the essential contributors to age changes in intact animals. Thus, the study of events leading to functional losses in cultured normal cells may provide useful insights into the biology of aging.

Diet-induced obesity promotes altered remodeling and exacerbated cardiac hypertrophy following pressure overload

PubMed Central

Holzem, Katherine M; Marmerstein, Joseph T; Madden, Eli J; Efimov, Igor R

2015-01-01

Heart failure (HF) is the end stage of cardiovascular disease, in which hypertrophic remodeling no longer meets cardiac output demand. Established animal models of HF have provided insights into disease pathogenesis. However, these models are developed on dissimilar metabolic backgrounds from humans – patients with HF are frequently overweight or obese, whereas animal models of HF are typically lean. Thus, we aimed to develop and investigate model for cardiac hypertrophy and failure that also recapitulates the cardiometabolic state of HF in humans. We subjected mice with established diet-induced obesity (DIO) to cardiac pressure overload provoked by transverse aortic constriction (TAC). Briefly, we fed WT male mice a normal chow or high-fat diet for 10 weeks prior to sham/TAC procedures and until surgical follow-up. We then analyzed cardiac hypertrophy, mechanical function, and electrophysiology at 5–6 weeks after surgery. In DIO mice with TAC, hypertrophy and systolic dysfunction were exacerbated relative to chow TAC animals, which showed minimal remodeling with our moderate constriction intensity. Normalized heart weight was 55.8% greater and fractional shortening was 30.9% less in DIO TAC compared with chow TAC hearts. However, electrophysiologic properties were surprisingly similar between DIO sham and TAC animals. To examine molecular pathways activated by DIO and TAC, we screened prohypertrophic signaling cascades, and the exacerbated remodeling was associated with early activation of the c-Jun-N-terminal kinase (JNK1/2) signaling pathway. Thus, DIO aggravates the progression of hypertrophy and HF caused by pressure overload, which is associated with JNK1/2 signaling, and cardiometabolic state can significantly modify HF pathogenesis. PMID:26290533

Peripheral Vision Can Influence Eye Growth and Refractive Development in Infant Monkeys

PubMed Central

Smith, Earl L.; Kee, Chea-su; Ramamirtham, Ramkumar; Qiao-Grider, Ying; Hung, Li-Fang

2006-01-01

PURPOSE Given the prominence of central vision in humans, it has been assumed that visual signals from the fovea dominate emmetropization. The purpose of this study was to examine the impact of peripheral vision on emmetropization. METHODS Bilateral, peripheral form deprivation was produced in 12 infant monkeys by rearing them with diffusers that had either 4- or 8-mm apertures centered on the pupils of each eye, to allow 24° or 37° of unrestricted central vision, respectively. At the end of the lens-rearing period, an argon laser was used to ablate the fovea in one eye of each of seven monkeys. Subsequently, all the animals were allowed unrestricted vision. Refractive error and axial dimensions were measured along the pupillary axis by retinoscopy and A-scan ultrasonography, respectively. Control data were obtained from 21 normal monkeys and 3 infants reared with binocular plano lenses. RESULTS Nine of the 12 treated monkeys had refractive errors that fell outside the 10th- and 90th-percentile limits for the age-matched control subjects, and the average refractive error for the treated animals was more variable and significantly less hyperopic/more myopic (+0.03 ± 2.39 D vs. +2.39 ± 0.92 D). The refractive changes were symmetric in the two eyes of a given animal and axial in nature. After lens removal, all the treated monkeys recovered from the induced refractive errors. No interocular differences in the recovery process were observed in the animals with monocular foveal lesions. CONCLUSIONS On the one hand, the peripheral retina can contribute to emmetropizing responses and to ametropias produced by an abnormal visual experience. On the other hand, unrestricted central vision is not sufficient to ensure normal refractive development, and the fovea is not essential for emmetropizing responses. PMID:16249469

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Regulation of microglial development: a novel role for thyroid hormone.

PubMed

Lima, F R; Gervais, A; Colin, C; Izembart, M; Neto, V M; Mallat, M

2001-03-15

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

Maternal influences on fetal microbial colonization and immune development

PubMed Central

Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

2014-01-01

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization. PMID:25310759

A comparison of cell proliferation in normal and neoplastic intestinal epithelia following either biogenic amine depletion or monoamine oxidase inhibition.

PubMed

Tutton, P J; Barkla, D H

1976-08-11

Epithelial cell proliferation was studied in the jejunum and in the colon of normal rats, in the colon of dimethylhydrazine-treated rats and in dimethylhydrazine-induced adenocarcinoma of the colon using a stathmokinetic technique. Estimates of cell proliferation rates in these four tissues were then repeated in animals which had been depleted of biogenic animes by treatment with reserpine and in animals whose monoamine oxidase was inhibited by treatment with nialamide. In amine-depleted animals cell proliferation essentially ceased in all four tissues examined. Inhibition of monoamine oxidase did not significantly influence cell proliferation in nonmalignant tissues but accelerated cell division in colonic tumours.

Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.

PubMed

Koshiba, Mamiko; Karino, Genta; Mimura, Koki; Nakamura, Shun; Yui, Kunio; Kunikata, Tetsuya; Yamanouchi, Hideo

2016-01-01

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer.

PubMed

Lanza, R P; Cibelli, J B; Diaz, F; Moraes, C T; Farin, P W; Farin, C E; Hammer, C J; West, M D; Damiani, P

2000-01-01

Approximately 100 species become extinct a day. Despite increasing interest in using cloning to rescue endangered species, successful interspecies nuclear transfer has not been previously described, and only a few reports of in vitro embryo formation exist. Here we show that interspecies nuclear transfer can be used to clone an endangered species with normal karyotypic and phenotypic development through implantation and the late stages of fetal growth. Somatic cells from a gaur bull (Bos gaurus), a large wild ox on the verge of extinction, (Species Survival Plan < 100 animals) were electrofused with enucleated oocytes from domestic cows. Twelve percent of the reconstructed oocytes developed to the blastocyst stage, and 18% of these embryos developed to the fetal stage when transferred to surrogate mothers. Three of the fetuses were electively removed at days 46 to 54 of gestation, and two continued gestation longer than 180 (ongoing) and 200 days, respectively. Microsatellite marker and cytogenetic analyses confirmed that the nuclear genome of the cloned animals was gaurus in origin. The gaur nuclei were shown to direct normal fetal development, with differentiation into complex tissue and organs, even though the mitochondrial DNA (mtDNA) within all the tissue types evaluated was derived exclusively from the recipient bovine oocytes. These results suggest that somatic cell cloning methods could be used to restore endangered, or even extinct, species and populations.

Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes.

PubMed

Castelli, Fulvia; Frith, Chris; Happé, Francesca; Frith, Uta

2002-08-01

Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporo-parietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.

Light Levels, Refractive Development, and Myopia – a Speculative Review

PubMed Central

Norton, Thomas T.; Siegwart, John T.

2013-01-01

Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways. PMID:23680160

Influence of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement on lipid profile in normal and diet-induced hypercholesterolemic rats.

PubMed

Satyam, Shakta Mani; Bairy, Laxminarayana Kurady; Pirasanthan, Rajadurai

2014-12-01

Zincovit tablet is combination of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement. To investigate the influence of single combined formulation of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement tablets (Zincovit) on lipid profile in normal and diet-induced hypercholesterolemic rats. Anti-hyperlipidemic activity of combined formulation of grape seed extract and Zincovit tablets doses ranged from 40 to 160 mg/kg, p.o. was evaluated in normal and diet-induced hypercholesterolemic rats. Hypercholesterolemic animals treated with combined formulation of grape seed extract and Zincovit tablets (nutritional food supplement) at 40, 80 and 160 mg/kg exhibited drastic decrease in serum triglycerides, total cholesterol, LDL-C, VLDL-C and rise of HDL-C in comparison to hypercholesterolemic control group animals. The anti-hyperlipidemic effect of single combined formulation of grape seed extract and Zincovit tablet was comparable with the standard drug atorvastatin treated animals and the variations were statistically non-significant. There was no significant impact of combined formulation of grape seed extract and Zincovit tablets on lipid profile among normal animals in comparison with normal control group. The present study demonstrated that the single combined formulation of grape seed extract and Zincovit tablet is the potential functional nutritional food supplements that could offer a novel therapeutic opportunity against diet-induced hypercholesterolemia in Wistar rats.

Peripheral nerve metabolism and zinc levels in streptozotocin induced diabetic rats. Effect of diets high in fish and corn oil

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

Burke, J.P.; Fenton, M.R.

1991-03-15

This study was designed to assess the effects of diets high in fish and corn oil on peripheral nerve metabolism in streptozotocin (STZ) induced diabetic rats. A type I diabetic state was induced in female Sprague-Dawley rats by injection of STZ. Animals were divided into three dietary groups; normal rat chow, high corn oil diet and high fish oil diet. After 4 weeks animals were analyzed for nerve conduction velocity, bled and then sacrificed. Sciatic nerves were removed, processed and several biochemical parameters determined. Plasma zinc levels were elevated in the STZ normal chow group compared to non-diabetic controls. Bothmore » corn oil and fish oil diets tended to eliminate the rise in plasma zinc. Differences in subcellular distribution of zinc in sciatic nerves were also observed. Normal chow STZ animals displayed a 20% decrease in nerve conduction velocity compared to control. Dietary supplementation with either fish or corn oil seemed to ameliorate these effects. Biochemical analysis of Na{sup +}-K{sup +}-ATPase and protein kinase C revealed a decrease in activity in normal chow animals compared to control groups. Again, dietary intervention with either fish or corn oil seemed to return these activities back to normal. The results suggest a link between zinc metabolism and peripheral nerve metabolism which can be modified by dietary intervention.« less

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

PubMed

Koontz, Bridget F; Verhaegen, Frank; De Ruysscher, Dirk

2017-01-01

Animal modelling is essential to the study of radiobiology and the advancement of clinical radiation oncology by providing preclinical data. Mouse models in particular have been highly utilized in the study of both tumour and normal tissue radiobiology because of their cost effectiveness and versatility. Technology has significantly advanced in preclinical radiation techniques to allow highly conformal image-guided irradiation of small animals in an effort to mimic human treatment capabilities. However, the biological and physical limitations of animal modelling should be recognized and considered when interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal tissue radioresponse has been shown to vary from human cellular and molecular pathways. Small animal irradiation techniques utilize different anatomical boundaries and may have different physical properties than human RT. This review addresses the difference between the human condition and mouse models and discusses possible strategies for future refinement of murine models of cancer and radiation for the benefit of both basic radiobiology and clinical translation.

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

PubMed Central

Verhaegen, Frank; De Ruysscher, Dirk

2017-01-01

Animal modelling is essential to the study of radiobiology and the advancement of clinical radiation oncology by providing preclinical data. Mouse models in particular have been highly utilized in the study of both tumour and normal tissue radiobiology because of their cost effectiveness and versatility. Technology has significantly advanced in preclinical radiation techniques to allow highly conformal image-guided irradiation of small animals in an effort to mimic human treatment capabilities. However, the biological and physical limitations of animal modelling should be recognized and considered when interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal tissue radioresponse has been shown to vary from human cellular and molecular pathways. Small animal irradiation techniques utilize different anatomical boundaries and may have different physical properties than human RT. This review addresses the difference between the human condition and mouse models and discusses possible strategies for future refinement of murine models of cancer and radiation for the benefit of both basic radiobiology and clinical translation. PMID:27612010

Possible role of the microbiome in the development of acute malnutrition and implications for food-based strategies to prevent and treat acute malnutrition

USDA-ARS?s Scientific Manuscript database

A pattern of changes in the microbiome composition have been observed in the normal maturation of the human gut. Perturbations from this pattern have been described in malnourished humans and reproduced in animal models of severe malnutrition. Treatment and prevention of malnutrition in the future m...

What underlies the diversity of brain tumors?

PubMed Central

Swartling, Fredrik J.; Hede, Sanna-Maria; Weiss, William A.

2012-01-01

Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children respectively. Recent genomic and transcriptional approaches present a complex group of diseases, and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development, and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development, and the potential for these animals to impact brain tumor research. PMID:23085857

Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

NASA Technical Reports Server (NTRS)

Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

2000-01-01

Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

Epilepsy, regulation of brain energy metabolism and neurotransmission.

PubMed

Cloix, Jean-François; Hévor, Tobias

2009-01-01

Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.

Reconstituted normal human breast in nude mice: effect of host pregnancy environment and human chorionic gonadotropin on proliferation.

PubMed

Popnikolov, N; Yang, J; Liu, A; Guzman, R; Nandi, S

2001-03-01

The proliferation of normal human breast epithelial cells in women is highest during the first trimester of pregnancy. In an attempt to analyze this hormonal environment in a model system, the effect of host mouse pregnancy and the administration of human chorionic gonadotropin (hCG) were assessed in normal human breast epithelial cells transplanted into athymic nude mice. Human breast epithelial cells, dissociated from reduction mammoplasty specimens and embedded inside the extracellular matrices comprised of collagen gel and Matrigel, were transplanted into nude mice. Proliferation was measured in vivo by BrdU labeling followed by immunostaining of sections from recovered gels in response to an altered hormonal environment of the host animal. The host animal was mated to undergo pregnancy and the complex hormonal environment of the host animal pregnancy stimulated growth of transplanted human cells. This effect increased with progression of pregnancy and reached the maximum during late pregnancy prior to parturition. In order to determine whether additional stimulation could be achieved, the transplanted human cells were exposed to a second cycle of host mouse pregnancy by immediately mating the animal after parturition. This additional exposure of host mouse pregnancy did not result in further increase of proliferation. The effect of hCG administration on transplanted human cells was also tested, since hCG level is highest during the first trimester of human pregnancy and coincides with the maximal breast cell proliferation. Administration of hCG alone stimulated proliferation of human cells in a dose-dependent manner, and could further enhance stimulation achieved with estrogen. The host mouse mammary gland also responded to hCG treatment resulting in increased branching and lobulo-alveolar development. However, the hCG effect on both human and mouse cells was dependent on intact ovary since the stimulation did not occur in ovariectomized animals. Although hCG receptor transcripts were detected in human breast epithelial cells, raising the possibility of a direct mitogenic action, the hCG effect observed in this study may have been mediated via the ovary by increased secretion of ovarian steroids. In summary, using our in vivo nude mice system, the proliferation of normal human breast epithelial cells could be stimulated by host mouse pregnancy and by administration of hCG.

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

PubMed Central

Banerjee, Anwesha; Engineer, Crystal T.; Sauls, Bethany L.; Morales, Anna A.; Kilgard, Michael P.; Ploski, Jonathan E.

2014-01-01

Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning. PMID:25429264

Effect of X-irradiation on the stomach of the rat

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

Breiter, N.; Trott, K.R.; Sassy, T.

1989-10-01

A model for localized 300 kV X-irradiation of the rat stomach was developed. After irradiation with single doses, three distinct gastric disorders were observed which occurred at different latency times. Acute death 2-3 weeks after irradiation was caused by an erosive and ulcerative gastritis and occurred in all animals given 28.5 Gy without diet, in 17% of the animals given 28.5 Gy plus diet, and in 13% of the animals given 23 Gy. Subacute to chronic fatal disorders 4 weeks to 7 months after irradiation were seen as stomach dilatation and gastroparesis, associated with the replacement of the normal gastricmore » mucosa by a hyperkeratinized multilayered squamous epithelium. These disorders occurred in 40-100% of the animals after doses between 16 Gy and 28.5 Gy (+diet). An ED 50 value of 19.2 Gy (16.5-21.2 Gy, 95% confidence interval) was calculated for this gastroparesis. Late gastric obstruction exceeding 7 months after irradiation was seen in the rats because of profound changes in the gastric wall in 13-18% of the animals after doses between 23 Gy and 14 Gy. In animals surviving these three periods, an atrophic mucosa and intestinal metaplasia developed. From functional and morphohistological studies, it can be concluded that there are differences in the pathogenesis of the fatal radiation damage for each of these periods after irradiation.« less

sirt1-null mice develop an autoimmune-like condition

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

Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie

2008-10-01

The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistentmore » with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.« less

Gravitational Effects on Reproduction, Growth, and Development of Mammals

NASA Technical Reports Server (NTRS)

Oyama, J.

1985-01-01

The broad objective of this research program is to determine the role which gravity plays in the growth and development of mammalian animals. Current studies are focused on the effects of graded hypergravitatinal field intensities on mice, rats and other small sized laboratory animals using the chronic centrifugation technique. They include studies on reproduction and prenatal and postnatel growth and development. Among the important questions addressed are: (1) what stage or stages in animal development are affected by hypergravity and what are the effects? (2) is there a minimum or critical body size for hypergravity to produce a significant effect on growth and development? (3) are there field intensity thresholds for the preceding questions? From analysis of the body masses at birth of rats conceived and allowed to undergo gestation under 2.1G and under normal gravity (1G), it was found that there was no significant difference between the two groups. Futhermore, their growth rates postnatally were the same until they reached a body mass of approximately 50 grams when the 2.1G group showed a significantly slower rate. Results from these studies support the conclusion that prenatal as well as the early postnatal stages of growth and development of the rat are refractory to hyper-G.

Perfluorocarbon-associated gas exchange in normal and acid-injured large sheep.

PubMed

Hernan, L J; Fuhrman, B P; Kaiser, R E; Penfil, S; Foley, C; Papo, M C; Leach, C L

1996-03-01

We hypothesized that a) perfluorocarbon-associated gas exchange could be accomplished in normal large sheep; b) the determinants of gas exchange would be similar during perfluorocarbon-associated gas exchange and conventional gas ventilation; c)in large animals with lung injury, perfluorocarbon-associated gas exchange could be used to enhance gas exchange without adverse effects on hemodynamics; and d) the large animal with lung injury could be supported with an FIO2 of <1.0 during perfluorocarbon-associated gas exchange. Prospective, observational animal study and prospective randomized, controlled animal study. An animal laboratory in a university setting. Thirty adult ewes. Five normal ewes (61.0 +/- 4.0 kg) underwent perfluorocarbon-associated gas exchange to ascertain the effects of tidal volume, end-inspiratory pressure, and positive end-expiratory pressure (PEEP) on oxygenation. Respiratory rate, tidal volume, and minute ventilation were studied to determine their effects on CO2 clearance. Sheep, weighing 58.9 +/- 8.3 kg, had lung injury induced by instilling 2 mL/kg of 0.05 Normal hydrochloric acid into the trachea. Five minutes after injury, PEEP was increased to 10 cm H2O. Ten minutes after injury, sheep with Pao2 values of <100 torr (<13.3 kPa) were randomized to continue gas ventilation (control, n=9) or to institute perfluorocarbon-associated gas exchange (n=9) by instilling 1.6 L of unoxygenated perflubron into the trachea and resuming gas ventilation. Blood gas and hemodynamic measurements were obtained throughout the 4-hr study. Both tidal volume and end-inspiratory pressure influenced oxygenation in normal sheep during perfluorocarbon-associated gas exchange. Minute ventilation determined CO2 clearance during perfluorocarbon-associated gas exchange in normal sheep. After acid aspiration lung injury, perfluorocarbon-associated gas exchange increased PaO2 and reduced intrapulmonary shunt fraction. Hypoxia and intrapulmonary shunting were unabated after injury in control animals. Hemodynamics were not influenced by the institution of perfluorocarbon-associated gas exchange. Tidal volume and end-inspiratory pressure directly influence oxygenation during perfluorocarbon-associated gas exchange in large animals. Minute ventilation influences clearance of CO2. In adult sheep with acid aspiration lung injury, perfluorocarbon-associated gas exchange at an FIO2 of <1.0 supports oxygenation and improves intrapulmonary shunting, without adverse hemodynamic effects, when compared with conventional gas ventilation.

Suppressive Effect of Immunization with Mouse Fetal Antigens on Growth of Cells Infected with Rauscher Leukemia Virus and on Plasma-Cell Tumors

PubMed Central

Hanna, M. G.; Tennant, R. W.; Coggin, J. H.

1971-01-01

The recovery of spleen cells infected with Rauscher leukemia virus (RLV) and grown in Millipore diffusion chambers, the development of RLV-induced splenomegaly, and the cumulative mortality from a transplanted ascites plasma-cell tumor were all suppressed in young adult BALB/c male mice previously primed at 3-weekly intervals with x-irradiated, syngeneic embryo cells. RLV-induced splenomegaly was also suppressed by adoptive transfer of postpartal spleen cells, as well as spleen cells for animals primed with syngeneic embryo cells. Similar suppressions were not observed in mice primed with neonatal or normal syngeneic cells. Further, injection of fetal cells was not effective in suppressing the immune function of normal spleen cells, as measured by ability to elaborate a primary immunoglobulin M response to heterologous erythrocyte antigen. The results of this study add to the broad spectrum of tumors of experimental animals and man known to contain neoantigens common to fetal cells. PMID:4942913

Pepsin egg white hydrolysate ameliorates metabolic syndrome in high-fat/high-dextrose fed rats.

PubMed

Moreno-Fernández, S; Garcés-Rimón, M; González, C; Uranga, J A; López-Miranda, V; Vera, G; Miguel, M

2018-01-24

The aim of this study was to examine the effect of a pepsin egg white hydrolysate (EWH) on metabolic complications using a high-fat/high-dextrose diet-induced Metabolic Syndrome (MetS) experimental model. Male Wistar rats were divided into 4 groups which received: standard diet and water (C), standard diet and a solution with 1 g kg -1 day -1 of EWH (CH), high-fat/high-dextrose diet and water (MS), and high-fat/high-dextrose diet and a solution with 1 g kg -1 day -1 of EWH (MSH). EWH consumption normalized body weight gain; abdominal obesity and peripheral neuropathy developed in MetS animals, and adipose tissue and liver weight, as well as plasma glucose were reduced. Oxidative stress and inflammation biomarkers were normalized in MSH animals. In conclusion, the oral administration of EWH could be used as a functional food ingredient to improve some complications associated with MetS induced by unhealthy diets.

Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis

PubMed Central

Bush, Ronald A.; Wei, Lisa L.; Sieving, Paul A.

2015-01-01

Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

PubMed

Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

2015-02-01

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis.

PubMed

Knudson, Inge M; Melcher, Jennifer R

2016-06-01

Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient.

[Characteristics of sodium metabolism in rats with experimental hypertension caused by chronic alimentary imbalance].

PubMed

Strekalova, V V; Khachirov, D G; Dedenkov, A N; Suvorov, Iu I

1991-01-01

Beginning from 1.5 month of life Wistar rats were kept under conditions of chronic 1 and 2% salt loading combined with a low-protein diet (6-8% of protein VS, as compared with 23-24% in the normal diet). At the age of 14-16 months when a stable hypertension developed due to the above alimentary imbalance, their sodium metabolism was studied using whole-body radiometry with 22Na. A three-chamber model of 22Na metabolism was developed for the analysis of 22Na excretion from the body. This helped in establishing the heterogeneity of sodium metabolism in experimental animals. Besides that, it has been shown that not only sodium retention in the body, but also its redistribution between intra- and extravascular sections play an important role in the development of hypertension. Protein deficiency in the diet aggravates sodium metabolism disorders in experimental animals.

The embryonic development of the cnidarian Hydractinia echinata.

PubMed

Kraus, Yulia; Flici, Hakima; Hensel, Katrin; Plickert, Günter; Leitz, Thomas; Frank, Uri

2014-01-01

With the rapid increase of the quantity of molecular data, many animals joined the ranks of the so-called 'emerging models' of Evo-Devo. One of the necessary steps in converting an emerging model into an established one is gaining comprehensive knowledge of its normal embryonic development. The marine colonial hydrozoan Hydractinia echinata - an excellent model for research on stem cells, metamorphosis, and allorecognition - has been studied for decades. Yet knowledge of its embryonic development remains fragmentary and incomplete. Here we provide a detailed account of H. echinata embryonic development using in vivo observations, histology, immunohistochemistry, and electron microscopy. Furthermore, we propose a model describing the cellular basis of the morphogenetic movements occurring during development and also reveal a functional link between canonical Wnt signaling and regional differences in the morphology of the embryo. Hydractinia embryogenesis is an example of the diversity and plasticity of hydrozoan development where multiple routes lead to the same result - the formation of a normal planula larva. © 2014 Wiley Periodicals, Inc.

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy.

PubMed

Sleeper, Meg M; Rosato, Bradley P; Bansal, Seema; Avadhani, Narayan G

2012-11-01

To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

A qualitative electron microscopic study of the corticopontine projections after neonatal cerebellar hemispherectomy.

PubMed

Leong, S K

1980-08-04

The present study shows that 3--5 days following lesions of the dentate and interposed nuclei in normal adult rats degenerating axons and axon terminals can be detected in the contralateral pontine gray. The degenerating axon terminals form Gray's type I axo-dendritic contacts with fine and intermediate dendrites measuring between 0.8--2.4 microns. The present study also investigates, by electron microscopy, the synaptic rearrangement of the sensorimotor corticopontine projections following neonatal left cerebellar hemispherectomy. Following neonatal left cerebellar hemispherectomy, the right sensorimotor and adjacent cortex (SMC) presents a very dense ipsilateral and a modest amount of contralateral corticopontine projections in contrast with a predominantly ipsilateral corticopontine projection seen in the normal adult rat. As with the ipsilateral corticopontine projection seen in the normal adult animal, the bilateral corticopontine projections seen in the experimental animals form contacts with dendrites suggestive of Gray's type I synapses. While the corticopontine projections in normal control animals form synapses with fine dendrites measuring 0.2--1.2 micron the corticopontine projections in the experimental animals form synaptic relations with fine dendrites and with intermediate dendrites measuring 0.2--2.4 microns. As the normal cerebellopontine fibers from the dentate and interposed nuclei also form axo-dendritic synapses on fine and intermediate dendrites and the contracts formed are also of Gray's type I synapses, it is possible that some of the newly formed corticopontine fibers in the experimental animals might have replaced the cerebellopontine fibers synapsing on intermediate dendrites. Synaptic rearrangement appears to take place as suggested by the presence of synaptic complexes in which one axon terminal contacts two or more dendrites or two or more axon terminals contact one dendrite. Such complexes are frequently seen to undergo degeneration following the right SMC lesion in the experimental animals. Other complex synaptic structures are also present in both the right and left pontine gray in the experimental animals. They are not seen to undergo degeneration following the right SMC lesions. Occasional features of neuronal reaction could still be seen in both sides of the pontine gray for as long as 3--6 months after the neonatal cerebellar lesions.

Cytoplasmic regionalization in starfish oocyte occurrence and localization of cytoplasmic determinants responsible for the formation of archenteron and primary mesenchyme in starfish ( asterias amurensis) oocytes

NASA Astrophysics Data System (ADS)

Zhang, Shicui; Wu, Xianhan; Zhou, Jing; Wang, Renxue; Wu, Shangqin

1990-09-01

Starfish oocytes with intact germinal vesicles (GVs) were cut along desired planes with glass needles or ligated using silk thread loops into two parts and allowed to mature in vitro, and inseminated. The experimental results showed that (1) only the parts with GVs or partial GV contents (PGVCs) cleaved, those without any GV materials did not; but nucleated and non-nucleated fragments cut from mature eggs were able to divide; (2) the development of animal parts of oocytes containing GVs or PGVCs was like that of animal fragments of matured oocytes with female pronuclei; most of them gave rise to permanent blastulae, and just a few formed ectodermal vesicles with a little primary mesenchyme; (3) a large part of vegetal fragments with GVs or PGVCs, and the vegetal parts of mature eggs without female pronuclei developed into small but normal embryos; (4) the fragments containing GVs or PGVCs obtained from the oocytes along a plane parallel to the animal-vegetal (A-V) axis developed as normally as the halves (with or without female pronuclei) severed from mature eggs along the same axis. Based on the data above, it was concluded that (1) the non-chromatin materials in the oocyte GVs are indispensable for successful fertilization and cleavage of starfish eggs; (2) some factor (s) located asymmetrically in the vegetal hemispheres of starfish oocytes is (are) responsible for formation of the archenteron and primary mesenchyme. It is evident from the above findings that the oocyte cytoplasm of the starfish had already regionalized before the GV break-down.

MARTI: man-machine animation real-time interface

NASA Astrophysics Data System (ADS)

Jones, Christian M.; Dlay, Satnam S.

1997-05-01

The research introduces MARTI (man-machine animation real-time interface) for the realization of natural human-machine interfacing. The system uses simple vocal sound-tracks of human speakers to provide lip synchronization of computer graphical facial models. We present novel research in a number of engineering disciplines, which include speech recognition, facial modeling, and computer animation. This interdisciplinary research utilizes the latest, hybrid connectionist/hidden Markov model, speech recognition system to provide very accurate phone recognition and timing for speaker independent continuous speech, and expands on knowledge from the animation industry in the development of accurate facial models and automated animation. The research has many real-world applications which include the provision of a highly accurate and 'natural' man-machine interface to assist user interactions with computer systems and communication with one other using human idiosyncrasies; a complete special effects and animation toolbox providing automatic lip synchronization without the normal constraints of head-sets, joysticks, and skilled animators; compression of video data to well below standard telecommunication channel bandwidth for video communications and multi-media systems; assisting speech training and aids for the handicapped; and facilitating player interaction for 'video gaming' and 'virtual worlds.' MARTI has introduced a new level of realism to man-machine interfacing and special effect animation which has been previously unseen.

Similarities and Differences for Swimming in Larval and Adult Lampreys.

PubMed

McClellan, Andrew D; Pale, Timothée; Messina, J Alex; Buso, Scott; Shebib, Ahmad

2016-01-01

The spinal locomotor networks controlling swimming behavior in larval and adult lampreys may have some important differences. As an initial step in comparing the locomotor systems in lampreys, in larval animals the relative timing of locomotor movements and muscle burst activity were determined and compared to those previously published for adults. In addition, the kinematics for free swimming in larval and adult lampreys was compared in detail for the first time. First, for swimming in larval animals, the neuromechanical phase lag between the onsets or terminations of muscle burst activity and maximum concave curvature of the body increased with increasing distance along the body, similar to that previously shown in adults. Second, in larval lampreys, but not adults, absolute swimming speed (U; mm s(-1)) increased with animal length (L). In contrast, normalized swimming speed (U'; body lengths [bl] s(-1)) did not increase with L in larval or adult animals. In both larval and adult lampreys, U' and normalized wave speed (V') increased with increasing tail-beat frequency. Wavelength and mechanical phase lag did not vary significantly with tail-beat frequency but were significantly different in larval and adult animals. Swimming in larval animals was characterized by a smaller U/V ratio, Froude efficiency, and Strouhal number than in adults, suggesting less efficient swimming for larval animals. In addition, during swimming in larval lampreys, normalized lateral head movements were larger and normalized lateral tail movements were smaller than for adults. Finally, larval animals had proportionally smaller lateral surface areas of the caudal body and fin areas than adults. These differences are well suited for larval sea lampreys that spend most of the time buried in mud/sand, in which swimming efficiency is not critical, compared to adults that would experience significant selection pressure to evolve higher-efficiency swimming to catch up to and attach to fish for feeding as well as engage in long-distance migration during spawning. Finally, the differences in swim efficiency for larval and adult lampreys are compared to other animals employing the anguilliform mode of swimming.

Mouse Models for Investigating the Developmental Bases of Human Birth Defects

PubMed Central

MOON, ANNE M.

2006-01-01

Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221

Recent advances in the cell biology of aging.

PubMed

Hayflick, L

1980-01-01

Cultured normal human and animal cells are predestined to undergo irreversible functional decrements that mimic age changes in the whole organism. When normal human embryonic fibroblasts are cultured in vitro, 50 +/- 10 population doublings occur. This maximum potential is diminished in cells derived from older donors and appears to be inversely proportional to their age. The 50 population doubling limit can account for all cells produced during a lifetime. The limitation on doubling potential of cultured normal cells is also expressed in vivo when serial transplants are made. There may be a direct correlation between the mean maximum life spans of several species and the population doubling potential of their cultured cells. A plethora of functional decrements occurs in cultured normal cells as they approach their maximum division capability. Many of these decrements are similar to those occurring in intact animals as they age. We have concluded that these functional decrements expressed in vitro, rather than cessation of cell division, are the essential contributors to age changes in intact animals. Thus, the study of events leading to functional losses in cultured normal cells may provide useful insights into the biology of aging.

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

NASA Astrophysics Data System (ADS)

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis.

