Master of Puppets: An Animation-by-Demonstration Computer Puppetry Authoring Framework

NASA Astrophysics Data System (ADS)

Cui, Yaoyuan; Mousas, Christos

2018-03-01

This paper presents Master of Puppets (MOP), an animation-by-demonstration framework that allows users to control the motion of virtual characters (puppets) in real time. In the first step, the user is asked to perform the necessary actions that correspond to the character's motions. The user's actions are recorded, and a hidden Markov model is used to learn the temporal profile of the actions. During the runtime of the framework, the user controls the motions of the virtual character based on the specified activities. The advantage of the MOP framework is that it recognizes and follows the progress of the user's actions in real time. Based on the forward algorithm, the method predicts the evolution of the user's actions, which corresponds to the evolution of the character's motion. This method treats characters as puppets that can perform only one motion at a time. This means that combinations of motion segments (motion synthesis), as well as the interpolation of individual motion sequences, are not provided as functionalities. By implementing the framework and presenting several computer puppetry scenarios, its efficiency and flexibility in animating virtual characters is demonstrated.

Blood harmane concentrations and dietary protein consumption in essential tremor

PubMed Central

Louis, E.D.; Zheng, W.; Applegate, L.; Shi, L.; Factor-Litvak, P.

2016-01-01

Background β-Carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown. Objective The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration. Methods Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA). Results The mean logHA was higher in 106 patients than 161 controls (0.61 ± 0.67 vs 0.43 ± 0.72 g−10/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 ± 19.6 vs 49.4 ± 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = −0.003, p = 0.98). Conclusions The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients. PMID:16087903

Self-Organizing Map With Time-Varying Structure to Plan and Control Artificial Locomotion.

PubMed

Araujo, Aluizio F R; Santana, Orivaldo V

2015-08-01

This paper presents an algorithm, self-organizing map-state trajectory generator (SOM-STG), to plan and control legged robot locomotion. The SOM-STG is based on an SOM with a time-varying structure characterized by constructing autonomously close-state trajectories from an arbitrary number of robot postures. Each trajectory represents a cyclical movement of the limbs of an animal. The SOM-STG was designed to possess important features of a central pattern generator, such as rhythmic pattern generation, synchronization between limbs, and swapping between gaits following a single command. The acquisition of data for SOM-STG is based on learning by demonstration in which the data are obtained from different demonstrator agents. The SOM-STG can construct one or more gaits for a simulated robot with six legs, can control the robot with any of the gaits learned, and can smoothly swap gaits. In addition, SOM-STG can learn to construct a state trajectory form observing an animal in locomotion. In this paper, a dog is the demonstrator agent.

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

PubMed

Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age-matched controls (49.8 ± 3.1 gray scales; P < .01). In a rat model of aging, old animals demonstrated diminished tendon-to-bone healing after rotator cuff injury and repair. Old animals had significantly decreased failure strength and collagen fiber organization at the tendon-to-bone junction compared with young animals. This study implies that animal age may need to be considered in future studies of rotator cuff repair in animal models. With increasing age and activity level of the population, the incidence of rotator cuff tears is predicted to rise. Despite advances in rotator cuff repair technique, the retear rate remains specifically high in elderly patients. The findings of this research suggest that aging negatively influences tendon-to-bone healing after rotator cuff repair in a validated animal model.

A Template Analysis of Intimate Partner Violence Survivors' Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention.

PubMed

Collins, Elizabeth A; Cody, Anna M; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R; Williams, James Herbert

2018-03-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors' health and safety.

A Template Analysis of Intimate Partner Violence Survivors’ Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention

PubMed Central

Collins, Elizabeth A.; Cody, Anna M.; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R.; Williams, James Herbert

2018-01-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors’ health and safety. PMID:29332521

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.

Diabetes Mellitus Alters the Mechanical Properties of the Native Tendon in an Experimental Rat Model

PubMed Central

Fox, Alice J. S.; Bedi, Asheesh; Deng, Xiang-Hua; Ying, Liang; Harris, Paul E.; Warren, Russell F.; Rodeo, Scott A.