PubMed

Boolbol, S K; Dannenberg, A J; Chadburn, A; Martucci, C; Guo, X J; Ramonetti, J T; Abreu-Goris, M; Newmark, H L; Lipkin, M L; DeCosse, J J; Bertagnolli, M M

1996-06-01

Inducible cyclooxygenase (Cox-2), also known as prostaglandin H synthase 2 (PGH-2) is a key enzyme in the formation of prostaglandins and thromboxanes. Cox-2 is the product of an immediate-early gene that is expressed in response to growth factors, tumor promoters, or cytokines. Overexpression of Cox-2 is associated with both human colon cancers and suppression of apoptosis in cultured epithelia] cells, an activity that is reversed by the nonsteroidal anti-inflammatory drug, sulindac sulfide. To address the relationship between Cox-2, apoptosis, and tumor development in vivo, we studied C57BL/6J-Min/+(Min) mice, a strain containing a fully penetrant dominant mutation in the Apc gene, leading to the development of gastrointestinal adenomas by 110 days of age. Min mice were fed AIN-76A chow diet and given sulindac (0.5 +/- 0.1 mg/day) in drinking water. Control Min mice and homozygous C57BL/6J-+/+ normal littermates lacking the Apc mutation (+/+) were fed AIN-76A diet and given tap water to drink. At 110 days of age, all mice were sacrificed, and their intestinal tracts were examined. Control Min mice had 11.9 +/- 7.8 tumors per mouse compared to 0.1 +/- 0.1 tumors for sulindac-treated Min mice. As expected, +/+ littermates had no macroscopic tumors. Examination of histologically normal-appearing small bowel from Min animals revealed increased amounts of Cox-2 and prostaglandin E(2) compared to +/+ littermates. Using two different in situ techniques, terminal transferase-mediated dUTP nick end labeling and a direct immunoperoxidase method, Min animals also demonstrated a 27-47% decrease in enterocyte apoptosis compared to +/+ animals. Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis. These data suggest that overexpression of Cox-2 is associated with tumorigenesis in the gastrointestinal epithelium, and that both are inhibited by sulindac administration.

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

PubMed

Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

2013-08-01

Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

[Investigation of neural stem cell-derived donor contribution in the inner ear following blastocyst injection].

PubMed

Volkenstein, S; Brors, D; Hansen, S; Mlynski, R; Dinger, T C; Müller, A M; Dazert, S

2008-03-01

Utilising the enormous proliferation and multi-lineage differentiation potentials of somatic stem cells represents a possible therapeutical strategy for diseases of non-regenerative tissues like the inner ear. In the current study, the possibility of murine neural stem cells to contribute to the developing inner ear following blastocyst injection was investigated. Fetal brain-derived neural stem cells from the embryonic day 14 cortex of male mice were isolated and expanded for four weeks in neurobasal media supplemented with bFGF and EGF. Neural stem cells of male animals were harvested, injected into blastocysts and the blastocysts were transferred into pseudo-pregnant foster animals. Each blastocyst was injected with 5-15 microspheres growing from single cell suspension from neurospheres dissociated the day before. The resulting mice were investigated six months POST PARTUM for the presence of donor cells. Brainstem evoked response audiometry (BERA) was performed in six animals. To visualize donor cells Lac-Z staining was performed on sliced cochleas of two animals. In addition, the cochleas of four female animals were isolated and genomic DNA of the entire cochlea was analyzed for donor contribution by Y-chromosome-specific PCR. All animals had normal thresholds in brainstem evoked response audiometry. The male-specific PCR product indicating the presence of male donor cells were detected in the cochleas of three of the four female animals investigated. In two animals, male donor cells were detected unilateral, in one animal bilateral. The results suggest that descendants of neural stem cells are detectable in the inner ear after injection into blastocysts and possess the ability to integrate into the developing inner ear without obvious loss in hearing function.

The Development of Mental State Attributions in Women with X-Monosomy, and the Role of Monoamine Oxidase B in the Sociocognitive Phenotype

ERIC Educational Resources Information Center

Lawrence, K.; Jones, A.; Oreland, L.; Spektor, D.; Mandy, W.; Campbell, R.; Skuse, D.

2007-01-01

We hypothesized that women with Turner syndrome (45,X) with a single X-chromosome inherited from their mother may show mentalizing deficits compared to women of normal karyotype with two X-chromosomes (46,X). Simple geometrical animation events (two triangles moving with apparent intention in relation to each other) which usually elicit…

Levetiracetam: the preclinical profile of a new class of antiepileptic drugs?

PubMed

Klitgaard, H

2001-01-01

Levetiracetam is a new antiepileptic drug (AED) devoid of anticonvulsant activity in the two classic screening models for AEDs, the maximal electroshock and pentylenetetrazol seizure tests in both mice and rats. This contrasts a potent seizure suppression in genetic and kindled mice and rats and against chemoconvulsants inducing partial seizures in rats. The highly selective action in "epileptic" animals distinguishes levetiracetam from classic and other new AEDs that have nearly equipotent effects in normal and "epileptic" animals. Levetiracetam induces minor behavioral alterations in normal and in kindled mice and rats. This results in an unusually high safety margin in animal models reflecting both partial and primary generalized epilepsy. Furthermore, experiments in the kindling model suggest that levetiracetam may possess antiepileptogenic properties due to a potent ability to prevent the development of kindling in mice and rats at doses devoid of adverse effects. Electrophysiologic recordings from different experimental models suggest that levetiracetam exerts a selective action against abnormal patterns of neuronal activity, which probably explains its selective protection in epileptic animals and its unique tolerability. This effect appears to derive from one or more novel mechanisms of action that do not involve a conventional interaction with traditional drug targets implicated in the modulation of inhibitory and excitatory neurotransmission. Instead, ligand-binding assays have disclosed a brain-specific binding site for levetiracetam. These studies reveal a unique preclinical profile of levetiracetam, distinct from that of all known AEDs, suggesting that levetiracetam could represent the first agent in a new class of AEDs.

Maintenance Fluid Therapy: Isotonic Versus Hypotonic Solutions.

PubMed

Hansen, Bernie; Vigani, Alessio

2017-03-01

The goal of maintenance fluid therapy in small animals is to replace normal ongoing losses of water and salts when oral intake is withheld. Hospitalized dogs and cats may have multiple stimuli for antidiuretic hormone release that disrupt normal osmoregulation and predispose to water retention. Severe illness promotes retention of both sodium and water as edema. Commercially available fluids have electrolyte concentrations that are very different from dietary maintenance requirements, and potential consequences include development of hypoosmolality, edema, or both when excesses of water or sodium are administered. Suggestions for tailoring fluid administration toward specific goals are provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs.

PubMed

Jaén, Maria Luisa; Vilà, Laia; Elias, Ivet; Jimenez, Veronica; Rodó, Jordi; Maggioni, Luca; Ruiz-de Gopegui, Rafael; Garcia, Miguel; Muñoz, Sergio; Callejas, David; Ayuso, Eduard; Ferré, Tura; Grifoll, Iris; Andaluz, Anna; Ruberte, Jesus; Haurigot, Virginia; Bosch, Fatima

2017-09-15

Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors. Here, we report the long-term (∼8 years) follow-up after a single administration of therapeutic vectors to diabetic dogs. Successful, multi-year control of glycemia was achieved without the need of supplementation with exogenous insulin. Metabolic correction was demonstrated through normalization of serum levels of fructosamine, triglycerides, and cholesterol and remarkable improvement in the response to an oral glucose challenge. The persistence of vector genomes and therapeutic transgene expression years after vector delivery was documented in multiple samples from treated muscles, which showed normal morphology. Thus, this study demonstrates the long-term efficacy and safety of insulin and glucokinase gene transfer in large animals and especially the ability of the system to respond to the changes in metabolic needs as animals grow older.

Term placenta shows methylation independent down regulation of Cyp19 gene in animals with retained fetal membranes.

PubMed

Ghai, Sandeep; Monga, Rachna; Mohanty, T K; Chauhan, M S; Singh, Dheer

2012-02-01

Retention of fetal membranes (RFM) is the major post-partum disorder in dairy cattle. Cyp19 gene encodes the aromatase enzyme responsible for catalyzing the rate limiting step in estrogen biosynthesis, an important hormone for placental maturation and expulsion. The present study was aimed for comparative analysis of Cyp19 gene expression and its epigenetic regulation in placental cotyledons of animals with and without RFM. Significantly lower expression of Cyp19 gene was found in placental samples of RFM affected animals in comparison to normal animals. Methylation analysis of 5 CpG dinucleotides of placenta specific Cyp19 gene promoter I.1 and proximal promoter, PII showed hypo-methylation of both PI.1 and PII in term placenta of normal and diseased animals. In conclusion, a mechanism other than promoter methylation is responsible for decreased aromatase expression in placental cotyledons of animals suffering from RFM. Copyright © 2010 Elsevier Ltd. All rights reserved.

In vitro cell response of Treponema pallidum-infected rabbits. III. Impairment in production of lymphocyte mitogenic factor.

PubMed Central

Wicher, V; Wicher, K

1977-01-01

Production of mitogenic factor was examined in rabbits infected intratesticularly with T. pallidum and in control animals injected with saline or saline extract of normal rabbits' testes. Lymph nodes and spleen from animals killed 2, 6 and 12 weeks after injection were used as the source of lymphocytes, cultured in serum-free medium in the presence of Reiter antigen. The active supernatants of lymph node cells (LNAS) and spleen cells (SPAS) were examined for the presence of mitogenic factor using normal rabbit peripheral lymphocytes. The LNAS of control animals showed a mitogenic index (MI) between 4 and 6 and the infected animals less than 2. The SPAS of infected and control rabbits showed an MI of less than 2. The lower mitogenicity in LNAS of infected and that of SPAS of infected and control animals seems to be due to the presence of inhibitors of DNA synthesis. PMID:303968

Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions

PubMed Central

Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.

2009-01-01

Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations. PMID:19075184

THE INFLUENCE OF BIOTIN UPON SUSCEPTIBILITY TO MALARIA

PubMed Central

Trager, William

1943-01-01

Biotin-deficient chickens and ducks developed much more severe infections with Plasmodium lophurae than did non-deficient control animals. While a very mild degree of biotin deficiency sufficed to increase susceptibility, even an extreme degree of pantothenic acid deficiency had no effect. Biotin deficiency also increased the susceptibility of ducks to P. cathemerium. In animals infected with P. lophurae, the concentration of biotin in the plasma as well as in the red cells rose during the course of the infection, reached a peak at about the same time as the parasite number reached its peak, and then returned to normal as the infection subsided. While the administration of additional biotin to animals partially deficient in biotin could be considered a specific measure tending to lessen the severity of infection with P. lophurae, the injection of biotin into animals fed a diet adequate in this vitamin had no antimalarial effects, perhaps because the excess biotin was rapidly removed from the blood. PMID:19871304

[Contribution of animal models to the study of reproduction, assisted reproductive technologies and of development].

PubMed

Jammes, Hélène; Fauque, Patricia; Jouannet, Pierre

2010-02-01

Children conceived through assisted reproductive technologies (ART) now account for a noteworthy proportion (-2.4%) of births in France. Considerable attention is being paid to the outcome of ART pregnancies. The vast majority of these children are apparently normal. However, they are at an increased risk of minor birth defects, low birth weight, and rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Silver Russel syndrome (SRS). Animal models are important for investigating the possible role of each step of ART (ovarian stimulation, gamete manipulation, in vitro fertilization, embryo culture and embryo transfer) in epigenetic reprogramming This review discusses these issues in the context of epigenetic and developmental abnormalities observed in animals following ART More research is needed on ART-induced errors, focusing not only on genomic imprinting but also on non-imprinted loci, which may help explain some of the more subtle longer-term health effects emerging from studies with animal models.

Modification of thermoregulatory responses in rabbits reared at elevated environmental temperatures.

PubMed Central

Cooper, K E; Ferguson, A V; Veale, W L

1980-01-01

1. Pregnant New Zealand white rabbits were kept from 14 days pre-partum at an environmental temperature of 33 degrees C, and their offspring were reared at this temperature. 2. In response to a 4 hr cold exposure, animals (aged 90-180 days) raised in this way showed significant drops in colonic temperature (-2.7 +/- 0.5 degrees C) while control animals reared at 20 degrees C did not (+0.05 +/- 0.1 degrees C). 3. A reduced, monophasic endotoxin fever was observed in animals reared at 33 degrees C, while a normal biphasic fever was seen in rabbits originally reared at 20 degrees C and subsequently acclimated to 33 degrees C. 4. A greatly reduced temperature response to intravenous infusion of noradrenaline was also found in animals raised at 33 degrees C. 5. It is proposed that thermal afferent input during early life may play an important role in the development of the thermoregulatory system. PMID:7431230

Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems

PubMed Central

Ardeshir, Amir; Narayan, Nicole R.; Méndez-Lagares, Gema; Lu, Ding; Rauch, Marcus; Huang, Yong; Van Rompay, Koen K. A.; Lynch, Susan V.; Hartigan-O'Connor, Dennis J.

2015-01-01

Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases. PMID:25186175

Asymmetric Distribution of Metals in the Xenopus Laevis Oocyte: a Synchrotron X-Ray Fluorescence Microprobe Study

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

Popescu, B.F.Gh.; Belak, Z.R.; Ignatyev, K.

2009-06-04

The asymmetric distribution of many components of the Xenopus oocyte, including RNA, proteins, and pigment, provides a framework for cellular specialization during development. During maturation, Xenopus oocytes also acquire metals needed for development, but apart from zinc, little is known about their distribution. Synchrotron X-ray fluorescence microprobe was used to map iron, copper, and zinc and the metalloid selenium in a whole oocyte. Iron, zinc, and copper were asymmetrically distributed in the cytoplasm, while selenium and copper were more abundant in the nucleus. A zone of high copper and zinc was seen in the animal pole cytoplasm. Iron was alsomore » concentrated in the animal pole but did not colocalize with zinc, copper, or pigment accumulations. This asymmetry of metal deposition may be important for normal development. Synchrotron X-ray fluorescence microprobe will be a useful tool to examine how metals accumulate and redistribute during fertilization and embryonic development.« less

Asymmetri Distribution of Metals in the Xenopus Laevis Oocyte: a Synchrotron X-Ray Fluorescence Microprobe Study

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

Popescu, B.F.G.; Belak, Z.R.; Ignatyev, K.

2009-04-29

The asymmetric distribution of many components of the Xenopus oocyte, including RNA, proteins, and pigment, provides a framework for cellular specialization during development. During maturation, Xenopus oocytes also acquire metals needed for development, but apart from zinc, little is known about their distribution. Synchrotron X-ray fluorescence microprobe was used to map iron, copper, and zinc and the metalloid selenium in a whole oocyte. Iron, zinc, and copper were asymmetrically distributed in the cytoplasm, while selenium and copper were more abundant in the nucleus. A zone of high copper and zinc was seen in the animal pole cytoplasm. Iron was alsomore » concentrated in the animal pole but did not colocalize with zinc, copper, or pigment accumulations. This asymmetry of metal deposition may be important for normal development. Synchrotron X-ray fluorescence microprobe will be a useful tool to examine how metals accumulate and redistribute during fertilization and embryonic development.« less

Anthropomorphic bias found in typically developing children is not found in children with autistic spectrum disorder.

PubMed

Chaminade, Thierry; Rosset, Delphine; Da Fonseca, David; Hodgins, Jessica K; Deruelle, Christine

2015-02-01

The anthropomorphic bias describes the finding that the perceived naturalness of a biological motion decreases as the human-likeness of a computer-animated agent increases. To investigate the anthropomorphic bias in autistic children, human or cartoon characters were presented with biological and artificial motions side by side on a touchscreen. Children were required to touch one that would grow while the other would disappear, implicitly rewarding their choice. Only typically developing controls depicted the expected preference for biological motion when rendered with human, but not cartoon, characters. Despite performing the task to report a preference, children with autism depicted neither normal nor reversed anthropomorphic bias, suggesting that they are not sensitive to the congruence of form and motion information when observing computer-animated agents' actions. © The Author(s) 2014.

9 CFR 145.6 - Specific provisions for participating hatcheries.

Code of Federal Regulations, 2011 CFR

2011-01-01

... hatcheries. 145.6 Section 145.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY... for sale under Plan terminology should be normal and typical of the breed, variety, cross, or other...

9 CFR 145.6 - Specific provisions for participating hatcheries.

Code of Federal Regulations, 2010 CFR

2010-01-01

... hatcheries. 145.6 Section 145.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY... for sale under Plan terminology should be normal and typical of the breed, variety, cross, or other...

Haematology and Plasma Biochemistry of Wild Black Flying-Foxes, (Pteropus alecto) in Queensland, Australia

PubMed Central

McMichael, Lee; Edson, Daniel; McLaughlin, Amanda; Mayer, David; Kopp, Steven; Meers, Joanne; Field, Hume

2015-01-01

This paper establishes reference ranges for hematologic and plasma biochemistry values in wild Black flying-foxes (Pteropus alecto) captured in South East Queensland, Australia. Values were found to be consistent with those of other Pteropus species. Four hundred and forty-seven animals were sampled over 12 months and significant differences were found between age, sex, reproductive and body condition cohorts in the sample population. Mean values for each cohort fell within the determined normal adult reference range, with the exception of elevated levels of alkaline phosphatase in juvenile animals. Hematologic and biochemistry parameters of injured animals showed little or no deviation from the normal reference values for minor injuries, while two animals with more severe injury or abscessation showed leucocytosis, anaemia, thrombocytosis, hyperglobulinemia and hypoalbuminemia. PMID:25938493

An immune reaction may be necessary for cancer development.

PubMed

Prehn, Richmond T

2006-02-03

The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years. In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject. The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction.

An immune reaction may be necessary for cancer development

PubMed Central

Prehn, Richmond T

2006-01-01

Background The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years. In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. Alternative model There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject. Conclusion The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction. PMID:16457723

Antagonism Between Luminal and Caffeine, Studied by the Use of Radioisotopes; RECHERCHES SUR LES BARBITURIQUES RADIOACTIFS: LA DISTRIBUTION DU LUMINAL DANS L'ORGANISME ANIMAL EN PRESENCE DE CAFEINE

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

Aliprandi, B.; Masironi, R.

1959-10-31

The normal pattern of distribution of luminal in the animal organism was determined in mice using a tracer technique. The effect of an antagonistic drug, e.g., caffeine, on this normal distribution pattern was studied. The results confirmed the hypothesis of the in vivo breaking of the barbituric ring. (J.S.R.)

Hypothalamic CART is a new anorectic peptide regulated by leptin.

PubMed

Kristensen, P; Judge, M E; Thim, L; Ribel, U; Christjansen, K N; Wulff, B S; Clausen, J T; Jensen, P B; Madsen, O D; Vrang, N; Larsen, P J; Hastrup, S

1998-05-07

The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

Duodenal Ca2+ absorption is not stimulated by calcitriol during early postnatal development of pigs.

PubMed

Schroeder, B; Dahl, M R; Breves, G

1998-08-01

The role of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was studied in newborn, suckling, and weaned control (Con) piglets and piglets suffering from inherited calcitriol deficiency (Def piglets). In addition, a group of Def piglets was treated with vitamin D3 (Def-D3 piglets), which normalized plasma calcitriol levels. Regardless of age, duodenal calbindin-D9k concentrations ranged between 1,839 and 2,846 microg/g mucosa in Con piglets, between 821 and 1,219 microg/g mucosa in Def piglets, and between 2,960 and 3,692 microg/g mucosa in Def-D3 animals. In weaned animals, active Ca2+ absorption as calculated from in vitro 45Ca2+ flux rate measurements in Ussing chambers could be related to calbindin-D9k levels. Thus active Ca2+ absorption was completely absent in Def animals but was reconstituted in Def-D3 animals. In contrast, in newborn Def piglets active Ca2+ absorption functioned normally despite the low plasma calcitriol and mucosal calbindin-D9k levels and could not be affected by treatment with vitamin D3. Similar results were obtained from suckling Def piglets. The microtubule-disrupting agent colchicine caused significant inhibition of transepithelial net Ca2+ absorption in duodenal epithelia from newborn piglets without exerting an effect in suckling and weaned animals. Colchicine had no effect on Ca2+ uptake across the brush border membrane of mucosal enterocytes or on glucose-dependent electrogenic net ion flux rates in duodenal preparations from newborn Con piglets. In conclusion, our findings reveal intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats.

PubMed

Ghoneim, Mona A M; Hassan, Amal I; Mahmoud, Manal G; Asker, Mohsen S

2016-01-01

The baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interleukin-1 β (IL-1 β), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GPX) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GPX and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200 µg/rats/day) showed predominantly normal myocardial structure and no inflammatory cell infiltration. It has been concluded that Baobab fruit pulp has cardio protective effect against ISP-induced oxidative stress in rats.

Agroterrorism: Minimizing the Consequences of Intentionally Introduced Foreign Animal Disease

DTIC Science & Technology

2010-04-01

responsibility and dedicate fewer resources to mitigate the threat. Unless they are zoonotic , animal and plant diseases do not 2 Ibid., 157. 3...of the United States and current FAD policies are inadequate. 4 Zoonotic diseases or...pathogens that can be transmitted from animals to people. Specifically, a zoonotic disease normally exists in animals can infect humans. 5 John Brogan

Experimental models of developmental hypothyroidism.

PubMed

Argumedo, G S; Sanz, C R; Olguín, H J

2012-02-01

Hypothyroidism is a systemic disease resulting from either thyroid gland's anatomical and functional absence or lack of hypophyseal stimulation, both of which can lead to deficiency in thyroid hormone (TH) production. TH is essential for human and animal development, growth, and function of multiple organs. Children with deficient TH can develop alterations in central nervous system (CNS), striated muscle, bone tissue, liver, bone marrow, and cardiorespiratory system. Among the clinical outlook are signs like breathing difficulty, cardiac insufficiency, dysphagia, and repeated bronchial aspiration, constipation, muscle weakness, cognitive alterations, cochlear dysfunction, reduced height, defects in temperature regulation, anaemia, jaundice, susceptibility to infection, and others. Experimental and clinical studies have shown that TH is very essential for normal brain development. Other research work based on mice pointed out that a reduced level of TH in pregnant mother leads to congenital hypothyroidism in animal models and it is associated with mental retardation, deep neurologic deficiency that impacts on cognitive, learning, and memory functions. The principal experimental model studies that have focused on hypothyroidism are reviewed in this study. This is important on considering the fact that almost all animal species require thyroid hormones for their metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma

PubMed Central

Wang, Rui-Hua

2015-01-01

The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett’s esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett’s esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett’s esophagus, which should help to develop better prevention and treatment strategies for Barrett’s esophagus. PMID:25954094

Germline Transgenic Pigs by Sleeping Beauty Transposition in Porcine Zygotes and Targeted Integration in the Pig Genome

PubMed Central

Garrels, Wiebke; Mátés, Lajos; Holler, Stephanie; Dalda, Anna; Taylor, Ulrike; Petersen, Björn; Niemann, Heiner; Izsvák, Zsuzsanna; Ivics, Zoltán; Kues, Wilfried A.

2011-01-01

Genetic engineering can expand the utility of pigs for modeling human diseases, and for developing advanced therapeutic approaches. However, the inefficient production of transgenic pigs represents a technological bottleneck. Here, we assessed the hyperactive Sleeping Beauty (SB100X) transposon system for enzyme-catalyzed transgene integration into the embryonic porcine genome. The components of the transposon vector system were microinjected as circular plasmids into the cytoplasm of porcine zygotes, resulting in high frequencies of transgenic fetuses and piglets. The transgenic animals showed normal development and persistent reporter gene expression for >12 months. Molecular hallmarks of transposition were confirmed by analysis of 25 genomic insertion sites. We demonstrate germ-line transmission, segregation of individual transposons, and continued, copy number-dependent transgene expression in F1-offspring. In addition, we demonstrate target-selected gene insertion into transposon-tagged genomic loci by Cre-loxP-based cassette exchange in somatic cells followed by nuclear transfer. Transposase-catalyzed transgenesis in a large mammalian species expands the arsenal of transgenic technologies for use in domestic animals and will facilitate the development of large animal models for human diseases. PMID:21897845

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels

PubMed Central

Hislop, A; Springall, D; Oliveira, H; Pollock, J; Polak, J; Haworth, S

1997-01-01

AIMS—To determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).
METHODS—A monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5 minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A semiquantitative scoring system was used to assess the distribution of endothelial NOS by light microscopy.
RESULTS—NOS was present in the arteries in all hypoxic animals. However, hypoxia from birth caused a reduction in NOS compared with those lungs normal at birth and those normal at 3 days. Hypoxia from 3-6 days led to a high density of NOS compared with normal lungs at 6 days. Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in room air after exposure to hypoxia from birth there was a transient increase in endothelial NOS after three days of recovery, mirroring that seen at three days in normal animals.
CONCLUSIONS—Suppression of NOS production in the first few days of life may contribute to pulmonary hypertension in neonates.

 Keywords: pulmonary circulation; nitric oxide synthase; hypoxia; endothelium; piglets PMID:9279177

The Translational Role of Diffusion Tensor Image Analysis in Animal Models of Developmental Pathologies

PubMed Central

Oguz, Ipek; McMurray, Matthew S.; Styner, Martin; Johns, Josephine M.

2013-01-01

Diffusion Tensor Magnetic Resonance Imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers. PMID:22627095

Adrenomedullin and Pregnancy: Perspectives from Animal Models to Humans

PubMed Central

Lenhart, Patricia M.; Caron, Kathleen M.

2012-01-01

A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With more extensive mechanistic studies and improved consistency in clinical measurements of adrenomedullin, there is great potential for the development of adrenomedullin as a clinically-relevant biomarker in pregnancy and pregnancy complications. PMID:22425034

9 CFR 3.128 - Space requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Space requirements. 3.128 Section 3... Mammals Facilities and Operating Standards § 3.128 Space requirements. Enclosures shall be constructed and maintained so as to provide sufficient space to allow each animal to make normal postural and social...

9 CFR 3.128 - Space requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Space requirements. 3.128 Section 3... Mammals Facilities and Operating Standards § 3.128 Space requirements. Enclosures shall be constructed and maintained so as to provide sufficient space to allow each animal to make normal postural and social...

9 CFR 3.128 - Space requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Space requirements. 3.128 Section 3... Mammals Facilities and Operating Standards § 3.128 Space requirements. Enclosures shall be constructed and maintained so as to provide sufficient space to allow each animal to make normal postural and social...

9 CFR 3.128 - Space requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Space requirements. 3.128 Section 3... Mammals Facilities and Operating Standards § 3.128 Space requirements. Enclosures shall be constructed and maintained so as to provide sufficient space to allow each animal to make normal postural and social...

9 CFR 3.128 - Space requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Space requirements. 3.128 Section 3... Mammals Facilities and Operating Standards § 3.128 Space requirements. Enclosures shall be constructed and maintained so as to provide sufficient space to allow each animal to make normal postural and social...

Role of Thyroxine in Space-Developed Jellyfish

NASA Technical Reports Server (NTRS)

Spangenberg, Dorothy B.

1997-01-01

The Aurelia Metamorphosis Test System was previously used to determine the effects of the space environment on the development and behavior of tiny (1-2 mm) jellyfish ephyrae during the SLS-1 and IML-2 missions. Results from the SLS-1 experiment included the discovery that statolith numbers were significantly reduced in Earth-formed ephyrae flown for nine days in space as compared with ground-based controls. In addition, upon return to Earth, six times more ephyrae which had developed in space than those developed on Earth had pulsing abnormalities, indicating that either these animals did not form their neuromuscular structures normally while in space or they were unable to adapt to the Ig environment upon return to Earth. The metamorphosis process, which enables the formation of ephyrae from polyps is influenced by a hormone, Jf-T4 Oellyfish thyroxine) which is synthesized following iodine administration. Two groups of polyps in space, however, formed ephyrae without iodine administration indicating that Jf-T4 synthesis, utilization, or excretion was different in. the ephyrae. Increased synthesis or build-up in the media of the hormone may also be linked to the increased demineralization of statoliths found in space-exposed ephyrae. In previous experiments, we found that externally administered thyroxine causes increased demineralization of statoliths on Earth. Abnormal pulsina in ephyrae following return to Earth during the SLS-1 mission may also be traced to increased Jf-T4 levels. Thyroxine is known to be important to the normal development and function of the nervous system, heart, and skeletal muscles in higher animals. For this third Jellyfish-in-Space experiment, we proposed to quantitate the levels of Jf- T4 and of T4 receptors in space-developed ephyrae and media and to compare these levels with those of animals developing and at Ig in space and on Earth. We expected to be able to determine whether Jf-T4 synthesis and/or secretion is different in space-flownjellyfish than in controls and to determine which cells (nerve, muscle, lithocytes, etc.)may have enhanced Jf-T4 levels. However, NASA deselected this experiment in August, 1997.

Long-wavelength (red) light produces hyperopia in juvenile and adolescent tree shrews.

PubMed

Gawne, Timothy J; Ward, Alexander H; Norton, Thomas T

2017-11-01

In infant tree shrews, exposure to narrow-band long-wavelength (red) light, that stimulates long-wavelength sensitive cones almost exclusively, slows axial elongation and produces hyperopia. We asked if red light produces hyperopia in juvenile and adolescent animals, ages when plus lenses are ineffective. Animals were raised in fluorescent colony lighting (100-300 lux) until they began 13days of red-light treatment at 11 (n=5, "infant"), 35 (n=5, "juvenile") or 95 (n=5, "adolescent") days of visual experience (DVE). LEDs provided 527-749 lux on the cage floor. To control for the higher red illuminance, a fluorescent control group (n=5) of juvenile (35 DVE) animals was exposed to ∼975 lux. Refractions were measured daily; ocular component dimensions at the start and end of treatment and end of recovery in colony lighting. These groups were compared with normals (n=7). In red light, the refractive state of both juvenile and adolescent animals became significantly (P<0.05) hyperopic: juvenile 3.9±1.0 diopters (D, mean±SEM) vs. normal 0.8±0.1D; adolescent 1.6±0.2D vs. normal 0.4±0.1D. The fluorescent control group refractions (0.6±0.3D) were normal. In red-treated juveniles the vitreous chamber was significantly smaller than normal (P<0.05): juvenile 2.67±0.03mmvs. normal 2.75±0.02mm. The choroid was also significantly thicker: juvenile 77±4μmvs. normal 57±3μm (P<0.05). Although plus lenses do not restrain eye growth in juvenile tree shrews, the red light-induced slowed growth and hyperopia in juvenile and adolescent tree shrews demonstrates that the emmetropization mechanism is still capable of restraining eye growth at these ages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Eliminating animal facility light-at-night contamination and its effect on circadian regulation of rodent physiology, tumor growth, and metabolism: a challenge in the relocation of a cancer research laboratory.

PubMed

Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

2011-05-01

Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR(-)) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O(2), glucose, total fatty acid and CO(2) production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine-threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen.

Eliminating Animal Facility Light-at-Night Contamination and Its Effect on Circadian Regulation of Rodent Physiology, Tumor Growth, and Metabolism: A Challenge in the Relocation of a Cancer Research Laboratory

PubMed Central

Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

2011-01-01

Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR–) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O2, glucose, total fatty acid and CO2 production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine–threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen. PMID:21640027

[Generation of functional organs from pluripotent stem cells].

PubMed

Miyamoto, Tatsuyuki; Nakauchi, Hiromitsu

2015-10-01

Hematopoietic stem cells (HSCs) have played a major role in stem cell biology, providing many conceptual ideas and models. Among them is the concept of the "niche", a special bone-marrow microenvironment that by exchanging cues regulates stem-cell fate. The HSC niche also plays an important role in HSC transplantation. Successful engraftment of donor HSCs depends on myeloablative pretreatment to empty the niche. The concept of the stem-cell niche has now been extended to the generation of organs. We postulated that an empty "organ niche" exists in a developing animal when development of an organ is genetically disabled. This organ niche should be developmentally compensated by blastocyst complementation using wild-type primary stem cells (PSCs). We proved the principle of organogenesis from xenogeneic PSCs in an embryo unable to form a specific organ, demonstrating the generation of functionally normal rat pancreas by injecting rat PSCs into pancreatogenesis-disabled mouse embryos. This principle has held in pigs. When pancreatogenesis-disabled pig embryos underwent complementation with blastomeres from wild-type pig embryos to produce chimeric pigs, the chimeras had normal pancreata and survived to adulthood. Demonstration of the generation of a functional organ from PSCs in pigs is a very important step toward generation of human cells, tissues, and organs from individual patients' own PSCs in large animals.

Maternal prenatal cortisol and infant cognitive development: moderation by infant-mother attachment.

PubMed

Bergman, Kristin; Sarkar, Pampa; Glover, Vivette; O'Connor, Thomas G

2010-06-01

Experimental animal studies suggest that early glucocorticoid exposure may have lasting effects on the neurodevelopment of the offspring; animal studies also suggest that this effect may be eliminated by positive postnatal rearing. The relevance of these findings to humans is not known. We prospectively followed 125 mothers and their normally developing children from pregnancy through 17 months postnatal. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infants were assessed at an average age of 17 months with the Bayley Scales of Infant Development, and ratings of infant-mother attachment classification were made from the standard Ainsworth Strange Situation assessment. Prenatal cortisol exposure, indexed by amniotic fluid levels, negatively predicted cognitive ability in the infant, independent of prenatal, obstetric, and socioeconomic factors. This association was moderated by child-mother attachment: in children with an insecure attachment, the correlation was [r(54) = -.47, p < .001]; in contrast, the association was nonexistent in children who had a secure attachment [r(70) = -.05, ns]. These findings mimic experimental animal findings and provide the first direct human evidence that increased cortisol in utero is associated with impaired cognitive development, and that its impact is dependent on the quality of the mother-infant relationship. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

PubMed

Thomas, M R; Miell, J P; Taylor, A M; Ross, R J; Arnao, J R; Jewitt, D E; McGregor, A M

1993-06-01

Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)

Noise in animal facilities: why it matters.

PubMed

Turner, Jeremy G; Bauer, Carol A; Rybak, Leonard P

2007-01-01

Environmental noise can alter endocrine, reproductive and cardiovascular function, disturb sleep/wake cycles, and can mask normal communication between animals. These outcomes indicate that noise in the animal facility might have wide-ranging affects on animals, making what laboratory animals hear of consequence for all those who use animals in research, not just the hearing researcher. Given the wide-ranging effects of noise on laboratory animals, routine monitoring of noise in animal facilities would provide important information on the nature and stability of the animal environment. This special issue will highlight the need for more thorough monitoring and will serve as an introduction to noise and its various effects on animals.

From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD).

PubMed

Eilam, David

2017-05-01

The application of similar analyses enables a direct projection from translational research in animals to human studies. Following is an example of how the methodology of a specific animal model of obsessive-compulsive disorder (OCD) was applied to study human patients. Specifically, the quinpirole rat model for OCD was based on analyzing the trajectories of travel among different locales, and scoring the set of acts performed at each locale. Applying this analytic approach in human patients unveiled various aspects of OCD, such as the repetition and addition of acts, incompleteness, and the link between behavior and specific locations. It is also illustrated how the same analytical approach could be applicable to studying other mental disorders. Finally, it is suggested that the development of OCD could be explained by the four-phase sequence of Repetition, Addition, Condensation, and Elimination, as outlined in the study of ontogeny and phylogeny and applied to normal development of behavior. In OCD, this sequence is curtailed, resulting in the abundant repetition and addition of acts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Symbiotic conversations are revealed under genetic interrogation

PubMed Central

Ruby, Edward G.

2013-01-01

The recent development and application of molecular genetics to the symbionts of invertebrate animal species have advanced our knowledge of the biochemical communication that occurs between the host and its bacterial symbionts. In particular, the ability to manipulate these associations experimentally by introducing genetic variants of the symbionts into naive hosts has allowed the discovery of novel colonization mechanisms and factors. In addition, the role of the symbionts in inducing normal host development has been revealed, and its molecular basis described. In this Review, I discuss many of these developments, focusing on what has been discovered in five well-understood model systems. PMID:18794913

Can teaching veterinary and animal-science students about animal welfare affect their attitude toward animals and human-related empathy?

PubMed

Hazel, Susan J; Signal, Tania D; Taylor, Nicola

2011-01-01

Attitudes toward animals are important in influencing how animals are treated. Few studies have investigated attitudes toward animals in veterinary or animal-science students, and no studies have compared attitudes to animals before and after a course teaching animal welfare and ethics. In this study, students enrolled in veterinary (first-year) or animal-science (first- and third-year) programs completed a questionnaire on attitudes toward different categories of animals before and after the course. Higher attitude scores suggest a person more concerned about how an animal is treated. Normally distributed data were compared using parametric statistics, and non-normally distributed data were compared using non-parametric tests, with significance p < .05. Attitudes toward pets (45.5-47.6) were higher than those toward pests (34.2-38.4) or profit animals (30.3-32.1). Attitude scores increased from before to after the course in the veterinary cohort on the Pest (36.9 vs. 38.4, respectively, n = 27, p < .05) and Profit (30.3 vs. 32.1, respectively, n = 28, p < .05) subscales, but not in the animal-science cohorts. Attitude scores in all categories were higher for women than for men. Currently having an animal was associated with higher pet scores (46.8 vs. 43.8, ns = 120 and 13, respectively, p < .05), and having an animal as a child was associated with higher profit scores (31.0 vs. 26.6, ns = 129 and 8, respectively, p < .05). Students electing to work with livestock had lower scores on the Pest and Profit subscales, and students wanting to work with wildlife had significantly higher scores on the Pest and Profit subscales. This study demonstrates attitudinal changes after an animal-welfare course, with significant increases in veterinary but not animal-science students.

Astressin B, a corticotropin-releasing hormone receptor antagonist, accelerates the return to normal luteal function after an inflammatory-like stress challenge in the rhesus monkey.

PubMed

Xiao, Ennian; Xia-Zhang, Linna; Vulliemoz, Nicolas; Rivier, Jean; Ferin, Michel

2007-02-01

Endogenous release of CRH in stress has been associated with a dysfunctional reproductive endocrine axis. In the rhesus monkey, an inflammatory-like stress challenge in the luteal phase decreases luteal secretory function. Here, we tested the effectiveness of astressin B, a nonspecific CRH receptor antagonist, in constraining the deleterious impact of a 10-d lipopolysaccharide (LPS) challenge on the menstrual cycle. Two protocols were carried out in nine animals. In the first, the animals, after showing two normal consecutive control cycles, were injected daily for 10 days with LPS (75-125 mug/d) during the luteal phase of the cycle. The animals were followed through the two postchallenge cycles. The second protocol, carried out in the following year, was identical with protocol 1, except that the animals were treated with astressin B (0.45 mg/kg) 1 h before each daily LPS challenge during the luteal phase. Blood samples were obtained daily to document cyclic hormones levels. The LPS challenge significantly decreased luteal progesterone and LH release during the challenge cycle. Inhibition of luteal progesterone extended to the two successive postchallenge cycles. Astressin B treatment prevented luteal LH but not luteal progesterone decrease during the treatment cycle and restored normal progesterone secretion during the two posttreatment cycles. We conclude that the deleterious impact of a short-term inflammatory stress challenge on luteal function is far longer than the stress period itself. Systemic administration of astressin B accelerates the return to normal luteal function, presumably by restoring normal neuroendocrine regulation of gonadotropin secretion.

Synchronisation of the follicular wave with GnRH and PGF2α analogue for a timed breeding programme in dromedary camels (Camelus dromedarius).

PubMed

Manjunatha, B M; Al-Bulushi, Samir; Pratap, N

2015-09-01

This study was conducted to develop a hormone protocol that precisely synchronises follicular development for a timed breeding (TB) programme in dromedary camels. To examine the effect of GnRH treatment at four known stages of follicular development, animals were treated with GnRH when the largest follicle of the wave was 4-7, 8-11, 12-17 and 18-27 mm in diameter. Transrectal ultrasonography was carried out daily up to 20 days after treatment. A hormone protocol (FWsynch) for the synchronisation of follicular wave and TB consisting of GnRH-1 (GnRH) on Day 0, PG-1 (PGF2α) on Day 7, GnRH-2 on Day 10 and PG-2 on Day 17 was initiated at four known stages of follicular development. Ovarian structures were monitored by ultrasonography. The FWsynch protocol was initiated at random stages of follicle development and animals were bred by natural mating at a fixed time at the research facility and in field. The pregnancy was diagnosed by ultrasonography. GnRH treatment in animals with a dominant follicle (DF) of ≥ 11 mm in diameter resulted in synchronous new follicular wave emergence, whereas in animals with a DF ≤ 10 mm, the treatment did not alter the development of the existing follicular wave. The FWsynch protocol was effective in synchronising the follicular wave for TB irrespective of the stage of follicular development at the beginning of the protocol. TB using FWsynch protocol resulted in a pregnancy rate of 60.2% in a research facility and 53.6% and 45.6% in normal and infertile camels respectively under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Crisis management and recovery from the damage to the laboratory animal production facility due to the Great East Japan Earthquake.

PubMed

Ikeda, Takuya

2012-01-01

Charles River Laboratories Japan produces laboratory animals, mainly mice and rats. In its history, we have experienced many crises such as mass food poisoning of staff and contamination of animals. However, we overcame these crises, accomplishing our corporate missions to secure steady supply of healthy animals. Under such circumstances, in 2008, we faced an unprecedented crisis involving a novel influenza possibly becoming pandemic. Therefore, we prepared a Crisis Management Plan (CMP) and Business Continuity Plan (BCP) to avoid the worst case scenario. Fortunately, the novel influenza did not develop into a pandemic and no major problems occurred in production of our laboratory animals. In March 2011, our Tsukuba Breeding Center was struck by the Great East Japan Earthquake. Many cages fell from racks, and consequently, 14,000 mice and rats were euthanized. Moreover, this animal production facility experienced not only blackouts and water outage but also various maintenance problems. After triage of the animals, almost half of the animals kept were eventually lost. However, we recovered and resumed shipment of animals two weeks after the disaster by utilizing the CMP and BCP we initially created as a countermeasure against novel influenza. After two months, our production volume returned to normal except for two strains. I sincerely hope this review, which highlights our experience and related issues, will be a useful resource in regard to crisis management for people who are engaged in laboratory animal care and use.

Real-time monitoring of cardiovascular function in rhesus macaques infected with Zaire ebolavirus.

PubMed

Kortepeter, Mark G; Lawler, James V; Honko, Anna; Bray, Mike; Johnson, Joshua C; Purcell, Bret K; Olinger, Gene G; Rivard, Robert; Hepburn, Matthew J; Hensley, Lisa E

2011-11-01

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

Resurrection of a bull by cloning from organs frozen without cryoprotectant in a -80 degrees c freezer for a decade.

PubMed

Hoshino, Yoichiro; Hayashi, Noboru; Taniguchi, Shunji; Kobayashi, Naohiko; Sakai, Kenji; Otani, Tsuyoshi; Iritani, Akira; Saeki, Kazuhiro

2009-01-01

Frozen animal tissues without cryoprotectant have been thought to be inappropriate for use as a nuclear donor for somatic cell nuclear transfer (SCNT). We report the cloning of a bull using cells retrieved from testicles that had been taken from a dead animal and frozen without cryoprotectant in a -80 degrees C freezer for 10 years. We obtained live cells from defrosted pieces of the spermatic cords of frozen testicles. The cells proliferated actively in culture and were apparently normal. We transferred 16 SCNT embryos from these cells into 16 synchronized recipient animals. We obtained five pregnancies and four cloned calves developed to term. Our results indicate that complete genome sets are maintained in mammalian organs even after long-term frozen-storage without cryoprotectant, and that live clones can be produced from the recovered cells.

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

Poston, Ted M.; Thrall, Karla D.; Penner, Jocelyn D.

I was asked to submit a response to the Protocol Review forum for the journal LabAnimal by Dr. Jerald Silverman. This forum request views and opinions on issues that are faced by research animal welfare committees. The particular issue is: Dr. John Smith, a distinguished investigator at Great Eastern University, had spent his career searching for a treatment for hearing loss. After 20 years of research, he developed a drug that potentially could improve auditory function after damage to the inner ear. The drug was administered by injection into the middle ear with the use of a fine needle insertedmore » through the eardrum. Smith submitted a protocol to the IACUC to conduct a small study on cats, proposing to treat one group of animals with the drug and another with saline, to determine if it prevented the changes in the anatomy of the inner ear that normally occur with aging.« less

Resurrection of a Bull by Cloning from Organs Frozen without Cryoprotectant in a −80°C Freezer for a Decade

PubMed Central

Hoshino, Yoichiro; Hayashi, Noboru; Taniguchi, Shunji; Kobayashi, Naohiko; Sakai, Kenji; Otani, Tsuyoshi; Iritani, Akira; Saeki, Kazuhiro

2009-01-01

Frozen animal tissues without cryoprotectant have been thought to be inappropriate for use as a nuclear donor for somatic cell nuclear transfer (SCNT). We report the cloning of a bull using cells retrieved from testicles that had been taken from a dead animal and frozen without cryoprotectant in a −80°C freezer for 10 years. We obtained live cells from defrosted pieces of the spermatic cords of frozen testicles. The cells proliferated actively in culture and were apparently normal. We transferred 16 SCNT embryos from these cells into 16 synchronized recipient animals. We obtained five pregnancies and four cloned calves developed to term. Our results indicate that complete genome sets are maintained in mammalian organs even after long-term frozen-storage without cryoprotectant, and that live clones can be produced from the recovered cells. PMID:19129919

Malformation of stria vascularis in the developing inner ear of the German waltzing guinea pig.

PubMed

Jin, Zhe; Mannström, Paula; Järlebark, Leif; Ulfendahl, Mats

2007-05-01

Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig (gw/gw). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner's membrane onto the hearing organ. The embryonic stria vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw stria vascularis. A gene involved in cochlear melanocyte development, Pax3, was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing stria vascularis of this type of guinea pig. Thus, malformation of the stria vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing stria vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to stria vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.

A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

PubMed

McBride, Sebastian D; Perentos, Nicholas; Morton, A Jennifer

2016-05-30

For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep. We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented. All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9±1.5 and for the reversal learning was 19.1±1.8. This is the first mobile semi-automated operant system developed for testing cognitive function in sheep. We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

PubMed

Russell, James C; Proctor, Spencer D

2006-01-01

Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.

Uniaxial Tensile Properties of Atherosclerotic Carotid Artery After Mobilization of Pushing on Qiao-Gong: A Safety Study Using an Animal Model of Carotid Atherosclerosis.

PubMed

Qi, Ji; Zhang, Shaoqun; Zhang, Lei; Ping, Ruiyue; Ping, Kaike; Ye, Da; Shen, Honggui; Chen, Yili; Li, Yikai

2018-02-01

This study aimed to preliminarily explore the effects of the soft tissue mobilization of pushing on Qiao-Gong (MPQ) on biomechanical properties of the carotid artery using an animal model of carotid atherosclerosis (CAS). Fifty rabbits were randomly divided into 4 groups: animals with CAS treated with MPQ (CAS-MPQ [n = 15]); animals with CAS treated without MPQ (CAS [n = 15]); normal animals treated with MPQ (normal-MPQ [n = 10]); and a blank control group (n = 10). The MPQ procedure consisted of soft tissue mobilization of the Qiao-Gong acupoint on the front edge of the sternocleidomastoid muscle applied from top to bottom, by flat pushing with the thumb repeatedly for 20 times. Disease in the CAS models was induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. At the end of modeling, carotid color Doppler ultrasonography examination was performed to confirm which animal models were successfully induced with CAS, excluding model rabbits without typical CAS at the same time. Then, MPQ was applied on rabbits in the CAS-MPQ and the normal-MPQ groups for 3 weeks. By contrast, rabbits in the other 2 groups were fed normally without MPQ. Uniaxial failure tests were later performed on carotid arteries in all 4 groups, and at the end of the study, a 2-way factorial analysis of variance of the results was conducted. (1) At the end of modeling, 10 rabbits in the CAS-MPQ group and 9 in the CAS group were included with typical carotid atherosclerotic characteristics. (2) Young's elastic modulus of the rabbit carotid artery increased more significantly in the CAS-MPQ group than the CAS group. (3) Compared with normal rabbit carotid arteries, atherosclerotic carotid arteries had lower levels of ultimate stress and ultimate strain but higher levels of ultimate load. The uniaxial tensile mechanical properties of the rabbit atherosclerotic carotid artery were impaired after MPQ. Copyright © 2018. Published by Elsevier Inc.

Magnetic resonance imaging analysis of cardiac cycle events in diabetic rats: the effect of angiotensin-converting enzyme inhibition

PubMed Central

Al-Shafei, Ahmad I M; Wise, R G; Gresham, G A; Carpenter, T A; Hall, L D; Huang, Christopher L-H

2002-01-01

Non-invasive magnetic resonance imaging (MRI) was used to characterize changes in left and right ventricular cardiac cycles following induction of experimental, streptozotocin (STZ)-induced, diabetes in male Wistar rats at different ages. The effects of the angiotensin-converting enzyme (ACE) inhibitor captopril upon such chronic physiological changes were then evaluated, also for the first time. Diabetes was induced at the age of 7 weeks in two experimental groups, of which one group was subsequently maintained on captopril (2 g l−1)-containing drinking water, and at 10 and 13 weeks in two further groups. The fifth group provided age-matched controls. All groups (each n = 4 animals) were scanned consistently at 16 weeks, in parallel with timings used in earlier studies that employed this experimental model. Cine magnetic resonance (MR) image acquisition provided transverse sections through both ventricles at twelve time points covering systole and most of diastole. These yielded reconstructions of cardiac anatomy used to derive critical functional indices and their dependence upon time following the triggering electrocardiographic R waves. The left and right ventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes (SV), and ejection fractions (EF) calculated from each, control and experimental, group showed matching values. This confirmed a necessary condition requiring balanced right and left ventricular outputs and further suggested that STZ-induced diabetes produced physiological changes in both ventricles. Absolute left and right ventricular SVs were significantly altered in all diabetic animals; EDVs and EFs significantly altered in animals diabetic from 7 and 10 but not 13 weeks. When normalized to body weight, left and right ventricular SVs had significantly altered in animals diabetic from 7 and 10 weeks but not 13 weeks. Normalized left ventricular EDVs were also significantly altered in animals diabetic from 7 and 10 weeks. However, normalized right ventricular EDVs were significantly altered only in animals made diabetic from 7 weeks. Diabetic hearts showed major kinetic changes in left and right ventricular contraction (ejection) and relaxation (filling). Both the initial rates of volume change (dV/dt) in both ventricles and the plots of dV/dt values through the cardiac cycle demonstrated more gradual developments of tension during systole and relaxation during diastole. Estimates of the derived left ventricular performance parameters of cardiac output, cardiac power output and stroke work in control animals were comparable with human values when normalized to both body (or cardiac) weight and heart rate. All deteriorated with diabetes. Comparisons of experimental groups diabetic from 7 weeks demonstrated that captopril treatment relieved the alterations in critical volumes, dependence of SV upon EDV, kinetics of systolic contraction and diastolic relaxation and in the derived indicators of ventricular performance. This study represents the first demonstration using non-invasive MRI of early, chronic changes in diastolic filling and systolic ejection in both the left and the right ventricles and of their amelioration by ACE inhibition following STZ-induction of diabetes in intact experimental animals. PMID:11790819

Effect of sharply lowered muscular activity on the thyroid gland of the white rat

NASA Technical Reports Server (NTRS)

Bekishev, K.

1980-01-01

The effect of hypokinesia on the thyroid gland of 200 white rats was studied. The rats were kept in 16x6x6 cm cages for 90 days. The functional activity of the thyroids increased after 24 hrs of partial immobilization and peaked after 15 days. After 30 days of immobilization, the functional activity returned to normal in one third of the test animals and after 60 days in all animals. After 15 days of immobilization, the test animals began to lose weight (in comparison to the controls) and remained underweight for the rest of the test period (up to 90 days). When returned to normal conditions, they caught up with and even overtook in weight the control animals after about 1 month. All changes produced by hypokinesia were reversible after 1 month.

Deep cytoplasmic rearrangements in ventralized Xenopus embryos

NASA Technical Reports Server (NTRS)

Brown, E. E.; Denegre, J. M.; Danilchik, M. V.

1993-01-01

Following fertilization in Xenopus, dramatic rearrangements of the egg cytoplasm relocalize maternally synthesized egg components. During the first cell cycle the vegetal yolk mass rotates relative to the egg surface, toward the sperm entry point (SEP) (J. P. Vincent, G. F. Oster, and J. C. Gerhart, 1986, Dev. Biol. 113, 484-500), while concomitant deep cytoplasmic rearrangements occur in the animal hemisphere (M. V. Danilchik and J. M. Denegre, 1991, Development 111, 845-856). In this paper we examine the role of vegetal yolk mass rotation in producing the animal cytoplasmic rearrangements. We inhibited rotation by uv-irradiating embryos during the first cell cycle, a treatment that yields an extremely ventralized phenotype. Both uv-irradiated embryos and unirradiated control embryos show cytoplasmic rearrangements in the animal hemisphere during the first cell cycle. Cytoplasmic rearrangements on the SEP side of the embryo associated with the path of the sperm pronucleus, plus a swirl on the anti-SEP (dorsal) side, are seen, whether or not yolk mass rotation has occurred. This result suggests a role for the expanding sperm aster in directing animal hemisphere cytoplasmic movements. In unirradiated control embryos the anti-SEP (dorsal) swirl is larger than that in uv-irradiated embryos and often extends into the vegetal hemisphere, consistent with the animal cytoplasm having been pulled dorsally and vegetally by the sliding vegetal yolk mass. Thus the yolk mass rotation may normally enhance the dorsalward cytoplasmic movement, begun by the sperm aster, enough to induce normal axis formation. We extended our observations of unirradiated control and uv-irradiated embryos through early cleavages. The vegetal extent of the anti-SEP (dorsal) swirl pattern seen in control embryos persists through the early cleavage period, such that labeled animal cytoplasm extends deep into dorsal third-tier blastomeres at the 32-cell stage. Significantly, in uv-irradiated embryos, which have not undergone vegetal rotation, most of this labeled material remains more equatorial.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

PubMed

Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

2015-07-01

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. © The Author(s) 2014.

RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.

PubMed

Bakthavachalu, Baskar; Huelsmeier, Joern; Sudhakaran, Indulekha P; Hillebrand, Jens; Singh, Amanjot; Petrauskas, Arnas; Thiagarajan, Devasena; Sankaranarayanan, M; Mizoue, Laura; Anderson, Eric N; Pandey, Udai Bhan; Ross, Eric; VijayRaghavan, K; Parker, Roy; Ramaswami, Mani

2018-05-16

Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo. Remarkably, ΔIDR mutants that lack neuronal RNP granules show normal animal development, survival, and fertility. However, they show defects in long-term memory formation/consolidation as well as in C9ORF72 dipeptide repeat or FUS-induced neurodegeneration. Together, our findings demonstrate (1) that higher-order mRNP assemblies contribute to long-term neuronal plasticity and memory, and (2) that a targeted reduction in RNP-granule formation efficiency can alleviate specific forms of neurodegeneration. Copyright © 2018 Elsevier Inc. All rights reserved.

THE INHIBITION OF THE BACTERIOSTATIC ACTION OF SULFONAMIDE DRUGS BY SUBSTANCES OF ANIMAL AND BACTERIAL ORIGIN

PubMed Central

MacLeod, Colin M.

1940-01-01

Sulfonamide inhibitor has been demonstrated in extracts of fresh normal muscle, pancreas, and spleen of certain animals. When autolysis of tissues takes place the amount of inhibitor is greatly increased. Fresh liver from beef, rabbit, and guinea pig is free of active inhibitor, although inhibitor is demonstrable in autolysates of this tissue. Fresh rabbit kidney is likewise free of active inhibitor. Following acid hydrolysis extracts of fresh rabbit liver and kidney cause sulfonamide inhibition. Normal human urine contains little or no active inhibitor. However, upon acid hydrolysis, inhibitor is uniformly present. Sulfonamide inhibitor is present in some, but not all, sterile serous effusions occurring during certain diseases. Inhibitor was found uniformly in pus. None was found in blood serum. In certain species of bacteria the inhibitor is found in the cells only and is not demonstrable in the culture medium, whereas in other species, the inhibitor is found in the culture supernatant, and the cells themselves are relatively free. The development of sulfapyridine fastness in a strain of Pneumococcus Type I is accompanied by a greatly increased production of sulfonamide inhibitor. PMID:19871019

Real-Time Confocal Imaging Of The Living Eye

NASA Astrophysics Data System (ADS)

Jester, James V.; Cavanagh, H. Dwight; Essepian, John; Shields, William J.; Lemp, Michael A.

1989-12-01

In 1986, we adapted the Tandem Scanning Reflected Light Microscope of Petran and Hadraysky to permit non-invasive, confocal imaging of the living eye in real-time. We were first to obtain stable, confocal optical sections in vivo, from human and animal eyes. Using confocal imaging systems we have now studied living, normal volunteers, rabbits, cats and primates sequentially, non-invasively, and in real-time. The continued development of real-time confocal imaging systems will unlock the door to a new field of cell biology involving for the first time the study of dynamic cellular processes in living organ systems. Towards this end we have concentrated our initial studies on three areas (1) evaluation of confocal microscope systems for real-time image acquisition, (2) studies of the living normal cornea (epithelium, stroma, endothelium) in human and other species; and (3) sequential wound-healing responses in the cornea in single animals to lamellar-keratectomy injury (cellular migration, inflammation, scarring). We believe that this instrument represents an important, new paradigm for research in cell biology and pathology and that it will fundamentally alter all experimental and clinical approaches in future years.

Easier detection of invertebrate "identification-key characters" with light of different wavelengths

PubMed Central

2011-01-01

The marine α-taxonomist often encounters two problems. Firstly, the "environmental dirt" that is frequently present on the specimens and secondly the difficulty in distinguishing key-features due to the uniform colours which fixed animals often adopt. Here we show that illuminating animals with deep-blue or ultraviolet light instead of the normal white-light abrogates both difficulties; dirt disappears and important details become clearly visible. This light regime has also two other advantages. It allows easy detection of very small, normally invisible, animals (0.1 μm range). And as these light wavelengths can induce fluorescence, new identification markers may be discovered by this approach. PMID:22040277

Disease relationship of domestic stock and wildlife

USGS Publications Warehouse

Shillinger, J.E.

1937-01-01

From the time that western civilization established itself on the North American continent until very recent years, little thought was given to the diseases, or other forms of loss, in game. In the process of bringing civilization and the incidental domestic arts and trades to the United States it appears to have been the policy to establish domestic farm stock on the land just as abundantly as the carrying capacity of land would tolerate. And judged by the low quality of many of our present farm animals, it is evident that in many cases the land was, and is now, overstocked and undermanaged. In traveling over this country one is impressed by the lack of uniformity, imperfect physical development, and poor state of nutrition of much of the domestic livestock. It would appear that the wild animals unhampered by fencing and other restraint such as controlled mating, feed selection, and enforced habitat in contaminated or polluted environment, have a better chance for perfect growth and complete development to a size and proportion normal for those species.While all of the factors mentioned produce a definitely deleterious result on the welfare of animal life, that of contaminated or polluted environment is by no means the least. The stunting action of disease on the growth of the young is too well known to admit of controversy. The impairment of function of vital organs due to minute cellular changes resulting from sub-acute or chronic infections prevents normal growth. Through centuries of enforced survival in densely congested pastures, pens, and stables, a certain degree of acquired resistance to many diseases has been built up in farm stock. If it were not so, very few barnyard animals would ever survive the conditions generally seen in our agricultural districts. Manure heaps, quantities of partly spoiled feed, and decaying masses of vegetation and refuse have come to be regarded as a natural part of the barnyard scene.

Remote automated multi-generational growth and observation of an animal in low Earth orbit

PubMed Central

Oczypok, Elizabeth A.; Etheridge, Timothy; Freeman, Jacob; Stodieck, Louis; Johnsen, Robert; Baillie, David; Szewczyk, Nathaniel J.

2012-01-01

The ultimate survival of humanity is dependent upon colonization of other planetary bodies. Key challenges to such habitation are (patho)physiologic changes induced by known, and unknown, factors associated with long-duration and distance space exploration. However, we currently lack biological models for detecting and studying these changes. Here, we use a remote automated culture system to successfully grow an animal in low Earth orbit for six months. Our observations, over 12 generations, demonstrate that the multi-cellular soil worm Caenorhabditis elegans develops from egg to adulthood and produces progeny with identical timings in space as on the Earth. Additionally, these animals display normal rates of movement when fully fed, comparable declines in movement when starved, and appropriate growth arrest upon starvation and recovery upon re-feeding. These observations establish C. elegans as a biological model that can be used to detect changes in animal growth, development, reproduction and behaviour in response to environmental conditions during long-duration spaceflight. This experimental system is ready to be incorporated on future, unmanned interplanetary missions and could be used to study cost-effectively the effects of such missions on these biological processes and the efficacy of new life support systems and radiation shielding technologies. PMID:22130552

The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

PubMed

Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

2009-04-01

The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.

Transplantable insulinoma in the rat

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

Chick, W.L.; Warren, S.; Chute, R.N.

1977-02-01

A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days following 1000 rads (10 J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5 to 1.5 cm in diameter decreased from 5 to 8 months in the first generation to 2 to 5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period ofmore » time (96 percent versus 69 percent). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 ..mu..g of immunoreactive somatostatin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2 to 4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300 mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100 ml in 2 to 4 days. These observations correlated with findings of marked atrophy and degranulation of the beta cells in the pancreata of tumor-bearing animals and with gradual return of normal light microscopic morphology following tumor removal.« less

Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache

PubMed Central

Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.

2014-01-01

Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523

Advantages of the experimental animal hollow organ mechanical testing system for the rat colon rupture pressure test.

PubMed

Ji, Chengdong; Guo, Xuan; Li, Zhen; Qian, Shuwen; Zheng, Feng; Qin, Haiqing

2013-01-01

Many studies have been conducted on colorectal anastomotic leakage to reduce the incidence of anastomotic leakage. However, how to precisely determine if the bowel can withstand the pressure of a colorectal anastomosis experiment, which is called anastomotic bursting pressure, has not been determined. A task force developed the experimental animal hollow organ mechanical testing system to provide precise measurement of the maximum pressure that an anastomotic colon can withstand, and to compare it with the commonly used method such as the mercury and air bag pressure manometer in a rat colon rupture pressure test. Forty-five male Sprague-Dawley rats were randomly divided into the manual ball manometry (H) group, the tracing machine manometry pressure gauge head (MP) group, and the experimental animal hollow organ mechanical testing system (ME) group. The rats in each group were subjected to a cut colon rupture pressure test after injecting anesthesia in the tail vein. Colonic end-to-end anastomosis was performed, and the rats were rested for 1 week before anastomotic bursting pressure was determined by one of the three methods. No differences were observed between the normal colon rupture pressure and colonic anastomotic bursting pressure, which were determined using the three manometry methods. However, several advantages, such as reduction in errors, were identified in the ME group. Different types of manometry methods can be applied to the normal rat colon, but the colonic anastomotic bursting pressure test using the experimental animal hollow organ mechanical testing system is superior to traditional methods. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Age-Related Changes in Mouse Taste Bud Morphology, Hormone Expression, and Taste Responsivity

PubMed Central

Shin, Yu-Kyong; Cong, Wei-na; Cai, Huan; Kim, Wook; Maudsley, Stuart; Martin, Bronwen

2012-01-01

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. PMID:22056740

Age-related changes in mouse taste bud morphology, hormone expression, and taste responsivity.

PubMed

Shin, Yu-Kyong; Cong, Wei-na; Cai, Huan; Kim, Wook; Maudsley, Stuart; Egan, Josephine M; Martin, Bronwen

2012-04-01

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact.

Synthesis of amino acids in weight bearing and non-weight bearing leg muscles of suspended rats

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Jaspers, S. R.

1982-01-01

The effect of hypokinesia (HYP) for 6 days on the de novo synthesis of glutamine (GLN) and glutamate (GLU), and of alanine was tested in isolated leg muscles of intact, adrenalectomized (ADX) and ADX cortisol-treated rats. The net synthesis of GLN and GLU was lower in soleus muscles of HYP animals of these three groups of rats. The synthesis of alanine was lowered by HYP in ADX animals and apparently raised by HYP in ADX cortisol-treated rats. No HYP effect was seen in the extensor digitorum longus (EDL) muscles of these animals. Although ADX lowered the synthesis of GLN and GLU in soleus muscles of control rats, while cortisol treatment restored this process to near normal, neither ADX nor cortisol treatment produced any effect in the HYP animals. However, effects of ADX and cortisol treatment on synthesis of GLN and GLU in EDL muscles and of alanine in both muscles seemed normal in HYP animals.

Infertility in transgenic mice overexpressing the bovine growth hormone gene: luteal failure secondary to prolactin deficiency.

PubMed

Cecim, M; Kerr, J; Bartke, A

1995-05-01

Overexpression of growth hormone (GH) in transgenic mice is associated with various degrees of impairment of female reproductive functions. Transgenic PEPCK.bGH mice express high GH levels, and only around 20% of the females will carry gestation to Day 7. The objective of the present study was to investigate luteal function in PEPCK.bGH mice during early pregnancy, when CL are fully dependent on the pituitary. Plasma progesterone levels measured on Days 2 or 7 postcoitum (p.c.) were lower in transgenic than in normal females. In transgenic females with a previous history of infertility, daily injections of 1 mg progesterone starting on Day 2 p.c. significantly increased the proportion of animals pregnant on Day 7. When ovaries from transgenic mice were transplanted into ovariectomized normal littermates, the recipients exhibited normal vaginal cycles and responded to mating by vaginal cytology changes consistent with pseudopregnancy. In contrast, ovariectomized transgenic females bearing transplants of ovaries from normal mice had slightly prolonged estrous cycles and failed to become pseudopregnant after mating. Plasma progesterone levels on Days 2 and 7 p.c. in normal females with transgenic ovaries were not different from plasma progesterone levels measured in normal females into which normal ovaries had been transplanted. Twice-daily injections of 100 micrograms of prolactin (PRL) in saline or in polyvinylpyrrolidone starting on the evening of Day 2 p.c. were able to rescue luteal function. The proportion of PRL-injected transgenic animals that were pregnant on Day 7 was significantly higher than that of saline-injected transgenic controls and resembled the pregnancy rate of normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Instant Cooked Giant Embryonic Rice on Body Fat Weight and Plasma Lipid Profile in High Fat-Fed Mice

PubMed Central

Chung, Soo Im; Kim, Tae Hyeong; Rico, Catherine W.; Kang, Mi Young

2014-01-01

The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity. PMID:24932656

Statistical studies of animal response data from USF toxicity screening test method

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Machado, A. M.

1978-01-01

Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

Maternal amino acid supplementation for intrauterine growth restriction

PubMed Central

Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

2011-01-01

Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

The effects of brain lesions on the "hopping reaction" in newborn and adult rabbits: a model for studying age dependent recovery.

PubMed

van Hof, M W; Hobbelen, J F; Gramsbergen, A

1990-01-01

In 5 groups of rabbits (0-1, 2-3, 4-5, 6-7 and 12-13 weeks old) the left frontal, parieto-temporal and occipital cortex were removed. Beginning two weeks after the operations the hopping reaction was tested during 15 weeks. It was found in the groups operated 0-1, 2-3 and 4-5 weeks after birth, that the hopping reaction developed normally. This was not the case in the animals operated 6-7 and 12-13 weeks after birth. Brightness descrimination with the left and right eye was tested in the same animals, beginning 12 weeks after the operation. Contrary to the motor system, no age-development recovery was found in the visual system. In all age groups, brightness discrimination with the eye contralateral to the lesion was impaired.

Hypervitaminosis D in Guinea Pigs with α-Mannosidosis

PubMed Central

Jensen, JanLee A; Brice, Angela K; Bagel, Jessica H; Mexas, Angela M; Yoon, Sea Young; Wolfe, John H

2013-01-01

A colony of guinea pigs (n = 9) with α-mannosidosis was fed a pelleted commercial laboratory guinea pig diet. Over 2 mo, all 9 guinea pigs unexpectedly showed anorexia and weight loss (11.7% to 30.0% of baseline weight), and 3 animals demonstrated transient polyuria and polydipsia. Blood chemistry panels in these 3 guinea pigs revealed high-normal total calcium, high-normal phosphate, and high ALP. Urine specific gravity was dilute (1.003, 1.009, 1.013) in the 3 animals tested. Postmortem examination of 7 animals that were euthanized after failing to respond to supportive care revealed renal interstitial fibrosis with tubular mineralization, soft tissue mineralization in multiple organs, hepatic lipidosis, and pneumonia. Analysis of the pelleted diet revealed that it had been formulated with a vitamin D3 content of more than 150 times the normal concentration. Ionized calcium and 25-hydroxyvitamin D values were both high in serum saved from 2 euthanized animals, confirming the diagnosis of hypervitaminosis D. This report discusses the clinical signs, blood chemistry results, and gross and histologic findings of hypervitaminosis D in a colony of guinea pigs. When unexpected signs occur colony-wide, dietary differentials should be investigated at an early time point. PMID:23582422

Hypervitaminosis D in guinea pigs with α-mannosidosis.

PubMed

Jensen, Janlee A; Brice, Angela K; Bagel, Jessica H; Mexas, Angela M; Yoon, Sea Young; Wolfe, John H

2013-04-01

A colony of guinea pigs (n = 9) with α-mannosidosis was fed a pelleted commercial laboratory guinea pig diet. Over 2 mo, all 9 guinea pigs unexpectedly showed anorexia and weight loss (11.7% to 30.0% of baseline weight), and 3 animals demonstrated transient polyuria and polydipsia. Blood chemistry panels in these 3 guinea pigs revealed high-normal total calcium, high-normal phosphate, and high ALP. Urine specific gravity was dilute (1.003, 1.009, 1.013) in the 3 animals tested. Postmortem examination of 7 animals that were euthanized after failing to respond to supportive care revealed renal interstitial fibrosis with tubular mineralization, soft tissue mineralization in multiple organs, hepatic lipidosis, and pneumonia. Analysis of the pelleted diet revealed that it had been formulated with a vitamin D3 content of more than 150 times the normal concentration. Ionized calcium and 25-hydroxyvitamin D values were both high in serum saved from 2 euthanized animals, confirming the diagnosis of hypervitaminosis D. This report discusses the clinical signs, blood chemistry results, and gross and histologic findings of hypervitaminosis D in a colony of guinea pigs. When unexpected signs occur colony-wide, dietary differentials should be investigated at an early time point.

Three-dimensional computer graphic animations for studying social approach behaviour in medaka fish: Effects of systematic manipulation of morphological and motion cues.

PubMed

Nakayasu, Tomohiro; Yasugi, Masaki; Shiraishi, Soma; Uchida, Seiichi; Watanabe, Eiji

2017-01-01

We studied social approach behaviour in medaka fish using three-dimensional computer graphic (3DCG) animations based on the morphological features and motion characteristics obtained from real fish. This is the first study which used 3DCG animations and examined the relative effects of morphological and motion cues on social approach behaviour in medaka. Various visual stimuli, e.g., lack of motion, lack of colour, alternation in shape, lack of locomotion, lack of body motion, and normal virtual fish in which all four features (colour, shape, locomotion, and body motion) were reconstructed, were created and presented to fish using a computer display. Medaka fish presented with normal virtual fish spent a long time in proximity to the display, whereas time spent near the display was decreased in other groups when compared with normal virtual medaka group. The results suggested that the naturalness of visual cues contributes to the induction of social approach behaviour. Differential effects between body motion and locomotion were also detected. 3DCG animations can be a useful tool to study the mechanisms of visual processing and social behaviour in medaka.

Three-dimensional computer graphic animations for studying social approach behaviour in medaka fish: Effects of systematic manipulation of morphological and motion cues

PubMed Central

Nakayasu, Tomohiro; Yasugi, Masaki; Shiraishi, Soma; Uchida, Seiichi; Watanabe, Eiji

2017-01-01

We studied social approach behaviour in medaka fish using three-dimensional computer graphic (3DCG) animations based on the morphological features and motion characteristics obtained from real fish. This is the first study which used 3DCG animations and examined the relative effects of morphological and motion cues on social approach behaviour in medaka. Various visual stimuli, e.g., lack of motion, lack of colour, alternation in shape, lack of locomotion, lack of body motion, and normal virtual fish in which all four features (colour, shape, locomotion, and body motion) were reconstructed, were created and presented to fish using a computer display. Medaka fish presented with normal virtual fish spent a long time in proximity to the display, whereas time spent near the display was decreased in other groups when compared with normal virtual medaka group. The results suggested that the naturalness of visual cues contributes to the induction of social approach behaviour. Differential effects between body motion and locomotion were also detected. 3DCG animations can be a useful tool to study the mechanisms of visual processing and social behaviour in medaka. PMID:28399163

Influence of cadmium on physiological parameters and efficiency of chickens-broilers

NASA Astrophysics Data System (ADS)

Lisunova, L. I.; Tokarev, V. S.; Lisunova, A. V.

2003-05-01

In modern conditions a basis of activity of the person becomes the principle of ecological rationality including development and practical use of systems, technologies and the ways providing reception of ecologically safe production of animal industries. Heavy metals concern to number of the most dangerous objects of an environment The sizes of their distribution and intensity of migration in an environment have got dangerous character for normal functioning and health of people. In this connection there is a real necessity of development of strategy of regulation of a level of heavy metals for system about “ground - an atmosphere - water - a plant - an animal - the person”, basing on the interconnected and mutually conditioned processes of their circulation. Cadmium concerns to group of heavy metals. Its increased contents in an organism of the person reduces ability to resist to illnesses. It has mutagen and cancerogenic properties, negatively influences on a heredity. It also promotes development of diseases of kidneys, and also a gastritis and an anemia.

Autophagy, programmed cell death and reactive oxygen species in sexual reproduction in plants.

PubMed

Kurusu, Takamitsu; Kuchitsu, Kazuyuki

2017-05-01

Autophagy is one of the major cellular processes of recycling of proteins, metabolites and intracellular organelles, and plays crucial roles in the regulation of innate immunity, stress responses and programmed cell death (PCD) in many eukaryotes. It is also essential in development and sexual reproduction in many animals. In plants, although autophagy-deficient mutants of Arabidopsis thaliana show phenotypes in abiotic and biotic stress responses, their life cycle seems normal and thus little had been known until recently about the roles of autophagy in development and reproduction. Rice mutants defective in autophagy show sporophytic male sterility and immature pollens, indicating crucial roles of autophagy during pollen maturation. Enzymatic production of reactive oxygen species (ROS) by respiratory burst oxidase homologues (Rbohs) play multiple roles in regulating anther development, pollen tube elongation and fertilization. Significance of autophagy and ROS in the regulation of PCD of transient cells during plant sexual reproduction is discussed in comparison with animals.

Phospholipid composition of oligodendroglial cells during normal development and in 18 day old hyperthyroid and malnourished rats.

PubMed

Kreda, S M; Pasquini, J M; Soto, E F

1992-09-01

The phospholipid composition of isolated oligodendroglial cell perikarya was studied in normal rats during development and in 18 day old malnourished and hyperthyroid rats. Phosphatidyl choline and phosphatidyl ethanolamine were found to be the major phospholipid constituents of oligodendroglial cells. Phospholipid content increased during development, mainly due to an increase of the above mentioned phospholipids. The major changes were observed in sphingomyelin, phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine between 18 and 30 days of age. The phospholipid and protein content per cell was significantly decreased in the oligodendroglial cells isolated from malnourished rats as compared to controls. When data were expressed as a function of total proteins, the composition was similar to that of normal animals. In the hyperthyroid rats on the other hand, there were no changes in the amount of phospholipids per cell, while phospholipids per milligram of total oligodendroglial cell protein were markedly decreased. The changes in myelin composition produced by hyperthyroidism that we have previously described, do not follow closely those produced by this experimental condition in oligodendroglial cells, suggesting that the metabolism of myelin might be to a certain extent, independent of that in the parent cell.

Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates.

PubMed

Lambeth, Sp; Schapiro, Sj; Bernacky, Bj; Wilkerson, Gk

2013-09-01

Chronic pain and distress are universally accepted conditions that may adversely affect an animal's quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in the USA, a veterinarian, who has physically examined the animal and reviewed the clinical records, ultimately decides when an animal has reached a humane endpoint. To aid in the difficult process of interpreting pain and distress, we have developed specific behavioural guidelines, in addition to standard clinical information, to help define unique characteristics and traits of primates to assess and promote discussion of an individual primate's QOL, and thereby, to assist in the decision-making process regarding euthanasia. These guidelines advocate the creation of a QOL team when the animal is diagnosed with a life-threatening or debilitating chronic condition, or at the time the animal is entered into a terminal study. The team compiles a list of characteristics unique to that individual animal by utilising a questionnaire and a behavioural ethogram. This list enables the team to quantitatively assess any deviations from the established normal behavioural repertoire of that individual. Concurrently, the QOL team determines the number of behavioural deviations that are needed to trigger an immediate discussion of the necessity for humane euthanasia of the animal. The team remains intact once created, and revisits the animal's condition as frequently as deemed necessary. This process improves animal welfare by continuing the quest to optimally define QOL for captive primates, and potentially for all captive animals.

Development and dosimetry of a small animal lung irradiation platform

PubMed Central

McGurk, Ross; Hadley, Caroline; Jackson, Isabel L.; Vujaskovic, Zeljko

2015-01-01

Advances in large scale screening of medical counter measures for radiation-induced normal tissue toxicity are currently hampered by animal irradiation paradigms that are both inefficient and highly variable among institutions. Here, we introduce a novel high-throughput small animal irradiation platform for use in orthovoltage small animal irradiators. We used radiochromic film and metal oxide semiconductor field effect transistor detectors to examine several parameters, including 2D field uniformity, dose rate consistency, and shielding transmission. We posit that this setup will improve efficiency of drug screens by allowing for simultaneous, targeted irradiation of multiple animals, improving efficiency within a single institution. Additionally, we suggest that measurement of the described parameters in all centers conducting counter measure studies will improve the translatability of findings among institutions. We also investigated the use of tissue equivalent phantoms in performing dosimetry measurements for small animal irradiation experiments. Though these phantoms are commonly used in dosimetry, we recorded a significant difference in both the entrance and target tissue dose rates between euthanized rats and mice with implanted detectors and the corresponding phantom measurement. This suggests that measurements using these phantoms may not provide accurate dosimetry for in vivo experiments. Based on these measurements, we propose that this small animal irradiation platform can increase the capacity of animal studies by allowing for more efficient animal irradiation. We also suggest that researchers fully characterize the parameters of whatever radiation setup is in use in order to facilitate better comparison among institutions. PMID:23091878

Radioprotective activity of Polyalthia longifolia standardized extract against X-ray radiation injury in mice.

PubMed

Jothy, Subramanion L; Saito, Tamio; Kanwar, Jagat R; Chen, Yeng; Aziz, Azlan; Yin-Hui, Leong; Sasidharan, Sreenivasan

2016-01-01

The radioprotective effect of Polyalthia longifolia was studied in mice. P. longifolia treatment showed improvement in mice survival compared to 100% mortality in the irradiated mice. Significant increases in hemoglobin concentration, and red blood cell, white blood cell and platelet counts were observed in the animals pretreated with leaf extract. Pre-irradiation administration of P. longifolia leaf extract also increased the CFU counts of the spleen colony and increased the relative spleen size. A dose-dependent decrease in lipid peroxidation levels was observed in the animals pretreated with P. longifolia. However, although the animals pretreated with P. longifolia exhibited a significant increase in superoxide dismutase and catalase activity, the values remained below normal in both liver and the intestine. Pre-irradiation administration of P. longifolia also resulted in the regeneration of the mucosal crypts and villi of the intestine. Moreover, pretreatment with P. longifolia leaf extract also showed restoration of the normal liver cell structure and a significant reduction in the elevated levels of ALT, AST and bilirubin. These results suggested the radioprotective ability of P. longifolia leaf extract, which is significant for future investigation for human applications in developing efficient, economically viable, non-toxic natural and clinically acceptable novel radioprotectors. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Stimulatory effects of Cuminum cyminum and flavonoid glycoside on Cyclosporine-A and restraint stress induced immune-suppression in Swiss albino mice.

PubMed

Chauhan, Prashant Singh; Satti, Naresh Kumar; Suri, Krishan Avtar; Amina, Musarat; Bani, Sarang

2010-04-15

Many herbs and spices are known to modulate the immune system and have been shown to restore the immunity in immuno-compromised individuals. Spices generally used to increase the taste and flavor of food also has the history of usage as an ayurvedic medicine. Therefore to explore the health modulating effects of Cuminum cyminum and to identify the active compound, immunomodulatory properties were evaluated using flowcytometry and ELISA in normal and immune-suppressed animals. C. cyminum and compound 1 stimulated the T cells and Th1 cytokines expression in normal animals. Swiss albino mice subjected to Cyclosporine-A induced immune-suppression were dosed orally with C. cyminum (25, 50, 100 and 200 mg/kg) on consecutive days. The results showed that administration significantly increased T cells (CD4 and CD8) count and Th1 predominant immune response in a dose dependent manner thereby suggesting immunomodulatory activity through modulation of T lymphocytes expression. In restraint stress induced immune-suppressed animals, compound 1 countered the depleted T lymphocytes, decreased the elevated corticosterone levels and size of adrenal glands and increased the weight of thymus and spleen. Based on the data we may conclude that C. cyminum is a potent immunomodulator and may develop as a lead to recover the immunity of immuno-compromised individuals. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Cloned cows with short telomeres deliver healthy offspring with normal-length telomeres.

PubMed

Miyashita, Norikazu; Kubo, Yasuaki; Yonai, Miharu; Kaneyama, Kanako; Saito, Norio; Sawai, Ken; Minamihashi, Akira; Suzuki, Toshiyuki; Kojima, Toshiyuki; Nagai, Takashi

2011-10-01

Dolly, the first mammal cloned from a somatic cell, had shorter telomeres than age-matched controls and died at an early age because of disease. To investigate longevity and lifetime performance in cloned animals, we produced cloned cows with short telomeres using oviductal epithelial cells as donor cells. At 5 years of age, despite the presence of short telomeres, all cloned cows delivered multiple healthy offspring following artificial insemination with conventionally processed spermatozoa from noncloned bulls, and their milk production was comparable to that of donor cows. Moreover, this study revealed that the offspring had normal-length telomeres in their leukocytes and major organs. Thus, cloned animals have normal functional germ lines, and therefore germ line function can completely restore telomere lengths in clone gametes by telomerase activity, resulting in healthy offspring with normal-length telomeres.

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

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

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Echocardiography parameters of clinically normal adult captive chimpanzees (Pan troglodytes).

PubMed

Sleeper, Meg M; Drobatz, Ken; Lee, D Richard; Lammey, Michael L

2014-04-15

To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes). Retrospective cohort study. 88 clinically normal adult chimpanzees. Echocardiographic data obtained between 2002 and 2011 from chimpanzees at the Alamogordo Primate Facility were reviewed (263 echocardiograms obtained from 158 individuals). Data from clinically normal individuals (33 females and 55 males) were analyzed. Basic cardiac parameters measured in all individuals included aortic root diameter and left atrial diameter in the short and long axis during diastole. Left ventricular measurements included left ventricular internal diameter in systole and diastole and diastolic septal and posterior wall thickness. The E point to septal separation was also measured. Spectral Doppler measurements included the peak flow velocity of the pulmonary artery and aorta and diastolic transmitral flow. The presence of arrhythmias was also noted. Standard echocardiographic findings for a large group of adult female and male chimpanzees were obtained. Female and male chimpanzees were grouped by age in 10-year blocks, and echocardiographic findings were analyzed statistically by 10-year block. In male chimpanzees, cardiac arrhythmias were noted to increase with age. Cardiovascular disease is an important cause of morbidity and death in captive chimpanzees; however, basic echocardiographic measurements from a large cohort of clinically normal animals have not previously been reported. The number of animals in the present study was insufficient to generate reference ranges; however, data from a large cohort of clinically normal animals are presented. This information will be useful for veterinarians working in clinical and research settings with this species.

RADIOGRAPHIC THORACIC ANATOMY OF THE RED PANDA (AILURUS FULGENS).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Groenewald, Hermanus B; Koeppel, Katja N

2016-09-01

The red panda ( Ailurus fulgens ) is classified as an endangered species by the International Union for Conservation of Nature and Natural Resources. The natural distribution of the red panda is in the Himalayas and southern China. Thoracic diseases such as dirofilariasis, hypertrophic cardiomyopathy, tracheal obstruction, lung worm infestation, and pneumonia have been reported in the red panda. The aim of this study was to describe the normal radiographic thoracic anatomy of captive red pandas as a species-specific reference for routine health examinations and clinical cases. Right lateral (RL) and dorsoventral (DV) inspiratory phase views of the thorax were obtained in 11 adult captive red pandas. Measurements were made and ratios calculated to establish reference ranges for the mean vertebral heart score on the RL (8.34 ± 0.25) and DV (8.78 ± 0.34) views and the mean ratios of the caudal vena cava diameter to the vertebral body length above tracheal bifurcation (0.67 ± 0.05) and tracheal diameter to the width of the third rib (2.75 ± 0.24). The majority of animals (10/11) had 14 thoracic vertebrae, except for one animal that had 15 thoracic vertebrae. Rudimentary clavicles were seen in 3/11 animals. The ovoid, oblique cardiac silhouette was more horizontally positioned and elongated in older animals. A redundant aortic arch was seen in the oldest animal. The trachea was seen with mineralized cartilage rings in all animals. The carina was clearly seen in the majority of animals (10/11). Variations exist in the normal radiographic thoracic anatomy of different species. Knowledge of the normal radiographic thoracic anatomy of the red panda should prove useful for routine health examinations and in the diagnosis of thoracic diseases.

Animal cloning: problems and prospects.

PubMed

Wells, D N

2005-04-01

An efficient animal cloning technology would provide many new opportunities for livestock agriculture, human medicine, and animal conservation. Nuclear cloning involves the production of animals that are genetically identical to the donor cells used in a technique known as nuclear transfer (NT). However, at present it is an inefficient process: in cattle, only around 6% of the embryos transferred to the reproductive tracts of recipient cows result in healthy, longterm surviving clones. Of concern are the high losses throughout gestation, during birth and in the post-natal period through to adulthood. Many of the pregnancy losses relate to failure of the placenta to develop and function correctly. Placental dysfunction may also have an adverse influence on postnatal health. These anomalies are probably due to incorrect epigenetic reprogramming of the donor genome following NT, leading to inappropriate patterns of gene expression during the development of clones. Whilst some physiological tests on surviving clones suggest normality, other reports indicate a variety of post-natal clone-associated abnormalities. This variability in outcome may reflect species-specific and/or cloning methodological differences. Importantly, to date it appears that these clone-associated phenotypes are not transmitted to offspring following sexual reproduction. This indicates that they represent epigenetic errors, rather than genetic errors, which are corrected during gametogenesis. Whilst this needs confirmation at the molecular level, it provides initial confidence in the first application of NT in agriculture, namely, the production of small numbers of cloned sires from genetically elite bulls, for natural mating, to effectively disseminate genetic gain. In addition to the animal welfare concerns with the technology, the underlying health of the animals and the consequential effect on food safety are critical aspects that require investigation to gain regulatory and consumer acceptance. Future improvements in animal cloning will largely arise from a greater understanding of the molecular mechanisms of reprogramming.

Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose

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

Sparks, R.B.; Aydogan, B.

In the development of new radiopharmaceuticals, animal studies are typically performed to get a first approximation of the expected radiation dose in humans. This study evaluates the performance of some commonly used data extrapolation techniques to predict residence times in humans using data collected from animals. Residence times were calculated using animal and human data, and distributions of ratios of the animal results to human results were constructed for each extrapolation method. Four methods using animal data to predict human residence times were examined: (1) using no extrapolation, (2) using relative organ mass extrapolation, (3) using physiological time extrapolation, andmore » (4) using a combination of the mass and time methods. The residence time ratios were found to be log normally distributed for the nonextrapolated and extrapolated data sets. The use of relative organ mass extrapolation yielded no statistically significant change in the geometric mean or variance of the residence time ratios as compared to using no extrapolation. Physiologic time extrapolation yielded a statistically significant improvement (p < 0.01, paired t test) in the geometric mean of the residence time ratio from 0.5 to 0.8. Combining mass and time methods did not significantly improve the results of using time extrapolation alone. 63 refs., 4 figs., 3 tabs.« less

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

PubMed Central

Contreras, Esteban G.; Sierralta, Jimena

2018-01-01

Background Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Results Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Conclusions Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. PMID:29621246

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

PubMed

Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

2018-01-01

Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

Tolerance of canine anastomoses to intraoperative radiation therapy

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

Tepper, J.E.; Sindelar, W.; Travis, E.L.

1983-07-01

Radiation has been given intraoperatively to various abdominal structures in dogs, using a fixed horizontal 11 MeV electron beam at the Armed Forces Radiobiologic Research Institute. Animals were irradiated with single doses of 2000, 3000 and 4500 rad to a field which extended from the bifurcation of the aorta to the rib cage. All animals were irradiated during laparotomy under general anesthesia. Because the clinical use of intraoperative radiotherapy in cancer treatment will occasionally require irradiation of anastomosed large vessels and blind loops of bowel, the tolerance of aortic anastomoses and the suture lines of blind loops of jejunum tomore » irradiation were studied. Responses in these experiments were scored at times up to one year after irradiation. In separate experiments both aortic and intestinal anastomoses were performed on each animal for evaluation of short term response. The dogs with aortic anastomoses showed adequate healing at all doses with no evidence of suture line weakening. On long-term follow-up one animal (2000 rad) had stenosis at the anastomosis and one animal (4500 rad) developed an arteriovenous fistula. Three of the animals that had an intestinal blind loop irradiated subsequently developed intussusception, with the irradiated loop acting as the lead point. One week after irradiation, bursting pressure of an intestinal blind loop was normal at 3000 rad, but markedly decreased at 4500 rad. No late complications were noted after the irradiation of the intestinal anastomosis. No late complicatons were observed after irradiation of intestinal anastomoses, but one needs to be cautious with regards to possible late stenosis at the site of an irradiated vascular anastomosis.« less

Prevalence of Prostate Cancer Metastases after Intravenous Inoculation Provides Clues into the Molecular Basis of Dormancy in the Bone Marrow Microenvironment1

PubMed Central

Jung, Younghun; Shiozawa, Yusuke; Wang, Jingcheng; McGregor, Natalie; Dai, Jinlu; Park, Serk In; Berry, Janice E; Havens, Aaron M; Joseph, Jeena; Kim, Jin Koo; Patel, Lalit; Carmeliet, Peter; Daignault, Stephanie; Keller, Evan T; McCauley, Laurie K; Pienta, Kenneth J; Taichman, Russell S

2012-01-01

Bone is the preferred metastasis site of advanced prostate cancer (PCa). Using an in vivo murine model of human PCa cell metastasis to bone, we noted that the majority of animals that develop skeletal metastasis have either spinal lesions or lesions in the bones of the hindlimb. Much less frequently, lesions develop in the bones of the forelimb. We therefore speculated whether the environment of the forelimb bones is not permissive for the growth of PCa. Consequently, data on tumor prevalence were normalized to account for the number of PCa cells arriving after intravascular injection, marrow cellularity, and number of hematopoietic stem cell niches. None of these factors were able to account for the observed differences in tumor prevalence. An analysis of differential gene and protein levels identified that growth arrest specific-6 (GAS6) levels were significantly greater in the forelimb versus hindlimb bone marrow. When murine RM1 cells were implanted into subcutaneous spaces in immune competent animals, tumor growth in the GAS6-/- animals was greater than in GAS6+/+ wild-type animals. In an osseous environment, the human PC3 cell line grew significantly better in vertebral body transplants (vossicles) derived from GAS6-/- animals than in vossicles derived from GAS6+/+ animals. Together, these data suggest that the differences in tumor prevalence after intravascular inoculation are a useful model to study the molecular basis of tumor dormancy. Importantly, these data suggest that therapeutic manipulation of GAS6 levels may prove useful as a therapy for metastatic disease. PMID:22745589

Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs

NASA Astrophysics Data System (ADS)

Kadakia, Sama; Young, Hunter; Richter, Claus-Peter

2013-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

Environmental assessment for the Satellite Power System (SPS): studies of honey bees exposed to 2. 45 GHz continuous-wave electromagnetic energy

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

Gary, N E; Westerdahl, B B

1980-12-01

A system for small animal exposure was developed for treating honey bees, Apis mellifera L., in brood and adult stages, with 2.45 GHz continuous wave microwaves at selected power densities and exposure times. Post-treatment brood development was normal and teratological effects were not detected at exposures of 3 to 50 mw/cm/sup 2/ for 30 minutes. Post-treatment survival, longevity, orientation, navigation, and memory of adult bees were also normal after exposures of 3 to 50 mw/cm/sup 2/ for 30 minutes. Post-treatment longevity of confined bees in the laboratory was normal after exposures of 3 to 50 mw/cm/sup 2/ for 24 hours.more » Thermoregulation of brood nest, foraging activity, brood rearing, and social interaction were not affected by chronic exposure to 1 mw/cm/sup 2/ during 28 days. In dynamic behavioral bioassays the frequency of entry and duration of activity of unrestrained, foraging adult bees was identical in microwave-exposed (5 to 40 mw/cm/sup 2/) areas versus control areas.« less

The intracellular responses of frog eggs to novel orientations to gravity

NASA Technical Reports Server (NTRS)

Radice, G. P.; Neff, A. W.; Malacinski, G. M.

1982-01-01

It is found that multiple short doses of ultraviolet light are as effective as a single large dose in producing neural defects. In addition, 180 deg rotation (inversion) of irradiated eggs reduces the ultraviolet effect. Since yolk platelets may be the gravity sensing mechanism, their size, density, and distribution in normal and inverted eggs are investigated. Large platelets are denser and for the most part are in a distinct zone in the vegetal hemisphere, whereas small platelets are less dense and occur in the animal hemisphere. When inverted, the large platelets flow into the animal hemisphere as a coherent mass and partially displace the small platelets. Inversion is thought to rearrange cytoplasmic components necessary for later neural development into an appropriate configuration.

Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats.

PubMed

Azkona, Garikoitz; Sagarduy, Ainhoa; Aristieta, Asier; Vazquez, Nerea; Zubillaga, Verónica; Ruíz-Ortega, José Angel; Pérez-Navarro, Esther; Ugedo, Luisa; Sánchez-Pernaute, Rosario

2014-04-01

Dopamine replacement with l-DOPA is the most effective therapy in Parkinson's disease. However, with chronic treatment, half of the patients develop an abnormal motor response including dyskinesias. The specific molecular mechanisms underlying dyskinesias are not fully understood. In this study, we used a well-characterized animal model to first establish the molecular differences between rats that did and did not develop dyskinesias. We then investigated the molecular substrates implicated in the anti-dyskinetic effect of buspirone, a 5HT1A partial agonist. Striatal protein expression profile of dyskinetic animals revealed increased levels of the dopamine receptor (DR)D3, ΔFosB and phospho (p)CREB, as well as an over-activation of the DRD1 signalling pathway, reflected by elevated ratios of phosphorylated DARPP32 and ERK2. Buspirone reduced the abnormal involuntary motor response in dyskinetic rats in a dose-dependent fashion. Buspirone (4 mg/kg) dramatically reduced the presence and severity of dyskinesias (by 83%) and normalized DARPP32 and ERK2 phosphorylation ratios, while the increases in DRD3, ΔFosB and pCREB observed in dyskinetic rats were not modified. Pharmacological experiments combining buspirone with 5HT1A and DRD3 antagonists confirmed that normalization of both pDARPP32 and pERK2 is required, but not sufficient, for blocking dyskinesias. The correlation between pDARPP32 ratio and dyskinesias was significant but not strong, pointing to the involvement of convergent factors and signalling pathways. Our results suggest that in dyskinetic rats DRD3 striatal over-expression could be instrumental in the activation of DRD1-downstream signalling and demonstrate that the anti-dyskinetic effect of buspirone in this model is correlated with DRD1 pathway normalization. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pancreatic islet blood flow and its measurement

PubMed Central

Jansson, Leif; Barbu, Andreea; Bodin, Birgitta; Drott, Carl Johan; Espes, Daniel; Gao, Xiang; Grapensparr, Liza; Källskog, Örjan; Lau, Joey; Liljebäck, Hanna; Palm, Fredrik; Quach, My; Sandberg, Monica; Strömberg, Victoria; Ullsten, Sara; Carlsson, Per-Ola

2016-01-01

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future. PMID:27124642

Mechanisms of nephroprotective effect of mitochondria-targeted antioxidants under rhabdomyolysis and ischemia/reperfusion.

PubMed

Plotnikov, E Y; Chupyrkina, A A; Jankauskas, S S; Pevzner, I B; Silachev, D N; Skulachev, V P; Zorov, D B

2011-01-01

Oxidative stress-related renal pathologies apparently include rhabdomyolysis and ischemia/reperfusion phenomenon. These two pathologies were chosen for study in order to develop a proper strategy for protection of the kidney. Mitochondria were found to be a key player in these pathologies, being both the source and the target for excessive production of reactive oxygen species (ROS). A mitochondria-targeted compound which is a conjugate of a positively charged rhodamine molecule with plastoquinone (SkQR1) was found to rescue the kidney from the deleterious effect of both pathologies. Intraperitoneal injection of SkQR1 before the onset of pathology not only normalized the level of ROS and lipid peroxidized products in kidney mitochondria but also decreased the level of cytochrome c in the blood, restored normal renal excretory function and significantly lowered mortality among animals having a single kidney exposed to ischemia/reperfusion. The SkQR1-derivative missing plastoquinone (C12R1) possessed some, although limited nephroprotective properties and enhanced animal survival after ischemia/reperfusion. SkQR1 was found to induce some elements of nephroprotective pathways providing ischemic tolerance such as an increase in erythropoietin levels and phosphorylation of glycogen synthase kinase 3β in the kidney. SkQR1 also normalized renal erythropoietin level lowered after kidney ischemia/reperfusion and injection of a well-known nephrotoxic agent gentamicin. Copyright © 2010 Elsevier B.V. All rights reserved.

Sexual differentiation of the copulatory neuromuscular system in green anoles (Anolis carolinensis): normal ontogeny and manipulation of steroid hormones.

PubMed

Holmes, Melissa M; Wade, Juli

2005-09-05

The copulatory neuromuscular system of green anoles is sexually dimorphic and differentiates during embryonic development, although details of the process were unknown. In Experiment 1, we determined the time course of normal ontogeny. Both male and female embryos possessed bilateral copulatory organs (hemipenes) and associated muscles until incubation day 13; the structures completely regressed in female embryos by incubation day 19 (total incubation 34 days). In Experiment 2, we treated eggs with testosterone, dihydrotestosterone, estradiol, or vehicle on both incubation days 10 and 13 to determine whether these steroid hormones mediate sexual differentiation. These time points fall between gonadal differentiation, which was determined in Experiment 1 to complete before day 10, and regression of the peripheral copulatory system in females. Tissue was collected on the day of hatching. Gonads were classified as testes or ovaries; presence versus absence of hemipenes and muscles, and the number and size of copulatory motoneurons were determined. Copulatory system morphology of vehicle-treated animals matched their gonadal sex. Hemipenes and muscles were absent in estradiol-treated animals, and androgens rescued the hemipenes and muscles in most females. Both testosterone and dihydrotestosterone treatment also caused hypertrophy of the hemipenes, which were everted in animals treated with these steroids. Copulatory motoneurons, assessed on the day of hatching in both experiments, were not dimorphic in size or number. Steroid treatment significantly increased motoneuron size and number overall, but no significant differences were detected in pairwise comparisons. These data demonstrate that differentiation of peripheral copulatory neuromuscular structures occurs during embryonic development and is influenced by gonadal steroids (regression by estradiol and enhancement by androgens), but associated motoneurons do not differentiate until later in life.

Extended Plasticity of Visual Cortex in Dark-Reared Animals May Result from Prolonged Expression of cpg15-Like Genes

PubMed Central

Lee, Wei-Chung Allen; Nedivi, Elly

2011-01-01

cpg15 is an activity-regulated gene that encodes a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. These properties make it an attractive candidate for participating in plasticity of the mammalian visual system. Here we compare cpg15 expression during normal development of the rat visual system with that seen in response to dark rearing, monocular blockade of retinal action potentials, or monocular deprivation. Our results show that the onset of cpg15 expression in the visual cortex is coincident with eye opening, and it increases until the peak of the critical period at postnatal day 28 (P28). This early expression is independent of both retinal activity and visual experience. After P28, a component of cpg15 expression in the visual cortex, lateral geniculate nucleus (LGN), and superior colliculus (SC) develops a progressively stronger dependence on retinally driven action potentials. Dark rearing does not affect cpg15 mRNA expression in the LGN and SC at any age, but it does significantly affect its expression in the visual cortex from the peak of the critical period and into adulthood. In dark-reared rats, the peak level of cpg15 expression in the visual cortex at P28 is lower than in controls. Rather than showing the normal decline with maturation, these levels are maintained in dark-reared animals. We suggest that the prolonged plasticity in the visual cortex that is seen in dark-reared animals may result from failure to downregulate genes such as cpg15 that could promote structural remodeling and synaptic maturation. PMID:11880509

Functional and biocompatibility performances of an integrated Maglev pump-oxygenator.

PubMed

Zhang, Tao; Cheng, Guangming; Koert, Andrew; Zhang, Juntao; Gellman, Barry; Yankey, G Kwame; Satpute, Aditee; Dasse, Kurt A; Gilbert, Richard J; Griffith, Bartley P; Wu, Zhongjun J

2009-01-01

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.

Understanding the Hows and Whys of Decision-Making: From Expected Utility to Divisive Normalization.

PubMed

Glimcher, Paul

2014-01-01

Over the course of the last century, economists and ethologists have built detailed models from first principles of how humans and animals should make decisions. Over the course of the last few decades, psychologists and behavioral economists have gathered a wealth of data at variance with the predictions of these economic models. This has led to the development of highly descriptive models that can often predict what choices people or animals will make but without offering any insight into why people make the choices that they do--especially when those choices reduce a decision-maker's well-being. Over the course of the last two decades, neurobiologists working with economists and psychologists have begun to use our growing understanding of how the nervous system works to develop new models of how the nervous system makes decisions. The result, a growing revolution at the interdisciplinary border of neuroscience, psychology, and economics, is a new field called Neuroeconomics. Emerging neuroeconomic models stand to revolutionize our understanding of human and animal choice behavior by combining fundamental properties of neurobiological representation with decision-theoretic analyses. In this overview, one class of these models, based on the widely observed neural computation known as divisive normalization, is presented in detail. The work demonstrates not only that a discrete class of computation widely observed in the nervous system is fundamentally ubiquitous, but how that computation shapes behaviors ranging from visual perception to financial decision-making. It also offers the hope of reconciling economic analysis of what choices we should make with psychological observations of the choices we actually do make. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Tetramethylammonium for in vivo marking of the cross-sectional area of the scala media in the guinea pig cochlea.

PubMed

Salt, A N; DeMott, J

1992-01-01

A physiologic technique was developed to measure endolymphatic cross-sectional area in vivo using tetramethylammonium (TMA) as a volume marker. The technique was evaluated in guinea pigs as an animal model. In the method, the cochlea was exposed surgically and TMA was injected into endolymph of the second turn at a constant rate by iontophoresis. The concentration of TMA was monitored during and after the injection using ion-selective electrodes. Cross-section estimates derived from the TMA concentration measurements were compared in normal animals and animals in which endolymphatic hydrops had been induced by ablation of the endolymphatic duct and sac 8 weeks earlier. The method demonstrated a mean increase in cross-sectional area of 258% in the hydropic group. Individually measured area values were compared with action potential threshold shifts and the magnitude of the endocochlear potential (EP). Hydropic animals typically showed an increase in threshold to 2 kHz stimuli and a decrease in EP. However, the degree of threshold shift or EP decrease did not correlate well with the degree of hydrops present.

Assessing acute effects of trapping, handling, and tagging on the behavior of wildlife using GPS telemetry: a case study of the common brushtail possum.

PubMed

Dennis, Todd E; Shah, Shabana F

2012-01-01

Trapping, handling, and deployment of tracking devices (tagging) are essential aspects of many research and conservation studies of wildlife. However, often these activities place nonhuman animals under considerable physical or psychological distress, which disrupts normal patterns of behavior and may ultimately result in deleterious effects on animal welfare and the validity of research results. Thus, knowledge of how trapping, handling, and tagging alter the behavior of research animals is essential if measures to ameliorate stress-related effects are to be developed and implemented. This article describes how time-stamped location data obtained by global-positioning-system telemetry can be used to retrospectively characterize acute behavioral responses to trapping, handling, and tagging in free-ranging animals used for research. Methods are demonstrated in a case study of the common brushtail possum, a semiarboreal phalangerid marsupial native to Australia. The study discusses possible physiological causes of observed effects and offers general suggestions regarding simple means to reduce trapping-handling-and-tagging-related stress in field studies of vertebrates.

Pasteurella multocida: from Zoonosis to Cellular Microbiology

PubMed Central

Ho, Mengfei

2013-01-01

SUMMARY In a world where most emerging and reemerging infectious diseases are zoonotic in nature and our contacts with both domestic and wild animals abound, there is growing awareness of the potential for human acquisition of animal diseases. Like other Pasteurellaceae, Pasteurella species are highly prevalent among animal populations, where they are often found as part of the normal microbiota of the oral, nasopharyngeal, and upper respiratory tracts. Many Pasteurella species are opportunistic pathogens that can cause endemic disease and are associated increasingly with epizootic outbreaks. Zoonotic transmission to humans usually occurs through animal bites or contact with nasal secretions, with P. multocida being the most prevalent isolate observed in human infections. Here we review recent comparative genomics and molecular pathogenesis studies that have advanced our understanding of the multiple virulence mechanisms employed by Pasteurella species to establish acute and chronic infections. We also summarize efforts being explored to enhance our ability to rapidly and accurately identify and distinguish among clinical isolates and to control pasteurellosis by improved development of new vaccines and treatment regimens. PMID:23824375

Real-time 3D motion tracking for small animal brain PET

NASA Astrophysics Data System (ADS)

Kyme, A. Z.; Zhou, V. W.; Meikle, S. R.; Fulton, R. R.

2008-05-01

High-resolution positron emission tomography (PET) imaging of conscious, unrestrained laboratory animals presents many challenges. Some form of motion correction will normally be necessary to avoid motion artefacts in the reconstruction. The aim of the current work was to develop and evaluate a motion tracking system potentially suitable for use in small animal PET. This system is based on the commercially available stereo-optical MicronTracker S60 which we have integrated with a Siemens Focus-220 microPET scanner. We present measured performance limits of the tracker and the technical details of our implementation, including calibration and synchronization of the system. A phantom study demonstrating motion tracking and correction was also performed. The system can be calibrated with sub-millimetre accuracy, and small lightweight markers can be constructed to provide accurate 3D motion data. A marked reduction in motion artefacts was demonstrated in the phantom study. The techniques and results described here represent a step towards a practical method for rigid-body motion correction in small animal PET. There is scope to achieve further improvements in the accuracy of synchronization and pose measurements in future work.

Image analysis for estimating the weight of live animals

NASA Astrophysics Data System (ADS)

Schofield, C. P.; Marchant, John A.

1991-02-01

Many components of animal production have been automated. For example weighing feeding identification and yield recording on cattle pigs poultry and fish. However some of these tasks still require a considerable degree of human input and more effective automation could lead to better husbandry. For example if the weight of pigs could be monitored more often without increasing labour input then this information could be used to measure growth rates and control fat level allowing accurate prediction of market dates and optimum carcass quality to be achieved with improved welfare at minimum cost. Some aspects of animal production have defied automation. For example attending to the well being of housed animals is the preserve of the expert stockman. He gathers visual data about the animals in his charge (in more plain words goes and looks at their condition and behaviour) and processes this data to draw conclusions and take actions. Automatically collecting data on well being implies that the animals are not disturbed from their normal environment otherwise false conclusions will be drawn. Computer image analysis could provide the data required without the need to disturb the animals. This paper describes new work at the Institute of Engineering Research which uses image analysis to estimate the weight of pigs as a starting point for the wider range of applications which have been identified. In particular a technique has been developed to

Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model

PubMed Central

Zou, Leilei; Liu, Rui; Zhang, Xiaohui; Chu, Renyuan; Dai, Jinhui; Zhou, Hao

2014-01-01

Purpose Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment. Methods Guinea pigs were assigned to four groups: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups. Results Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes. Conclusions We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression. PMID:25018620

The Electrophysiologic Mechanisms of Halogenated Alkane Arrhythmogenesis.

DTIC Science & Technology

1983-03-01

recording of normal parameters (Fig. 19), the animal was tested with several con- centrations of isoproterenol to determine an arrhythmogenic dose...agent to control these seizures, several compounds were tested . Valium at a dose of 10 mg per animal or 20 mg per animal of Rompun did not induce the... animals tested in the following experiments were pretreated with this dose (15 mg/kg) of phenobarbital. Table 16 summarizes the results of 10 dogs breathing

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence.

PubMed

Harvie, Michelle; Howell, Anthony

2017-01-19

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence

PubMed Central

Harvie, Michelle; Howell, Anthony

2017-01-01

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation. PMID:28106818

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

PubMed

Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

2017-11-01

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors.

PubMed

Kang, Jaeseung; Kim, Eunjoon

2015-01-01

Animals prenatally exposed to valproic acid (VPA), an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs). Previous studies have identified enhanced NMDA receptor (NMDAR) function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memantine, an NMDAR antagonist, administered to VPA mice rescues both social deficits and repetitive behaviors such as self-grooming and jumping. These results suggest that suppression of elevated NMDAR function in VPA animals normalizes repetitive behaviors in addition to social deficits.

Target structures in the cochlea for infrared neural stimulation (INS)

NASA Astrophysics Data System (ADS)

Young, Hunter; Tan, Xiaodong; Richter, Claus-Peter

2014-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also result in the generation of a stress relaxation wave causing mechanical stimulation of hair cells in the cochlea, creating an optoacoustic response. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

Stem cells: a model for screening, discovery and development of drugs.

PubMed

Kitambi, Satish Srinivas; Chandrasekar, Gayathri

2011-01-01

The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.

Characterization of anemia induced by avian osteopetrosis virus.

PubMed Central

Paterson, R W; Smith, R E

1978-01-01

Chickens infected intravenously at 8 days after hatching with an avian osteopetrosis virus developed a severe, progressive anemia in the absence of osteopetrosis. The anemia was characterized as a pancytopenia, in which erythrocytes, granulocytes, and thrombocytes decreased concomitantly. Serum bilirubin levels were normal, whereas erythrocytes from infected chickens demonstrated a slightly elevated osmotic fragility. A negative Coombs test indicated that there was no evidence for erythrocyte-bound antibody. Erythrocytes from infected animals had slightly decreased 51Cr-labeled erythrocyte survival time when compared with normal. Examination of marrow histological preparations, together with ferrokinetic studies with 59Fe, indicated that marrow failure occurred during the acute phase of the anemia. Circulating virus was present during the development and acute phases of the anemia, but disappeared during the recovery phase of the disease. Neutralizing antibody appeared after the disappearance of circulating virus. It is concluded that virus infection induced both marrow failure (aplastic crisis) and decreased erythrocyte survival. Images PMID:215554

Zoonotic Poxviruses Associated with Companion Animals

PubMed Central

Tack, Danielle M.; Reynolds, Mary G.

2011-01-01

Simple Summary Contemporary enthusiasm for the ownership of exotic animals and hobby livestock has created an opportunity for the movement of poxviruses—such as monkeypox, cowpox, and orf—outside their traditional geographic range bringing them into contact with atypical animal hosts and groups of people not normally considered at risk. It is important that pet owners and practitioners of human and animal medicine develop a heightened awareness for poxvirus infections and understand the risks that can be associated with companion animals and livestock. This article reviews the epidemiology and clinical features of zoonotic poxviruses that are most likely to affect companion animals. Abstract Understanding the zoonotic risk posed by poxviruses in companion animals is important for protecting both human and animal health. The outbreak of monkeypox in the United States, as well as current reports of cowpox in Europe, point to the fact that companion animals are increasingly serving as sources of poxvirus transmission to people. In addition, the trend among hobbyists to keep livestock (such as goats) in urban and semi-urban areas has contributed to increased parapoxvirus exposures among people not traditionally considered at high risk. Despite the historic notoriety of poxviruses and the diseases they cause, poxvirus infections are often missed. Delays in diagnosing poxvirus-associated infections in companion animals can lead to inadvertent human exposures. Delays in confirming human infections can result in inappropriate treatment or prolonged recovery. Early recognition of poxvirus-associated infections and application of appropriate preventive measures can reduce the spread of virus between companion animals and their owners. This review will discuss the epidemiology and clinical features associated with the zoonotic poxvirus infections most commonly associated with companion animals. PMID:26486622

NanoLuc reporter for dual luciferase imaging in living animals.

PubMed

Stacer, Amanda C; Nyati, Shyam; Moudgil, Pranav; Iyengar, Rahul; Luker, Kathryn E; Rehemtulla, Alnawaz; Luker, Gary D

2013-10-01

Bioluminescence imaging is widely used for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on the high signal to background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events, as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, adenosine triphosphate–independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc [NL]) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although the detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in transforming growth factor β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as a new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development.

NanoLuc Reporter for Dual Luciferase Imaging in Living Animals

PubMed Central

Stacer, Amanda C.; Nyati, Shyam; Moudgil, Pranav; Iyengar, Rahul; Luker, Kathryn E.; Rehemtulla, Alnawaz; Luker, Gary D.

2014-01-01

Bioluminescence imaging is utilized widely for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on high signal-to-background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, ATP-independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc, NL) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in TGF-β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development. PMID:24371848

TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development.

PubMed

Flanagan-Steet, Heather; Christian, Courtney; Lu, Po-Nien; Aarnio-Peterson, Megan; Sanman, Laura; Archer-Hartmann, Stephanie; Azadi, Parastoo; Bogyo, Matthew; Steet, Richard A

2018-03-13

Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S). In MLII, elevated C4-S corresponds with TGF-ß-mediated increases in chst11 expression. Inhibiting chst11 impairs the proteolytic activation of Ctsk and alleviates the MLII phenotypes. These findings uncover a regulatory loop between TGF-ß signaling and Ctsk activation that is altered in the context of lysosomal disease. This work highlights the power of ABPs to identify mechanisms underlying pathogenic development in living animals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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

Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.

Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/-more » mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.« less

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

PubMed

Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O

2017-12-01

Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

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

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

[Effect of selenium deficiency on the F344 inbred line offspring rats' neuro-behavior, ability of learning and memory].

PubMed

Hong, Liang-Li; Tian, Dong-Ping; Su, Min; Shen, Xiu-Na; Gao, Yuxia

2006-01-01

To establish the selenium (Se) deficient animal model on F344 inbred line rats and observe the effects of a long-term Se-deficiency on the offspring's neuro-behavior, abilities of learning and memory. Feeding F344 inbred line rats on Se-deficient diet to establish Se-deficient animal model. For the offspring, the body weight, physiological indexes nervous reflections for growth and development were monitored during the early postnatal period. The Se-deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH-Px) activity in blood of the Se-deficient group rats is lower than the Se-normal group after feeding on Se-deficient diet for 4 weeks. For the offspring, the birth weight and the body weight of Se-deficient group were obviously lower than the Se-normal group before weaning. Se-deficient offspring rats differed from Se-normal controls in lower scores in surface righting reflex (RR) test at postnatal 4th day after delivery, cliff avoidance test at postnatal 7th day and auditory acuity trial at postnatal 10th day respectively. But these differences disappear after a few days in the same tests. In addition, no significant differences between two groups in suspending test and walking ability test at postnatal 12th and 14th day. In open field test, Se-deficient male offspring stayed less time in the middle grid and moved less. In Morris water maze test, the Se-deficient offspring spent more time to find the hidden platform at the 6th and 9th training tests in the place navigation trial. Furthermore, the Se-deficient group spent less time in target quadrant when giving the spatial probe trial. A Se-deficient animal model have been established on F344 inbred line rats successfully. A long-term Se deficiency could retard the development of the offspring in uterus and after delivery. Se deficiency also decreased the offspring's abilities of spatial learning and memory in Morris water maze test and resulted in the male offspring's nervousness to new stimulant.

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

PubMed Central

Mazcko, Christina; Hanna, Engy; Kachala, Stefan; LeBlanc, Amy; Newman, Shelley; Vail, David; Henry, Carolyn; Thamm, Douglas; Sorenmo, Karin; Hajitou, Amin; Pasqualini, Renata; Arap, Wadih

2009-01-01

Background Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5×1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies. PMID:19330034

Expression of SIRT1 in the ovaries of rats with polycystic ovary syndrome before and after therapeutic intervention with exenatide

PubMed Central

Tao, Xin; Zhang, Xiao; Ge, Shu-Qi; Zhang, Er-Hong; Zhang, Bin

2015-01-01

Aim: To investigate the expression of silent information regulator 1 (SIRT1) in rats with polycystic ovary syndrome (PCOS) and its alteration after exenatide treatment. Methods: PCOS rat model was established by dehydroepiandrosterone induction. The animals were randomly divided into exenatide treatment group (EX group, n = 10), metformin treatment group (MF group, n = 10), PCOS group (PCOS group, n = 9) and normal control group (NC group, n = 10). Histological changes of the ovarian tissues were examined by HE staining. SIRT1 expression in the ovarian tissue was detected by RT-PCR and immunohistochemistry. Results: Rats in the PCOS group lost their estrous cycle. Histological observation of the ovary showed saccular dilatation of the follicle, decreased number of corpora lutea, fewer layers of granulosa cells aligned loosely, and thickened layer of theca cells. The changes in reproductive hormones and the development of insulin resistance suggested the successful establishment of the animal models. Immunohistochemistry and Q-PCR detected the mRNA and protein expressions of SIRT1 in the ovary tissues of rats in the normal control group. The SIRT1 expression was significantly lower in PCOS group than in control group (P < 0.05); after drug intervention, the SIRT1 expression significantly increased in EX and MF groups (compared with the PCOS group), whereas no significant difference was noted between the EX group and MF group. Conclusions: The SIRT1 expression in the ovary tissue decreases in PCOS rats (compare with the normal rats) but can be up-regulated after Ex or MF treatment. These drugs may affect the process and development of PCOS by regulating the SIRT1 expression. Exenatide may be therapeutic for PCOS by up-regulating the SITR1 expression. PMID:26339397

Expression of SIRT1 in the ovaries of rats with polycystic ovary syndrome before and after therapeutic intervention with exenatide.

PubMed

Tao, Xin; Zhang, Xiao; Ge, Shu-Qi; Zhang, Er-Hong; Zhang, Bin

2015-01-01

To investigate the expression of silent information regulator 1 (SIRT1) in rats with polycystic ovary syndrome (PCOS) and its alteration after exenatide treatment. PCOS rat model was established by dehydroepiandrosterone induction. The animals were randomly divided into exenatide treatment group (EX group, n = 10), metformin treatment group (MF group, n = 10), PCOS group (PCOS group, n = 9) and normal control group (NC group, n = 10). Histological changes of the ovarian tissues were examined by HE staining. SIRT1 expression in the ovarian tissue was detected by RT-PCR and immunohistochemistry. Rats in the PCOS group lost their estrous cycle. Histological observation of the ovary showed saccular dilatation of the follicle, decreased number of corpora lutea, fewer layers of granulosa cells aligned loosely, and thickened layer of theca cells. The changes in reproductive hormones and the development of insulin resistance suggested the successful establishment of the animal models. Immunohistochemistry and Q-PCR detected the mRNA and protein expressions of SIRT1 in the ovary tissues of rats in the normal control group. The SIRT1 expression was significantly lower in PCOS group than in control group (P < 0.05); after drug intervention, the SIRT1 expression significantly increased in EX and MF groups (compared with the PCOS group), whereas no significant difference was noted between the EX group and MF group. The SIRT1 expression in the ovary tissue decreases in PCOS rats (compare with the normal rats) but can be up-regulated after Ex or MF treatment. These drugs may affect the process and development of PCOS by regulating the SIRT1 expression. Exenatide may be therapeutic for PCOS by up-regulating the SITR1 expression.

Animal models to guide clinical drug development in ADHD: lost in translation?

PubMed Central

Wickens, Jeffery R; Hyland, Brian I; Tripp, Gail

2011-01-01

We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open-field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6-hydroxydopamine-lesioned (6-OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6-OHDA-lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21480864

Effect of a bearing gap on hemolytic property in a hydrodynamically levitated centrifugal blood pump with a semi-open impeller.

PubMed

Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu; Yambe, Tomoyuki; Imachi, Kou; Yamane, Takashi

2013-01-01

We have developed a hydrodynamically levitated centrifugal blood pump with a semi-open impeller for long-term circulatory assist. The pump uses hydrodynamic bearings to enhance durability and reliability without additional displacement-sensors or control circuits. However, a narrow bearing gap of the pump has a potential for hemolysis. The purpose of this study is to develop the hydrodynamically levitated centrifugal blood pump with a semi-open impeller, and to evaluate the effect of a bearing gap on hemolytic property. The impeller levitates using a spiral-groove type thrust bearing, and a herringbone-groove type radial bearing. The pump design was improved by adopting a step type thrust bearing and optimizing the pull-up magnetic force. The pump performance was evaluated by a levitation performance test, a hemolysis test and an animal experiment. In these tests, the bearing gap increased from 1 to 63 μm. In addition, the normalized index of hemolysis (NIH) improved from 0.415 to 0.005 g/100 l, corresponding to the expansion of the bearing gap. In the animal experiment for 24 h, the plasma-free hemoglobin remained within normal ranges (<4.0 mg/dl). We confirmed that the hemolytic property of the pump was improved to the acceptable level by expanding the bearing gap greater than 60 μm.

On the influence of altered gravity on the growth of fish inner ear otoliths

NASA Astrophysics Data System (ADS)

Beier, Marion

1999-09-01

Inner ear stones (otoliths) of developing cichlid fish ( Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a long-term (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.

Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

NASA Technical Reports Server (NTRS)

Meyerson, F. Z.; Kapelko, V. I.; Gorina, M. S.; Shchegolkov, A. N.; Larinov, N. P.

1980-01-01

Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

Animal Model of Dermatophytosis

PubMed Central

Shimamura, Tsuyoshi; Kubota, Nobuo; Shibuya, Kazutoshi

2012-01-01

Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects. PMID:22619489

Assessing animal welfare in sow herds using data on meat inspection, medication and mortality.

PubMed

Knage-Rasmussen, K M; Rousing, T; Sørensen, J T; Houe, H

2015-03-01

This paper aims to contribute to the development of a cost-effective alternative to expensive on-farm animal-based welfare assessment systems. The objective of the study was to design an animal welfare index based on central database information (DBWI), and to validate it against an animal welfare index based on-farm animal-based measurements (AWI). Data on 63 Danish sow herds with herd-sizes of 80 to 2500 sows and an average herd size of 501 were collected from three central databases containing: Meat inspection data collected at animal level in the abattoir, mortality data at herd level from the rendering plants of DAKA, and medicine records at both herd and animal group level (sow with piglets, weaners or finishers) from the central database Vetstat. Selected measurements taken from these central databases were used to construct the DBWI. The relative welfare impacts of both individual database measurements and the databases overall were assigned in consultation with a panel consisting of 12 experts. The experts were drawn from production advisory activities, animal science and in one case an animal welfare organization. The expert panel weighted each measurement on a scale from 1 (not-important) to 5 (very important). The experts also gave opinions on the relative weightings of measurements for each of the three databases by stating a relative weight of each database in the DBWI. On the basis of this, the aggregated DBWI was normalized. The aggregation of AWI was based on weighted summary of herd prevalence's of 20 clinical and behavioural measurements originating from a 1 day data collection. AWI did not show linear dependency of DBWI. This suggests that DBWI is not suited to replace an animal welfare index using on-farm animal-based measurements.

Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

NASA Technical Reports Server (NTRS)

Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

1996-01-01

To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

A two-degree-of-freedom hip exoskeleton device for an immature animal model of exercise-induced Legg-Calvé-Perthes disease.

PubMed

Zhang, J F; Yang, C J; Wu, T; Li, J H; Xu, Z S; Chen, Y

2009-11-01

Legg-Calvé-Perthes disease (LCPD) is a significant problem in healthcare because it so commonly affects young adults and immature athletes, primarily gymnasts. In this paper, a two-degree-of-freedom (2-DOF) hip exoskeleton device was developed for study on an immature animal model of exercise-induced LCPD. The exoskeleton device can reproduce the repetitive actions and forceful centrality impingements on the coxafemoral head that occur in sports such as gymnastics and acrobatics. It initiated a new method rather than the traditional medical or physiological operation method to establish an animal model of LCPD and allowed for the development and testing of new treatments. Ten immature New Zealand white rabbits were selected for the experiment. Their right legs were driven to achieve repetitive extension/ flexion and abduction/adduction beyond the normal range of motion, with centrality impingements at the maximum flexion position, while their left legs were kept in the initial healthy status and acted as the comparing reference. Four weeks later, the basic symptoms of early LCPD of the femoral head appeared. The results of X-ray, magnetic resonance imaging (MRI), gross anatomy observation, and H-E section also revealed it.

Use of enzyme-linked immunoassays for antibody to types C and D botulinum toxins for investigations of botulism in cattle.

PubMed

Gregory, A R; Ellis, T M; Jubb, T F; Nickels, R J; Cousins, D V

1996-02-01

The development of specific enzyme-linked immunosorbent assays (ELISA) for antibody to types C and D Clostridium botulinum toxins for investigation of botulism in cattle is described. Partially purified type C and D toxins were used as antigens to develop these ELISAs. Specificity of the ELISAs was evaluated on sera from 333 adult beef and dairy cattle from areas with no history or evidence of botulism in animals or water birds. The test was also evaluated on sera from 41 herds that included herds vaccinated against botulism, confirmed botulism cases and herds from areas where the disease is considered endemic. The ELISAs detected the presence of antibody to botulinum toxins in samples from vaccinated cattle and both convalescent and clinically normal animals from unvaccinated herds with outbreaks of botulism. Antibody was also found in unvaccinated animals from herds in which there had been no diagnosed botulism cases in areas where botulism was considered endemic. Sera from some unvaccinated cattle with high ELISA reactivity was shown to be protective for mice in botulinum toxin neutralisation tests. The use of these tests in investigations of botulism in cattle is discussed.

Cross-species approaches to pathological gambling: a review targeting sex differences, adolescent vulnerability and ecological validity of research tools.

PubMed

van den Bos, Ruud; Davies, William; Dellu-Hagedorn, Francoise; Goudriaan, Anna E; Granon, Sylvie; Homberg, Judith; Rivalan, Marion; Swendsen, Joel; Adriani, Walter

2013-12-01

Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often lead to an inability to make profitable long-term decisions. As a case in point, pathological gamblers continue gambling despite the fact that this disrupts their personal, professional or financial life. The prevalence of pathological gambling will likely increase in the coming years due to expanding possibilities of on-line gambling through the Internet and increasing liberal attitudes towards gambling. It therefore represents a growing concern for society. Both human and animal studies rapidly advance our knowledge on brain-behaviour processes relevant for understanding normal and pathological gambling behaviour. Here, we review in humans and animals three features of pathological gambling which hitherto have received relatively little attention: (1) sex differences in (the development of) pathological gambling, (2) adolescence as a (putative) sensitive period for (developing) pathological gambling and (3) avenues for improving ecological validity of research tools. Based on these issues we also discuss how research in humans and animals may be brought in line to maximize translational research opportunities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

PubMed Central

Muldoon, L. L.; Neuwelt, E. A.; Pagel, M. A.; Weiss, D. L.

1994-01-01

The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8178934

Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

PubMed

Muldoon, L L; Neuwelt, E A; Pagel, M A; Weiss, D L

1994-05-01

The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy.

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

Correlates of diuretic renography in experimental hydronephrosis

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

Kekomaeki, M.R.; Rikalainen, H.; Ruotsalainen, P.

1989-02-01

We studied the correlations between diuretic renographs and kidney function in experimental hydronephrosis in rabbits. Features of furosemide-stimulated /sup 99m/Tc-diethylenetriamine-pentaacetic acid renographs were compared to the growth rate, thirst test and endogenous creatinine clearance rate in a chronic solitary-kidney animal model. Intravenous pyelograms, done four weeks after laparotomy, left nephrectomy, bladder resection and constriction of the right pyeloureteric junction, showed signs of obstruction in all the 12 animals of the experimental group. An absent tracer washout after intravenous furosemide, found in five animals, was associated with retarded growth, isosthenuria and an abnormal creatinine clearance. In all of the other sevenmore » animals, a distinct tracer washout after intravenous furosemide was accompanied with a normal growth rate and creatinine clearance. However, no one of these seven animals had a normal ability to retain water and concentrate urine in the thirst test. We conclude that, in this experimental model, a furosemide-induced tracer washout from the kidney pelvis cannot be taken as a proof of the absence of any upper urinary tract obstruction.« less

The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

ERIC Educational Resources Information Center

Hirai, Masahiro; Hiraki, Kazuo

2006-01-01

We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

Effect of desmopressin on normal and impaired memory

PubMed Central

Jenkins, JS; Mather, HM; Coughlan, AK

1982-01-01

In view of the reported influence of vasopressin on the memory process of animals, trials were carried out on normal subjects and patients with memory disorders using the vasopressin analogue desmopressin. No beneficial effects could be demonstrated. PMID:7131017

Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation.

PubMed

Rogers, R F; Matzel, L D

1996-01-01

Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.

Diet-induced obesity reduces core body temperature across the estrous cycle and pregnancy in the rat.

PubMed

Crew, Rachael C; Waddell, Brendan J; Maloney, Shane K; Mark, Peter J

2018-04-16

Obesity during pregnancy causes adverse maternal and fetal health outcomes and programs offspring for adult-onset diseases, including cardiovascular disease. Obesity also disrupts core body temperature (T c ) regulation in nonpregnant rodents; however, it is unknown whether obesity alters normal maternal T c adaptations to pregnancy. Since T c is influenced by the circadian system, and both obesity and pregnancy alter circadian biology, it was hypothesized that obesity disrupts the normal rhythmic patterns of T c before and during gestation. Obesity was induced by cafeteria (CAF) feeding in female Wistar rats for 8 weeks prior to and during gestation, whereas control (CON) animals had free access to chow. Intraperitoneal temperature loggers measured daily T c profiles throughout the study, while maternal body composition and leptin levels were assessed near term. Daily temperature profiles were examined for rhythmic features (mesor, amplitude and acrophase) by cosine regression analysis. CAF animals exhibited increased fat mass (93%) and associated hyperleptinemia (3.2-fold increase) compared to CON animals. CAF consumption reduced the average T c (by up to 0.29°C) across the estrous cycle and most of pregnancy; however, T c for CAF and CON animals converged toward the end of gestation. Obesity reduced the amplitude of T c rhythms at estrus and proestrus and on day 8 of pregnancy, but increased the amplitude at day 20 of pregnancy. Photoperiod analysis revealed that obesity reduced T c exclusively in the light period during pre-pregnancy but only during the dark period in late gestation. In conclusion, obesity alters rhythmic T c profiles and reduces the magnitude of the T c decline late in rat gestation, which may have implications for maternal health and fetal development.

A probe-based qRT-PCR method to profile immunological gene expression in blood of captive beluga whales (Delphinapterus leucas)

PubMed Central

Wang, Jiann-Hsiung; Chou, Shih-Jen; Li, Tsung-Hsien; Leu, Ming-Yih; Ho, Hsiao-Kuan

2017-01-01

Cytokines are fundamental for a functioning immune system, and thus potentially serve as important indicators of animal health. Quantitation of mRNA using quantitative reverse transcription polymerase chain reaction (qRT-PCR) is an established immunological technique. It is particularly suitable for detecting the expression of proteins against which monoclonal antibodies are not available. In this study, we developed a probe-based quantitative gene expression assay for immunological assessment of captive beluga whales (Delphinapterus leucas) that is one of the most common cetacean species on display in aquariums worldwide. Six immunologically relevant genes (IL-2Rα, -4, -10, -12, TNFα, and IFNγ) were selected for analysis, and two validated housekeeping genes (PGK1 and RPL4) with stable expression were used as reference genes. Sixteen blood samples were obtained from four animals with different health conditions and stored in RNAlater™ solution. These samples were used for RNA extraction followed by qRT-PCR analysis. Analysis of gene transcripts was performed by relative quantitation using the comparative Cq method with the integration of amplification efficiency and two reference genes. The expression levels of each gene in the samples from clinically healthy animals were normally distributed. Transcript outliers for IL-2Rα, IL-4, IL-12, TNFα, and IFNγ were noticed in four samples collected from two clinically unhealthy animals. This assay has the potential to identify immune system deviation from normal state, which is caused by health problems. Furthermore, knowing the immune status of captive cetaceans could help both trainers and veterinarians in implementing preventive approaches prior to disease onset. PMID:28970970

A probe-based qRT-PCR method to profile immunological gene expression in blood of captive beluga whales (Delphinapterus leucas).

PubMed

Tsai, Ming-An; Chen, I-Hua; Wang, Jiann-Hsiung; Chou, Shih-Jen; Li, Tsung-Hsien; Leu, Ming-Yih; Ho, Hsiao-Kuan; Yang, Wei Cheng

2017-01-01

Cytokines are fundamental for a functioning immune system, and thus potentially serve as important indicators of animal health. Quantitation of mRNA using quantitative reverse transcription polymerase chain reaction (qRT-PCR) is an established immunological technique. It is particularly suitable for detecting the expression of proteins against which monoclonal antibodies are not available. In this study, we developed a probe-based quantitative gene expression assay for immunological assessment of captive beluga whales ( Delphinapterus leucas ) that is one of the most common cetacean species on display in aquariums worldwide. Six immunologically relevant genes (IL-2Rα, -4, -10, -12, TNFα, and IFNγ) were selected for analysis, and two validated housekeeping genes (PGK1 and RPL4) with stable expression were used as reference genes. Sixteen blood samples were obtained from four animals with different health conditions and stored in RNA later ™ solution. These samples were used for RNA extraction followed by qRT-PCR analysis. Analysis of gene transcripts was performed by relative quantitation using the comparative Cq method with the integration of amplification efficiency and two reference genes. The expression levels of each gene in the samples from clinically healthy animals were normally distributed. Transcript outliers for IL-2Rα, IL-4, IL-12, TNFα, and IFNγ were noticed in four samples collected from two clinically unhealthy animals. This assay has the potential to identify immune system deviation from normal state, which is caused by health problems. Furthermore, knowing the immune status of captive cetaceans could help both trainers and veterinarians in implementing preventive approaches prior to disease onset.

Establishing ‘quality of life’ parameters using behavioural guidelines for humane euthanasia of captive non-human primates

PubMed Central

Lambeth, SP; Schapiro, SJ; Bernacky, BJ; Wilkerson, GK

2014-01-01

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in the USA, a veterinarian, who has physically examined the animal and reviewed the clinical records, ultimately decides when an animal has reached a humane endpoint. To aid in the difficult process of interpreting pain and distress, we have developed specific behavioural guidelines, in addition to standard clinical information, to help define unique characteristics and traits of primates to assess and promote discussion of an individual primate’s QOL, and thereby, to assist in the decision-making process regarding euthanasia. These guidelines advocate the creation of a QOL team when the animal is diagnosed with a life-threatening or debilitating chronic condition, or at the time the animal is entered into a terminal study. The team compiles a list of characteristics unique to that individual animal by utilising a questionnaire and a behavioural ethogram. This list enables the team to quantitatively assess any deviations from the established normal behavioural repertoire of that individual. Concurrently, the QOL team determines the number of behavioural deviations that are needed to trigger an immediate discussion of the necessity for humane euthanasia of the animal. The team remains intact once created, and revisits the animal’s condition as frequently as deemed necessary. This process improves animal welfare by continuing the quest to optimally define QOL for captive primates, and potentially for all captive animals. PMID:25505822

A special role for binocular visual input during development and as a component of occlusion therapy for treatment of amblyopia.

PubMed

Mitchell, Donald E

2008-01-01

To review work on animal models of deprivation amblyopia that points to a special role for binocular visual input in the development of spatial vision and as a component of occlusion (patching) therapy for amblyopia. The studies reviewed employ behavioural methods to measure the effects of various early experiential manipulations on the development of the visual acuity of the two eyes. Short periods of concordant binocular input, if continuous, can offset much longer daily periods of monocular deprivation to allow the development of normal visual acuity in both eyes. It appears that the visual system does not weigh all visual input equally in terms of its ability to impact on the development of vision but instead places greater weight on concordant binocular exposure. Experimental models of patching therapy for amblyopia imposed on animals in which amblyopia had been induced by a prior period of early monocular deprivation, indicate that the benefits of patching therapy may be only temporary and decline rapidly after patching is discontinued. However, when combined with critical amounts of binocular visual input each day, the benefits of patching can be both heightened and made permanent. Taken together with demonstrations of retained binocular connections in the visual cortex of monocularly deprived animals, a strong argument is made for inclusion of specific training of stereoscopic vision for part of the daily periods of binocular exposure that should be incorporated as part of any patching protocol for amblyopia.

DNA methylation analysis on satellite I region in blastocysts obtained from somatic cell cloned cattle.

PubMed

Yamanaka, Ken-Ichi; Kaneda, Masahiro; Inaba, Yasushi; Saito, Koji; Kubota, Kaiyu; Sakatani, Miki; Sugimura, Satoshi; Imai, Kei; Watanabe, Shinya; Takahashi, Masashi

2011-08-01

Many observations have been made on cloned embryos and on adult clones by somatic cell nuclear transfer (SCNT), but it is still unclear whether the progeny of cloned animals is presenting normal epigenetic status. Here, in order to accumulate the information for evaluating the normality of cloned cattle, we analyzed the DNA methylation status on satellite I region in blastocysts obtained from cloned cattle. Embryos were produced by artificial insemination (AI) to non-cloned or cloned dams using semen from non-cloned or cloned sires. After 7 days of AI, embryos at blastocyst stage were collected by uterine flushing. The DNA methylation levels in embryos obtained by using semen and/or oocytes from cloned cattle were similar to those in in vivo embryos from non-cloned cattle. In contrast, the DNA methylation levels in SCNT embryos were significantly higher (P < 0.01) than those in in vivo embryos from non-cloned and cloned cattle, approximately similar to those in somatic cells used as donor cells. Thus, this study provides useful information that epigenetic status may be normal in the progeny of cloned cattle, suggesting the normality of germline cells in cloned cattle. 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Production and characterization of murine models of classic and intermediate maple syrup urine disease

PubMed Central

Homanics, Gregg E; Skvorak, Kristen; Ferguson, Carolyn; Watkins, Simon; Paul, Harbhajan S

2006-01-01

Background Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. Methods To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. Results By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. Conclusion These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease. PMID:16579849

On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock

PubMed Central

Errington, M. L.; e Silva, M. Rocha

1974-01-01

1. Long-lasting haemorrhagic hypotension (4·5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP9a), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP9a was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days. 2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock. 3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock. 4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period. 5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock. 6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period. 7. BPP9a had no measurable effect on the course of endotoxic shock. 8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed. PMID:4373570

Transgenic mice: an irreplaceable tool for the study of mammalian development and biology.

PubMed

Babinet, C

2000-11-01

Stable integration into the mouse genome of exogenous genetic information, i.e., the creation of transgenic mice, has become a privileged way of analyzing gene function in normal development and pathology. Both gene addition and gene replacement may be performed. This has allowed, in particular, the creation of mice in which precise mutations are introduced into a given gene. Furthermore, in recent years, strategies that induce the expression of a mutation in a given type of cell and/or at a given time in development have been developed. Thus, the transgenic methodology affords a unique and irreplaceable tool for the study of mammalian development and biology and for the creation of animal models for human genetic diseases.

Ecological theory as a foundation to control pathogenic invasion in aquaculture

PubMed Central

De Schryver, Peter; Vadstein, Olav

2014-01-01

Detrimental host–pathogen interactions are a normal phenomenon in aquaculture animal production, and have been counteracted by prophylactic use of antibiotics. Especially, the youngest life stages of cultivated aquatic animals are susceptible to pathogen invasion, resulting in disease and mortality. To establish a more sustainable aquatic food production, there is a need for new microbial management strategies that focus on ‘join them' and not the traditional ‘beat them' approaches. We argue that ecological theory could serve as a foundation for developing sustainable microbial management methods that prevent pathogenic disease in larviculture. Management of the water microbiota in aquaculture systems according to ecological selection principles has been shown to decrease opportunistic pathogen pressure and to result in an improved performance of the cultured animals. We hypothesize that manipulation of the biodiversity of the gut microbiota can increase the host's resistance against pathogenic invasion and infection. However, substantial barriers need to be overcome before active management of the intestinal microbiota can effectively be applied in larviculture. PMID:24892581

Impact of simulated microgravity on the normal developmental time line of an animal-bacteria symbiosis

PubMed Central

Foster, Jamie S.; Khodadad, Christina L. M.; Ahrendt, Steven R.; Parrish, Mirina L.

2013-01-01

The microgravity environment during space flight imposes numerous adverse effects on animal and microbial physiology. It is unclear, however, how microgravity impacts those cellular interactions between mutualistic microbes and their hosts. Here, we used the symbiosis between the host squid Euprymna scolopes and its luminescent bacterium Vibrio fischeri as a model system. We examined the impact of simulated microgravity on the timeline of bacteria-induced development in the host light organ, the site of the symbiosis. To simulate the microgravity environment, host squid and symbiosis-competent bacteria were incubated together in high-aspect ratio rotating wall vessel bioreactors and examined throughout the early stages of the bacteria-induced morphogenesis. The host innate immune response was suppressed under simulated microgravity; however, there was an acceleration of bacteria-induced apoptosis and regression in the host tissues. These results suggest that the space flight environment may alter the cellular interactions between animal hosts and their natural healthy microbiome. PMID:23439280

Quantitative diagnosis of tongue cancer from histological images in an animal model

NASA Astrophysics Data System (ADS)

Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo G.; Fei, Baowei

2016-03-01

We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin stained tissue from tongue sections were captured for classifying tumor and non-tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer.

Describing temporal variation in reticuloruminal pH using continuous monitoring data.

PubMed

Denwood, M J; Kleen, J L; Jensen, D B; Jonsson, N N

2018-01-01

Reticuloruminal pH has been linked to subclinical disease in dairy cattle, leading to considerable interest in identifying pH observations below a given threshold. The relatively recent availability of continuously monitored data from pH boluses gives new opportunities for characterizing the normal patterns of pH over time and distinguishing these from abnormal patterns using more sensitive and specific methods than simple thresholds. We fitted a series of statistical models to continuously monitored data from 93 animals on 13 farms to characterize normal variation within and between animals. We used a subset of the data to relate deviations from the normal pattern to the productivity of 24 dairy cows from a single herd. Our findings show substantial variation in pH characteristics between animals, although animals within the same farm tended to show more consistent patterns. There was strong evidence for a predictable diurnal variation in all animals, and up to 70% of the observed variation in pH could be explained using a simple statistical model. For the 24 animals with available production information, there was also a strong association between productivity (as measured by both milk yield and dry matter intake) and deviations from the expected diurnal pattern of pH 2 d before the productivity observation. In contrast, there was no association between productivity and the occurrence of observations below a threshold pH. We conclude that statistical models can be used to account for a substantial proportion of the observed variability in pH and that future work with continuously monitored pH data should focus on deviations from a predictable pattern rather than the frequency of observations below an arbitrary pH threshold. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Increased urinary excretion of platelet activating factor in mice with lupus nephritis

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

Macconi, D.; Noris, M.; Benfenati, E.

1991-01-01

Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that:more » (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.« less

Susceptibility to kinetotic Behaviour during Parabolic Aircraft Flights and otolithic Calcium Incorporation in Fish

NASA Astrophysics Data System (ADS)

Forster, A.; Anken, R.; Hilbig, R.

According to an earlier concept, otolith (or statolith) asymmetry is the cause for susceptibility to kinetoses (e.g., human static space sickness). Indeed, we could recently show that fish showing a kinetotic behaviour after development at hypergravity had incorporated significantly more otolithic calcium (and had an higher otolith asymmetry concerning calcium incorporation) as had normally swimming hyper-g specimens. In order to determine whether a (predispositioned) high asymmetry of otolithic calcium incorporation may also be the cause for kinetosis susceptibility in the microgravity environment (to be achived during parabolic aircraft flights, PFs), larval cichlid fish (Oreochromis mossambicus) were (prior to the PFs) maintained in aquarium water containing alizarin-complexone (AC), a fluorescent calcium tracer. Subsequently, the behaviour of the animals during the microgravity phases of the PF experiment was qualitatively assessed and the specimens were seperated into normally and kinetotically swimming individuals (the latter performed spinning movements). Finally, otolithic AC (and thus calzium) incorporation was densitometrically determined in the otoliths and correlated with the animals' behavior. The respective data will be communicated at the meeting. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

Transplanting Human Skin Grafts onto Nude Mice to Model Skin Scars.

PubMed

Ding, Jie; Tredget, Edward E

2017-01-01

Hypertrophic scar (HTS) is a common outcome of deep dermal wound healing mainly followed mechanical, chemical, and thermal injuries in the skin. Because of the lack of the most effective prevention and treatment, it is particularly important to establish an ideal dermal animal model for improving the understanding of the pathogenesis and exploring therapeutic approaches of HTS. Compared to other dermal fibrotic animal models in rabbits, red Duroc pigs, guinea pigs, rats, and mice, the approach that uses normal human split-thickness skin grafted onto nude or other immunodeficient mice which develop scars that resemble human HTS offers the advantages of lower cost, easier manipulation, and shorter research period. In this chapter, we will introduce the detailed procedures to create the ideal dermal fibrotic mouse model.

FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach.

PubMed

Busk, Morten; Munk, Ole L; Jakobsen, Steen; Frøkiær, Jørgen; Overgaard, Jens; Horsman, Michael R

2017-05-01

Current [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) procedures in tumor-bearing mice typically includes fasting, anesthesia, and standardized uptake value (SUV)-based quantification. Such procedures may be inappropriate for prolonged multiscan experiments. We hypothesize that normalization of tumor FDG retention relative to a suitable reference tissue may improve accuracy as this method may be less susceptible to uncontrollable day-to-day changes in blood glucose levels, physical activity, or unnoticed imperfect tail vein injections. Fed non-anesthetized tumor-bearing mice were administered FDG intravenously (i.v.) or intraperitoneally (i.p.) and PET scanned on consecutive days using a Mediso nanoScan PET/magnetic resonance imaging (MRI). Reproducibility of various PET-deduced measures of tumor FDG retention, including normalization to FDG signal in reference organs and a conventional SUV approach, was evaluated. Day-to-day variability in i.v. injected mice was lower when tumor FDG retention was normalized to brain signal (T/B), compared to normalization to other tissues or when using SUV-based normalization. Assessment of tissue radioactivity in dissected tissues confirmed the validity of PET-derived T/B ratios. Mean T/B and SUV values were similar in i.v. and i.p. administered animals, but SUV normalization was more robust in the i.p. group than in the i.v. group. Multimodality scanners allow tissue delineation and normalization of tumor FDG uptake relative to reference tissues. Normalization to brain, but not liver or kidney, improved scan reproducibility considerably and was superior to traditional SUV quantification in i.v. tracer-injected animals. Day-to-day variability in SUV's was lower in i.p. than in i.v. injected animals, and i.p. injections may therefore be a valuable alternative in prolonged rodent studies, where repeated vein injections are undesirable.

Effects of oxygen toxicity on cuprolinic blue-stained proteoglycans in alveolar basement membranes.

PubMed

Ferrara, T B; Fox, R B

1992-02-01

Effects of oxygen toxicity on distribution and density of proteoglycans in basement membranes of newborn rat lungs were assessed by electron microscopic analysis of tissues processed with cuprolinic blue, a cationic label that characteristically labels these anionically charged macromolecules. Newborn rats placed in greater than 95% oxygen at birth were killed at weekly intervals for 4 wk, and lung tissues fixed in 2.5% glutaraldehyde with 0.2% cuprolinic blue were processed for electron microscopy. Alveolar basement membranes from oxygen-treated and control animals were compared for differences in thickness and proteoglycan concentration and distribution. Results showed progressive thickening of alveolar basement membranes with increased duration of oxygen exposure. The normal distribution of proteoglycans, which is predominantly in the lamina rara externa of alveolar basement membranes, was frequently lost in thickened membranes found in oxygen-treated animals. Density of proteoglycans in these membranes decreased to 56% of normal by 2 wk of age and remained low with continued oxygen administration. Proteoglycan concentration in basement membranes on the interstitial side of alveolar capillaries in both control and oxygen-treated animals was low compared with proteoglycan concentration in basement membranes that opposed the alveolar air space, and administration of oxygen diminished these differences. These results demonstrate a direct alteration of proteoglycan distribution and density in the developing lung as a result of oxygen toxicity. This could result in decreased cell adhesion, influence the cellular response to lung injury, and contribute to the increased permeability seen with this disorder.

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

Che, Magnus M.; Conti, Michele; Chanda, Soma

We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarinmore » exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.« less

Axonal sprouting and laminin appearance after destruction of glial sheaths.

PubMed Central

Masuda-Nakagawa, L M; Muller, K J; Nicholls, J G

1993-01-01

Laminin, a large extracellular matrix molecule, is associated with axonal outgrowth during development and regeneration of the nervous system in a variety of animals. In the leech central nervous system, laminin immunoreactivity appears after axon injury in advance of the regenerating axons. Although studies of vertebrate nervous system in culture have implicated glial and Schwann cells as possible sources, the cells that deposit laminin at sites crucial for regeneration in the living animal are not known. We have made a direct test to determine whether, in the central nervous system of the leech, cells other than ensheathing glial cells can produce laminin. Ensheathing glial cells of adult leeches were ablated selectively by intracellular injection of a protease. As a result, leech laminin accumulated within 10 days in regions of the central nervous system where it is not normally found, and undamaged, intact axons began to sprout extensively. In normal leeches laminin immunoreactivity is situated only in the basement membrane that surrounds the central nervous system, whereas after ablation of ensheathing glia it appeared in spaces through which neurons grew. Within days of ablation of the glial cell, small mobile phagocytes, or microglia, accumulated in the spaces formerly occupied by the glial cell. Microglia were concentrated at precisely the sites of new laminin appearance and axon sprouting. These results suggest that in the animal, as in culture, leech laminin promotes sprouting and that microglia may be responsible for its appearance. Images Fig. 1 Fig. 2 Fig. 3 PMID:8506343

Clinicopathological studies on facial eczema outbreak in sheep in Southwest Turkey.

PubMed

Ozmen, Ozlem; Sahinduran, Sima; Haligur, Mehmet; Albay, Metin Koray

2008-10-01

After very hot summer, 22 sheep from 5 different flocks consisting of approximately 150-200 animals each were diagnosed with facial eczema in September 2005, in southwest Turkey. Photophobia, corneal opacity, severe ulcers of the facial skin, especially localized around the eyes and mouth, and 3% mortality were the most prominent clinical symptoms. GGT levels of the animals were very high and varying between 261- 328 U/l. While the activities of ALT and total bilirubin were elevated and AST was normal in affected sheep. Total bilirubin level was higher than normal. Seven of the 22 sheep were euthanatized and necropsy was performed on all of these animals. Severe icterus, hepatomegaly, enlarged gallbladder, congestion of mesenteric vessels were the common necropsy findings. Histopathological changes of the liver included necrosis of the hepatocytes, cholangiohepatitis characterized by mononuclear inflammatory cell infiltrate in the portal area and mild to severe fibrosis around bile ducts. A diagnosis of sporidesmin toxicosis was made based on the histopathology of the livers, the elevation in liver enzymes, and the development of cutaneous lesions consistent with photosensitization and high spore counts in the ruminal contents. Surviving sheep were treated with procaine penicillin + dihidrostreptomycin sulfate, multivitamin complexes and flunixin meglumine. Additionally, zinc sulphate was also given at a dose of 6 gr per 100 lt drinking water for 28 days. All treated sheep recovered. Pasture spore counts were between 96,300- 267,500 spores/g grass.

Development of space-fertilized eggs and formation of primordial germ cells in the embryos of medaka fish

NASA Astrophysics Data System (ADS)

Ijiri, K.

In the second International Microgravity Laboratory (IML-2) mission in 1994, four small Japanese killifish (Medaka, Oryzias latipes) made a space travel of 15 days aboard a space shuttle. These four adult Medaka fish successfully mated in space for the first time among vertebrate animals. Moreover, the eggs they laid developed normally, at least in their external appearance, hatching as fry (baby fish) in space. Fish mated and laid eggs every day during the first week. Near the end of the mission most of the eggs had a well-developed body with two pigmented eyes. In total, 43 eggs were laid (detected), out of which 8 fry hatched in space, as truly `space-originated' babies. A further 30 fry hatched within 3 days after landing. This is the normal hatching rate, compared with the ground-based data. Among the 8 space-originated fry, four were killed for histological sections, and germ cells at the gonadal region were counted for each fry. Their numbers were in the range of the germ cells of the normal control fry (ground-kept samples). Thus, as embryos developed normally in their external appearance, inside the embryos the formation of primordial germ cells took place normally in space, and their migration to the genital ridges was not hindered by microgravity. The two of the remaining space-originated fry have grown up and been creating their offspring in the laboratory. This proved that the primordial germ cells formed in space were also normal from a functional point of view. The four space-travelled adult fish re-started mating and laying eggs on the 7th day after landing and continued to do so every day afterward. Fertilization rate and hatchability of these eggs were as high as the eggs laid by the laboratory-kept fish. This fact implies that in gametogenesis of adult fish, there are no specific stages of germ cells extremely susceptible to microgravity.

Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

PubMed Central

Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

2015-01-01

Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

Evaluation of rodent spaceflight in the NASA animal enclosure module for an extended operational period (up to 35 days).

PubMed

Moyer, Eric L; Dumars, Paula M; Sun, Gwo-Shing; Martin, Kara J; Heathcote, David G; Boyle, Richard D; Skidmore, Mike G

2016-01-01

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats.

The rodent Research Animal Holding Facility as a barrier to environmental contamination

NASA Technical Reports Server (NTRS)

Savage, P. D., Jr.; Jahns, G. C.; Dalton, B. P.; Hogan, R. P.; Wray, A. E.

1989-01-01

The rodent Research Animal Holding Facility (RAHF), developed by NASA Ames Research Center (ARC) to separately house rodents in a Spacelab, was verified as a barrier to environmental contaminants during a 12-day biocompatibility test. Environmental contaminants considered were solid particulates, microorganisms, ammonia, and typical animal odors. The 12-day test conducted in August 1988 was designed to verify that the rodent RAHF system would adequately support and maintain animal specimens during normal system operations. Additional objectives of this test were to demonstrate that: (1) the system would capture typical particulate debris produced by the animal; (2) microorganisms would be contained; and (3) the passage of animal odors was adequately controlled. In addition, the amount of carbon dioxide exhausted by the RAHF system was to be quantified. Of primary importance during the test was the demonstration that the RAHF would contain particles greater than 150 micrometers. This was verified after analyzing collection plates placed under exhaust air ducts and and rodent cages during cage maintenance operations, e.g., waste tray and feeder changeouts. Microbiological testing identified no additional organisms in the test environment that could be traced to the RAHF. Odor containment was demonstrated to be less than barely detectable. Ammonia could not be detected in the exhaust air from the RAHF system. Carbon dioxide levels were verified to be less than 0.35 percent.

The rodent research animal holding facility as a barrier to environmental contamination

NASA Technical Reports Server (NTRS)

Savage, P. D., Jr.; Jahns, G. C.; Dalton, B. P.; Hogan, R. P.; Wray, A. E.

1989-01-01

The rodent Research Animal Holding Facility (RAHF), developed by NASA Ames Research Center (ARC) to separately house rodents in a Spacelab, was verified as a barrier to environmental contaminants during a 12-day biocompatibility test. Environmental contaminants considered were solid particulates, microorganisms, ammonia, and typical animal odors. The 12-day test conducted in August 1988 was designed to verify that the rodent RAHF system would adequately support and maintain animal specimens during normal system operations. Additional objectives of this test were to demonstrate that: (1) the system would capture typical particulate debris produced by the animal; (2) microorganisms would be contained; and (3) the passage of animal odors was adequately controlled. In addition, the amount of carbon dioxide exhausted by the RAHF system was to be quantified. Of primary importance during the test was the demonstration that the RAHF would contain particles greater than 150 micrometers. This was verified after analyzing collection plates placed under exhaust air ducts and rodent cages during cage maintenance operations, e.g., waste tray and feeder changeouts. Microbiological testing identified no additional organisms in the test environment that could be traced to the RAHF. Odor containment was demonstrated to be less than barely detectable. Ammonia could not be detected in the exhaust air from the RAHF system. Carbon dioxide levels were verified to be less than 0.35 percent.

Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

PubMed

Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

2012-01-01

Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

Novel In Vivo Model for Combinatorial Fluorescence Labeling in Mouse Prostate

PubMed Central

Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J. Mark; Balaji, K.C.

2015-01-01

BACKGROUND The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. METHODS We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-RasG12D knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. RESULTS In vivo XFP signals were observed in prostate of PKD1 knock-out, K-RasG12D knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. CONCLUSIONS The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. PMID:25753731

Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.

PubMed

Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J Mark; Balaji, K C

2015-06-15

The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. In vivo XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. © 2015 Wiley Periodicals, Inc.

H2S induces a suspended animation-like state in mice.

PubMed

Blackstone, Eric; Morrison, Mike; Roth, Mark B

2005-04-22

Mammals normally maintain their core body temperature (CBT) despite changes in environmental temperature. Exceptions to this norm include suspended animation-like states such as hibernation, torpor, and estivation. These states are all characterized by marked decreases in metabolic rate, followed by a loss of homeothermic control in which the animal's CBT approaches that of the environment. We report that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species, the house mouse (Mus musculus). This state is readily reversible and does not appear to harm the animal. This suggests the possibility of inducing suspended animation-like states for medical applications.

Fungus Infections: Tinea

MedlinePlus

... JAOCD Information for Authors Information for Reviewers Human & Animal Rights Job Postings Sections of the JAOCD JAOCD Archive ... up with appropriate creams. If due to an animal, even if it has no signs of a ... moth-eaten but with the right treatment the hair will grow back normally and ...

Early Development of Gravity-Sensing Organs in Microgravity

NASA Technical Reports Server (NTRS)

Wiederhold, Michael L.; Gao, Wenyuan; Harrison, Jeffrey L.; Parker, Kevin A.

2003-01-01

Most animals have organs that sense gravity. These organs use dense stones (called otoliths or statoconia), which rest on the sensitive hairs of specialized gravity- and motion-sensing cells. The weight of the stones bends the hairs in the direction of gravitational pull. The cells in turn send a coded representation of the gravity or motion stimulus to the central nervous system. Previous experiments, in which the eggs or larvae of a marine mollusk (Aplysia californica, the sea hare) were raised on a centrifuge, demonstrated that the size of the stones (or test mass) was reduced in a graded manner as the gravity field was increased. This suggests that some control mechanism was acting to normalize the weight of the stones. The experiments described here were designed to test the hypothesis that, during their initial development, the mass of the stones is regulated to achieve a desired weight. If this is the case, we would expect a larger-than-normal otolith would develop in animals reared in the weightlessness of space. To test this, freshwater snails and swordtail fish were studied after spaceflight. The snails mated in space, and the stones (statoconia) in their statocysts developed in microgravity. Pre-mated adult female swordtail fish were flown on the Space Shuttle, and the developing larvae were collected after landing. Juvenile fish, where the larval development had taken place on the ground, were also flown. In snails that developed in space, the total volume of statoconia forming the test mass was 50% greater than in size-matched snails reared in functionally identical equipment on the ground. In the swordtail fish, the size of otoliths was compared between ground- and flight-reared larvae of the same size. For later-stage larvae, the growth of the otolith was significantly greater in the flight-reared fish. However, juvenile fish showed no significant difference in otolith size between flight- and ground-reared fish. Thus, it appears that fish and snails reared in space do produce larger-than-normal otoliths (or their analogs), apparently in an attempt to compensate for the reduced weight of the stones in space. The fish data suggest that there is a critical period during which altered gravity can affect the size of the test mass, since the larval, but not the juvenile, fish showed the changes.

Variation in external representations as part of the classroom lecture:An investigation of virtual cell animations in introductory photosynthesis instruction.

PubMed

Goff, Eric E; Reindl, Katie M; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G; Schroeder, Noah L; White, Alan R

2017-05-01

The use of external representations (ERs) to introduce concepts in undergraduate biology has become increasingly common. Two of the most prevalent are static images and dynamic animations. While previous studies comparing static images and dynamic animations have resulted in somewhat conflicting findings in regards to learning outcomes, the benefits of each have been shown individually. Using ERs developed by the Virtual Cell Animation project, we aim to further investigate student learning using different ERs as part of an introductory biology lecture. We focus our study on the topic of photosynthesis as reports have noted that students struggle with a number of basic photosynthesis concepts. Students (n = 167) in ten sections of introductory biology laboratory were introduced to photosynthesis concepts by instructional lectures differing only in the format of the embedded ERs. Normalized gain scores were calculated, showing that students who learned with dynamic animations outperformed students who learned from static images on the posttest. The results of this study provide possible instructional guidelines for those delivering photosynthesis instruction in the introductory biology classroom. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):226-234, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research.

PubMed

Anker, Justin J; Carroll, Marilyn E

2010-11-01

This review summarizes findings from human and animal research investigating the influence of progesterone and its metabolites allopreganolone and pregnanolone (progestins) on the effects of cocaine and other drugs of abuse. Since a majority of these studies have used cocaine, this will be the primary focus; however, the influence of progestins on other drugs of abuse will also be discussed. Collectively, findings from these studies support a role for progestins in (1) attenuating the subjective and physiological effects of cocaine in humans, (2) blocking the reinforcing and other behavioral effects of cocaine in animal models of drug abuse, and (3) influencing behavioral responses to other drugs of abuse such as alcohol and nicotine in animals. Administration of several drugs of abuse in both human and nonhuman animals significantly increased progestin levels, and this is explained in terms of progestins acting as homeostatic regulators that decrease and normalize heightened stress and reward responses which lead to increased drug craving and relapse. The findings discussed here highlight the complexity of progestin-drug interactions, and they suggest a possible use for these agents in understanding the etiology of and developing treatments for drug abuse. Copyright © 2010 Elsevier Ltd. All rights reserved.

Biological Function of Plasma Kallikrein in Mammary Gland Stromal Development and Tumor Metastasis

DTIC Science & Technology

2008-03-01

mammary gland as well as to identify targets of PKal activity during involution. Furthermore, mast cells are required for normal mammary duct branching...litters were generated, and no live homozygous mutant animals were identified . Wild-type and heterozygous mice appeared in nearly all litters, and of...to identify homozygous mutants in utero. F2 litters from heterozygous crosses were analyzed at embryonic day (E) 12, 10.5, 9.5, 8, and 7.5. At E12

Preliminary Study of the Effects of Prolonged Acceleration on Spinal Dynamics of Baboons. 1. Acceleration. 2. Biomechanical Analysis

DTIC Science & Technology

1981-06-01

two systems to reduce distraction between the animals, The assigned (numbered) ECG leads were connected via long cables to the proper amplifier...midsection of the intervertebral disks, the articular capsules were sectioned, and the vertebral budies were cut away at the baa. of the pediclei using...on Normal and Avulsed Developing Avian Radii," .4viai- Space Environ, Med., 47?- 8214825. Negulesco, J. A. and T. Kossler, 1978, "Response of Articular

Zoo agent's measure in applying the five freedoms principles for animal welfare.

PubMed

Demartoto, Argyo; Soemanto, Robertus Bellarminus; Zunariyah, Siti

2017-09-01

Animal welfare should be prioritized not only for the animal's life sustainability but also for supporting the sustainability of living organism's life on the earth. However, Indonesian people have not understood it yet, thereby still treating animals arbitrarily and not appreciating either domesticated or wild animals. This research aimed to analyze the zoo agent's action in applying the five freedoms principle for animal welfare in Taman Satwa Taru Jurug (thereafter called TSTJ) or Surakarta Zoo and Gembira Loka Zoo (GLZ) of Yogyakarta Indonesia using Giddens structuration theory. The informants in this comparative study with explorative were organizers, visitors, and stakeholders of zoos selected using purposive sampling technique. The informants consisted of 19 persons: 8 from TSTJ (Code T) and 10 from GLZ (Code G) and representatives from Natural Resource Conservation Center of Central Java (Code B). Data were collected through observation, in-depth interview, and Focus Group Discussion and Documentation. Data were analyzed using an interactive model of analysis consisting of three components: Data reduction, data display, and conclusion drawing. Data validation was carried out using method and data source triangulations. Food, nutrition, and nutrition level have been given consistent with the animals' habit and natural behavior. Animal keepers always maintain their self-cleanliness. GLZ has provided cages according to the technical instruction of constructing ideal cages, but the cages in TSTJ are worrying as they are not consistent with standard, rusty, and damaged, and animals have no partner. Some animals in GLZ are often sick, whereas some animals in TSTJ are dead due to poor maintenance. The iron pillars of cages restrict animal behavior in TSTJ so that they have not had freedom to behave normally yet, whereas, in GLZ, they can move freely in original habitat. The animals in the two zoos have not been free from disruption, stress, and pressure due to the passing over vehicles. There should be strategic communication, information, and education, community development, and law enforcement for the animal welfare.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

PubMed

Poirier, Guillaume L; Huang, Wei; Tam, Kelly; DiFranza, Joseph R; King, Jean A

2017-09-01

Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

PubMed

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

PubMed Central

Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

2014-01-01

Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

Endocrine Profiles, Haematology and Pregnancy Outcomes of Late Pregnant Holstein Dairy Heifers Sired by Bulls Giving a High or Low Incidence of Stillbirth

PubMed Central

Kornmatitsuk, B; Dahl, E; Ropstad, E; Beckers, JF; Gustafsson, H; Kindahl, H

2004-01-01

The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth. Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with 3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology, placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2 followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition (<1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4 and PAGs were slightly lower during 30–50 days prior to delivery and increased with a lower magnitude at the time of parturition. In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins (PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in animals with a high risk of stillbirth at term. PMID:15535086

Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus

PubMed Central

di Pietro, Massimiliano; Lao-Sirieix, Pierre; Boyle, Shelagh; Cassidy, Andy; Castillo, Dani; Saadi, Amel; Eskeland, Ragnhild; Fitzgerald, Rebecca C.

2012-01-01

Barrett esophagus (BE) is a human metaplastic condition that is the only known precursor to esophageal adenocarcinoma. BE is characterized by a posterior intestinal-like phenotype in an anterior organ and therefore it is reminiscent of homeotic transformations, which can occur in transgenic animal models during embryonic development as a consequence of mutations in HOX genes. In humans, acquired deregulation of HOX genes during adulthood has been linked to carcinogenesis; however, little is known about their role in the pathogenesis of premalignant conditions. We hypothesized that HOX genes may be implicated in the development of BE. We demonstrated that three midcluster HOXB genes (HOXB5, HOXB6, and HOXB7) are overexpressed in BE, compared with the anatomically adjacent normal esophagus and gastric cardia. The midcluster HOXB gene signature in BE is identical to that seen in normal colonic epithelium. Ectopic expression of these three genes in normal squamous esophageal cells in vitro induces markers of intestinal differentiation, such as KRT20, MUC2, and VILLIN. In BE-associated adenocarcinoma, the activation midcluster HOXB gene is associated with loss of H3K27me3 and gain of AcH3, compared with normal esophagus. These changes in histone posttranslational modifications correlate with specific chromatin decompaction at the HOXB locus. We suggest that epigenetically regulated alterations of HOX gene expression can trigger changes in the transcriptional program of adult esophageal cells, with implications for the early stages of carcinogenesis. PMID:22603795

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

PubMed

Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

Hemispheric Language Dominance of Language-Disordered, Articulation-Disordered, and Normal Children.

ERIC Educational Resources Information Center

Pettit, John M.; Helms, Suzanne B.

1979-01-01

The hemispheric dominance for language of three groups of six- to nine- year-olds (ten language-disordered, ten articulation-disordered, and ten normal children) was compared, and two dichotic listening tests (digits and animal names) were administered. (Author/CL)

Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex

NASA Technical Reports Server (NTRS)

DeFelipe, J.; Arellano, J. I.; Merchan-Perez, A.; Gonzalez-Albo, M. C.; Walton, K.; Llinas, R.

2002-01-01

The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.

Preclinical evaluation of implantable cardioverter-defibrillator developed for magnetic resonance imaging use.

PubMed

Gold, Michael R; Kanal, Emanuel; Schwitter, Juerg; Sommer, Torsten; Yoon, Hyun; Ellingson, Michael; Landborg, Lynn; Bratten, Tara

2015-03-01

Many patients with an implantable cardioverter-defibrillator (ICD) have indications for magnetic resonance imaging (MRI). However, MRI is generally contraindicated in ICD patients because of potential risks from hazardous interactions between the MRI and ICD system. The purpose of this study was to use preclinical computer modeling, animal studies, and bench and scanner testing to demonstrate the safety of an ICD system developed for 1.5-T whole-body MRI. MRI hazards were assessed and mitigated using multiple approaches: design decisions to increase safety and reliability, modeling and simulation to quantify clinical MRI exposure levels, animal studies to quantify the physiologic effects of MRI exposure, and bench testing to evaluate safety margin. Modeling estimated the incidence of a chronic change in pacing capture threshold >0.5 V and 1.0 V to be less than 1 in 160,000 and less than 1 in 1,000,000 cases, respectively. Modeling also estimated the incidence of unintended cardiac stimulation to occur in less than 1 in 1,000,000 cases. Animal studies demonstrated no delay in ventricular fibrillation detection and no reduction in ventricular fibrillation amplitude at clinical MRI exposure levels, even with multiple exposures. Bench and scanner testing demonstrated performance and safety against all other MRI-induced hazards. A preclinical strategy that includes comprehensive computer modeling, animal studies, and bench and scanner testing predicts that an ICD system developed for the magnetic resonance environment is safe and poses very low risks when exposed to 1.5-T normal operating mode whole-body MRI. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Effects of indomethacin on plasma homovanillic acid concentration in normal subjects: a study of prostaglandin-dopamine interactions.

PubMed

Kahn, R S; Davidson, M; Kanof, P; McQueeney, R T; Singh, R R; Davis, K L

1991-01-01

In laboratory animals, prostaglandins have been shown to act as endogenous neuromodulators of central dopamine (DA) activity. To examine the interaction between prostaglandins and DA in man, the effect of a prostaglandin synthesis inhibitor, indomethacin, was studied on plasma concentrations of the DA metabolite, homovanillic acid (pHVA). Indomethacin (150 mg PO) as compared to placebo significantly elevated mean pHVA concentrations in eight normal subjects. Results of this study support the hypothesis that, as in animals, inhibition of prostaglandin synthesis increases central DA turnover in man.

Cancer vaccine development: Designing tumor cells for greater immunogenicity

PubMed Central

Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy

2014-01-01

Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822

Tumor-homing peptides as tools for targeted delivery of payloads to the placenta

PubMed Central

King, Anna; Ndifon, Cornelia; Lui, Sylvia; Widdows, Kate; Kotamraju, Venkata R.; Agemy, Lilach; Teesalu, Tambet; Glazier, Jocelyn D.; Cellesi, Francesco; Tirelli, Nicola; Aplin, John D.; Ruoslahti, Erkki; Harris, Lynda K.

2016-01-01

The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics. PMID:27386551

Physiological and toxicological aspects of smoke produced during the combustion of polymeric materials.

PubMed Central

Einhorn, I N

1975-01-01

Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. PMID:170077

Epileptogenesis and companion animals.

PubMed

Patterson, Edward Ned E

2013-05-01

Epileptogenesis is the process by which a normal brain develops into an epileptic brain. There are 3 distinct phases of epileptogenesis-the latent period before seizures occur, the occurrence of recurrent seizures, and in about 30% of patients, the development of refractory epilepsy. Understanding the basic epileptic circuit abnormalities associated with recurrent seizures via aberrations in glutamate, gamma-aminobutyric acid, and ligand- and voltage-gated ion channel activity can help the small-animal practitioner understand the mechanism of action of the antiepileptic drugs currently used for dogs and cats for new-onset and refractory epilepsy. Understanding the latest research results and theories about the pathophysiology of the latent period of epileptogenesis, where recurrent seizures have not yet developed, would help the practitioner understand possible target areas for future treatments to treat epilepsy by preventing it rather than just symptomatically preventing recurrent seizures. The current areas of focus of research on the latent period include neurodegeneration, neurogenesis, axonal sprouting, glial cell activation, invasion of inflammatory cells, angiogenesis, and subclinical alteration of ligand- and receptor-gated ion channels. © 2013 Elsevier Inc. All rights reserved.

The controlled-environment chamber: a new mouse model of dry eye.

PubMed

Barabino, Stefano; Shen, Linling; Chen, Lu; Rashid, Saadia; Rolando, Maurizio; Dana, M Reza

2005-08-01

To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.

[Features of the biochemical action of paraquat on oxidative deamination of biogenic amines and other nitrogen compounds].

PubMed

Amanov, K; Mamadiev, M; Khuzhamberdiev, M A; Gorkin, V Z

1994-01-01

Intoxication of rats with the herbicide paraquat (1,1-dimethyl-4,4-bipyridilium dichloride) was accompanied by accumulation in lungs, brain, heart, liver or kidney of malonic dialdehyde (MDA) (the compounds reacting with 2-thiobarbituric acid), indicating that the intoxication stimulated lipid peroxidation (LPO) in biomembranes. Treatment of the intoxicated rats with the antioxidant diludin (2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine) or with the nucleophilic reagents sodium ascorbate or thiosulphate normalized the content of MDA in lungs, brain, heart, liver or kidney demonstrating the reversibility of the LPO stimulation caused by paraquat. On incubation of mitochondrial fractions of homogenates of lungs, brain, heart, liver or kidney of the intoxicated rats (as compared with the corresponding fractions from the intact animals) a decrease was noted in deamination of the substrates of monoamine oxidases serotonin, tryptamine, benzylamine, tyramine; at the same time, deamination of glucosamine and gamma-aminobutyric acid was increased and deamination of putrescine and L-lysine appeared. These impairments in deamination of nitrogenous compounds caused by paraquat were reversible. All the impairments were normalized by the treatment of the experimental animals with the antioxidative and nucleophilic reagents; a decrease was noted in the rate of development of the lethal paraquat intoxication and appearance of morphological manifestations of normalization. The data obtained suggest that the reversible, qualitative modification ("transformation") of the monoamine oxidases of the type A might explain the peculiarities of the alterations in deamination of nitrogenous compounds in paraquat intoxication.

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

PubMed

Witsch, Thilo J; Turowski, Pawel; Sakkas, Elpidoforos; Niess, Gero; Becker, Simone; Herold, Susanne; Mayer, Konstantin; Vadász, István; Roberts, Jesse D; Seeger, Werner; Morty, Rory E

2014-02-01

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD.

Probing the Electrophysiology of the Developing Heart

PubMed Central

Watanabe, Michiko; Rollins, Andrew M.; Polo-Parada, Luis; Ma, Pei; Gu, Shi; Jenkins, Michael W.

2016-01-01

Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes. PMID:29367561

Serotonergic hallucinogens as translational models relevant to schizophrenia.

PubMed

Halberstadt, Adam L; Geyer, Mark A

2013-11-01

One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT(2A) receptor. These compounds produce a 'model psychosis' in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioural effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects and their translational relevance. Despite the difficulty of modelling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents.

Serotonergic Hallucinogens as Translational Models Relevant to Schizophrenia

PubMed Central

Halberstadt, Adam L.; Geyer, Mark A.

2014-01-01

One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT2A receptor. These compounds produce a “model psychosis” in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioral effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects, and their translational relevance. Despite the difficulty of modeling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents. PMID:23942028

SUBCLINICAL INFECTION OF DOGS BY CANINE-ADAPTED MEASLES VIRUS EVIDENCED BY THEIR SUBSEQUENT IMMUNITY TO CANINE DISTEMPER VIRUS

PubMed Central

Moura, Roberto A.; Warren, Joel

1961-01-01

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702–705. 1961.—Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time. PMID:14476677

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

Animal-assisted interventions in internal and rehabilitation medicine: a review of the recent literature.

PubMed

Muñoz Lasa, S; Ferriero, G; Brigatti, E; Valero, R; Franchignoni, F

2011-06-01

While conventional wisdom has always affirmed the value of animals in promoting human well-being, only recently has their therapeutic role in medicine become the focus of dedicated research. Therapeutic modalities that use animals as a tool for improving the physical, emotional, cognitive and/or social functioning of humans are called animal-assisted interventions (AAI), and are classified into: animal-assisted activities (AAA); animal-assisted therapy (AAT); and service animal programs (SAP). The aim of this review is to analyze the papers published between 2001 and 2010 in the most influential medical journals dealing with AAI, and discuss their findings in the light of what may be of interest for internal medicine and rehabilitation. A total of 35 articles met the strict inclusion criteria for this review: 18 papers dealing with AAA, 8 with AAT, and 9 with SAP. The therapeutic outcomes associated with AAA are: enhancement of socialization; reduction of stress, anxiety and loneliness; improvement in mood and general well-being; and development of leisure/recreation skills. Regarding AAT, horses are often used as a complementary strategy to facilitate the normalization of muscle tone and improve motor skills in children with cerebral palsy and persons with lower limb spasticity. Finally, most SAP utilize dogs, that assist people with various disabilities in performing everyday activities, thus reducing their dependence on other persons. Further studies are needed to better define the fields and programs for the therapeutic use of animals and to increase their utilization in medicine, as a promising, complementary and natural means to improve both functional autonomy and quality of life.

Effects of short-term weightlessness on inner ear carbonic anhydrase reactivity in fish - a parabolic aircraft flight study

NASA Astrophysics Data System (ADS)

Anken, Ralf; Hilbig, Reinhard; Weigele, Jochen; Anken, Ralf

We have shown earlier that some fish of a given batch reveal motion sickness (a kinetosis) at the transition from increased gravity (hypergravity, hg; centrifuge) to 1g earth gravity. Total macular carbonic anhydrase (CA)-reactivity as well as the difference in reactivities between left and right maculae (asymmetry) were significantly lower in normally swimming hg-animals as compared to the kinetotically behaving hg-fish. This result clearly indicated the existence of a regulatory mechanism, which adjusts otolithic calcium carbonate incorporation via CA- reactivity towards the gravity vector. Thus, we were prompted to investigate, whether fish swimming kinetotically under weightlessness also would reveal an asymmetric CA-reactivity. Therefore, larval cichlid fish (Oreochromis mossambicus) were subjected to parabolic aircraft flights. During the flights, the animals were videorecorded. Subsequently, fish were separated according to their respective swimming behaviour into normally and abnormally (kinetotic) moving individuals (the latter performed spinning movements, i.e., turns around their longitudinal axis). Finally, CA was localized histochemically and densitometrically determined in inner ear maculae. It was found that the total macular CA-reactivity did not differ between ground controls and kinetotically or normally swimming experimental fish. Asymmetry of CA- reactivity, however, was considerably higher in experimental animals as compared to the ground controls. No difference in asymmetry of CA-reactivity was obtained when comparing kinetotic with normally behaving individuals. These results indicate that parabolic flights do not affect CA-reactivity in general, possibly due to the relatively quickly alternating G-levels (g-profile of single parabola: 1g/1.8g/0.04g/1.8g/1g, performed in 70 seconds) in up to 30 parabolas per flight day. The high asymmetry of CA-reactivity in the experimental animals - irrespective of their behaviour - probably indicates an adaptation process, which has presumably been successful in the normally swimming samples. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 0527).

Reduction of intimal hyperplasia and enhanced reactivity of experimental vein bypass grafts with verapamil treatment.

PubMed Central

el-Sanadiki, M N; Cross, K S; Murray, J J; Schuman, R W; Mikat, E; McCann, R L; Hagen, P O

1990-01-01

Recent studies have shown that calcium antagonists exert an antiatherogenic effect in animals fed cholesterol. Vein graft intimal hyperplasia is believed to be an early event in atherosclerotic lesion formation, which is a significant cause of graft failure. Altered vasoreactivity has also been postulated in the etiology of vein graft failure. Therefore this study examined the effect of verapamil treatment on the development of intimal hyperplasia and the vasoreactivity of experimental vein bypass grafts. The right external jugular vein was grafted into the right carotid artery of 30 male New Zealand white rabbits fed normal rabbit chow. The left external jugular vein was used as the control vein. Fifteen animals received verapamil (1.25 mg/day for 28 days) via the femoral vein by means of an osmotic pump. In 15 control animals the pump contained saline. Plasma verapamil concentration was 50.9 +/- 13.2 ng/mL (x +/- SEM), a dose that showed no effect on either blood pressure, total serum cholesterol, or in vitro platelet aggregation to ADP. Fourteen of fifteen grafts were patent in each group, for a patency rate of 93%. Histologic examination using computer morphometry showed significant reduction of intimal hyperplasia at the proximal, middle, and distal graft segments (p less than 0.05). In addition in vitro isometric tension studies of the vein grafts and control veins showed that verapamil causes enhanced reactivity of both vein grafts and control veins in response to norepinephrine and histamine (p less than 0.05). Reactivity of vein grafts to serotonin was unaltered. While none of the normal veins in the control group responded to serotonin, normal veins treated with verapamil contracted readily in response to serotonin. Endothelial-dependent relaxation to acetylcholine was absent in both control and verapamil-treated vein grafts, while normal veins from both groups responded to the same extent to acetylcholine. Because we could not demonstrate any difference in platelet or endothelium function between untreated and verapamil-treated animals, we examined the direct effect of verapamil on smooth muscle. Verapamil significantly inhibited [3H]-thymidine incorporation into DNA in vascular smooth muscle cells in culture in a dose-dependent manner. Verapamil treatment significantly reduces intimal hyperplasia in experimental vein grafts and inhibits smooth muscle cell proliferation in culture. Furthermore the enhanced reactivity to norepinephrine and histamine in the verapamil-treated vessels has no detrimental effect on the patency rate at 4 weeks. Thus by inhibiting intimal hyperplasia, calcium antagonists may improve the long-term patency of vein bypass grafts. Images Figs. 1A-C. PMID:2363608

The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats.

PubMed

Benis, K A; Schneider, G B

1996-10-15

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein-macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis.

Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity.

PubMed

Liu, Yan; Li, Xuemei; Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

2016-01-01

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration.

Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity

PubMed Central

Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

2016-01-01

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE’s effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration. PMID:27054886

The Ferret as a Surgical Model for Vocal Fold Scar Creation and Treatment.

PubMed

Kodama, Haruka; Kumai, Yoshihiko; Nishimoto, Kohei; Toya, Yutaka; Miyamaru, Satoru; Furushima, Shinobu; Yumoto, Eiji

2018-03-01

To develop a vocal fold (VF) scarring procedure in the ferret, characterize the scars histologically, and test the injectability of the lamina propria (LP). Secondarily, to compare laryngeal anatomy of the ferret with rat and rabbit. The larynges of 18 male ferrets were prepared by unilateral scarring, and normal larynges from 6 female Wistar rats and 5 male albino rabbits were used for comparative purposes. For scarring, the right VF were electrocauterized, ablating the entire LP. Prior to harvesting the larynges at 4 and 16 weeks, each ferret was re-anesthetized, and in 3 animals, India ink was injected into the LPs of both normal and scarred VFs. Laryngoscopic methods and instrumentation for precise visualization, scarring, and injection were developed. The scarred VFs had reduced hyaluronic acid and increased collagen type I, III, and fibronectin compared with normal VFs. The 2 timepoints (4 and 16 weeks) differed significantly only in collagen type III level (levels were higher at 4 weeks). Injected ink migrated from scarred LP to muscle layer just beneath the scarred tissue 3 hours after injection. The ferret is a promising species for creation and experimental treatment of vocal fold scar.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon. PMID:21734804

Feeding and reward: Perspectives from Three Rat Models of Binge Eating

PubMed Central

Cowin, Rebecca L; Avena, Nicole M.; Boggiano, Mary M.

2011-01-01

Research has focused on understanding how overeating can affect brain reward mechanisms and subsequent behaviors, both preclinically and in clinical research settings. This work is partly driven by the need to uncover the etiology and possible treatments for the ongoing obesity epidemic. However, overeating, or non-homeostatic feeding behavior, can occur independent of obesity. Isolating the variable of overeating from the consequence of increased body weight is of great utility, as it is well known that increased body weight or obesity can impart its own deleterious effects on physiology, neural processes, and behavior. In this review, we present data from three selected animal models of normal-weight non-homeostatic feeding behavior that have been significantly influenced by Bart Hoebel’s 40+-yr career studying motivation, feeding, reinforcement, and the neural mechanisms that participate in the regulation of these processes. First, a model of sugar bingeing is described (Avena/Hoebel), in which animals with repeated, intermittent access to a sugar solution develop behaviors and brain changes that are similar to the effects of some drugs of abuse, serving as the first animal model of food addiction. Second, another model is described (Boggiano) in which a history of dieting and stress can perpetuate further binge eating of palatable and non-palatable food. In addition, a model (Boggiano) is described that allows animals to be classified as having a binge-prone vs. binge-resistant phenotype. Lastly, a limited access model is described (Corwin) in which non-food deprived rats with sporadic limited access to a high-fat food develop binge-type behaviors. These models are considered within the context of their effects on brain reward systems, including dopamine, the opioids, cholinergic systems, serotonin, and GABA. Collectively, the data derived from the use of these models clearly show that behavioral and neuronal consequences of bingeing on a palatable food, even when at a normal body weight, are different from those that result from simply consuming the palatable food in a non-binge manner. These findings may be important in understanding how overeating can influence behavior and brain chemistry. PMID:21549136

Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

PubMed Central

Van Den Berg, Pleuntje; Radl, J.; Löwenberg, B.; Swart, A. C. W.

1976-01-01

Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP–Rhesus albumin and IgA1λ-10S human paraprotein. One or more transient homogeneous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP–Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. ImagesFig. 1

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Reprogramming of Sheep Fibroblasts into Pluripotency under a Drug-Inducible Expression of Mouse-Derived Defined Factors

PubMed Central

Li, Yang; Cang, Ming; Lee, Andrew Stephen; Zhang, Kehua; Liu, Dongjun

2011-01-01

Animal embryonic stem cells (ESCs) provide powerful tool for studies of early embryonic development, gene targeting, cloning, and regenerative medicine. However, the majority of attempts to establish ESC lines from large animals, especially ungulate mammals have failed. Recently, another type of pluripotent stem cells, known as induced pluripotent stem cells (iPSCs), have been successfully generated from mouse, human, monkey, rat and pig. In this study we show sheep fibroblasts can be reprogrammed to pluripotency by defined factors using a drug-inducible system. Sheep iPSCs derived in this fashion have a normal karyotype, exhibit morphological features similar to those of human ESCs and express AP, Oct4, Sox2, Nanog and the cell surface marker SSEA-4. Pluripotency of these cells was further confirmed by embryoid body (EB) and teratoma formation assays which generated derivatives of all three germ layers. Our results also show that the substitution of knockout serum replacement (KSR) with fetal bovine serum in culture improves the reprogramming efficiency of sheep iPSCs. Generation of sheep iPSCs places sheep on the front lines of large animal preclinical trials and experiments involving modification of animal genomes. PMID:21253598

Placentophagy: therapeutic miracle or myth?

PubMed

Coyle, Cynthia W; Hulse, Kathryn E; Wisner, Katherine L; Driscoll, Kara E; Clark, Crystal T

2015-10-01

Postpartum women are consuming their placentas encapsulated, cooked, and raw for the prevention of postpartum depression (PPD), pain relief, and other health benefits. Placentophagy is supported by health advocates who assert that the placenta retains hormones and nutrients that are beneficial to the mother. A computerized search was conducted using PubMed, Medline Ovid, and PsychINFO between January 1950 and January 2014. Keywords included placentophagy, placentophagia, maternal placentophagia, maternal placentophagy, human placentophagia, and human placentophagy. A total of 49 articles were identified. Empirical studies of human or animal consumption of human placentas were included. Editorial commentaries were excluded. Animal placentophagy studies were chosen based on their relevance to human practice. Ten articles (four human, six animal) were selected for inclusion. A minority of women in developed countries perceive placentophagy to reduce PPD risk and enhance recovery. Experimental animal research in support of pain reduction has not been applied in humans. Studies investigating placenta consumption for facilitating uterine contraction, resumption of normal cyclic estrogen cycle, and milk production are inconclusive. The health benefits and risks of placentophagy require further investigation of the retained contents of raw, cooked, and encapsulated placenta and its effects on the postpartum woman.

Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury

PubMed Central

Werneck, Claudio C.; Vicente, Cristina P.; Weinberg, Justin S.; Shifren, Adrian; Pierce, Richard A.; Broekelmann, Thomas J.; Tollefsen, Douglas M.

2008-01-01

Mice lacking the extracellular matrix protein microfibril-associated glycoprotein-1 (MAGP1) display delayed thrombotic occlusion of the carotid artery following injury as well as prolonged bleeding from a tail vein incision. Normal occlusion times were restored when recombinant MAGP1 was infused into deficient animals prior to vessel wounding. Blood coagulation was normal in these animals as assessed by activated partial thromboplastin time and prothrombin time. Platelet number was lower in MAGP1-deficient mice, but the platelets showed normal aggregation properties in response to various agonists. MAGP1 was not found in normal platelets or in the plasma of wild-type mice. In ligand blot assays, MAGP1 bound to fibronectin, fibrinogen, and von Willebrand factor, but von Willebrand factor was the only protein of the 3 that bound to MAGP1 in surface plasmon resonance studies. These findings show that MAGP1, a component of microfibrils and vascular elastic fibers, plays a role in hemostasis and thrombosis. PMID:18281502

Metabolomic phenotyping of a cloned pig model

PubMed Central

2011-01-01

Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals. PMID:21859467

Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition.

PubMed

Heo, Hye J; Tozour, Jessica N; Delahaye, Fabien; Zhao, Yongmei; Cui, Lingguang; Barzilai, Nir; Einstein, Francine Hughes

2016-10-01

Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers' nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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.

Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development

PubMed Central

Bratic, Ivana; Hench, Jürgen; Henriksson, Johan; Antebi, Adam; Bürglin, Thomas R; Trifunovic, Aleksandra

2009-01-01

A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase. PMID:19181702

Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

PubMed

Capelozzi, Marco A; Leick-Maldonado, Edna A; Parra, Edwin R; Martins, Mílton A; Tibério, Iolanda F L C; Capelozzi, Vera L

2007-05-14

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

21 CFR 520.2345b - Tetracycline tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... use. Dogs—(1) Amount. 25 milligrams per pound of body weight per day in divided doses every 6 hours... disease have subsided and temperature is normal for 48 hours; not for use in animals raised for food...

21 CFR 520.2345b - Tetracycline tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... use. Dogs—(1) Amount. 25 milligrams per pound of body weight per day in divided doses every 6 hours... disease have subsided and temperature is normal for 48 hours; not for use in animals raised for food...

21 CFR 520.2345b - Tetracycline tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... use. Dogs—(1) Amount. 25 milligrams per pound of body weight per day in divided doses every 6 hours... disease have subsided and temperature is normal for 48 hours; not for use in animals raised for food...

9 CFR 313.2 - Handling of livestock.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CERTIFICATION HUMANE SLAUGHTER OF LIVESTOCK § 313.2 Handling of livestock. (a) Driving of livestock from the... normal walking speed. (b) Electric prods, canvas slappers, or other implements employed to drive animals..., would cause injury or unnecessary pain to the animal shall not be used to drive livestock. (d) Disabled...

9 CFR 313.2 - Handling of livestock.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CERTIFICATION HUMANE SLAUGHTER OF LIVESTOCK § 313.2 Handling of livestock. (a) Driving of livestock from the... normal walking speed. (b) Electric prods, canvas slappers, or other implements employed to drive animals..., would cause injury or unnecessary pain to the animal shall not be used to drive livestock. (d) Disabled...

9 CFR 313.2 - Handling of livestock.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CERTIFICATION HUMANE SLAUGHTER OF LIVESTOCK § 313.2 Handling of livestock. (a) Driving of livestock from the... normal walking speed. (b) Electric prods, canvas slappers, or other implements employed to drive animals..., would cause injury or unnecessary pain to the animal shall not be used to drive livestock. (d) Disabled...

Exercise, Animal Aerobics, and Interpretation?

ERIC Educational Resources Information Center

Oliver, Valerie

1996-01-01

Describes an aerobic activity set to music for children that mimics animal movements. Example exercises include walking like a penguin or jumping like a cricket. Stresses basic aerobic principles and designing the program at the level of children's motor skills. Benefits include reaching people who normally don't visit nature centers, and bridging…

21 CFR 524.390b - Chloramphenicol ophthalmic solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS... susceptible to chloramphenicol. Therapy should be continued for 48 hours after the eye appears normal. (3) Limitations. Therapy for cats should not exceed 7 days. As with other antibiotics, prolonged use may result in...

Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection.

PubMed

Qiao, Hui; Zhang, Hualei; Zheng, Yuanjie; Ponde, Datta E; Shen, Dinggang; Gao, Fabao; Bakken, Ashley B; Schmitz, Alexander; Kung, Hank F; Ferrari, Victor A; Zhou, Rong

2009-03-01

To use magnetic resonance (MR) imaging and positron emission tomography (PET) dual detection of cardiac-grafted embryonic stem cells (ESCs) to examine (a) survival and proliferation of ESCs in normal and infarcted myocardium, (b) host macrophage versus grafted ESC contribution to serial MR imaging signal over time, and (c) cardiac function associated with the formation of grafts and whether improvement in cardiac function is related to cardiac differentiation of ESCs. All animal procedures were approved by the institutional animal care and use committee. Murine ESCs were stably transfected with a mutant version of herpes simplex virus type 1 thymidine kinase, HSV1-sr39tk, and also were labeled with superparamagnetic iron oxide (SPIO) particles. Cells were injected directly in the border zone of the infarcted heart or in corresponding regions of normal hearts in athymic rats. PET and MR imaging were performed longitudinally for 4 weeks in the same animals. ESCs survived and underwent proliferation in the infarcted and normal hearts, as demonstrated by serial increases in 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine PET signals. In parallel, the hypointense areas on MR images at the injection sites decreased over time. Double staining for host macrophages and SPIO particles revealed that the majority of SPIO-containing cells were macrophages at week 4 after injection. Left ventricular ejection fraction increased in the ESC-treated rats but decreased in culture media-treated rats, and border-zone function was preserved in ESC-treated animals; however, cardiac differentiation of ESCs was less than 0.5%. Dual-modality imaging permits complementary information in regard to cell survival and proliferation, graft formation, and effects on cardiac function. http://radiology.rsnajnls.org/cgi/content/full/250/3/821/DC1. RSNA, 2009

Nitric oxide synthase and soluble guanylate cyclase are involved in spinal cord wind-up activity of monoarthritic, but not of normal rats.

PubMed

Laurido, Claudio; Hernández, Alejandro; Constandil, Luis; Pelissier, Teresa

2003-11-27

While increasing evidence points to a role for the nitric oxide (NO)/cyclic guanosine 3,5-monophosphate (GMPc) cascade in hyperalgesia and allodynia, participation of the NO/GMPc pathway in synaptic processing in the spinal cord, i.e. wind-up activity, is less clear. We studied the effects of intrathecal administration of Nomega-nitro-L-arginine methyl ester (L-NAME) and methylene blue, inhibitors of NO synthase and guanylate cyclase respectively, on wind-up activity developed in a C-fiber reflex response paradigm. 5, 10 and 20 microg i.t. of L-NAME or methylene blue did not modify spinal wind-up in normal rats, while a dose-dependent inhibition of wind-up was observed in monoarthritic rats. Results suggest that the NO/GMPc pathway plays a non-significant role in wind-up activity evoked in normal animals, while it may be essential in chronic pain processing.

Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

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

Hammel, Markus; Michel, Geert; Hoefer, Christina

2007-08-10

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies inmore » type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.« less

Histologic assessment of mesh fixation following laser-assisted tissue soldering in a lapine model.

PubMed

Lanzafame, Raymond J; Brondon, Philip; Stadler, Istvan; DeVore, Dale P; Soltz, Robert; Soltz, Barbara A

2005-08-01

Wound histology and mesh bioincorporation following intraperitoneal fixation using laser-assisted soldering was evaluated. 2.8-3.2 kg NZW rabbits underwent laparotomy. Controls had 2x2 cm segments of Mersilene stapled to peritoneum. Group 2 segments were affixed with 55% collagen solder onlay by fiber-coupled diode laser (1.43 +/- 10 micro, 2.5 W CW, 4 mm spot, 60 degrees C set temperature). Group 4 had Mersilene inlaid into melted solder. Group 3 had solder-embedded Vicryl mesh affixed. Animals were euthanized at 0, 2, 4, 6 weeks. Fixed sections were assessed for integrity, inflammation, and fibrosis using H & E, Masson's Trichrome and Evans Van Gieson staining. Histology demonstrated cell types, local mesh reaction, and progressive evidence of solder reabsorption mimicking normal healing and bioincorporation. Mersilene groups demonstrated normal arrangement of collagen-rich layers around mesh. Collagen-based tissue soldering permits normal wound healing and may mitigate use of staples. Further development of this strategy is warranted. (c) 2005 Wiley-Liss, Inc.

Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer.

PubMed

Scsukova, Sona; Rollerova, Eva; Bujnakova Mlynarcikova, Alzbeta

2016-12-01

A growing body of evidence suggests that exposure to chemical substances designated as endocrine disrupting chemicals (EDCs) due to their ability to disturb endocrine (hormonal) activity in humans and animals, may contribute to problems with fertility, pregnancy, and other aspects of reproduction. The presence of EDCs has already been associated with reproductive malfunction in wildlife species, but it remains difficult to prove causal relationships between the presence of EDCs and specific reproductive problems in vivo, especially in females. On the other hand, the increasing number of experiments with laboratory animals and in vitro research indicate the ability of different EDCs to influence the normal function of female reproductive system, and even their association with cancer development or progression. Research shows that EDCs may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming. In this review article, we aim to point out a possible contribution of EDCs to the onset and development of female reproductive disorders and endocrine-related cancers with regard to the period of exposure to EDCs and affected endpoints (organs or processes). Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Suicide among animals: a review of evidence.

PubMed

Preti, Antonio

2007-12-01

Naturalists have not identified suicide in nonhuman species in field situations, despite intensive study of thousands of animal species. In this review, evidence on suicidal behavior among animals is analyzed to discover analogies with human suicidal behavior. Literature was retrieved by exploring Medline/PubMed and PsychINFO databases (1967-2007) and through manual literature searches. Keyword terms were "suicide or suicidal behavior" and "animal or animal behavior." Few empirical investigations have been carried out on this topic. Nevertheless, sparse evidence supports some resemblance between the self-endangering behavior observed in the animal kingdom, particularly in animals held in captivity or put under pressure by environmental challenges, and suicidal behavior among humans. Animal models have contributed to the study of both normal and pathological human behaviors: discovering some correlates of suicide among animals could be a valid contribution to the field.

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Baldwin, Kenneth M.

1995-01-01

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

PubMed

Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

2010-08-01

The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

Computed Tomography of the Abdomen in Eight Clinically Normal Common Marmosets (Callithrix jacchus).

PubMed

du Plessis, W M; Groenewald, H B; Elliott, D

2017-08-01

The aim of this study was to provide a detailed anatomical description of the abdomen in the clinically normal common marmoset by means of computed tomography (CT). Eight clinically healthy mature common marmosets ranging from 12 to 48 months and 235 to 365 g bodyweight were anesthetized and pre- and post-contrast CT examinations were performed using different CT settings in dorsal recumbency. Abdominal organs were identified and visibility noted. Diagnostic quality abdominal images could be obtained of the common marmoset despite its small size using a dual-slice CT scanner. Representative cross-sectional images were chosen from different animals illustrating the abdominal CT anatomy of clinically normal common marmosets. Identification or delineation of abdominal organs greatly improved with i.v. contrast. A modified high-frequency algorithm with edge enhancement added valuable information for identification of small structures such as the ureters. The Hounsfield unit (HU) of major abdominal organs differed from that of small animals (domestic dogs and cats). Due to their size and different anatomy, standard small animal CT protocols need to be critically assessed and adapted for exotics, such as the common marmoset. The established normal reference range of HU of major abdominal organs and adapted settings for a CT protocol will aid clinical assessment of the common marmoset. © 2017 Blackwell Verlag GmbH.

Sex determination strategies in 2012: towards a common regulatory model?

PubMed Central

2012-01-01

Sex determination is a complicated process involving large-scale modifications in gene expression affecting virtually every tissue in the body. Although the evolutionary origin of sex remains controversial, there is little doubt that it has developed as a process of optimizing metabolic control, as well as developmental and reproductive functions within a given setting of limited resources and environmental pressure. Evidence from various model organisms supports the view that sex determination may occur as a result of direct environmental induction or genetic regulation. The first process has been well documented in reptiles and fish, while the second is the classic case for avian species and mammals. Both of the latter have developed a variety of sex-specific/sex-related genes, which ultimately form a complete chromosome pair (sex chromosomes/gonosomes). Interestingly, combinations of environmental and genetic mechanisms have been described among different classes of animals, thus rendering the possibility of a unidirectional continuous evolutionary process from the one type of mechanism to the other unlikely. On the other hand, common elements appear throughout the animal kingdom, with regard to a) conserved key genes and b) a central role of sex steroid control as a prerequisite for ultimately normal sex differentiation. Studies in invertebrates also indicate a role of epigenetic chromatin modification, particularly with regard to alternative splicing options. This review summarizes current evidence from research in this hot field and signifies the need for further study of both normal hormonal regulators of sexual phenotype and patterns of environmental disruption. PMID:22357269

Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens.

PubMed

Bartmann, M; Schaeffel, F; Hagel, G; Zrenner, E

1994-01-01

Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.

32 CFR 651.33 - Actions normally requiring an EA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

32 CFR 651.33 - Actions normally requiring an EA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

32 CFR 651.33 - Actions normally requiring an EA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

Follicular helper T cells in immunity and systemic autoimmunity.

PubMed

Craft, Joseph E

2012-05-01

Follicular helper T (T(FH)) cells are essential for B-cell maturation and immunoglobulin production after immunization with thymus-dependent antigens. Nevertheless, the development and function of T(FH) cells have been less clearly defined than classic CD4(+) effector T-cell subsets, including T-helper-1 (T(H)1), T(H)2 and T(H)17 cells. As such, our understanding of the genesis of T(FH) cells in humans and their role in the development of autoimmunity remains incomplete. However, evidence from animal models of systemic lupus erythematosus (SLE) and patients with systemic autoimmune diseases suggests that these cells are necessary for pathogenic autoantibody production, in a manner analogous to their role in promotion of B-cell maturation during normal immune responses. In this Review, I discuss the findings that have increased our knowledge of T(FH)-cell development and function in normal and aberrant immune responses. Such information might improve our understanding of autoimmune diseases, such as SLE, and highlights the potential of T(FH) cells as therapeutic targets in these diseases.

Sustained Perceptual Deficits from Transient Sensory Deprivation

PubMed Central

Sanes, Dan H.

2015-01-01

Sensory pathways display heightened plasticity during development, yet the perceptual consequences of early experience are generally assessed in adulthood. This approach does not allow one to identify transient perceptual changes that may be linked to the central plasticity observed in juvenile animals. Here, we determined whether a brief period of bilateral auditory deprivation affects sound perception in developing and adult gerbils. Animals were reared with bilateral earplugs, either from postnatal day 11 (P11) to postnatal day 23 (P23) (a manipulation previously found to disrupt gerbil cortical properties), or from P23-P35. Fifteen days after earplug removal and restoration of normal thresholds, animals were tested on their ability to detect the presence of amplitude modulation (AM), a temporal cue that supports vocal communication. Animals reared with earplugs from P11-P23 displayed elevated AM detection thresholds, compared with age-matched controls. In contrast, an identical period of earplug rearing at a later age (P23-P35) did not impair auditory perception. Although the AM thresholds of earplug-reared juveniles improved during a week of repeated testing, a subset of juveniles continued to display a perceptual deficit. Furthermore, although the perceptual deficits induced by transient earplug rearing had resolved for most animals by adulthood, a subset of adults displayed impaired performance. Control experiments indicated that earplugging did not disrupt the integrity of the auditory periphery. Together, our results suggest that P11-P23 encompasses a critical period during which sensory deprivation disrupts central mechanisms that support auditory perceptual skills. SIGNIFICANCE STATEMENT Sensory systems are particularly malleable during development. This heightened degree of plasticity is beneficial because it enables the acquisition of complex skills, such as music or language. However, this plasticity comes with a cost: nervous system development displays an increased vulnerability to the sensory environment. Here, we identify a precise developmental window during which mild hearing loss affects the maturation of an auditory perceptual cue that is known to support animal communication, including human speech. Furthermore, animals reared with transient hearing loss display deficits in perceptual learning. Our results suggest that speech and language delays associated with transient or permanent childhood hearing loss may be accounted for, in part, by deficits in central auditory processing mechanisms. PMID:26224865

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals

PubMed Central

Rich, Alisa L.; Phipps, Laura M.; Tiwari, Sweta; Rudraraju, Hemanth; Dokpesi, Philip O.

2016-01-01

An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID:27660460

Photopic visual input is necessary for emmetropization in mice

PubMed Central

Tkatchenko, Tatiana V.; Shen, Yimin; Braun, Rod D.; Bawa, Gurinder; Kumar, Pradeep; Avrutsky, Ivan; Tkatchenko, Andrei V.

2013-01-01

It was recently demonstrated that refractive errors in mice stabilize around emmetropic values during early postnatal development, and that they develop experimental myopia in response to both visual form deprivation and imposed optical defocus similar to other vertebrate species. Animal studies also suggest that photopic vision plays critical role in emmetropization in diurnal species; however, it is unknown whether refractive eye development is guided by photopic vision in the mouse, which is a nocturnal species. We used an infrared mouse photorefractor and a high-resolution MRI to clarify the role of photopic visual input in refractive eye development in the mouse. Refractive eye development and form-deprivation myopia in P21-P89 C57BL/6J mice were analyzed under 12:12 h light-dark cycle, constant light and constant darkness regimens. Animals in all experimental groups were myopic at P21 (-13.2 ± 1.6 D, light-dark cycle; -12.5 ± 0.9 D, constant light; -12.5 ± 2.0 D, constant dark). The mean refractive error in the light-dark-cycle-reared animals was -0.5 ± 1.3 D at P32 and, and did not change significantly until P40 (+0.3 ± 0.6 D, P40). Animals in this group became progressively hyperopic between P40 and P89 (+2.2 ± 0.6, P67; +3.7 ± 2.0, P89). The mean refractive error in the constant-light-reared mice was -1.0 ± 0.7 D at P32 and remained stable until P89 (+0.1 ± 0.6, P40; +0.3 ± 0.6, P67; 0.0 ± 0.4, P89). Dark-reared animals exhibited highly hyperopic refractive errors at P32 (+5.2 ± 1.8) and became progressively more hyperopic with age (+8.7 ± 1.9, P40; +11.2 ± 1.4, P67). MRI analysis revealed that emmetropization in the P40-P89 constant-light-reared animals was associated with larger eyes, a longer axial length and a larger vitreous chamber compared to the light-dark-cycle-reared mice. Constant-light-reared mice also developed 4 times higher degrees of form-deprivation myopia on average compared to light-dark-cycle-reared animals (-12.0 ± 1.4, constant light; -2.7 ± 0.7, light-dark cycle). Dark-rearing completely prevented the development of form-deprivation myopia (-0.3 ± 0.5). Thus, photopic vision plays important role in normal refractive eye development and ocular response to visual form deprivation in the mouse. PMID:23838522

Developmental effects of simulated microgravity on zebrafish, (Danio rerio)

NASA Astrophysics Data System (ADS)

Stoyek, Matthew; Edsall, Sara; Franz-Odendaal, Tamara; Smith, Frank; Croll, Roger

Zebrafish are widely used model vertebrates in research and recently this species has been used to study the effects of microgravity on fundamental biological processes. In this study we used a NASA-designed rotating wall vessel (RWV) to investigate the effects of simulated microgravity (SMG) on zebrafish development up to 14 days post fertilization (dpf). At developmental stages beyond the 3-4 somite stage we found SMG-exposed embryos reached key developmental stag-ing points more rapidly than fish raised within a non-rotating vessel. By the 21 somite stage, both groups were again synchronized in their developmental staging. However, SMG-exposed embryos eventually exhibited a delay in hatching time compared to controls. Otolith and to-tal body size were observed to be greater in larvae raised in SMG. In addition, pigmentation patterns in SMG exposed fish differed, with larger and differentially aggregated melanocytes . Heart development was slowed in SMG exposed fish, but no change in nervous system de-velopment was detected. Ongoing research will focus on differences in heart and respiration rates. Finally, by developing a method to extend the duration of SMG exposure, we found the swimming behaviour of SMG-exposed animals was altered with time in the RWV. Initially SMG-exposed animals swam in the direction of RWV rotation (5-9dpf) but older (9+dpf) fish swam against rotation and demonstrated righting behaviour with each rotation. These results suggest that vestibular reflexes may develop normally and be maintained in animals exposed to SMG. Together, our data provide insights into how zebrafish may develop when flown in space, permitting better formulation of experiments to test mechanisms by which microgravity may affect ontogeny of this model organism. Keywords: microgravity, zebrafish, growth, development

From experimental zoology to big data: Observation and integration in the study of animal development.

PubMed

Bolker, Jessica; Brauckmann, Sabine

2015-06-01

The founding of the Journal of Experimental Zoology in 1904 was inspired by a widespread turn toward experimental biology in the 19th century. The founding editors sought to promote experimental, laboratory-based approaches, particularly in developmental biology. This agenda raised key practical and epistemological questions about how and where to study development: Does the environment matter? How do we know that a cell or embryo isolated to facilitate observation reveals normal developmental processes? How can we integrate descriptive and experimental data? R.G. Harrison, the journal's first editor, grappled with these questions in justifying his use of cell culture to study neural patterning. Others confronted them in different contexts: for example, F.B. Sumner insisted on the primacy of fieldwork in his studies on adaptation, but also performed breeding experiments using wild-collected animals. The work of Harrison, Sumner, and other early contributors exemplified both the power of new techniques, and the meticulous explanation of practice and epistemology that was marshaled to promote experimental approaches. A century later, experimentation is widely viewed as the standard way to study development; yet at the same time, cutting-edge "big data" projects are essentially descriptive, closer to natural history than to the approaches championed by Harrison et al. Thus, the original questions about how and where we can best learn about development are still with us. Examining their history can inform current efforts to incorporate data from experiment and description, lab and field, and a broad range of organisms and disciplines, into an integrated understanding of animal development. © 2015 Wiley Periodicals, Inc.

Hormonal control of aging in rodents: The somatotropic axis

PubMed Central

Brown-Borg, Holly M.

2015-01-01

There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences.

PubMed

Allegrucci, M; Young-Cooper, G O; Alexander, C B; Newman, B A; Mage, R G

1991-02-01

The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.

Reference genes for real-time PCR quantification of messenger RNAs and microRNAs in mouse model of obesity.

PubMed

Matoušková, Petra; Bártíková, Hana; Boušová, Iva; Hanušová, Veronika; Szotáková, Barbora; Skálová, Lenka

2014-01-01

Obesity and metabolic syndrome is increasing health problem worldwide. Among other ways, nutritional intervention using phytochemicals is important method for treatment and prevention of this disease. Recent studies have shown that certain phytochemicals could alter the expression of specific genes and microRNAs (miRNAs) that play a fundamental role in the pathogenesis of obesity. For study of the obesity and its treatment, monosodium glutamate (MSG)-injected mice with developed central obesity, insulin resistance and liver lipid accumulation are frequently used animal models. To understand the mechanism of phytochemicals action in obese animals, the study of selected genes expression together with miRNA quantification is extremely important. For this purpose, real-time quantitative PCR is a sensitive and reproducible method, but it depends on proper normalization entirely. The aim of present study was to identify the appropriate reference genes for mRNA and miRNA quantification in MSG mice treated with green tea catechins, potential anti-obesity phytochemicals. Two sets of reference genes were tested: first set contained seven commonly used genes for normalization of messenger RNA, the second set of candidate reference genes included ten small RNAs for normalization of miRNA. The expression stability of these reference genes were tested upon treatment of mice with catechins using geNorm, NormFinder and BestKeeper algorithms. Selected normalizers for mRNA quantification were tested and validated on expression of quinone oxidoreductase, biotransformation enzyme known to be modified by catechins. The effect of selected normalizers for miRNA quantification was tested on two obesity- and diabetes- related miRNAs, miR-221 and miR-29b, respectively. Finally, the combinations of B2M/18S/HPRT1 and miR-16/sno234 were validated as optimal reference genes for mRNA and miRNA quantification in liver and 18S/RPlP0/HPRT1 and sno234/miR-186 in small intestine of MSG mice. These reference genes will be used for mRNA and miRNA normalization in further study of green tea catechins action in obese mice.

Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model.

PubMed

Ballester, Ashley; Gould, François; Bond, Laura; Stricklen, Bethany; Ohlemacher, Jocelyn; Gross, Andrew; DeLozier, Katherine; Buddington, Randall; Buddington, Karyl; Danos, Nicole; German, Rebecca

2018-02-24

The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.

Technologies For Maintaining Animals In Space: Lighting, Air Quality, Noise, Food And Water

NASA Technical Reports Server (NTRS)

Winget, C. M.; Skidmore, M. G.; Holley, D. C.; Dalton, Bonnie P. (Technical Monitor)

1995-01-01

In the terrestrial environment multiple time cues exist. Zeitgebers have been identified and studied for their ability to convey temporal information to various physiological systems. In the microgravity experiment it is necessary to define time cues within the flight hardware prior to flight. During flight if changes in the Circadian System (e.g., mean, phase angle, period) occur this would indicate that the gravity vector is important relative to biological timing. This presentation is concerned with the environmental parameter: to support rodent experiments in microgravity. The Animal Enclosure Module (AEM) provides solid food bars and water via lixits and ad libitum. Flight animals (Sprague-Dawley rats, 60 - 300g) when compared to ground controls show similar growth (mean growth per day g, plus or minus SD; flight 5.4 plus or minus 2.0, ground 5.9 plus or minus 2.1). Current AEMs use incandescent lighting (approx. 5 Lux). Light emitting diode (LED) arrays are being developed that provide a similar light environment as cool-white fluorescent sources (40 Lux). In ground based tests (12L:12D), these arrays show normal circadian entrainment (Tau = 24.0) with respect to the behavioral responses, measured (drinking, eating, gross locomotor activity). A newly developed ultra high efficiency filter system can entrap all feces, urine and odors from 6 rats for 24 days. Maximum sound level exposure limits (per octave band 22 Hz - 179 kHz) have been established. The AEM will effectively support animal experiments in microgravity.

Technologies for Maintaining Animals in Space: Lighting, Air Quality, Noise, Food and Water

NASA Technical Reports Server (NTRS)

Winget, C. M.; Skidmore, M. G.; Holley, D. C.; Dalton, Bonnie P. (Technical Monitor)

1995-01-01

In the terrestrial environment multiple time cues exist. Zeitgebers have been identified and studied for their ability to convey temporal information to various physiological systems, In the microgravity experiment it is necessary to define time cues within the flight hardware prior to flight. During flight if changes in the Circadian System (e.g., mean, phase angle, period) occur this would indicate that the gravity vector is important relative to biological timing. This presentation is concerned with the environmental parameters to support rodent experiments in microgravity. The Animal Enclosure Module (AEM) provides solid food bars and water via lixits ad libitum. Flight animals (Sprague-Dawley rats, 60 - 300g) when compared to ground controls show similar growth (mean growth per day, g +/- SD; flight 5.4 +/- 2.0, ground 5.9 +/- 2.1). Current AEMs use incandescent lighting (approx. 5 Lux). Light emitting diode (LED) arrays are being developed that provide a similar light environment as cool-white fluorescent sources (40 Lux). In ground based tests (12L:12D), these arrays show normal circadian entrainment (Tau = 24.0) with respect to the behavioral responses. measured (drinking, eating, gross locomotor activity). A newly developed ultra high efficiency filter system can entrap all feces, urine and odors from 6 rats for 24 days. Maximum sound level exposure limits (per octave band 22 Hz - 179 kHz) have been established. The AEM will effectively support animal experiments in microgravity.

Early Feasibility Testing and Engineering Development of a Sutureless Beating Heart (SBH) Connector for Left Ventricular Assist Devices (LVAD)

PubMed Central

Koenig, Steven C; Jimenez, Jorge H; West, Seth D; Sobieski, Michael A; Choi, Young; Monreal, Gretel; Giridharan, Guruprasad A; Soucy, Kevin G; Slaughter, Mark S

2014-01-01

APK Advanced Medical Technologies (Atlanta, GA) is developing a sutureless beating heart (SBH) left ventricular assist device (LVAD) connector system consisting of anchoring titanium coil, titanium cannula with integrated silicone hemostatic valve, coring and delivery tool, and LVAD locking mechanism to facilitate LVAD inflow surgical procedures. Feasibility testing was completed in human cadavers (n=4) under simulated normal and hypertensive conditions using saline to observe seal quality in degraded human tissue and assess anatomic fit; acutely in ischemic heart failure (IHF) bovine model (n=2) to investigate short-term performance and ease of use; and chronically for 30-days in healthy calves (n=2) implanted with HeartWare HVAD to evaluate performance and biocompatibility. Complete hemostasis was achieved in human cadavers and animals at LV pressures up to 170 mmHg. In animals, off pump (no cardiopulmonary bypass) anchoring of the connector was accomplished in less than 1 minute with no residual bleeding after full delivery and locking of the LVAD; and implant of connector and LVAD were successfully completed in under 10 minutes with total procedure blood loss less than 100mL. In chronic animals prior to necropsy, no signs of leakage or disruption at the attachment site were observed at systolic LV pressures >200 mmHg. PMID:25238500

Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder.

PubMed

Ariel, Lior; Inbar, Sapir; Edut, Schachaf; Richter-Levin, Gal

2017-11-30

Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood. Since not all individuals develop PTSD following a trauma, comparing only group means is not the adequate type of analysis. We employed a behavioral profiling approach, which analyzes individual differences compared to the normal behavior of a control group. Animals exposed to JVS exhibited a higher proportion of affected animals as measured using the elevated plus maze 8 weeks after JVS. Fluoxetine treatment following the JVS significantly decreased the proportion of affected animals as measured in adulthood. Fluoxetine treatment in adulthood was not effective. The results support the notion that childhood is not only a vulnerable period but also an effective period for preventive treatment.

Physiological frailty index (PFI): quantitative in-life estimate of individual biological age in mice.

PubMed

Antoch, Marina P; Wrobel, Michelle; Kuropatwinski, Karen K; Gitlin, Ilya; Leonova, Katerina I; Toshkov, Ilia; Gleiberman, Anatoli S; Hutson, Alan D; Chernova, Olga B; Gudkov, Andrei V

2017-03-19

The development of healthspan-extending pharmaceuticals requires quantitative estimation of age-related progressive physiological decline. In humans, individual health status can be quantitatively assessed by means of a frailty index (FI), a parameter which reflects the scale of accumulation of age-related deficits. However, adaptation of this methodology to animal models is a challenging task since it includes multiple subjective parameters. Here we report a development of a quantitative non-invasive procedure to estimate biological age of an individual animal by creating physiological frailty index (PFI). We demonstrated the dynamics of PFI increase during chronological aging of male and female NIH Swiss mice. We also demonstrated acceleration of growth of PFI in animals placed on a high fat diet, reflecting aging acceleration by obesity and provide a tool for its quantitative assessment. Additionally, we showed that PFI could reveal anti-aging effect of mTOR inhibitor rapatar (bioavailable formulation of rapamycin) prior to registration of its effects on longevity. PFI revealed substantial sex-related differences in normal chronological aging and in the efficacy of detrimental (high fat diet) or beneficial (rapatar) aging modulatory factors. Together, these data introduce PFI as a reliable, non-invasive, quantitative tool suitable for testing potential anti-aging pharmaceuticals in pre-clinical studies.

Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models.

PubMed

Nalloor, Thomas John Philip; Kumar, Nitesh; Narayanan, Kasinathan; Palanimuthu, Vasanth Raj

2017-05-01

Butter is one of the widely used fats present in the diet. However, there is no satisfactory study available that evaluates the effect of a high-fat diet containing butter as the principal fat on the development of non-alcoholic fatty liver disease (NAFLD). In the present study, butter was used for the development of steatosis in Chang liver cells in an in vitro study and Swiss albino mice in an in vivo study. In vitro steatosis was established, and butter was compared with oleic acid in Chang liver cells using an oil red O (ORO)-based colorimetric assay. In the in vivo study, a butter-rich special diet was fed for 15 weeks to mice, who showed no significant change in body weight. The expression pattern of phosphatase and tensin homolog (PTEN) and miR-21 was compared by reverse transcriptase-PCR. Special diet-fed animals showed downregulated PTEN compared to normal diet-fed animals, while levels of miR-21 remained the same. Elevations in biochemical parameters, viz., triglycerides and liver function tests showed symptoms of onset of NAFLD. Histophathological study of livers of test animals confirmed mild-to-moderate degree of NAFLD.

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro.

PubMed

de Cabo, Rafael; Liu, Lijuan; Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M

2015-03-01

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro

PubMed Central

Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M.

2015-01-01

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes. (185 words). PMID:25855056

Changes in cell proliferation and morphology in the large intestine of normal and DMH-treated rats following colostomy.

PubMed

Barkla, D H; Tutton, P J

1987-04-01

Colostomies were formed in the midcolon of normal and DMH-treated rats. Changes in cell proliferation in the mucosa adjacent to the colostomy and in the defunctioned distal segment were measured at seven, 14, 30, and 72 days using a stathmokinetic technique. Animals were given intraperitoneal injections of vinblastine and sacrificed three hours later; counts of mitotic and nonmitotic cells were made in tissue sections, and three-hour accumulated mitotic indexes were estimated. The results show that, except at seven days in DMH-treated rats, cell proliferation was unchanged in the colon proximal to the colostomy. Morphologic evidence of hyperplasia was seen in some animals at seven and 14 days. The defunctioned segment showed rapid atrophy of both mucosa and muscularis and a gradual but progressive decrease in cell proliferation. The morphology of the mucosa adjacent to the suture line in both functioning and defunctioned segments in normal and DMH-treated rats was abnormal in many animals. Abnormalities that were seen included collections of dysplastic epithelial cells in the submucosa, focal adenomatous changes, and intramural carcinoma formation. Aggregates of lymphoid tissue often were associated with carcinomas.

Vulnerability of Gastric Mucosa in Diabetic Rats, Its Pathogenesis and Amelioration by Cuminum cyminum

PubMed Central

Vador, N.; Jagtap, Aarti G.; Damle, Archana

2012-01-01

Various studies have indicated that peptic ulcers occurring during the course of diabetic state are more severe and often associated with complications such as gastrointestinal bleeding. This study is the first attempt to understand the pathogenesis of gastric ulcers occurring during the diabetic state considering alternate biochemical pathways using suitable markers and its amelioration by Cuminum cyminum. In this study, diabetic rats showed a progressive increase in the stomach advanced glycated end products formation, gastric mucosal tumour necrosis factor-α and Thiobarbituric acid reactive substances levels as compared to normal control (nondiabetic) rats. There was decrease in gastric mucosal content, antioxidant enzymes and cellular ATPase enzyme levels of diabetic gastric mucosa when compared to the normal control group. mRNA expression of epidermal growth factor was found to be significantly higher as compared to normal control animals. Further methanol extract of Cuminum cyminum treatment to diabetic animals caused a reduction in blood glucose, and ulcer score when compared to diabetic control rats. It significantly increased gastric mucus content, antioxidant status and cellular ATPase enzyme levels as compared to diabetic control animals. Methanol extract of Cuminum cyminum inhibited advanced glycated end products formation in vitro as well as in vivo. PMID:23716866

RADIOGRAPHIC ABDOMINAL ANATOMY IN CAPTIVE RED PANDAS ( AILURUS FULGENS).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Groenewald, Hermanus B; Koeppel, Katja N

2018-03-01

The red panda ( Ailurus fulgens) is classified as an endangered species by the International Union for Conservation of Nature and Natural Resources. The aim of this study was to describe the normal radiographic abdominal anatomy in red pandas to provide guidance for clinical use. Radiography of the abdomen was performed in nine captive red pandas during their annual health examinations. Seven of nine animals had six lumbar vertebrae. The sacrum consisted mainly (8/9) of three fused segments. Hypaxial muscles were easily seen in animals weighing 5 kg and above. The pylorus was located to the right of the midline and cranially to the fundus in 8/9 individuals. Bunching of small intestine in the right central abdomen occurred in animals weighing 6 kg and above. The spleen was prominent. Knowledge of the normal radiographic abdominal anatomy of red pandas is important in the diagnosis of diseases and in routine health examinations.