2017-01-01

The purpose of this study was to determine the effect of the diabetic phenotype on the mechanical properties of the native patellar tendon and its enthesis. Diabetes was induced via intraperitoneal injection of streptozotocin in Lewis rats. Control (n = 18) and diabetic animals(n = 20) were killed at 12 and 19 days for analysis. Statistical comparisons were performed using Student’s t-tests and a two-tailed Fisher test with significance set at p < 0.05. Pre- and post-injection intraperitoneal glucose tolerance tests demonstrated significant impairment of glycemic control in the diabetic compared to control animals (p = 0.001). Mean serum hemoglobin A1c levels at 19 days was 10.6 ± 2.7% and 6.0 ± 1.0% for the diabetic and control groups, respectively (p = 0.0001). Fifteen of sixteen diabetic animals demonstrated intrasubstance failure of the patellar tendon, while only 7 of 14 control specimens failed within the tendon substance. The Young’s modulus of the diabetic tendon was significantly lower than control specimens by 19 days post-induction (161 ± 10 N m−2 compared to 200 ± 46 N m−2, respectively) (p = 0.02). The metabolic condition of poorly controlled diabetes negatively affects the mechanical properties of the native patellar tendon. These altered structural properties may predispose diabetic patients to a greater risk of tendinopathy and/or traumatic rupture. PMID:21246619

Animal Respiratory Control Mechanisms: A Quantitative Demonstration.

ERIC Educational Resources Information Center

Cizadlo, Gerald R.; Brown, Gregory W.

1980-01-01

Describes an inexpensive, easy-to-construct manometric device that is a substitute for an expensive commercial transducer that is sensitive to slight pressure fluctuations. An activity for demonstrating the importance of CO-2 as a humoral regulator of respiration is described. (Author/SA)

In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth Factor

PubMed Central

Mathison, Megumi; P. Gersch, Robert; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G.; Rosengart, Todd K.

2012-01-01

Background In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Methods and Results Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF‐All6A+) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12±2% vs 24±3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4‐fold. GMT‐treated animals also demonstrated greater density of cardiomyocyte‐specific marker beta myosin heavy chain 7+ cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12±3% vs −7±3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4‐fold greater in GMT/VEGF vs GMT/null animals (17±2% vs 4±1%, P<0.05). Conclusions VEGF administration to infarcted myocardium enhances the efficacy of GMT‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone. PMID:23316332

Knowledge, Attitudes and Practices of Law Enforcement Officers on Rabies and Animal Control Issues in Kansas.

PubMed

Straily, A; Trevino-Garrison, I

2017-03-01

Rabies is a deadly zoonoses endemic in the United States, including Kansas. Animal control programmes that emphasize vaccination of dogs and cats, removal of stray animals and enforcement of licensure programmes have historically been essential in reducing the risk of rabies exposures to humans (Beran, 1991). Kansas does not mandate the use of animal control officers [ACOs] and in areas where there is no designated animal control officer, law enforcement officers [LEOs] are required to fill that role. Little is known about LEOs' knowledge of rabies, their current practices in responding to animal-related calls or if they receive any specialized training to perform the duties of an ACO. A web-based, voluntary and anonymous survey was sent to law enforcement officers in Kansas in January 2014. The survey included questions about animal control practices and a self-assessment of rabies knowledge. The response rate was 16.2%. All respondents indicated LEOs will respond to animal-related calls, even if there was an ACO available in their department or jurisdiction. A majority of respondents indicated they had not received training on safe animal handling (62.9%, 61/97) or zoonoses prevention (85.6%, 83/97), even though a strong majority considered such training important (89.7% and 79.4%, respectively). Most respondents (>80%) were able to correctly identify animals capable of transmitting rabies but were less aware of how rabies was transmitted or the severity of rabies in humans. Our results demonstrate that Kansas LEOs perform animal control duties, many without the proper training, even though most consider such training to be important to be able to perform their duties safely. Training on safe animal handling and zoonoses prevention should be provided to all LEOs in Kansas to enable them to safely execute their duties and provide timely and accurate information to citizens regarding rabies prevention. © 2016 Blackwell Verlag GmbH.

Training for Certification: Demonstration & Research Pest Control.

ERIC Educational Resources Information Center

Mississippi State Univ., State College. Cooperative Extension Service.

This Cooperative Extension Service publication from Mississippi State University is a training guide for commercial pesticide applicators. Focusing on agricultural pest control, this publication includes a full range of topics from uses of pesticides for agricultural animal pest control to the toxicity of common pesticides to fish and bees.…

A Prototype Lisp-Based Soft Real-Time Object-Oriented Graphical User Interface for Control System Development

NASA Technical Reports Server (NTRS)

Litt, Jonathan; Wong, Edmond; Simon, Donald L.

1994-01-01

A prototype Lisp-based soft real-time object-oriented Graphical User Interface for control system development is presented. The Graphical User Interface executes alongside a test system in laboratory conditions to permit observation of the closed loop operation through animation, graphics, and text. Since it must perform interactive graphics while updating the screen in real time, techniques are discussed which allow quick, efficient data processing and animation. Examples from an implementation are included to demonstrate some typical functionalities which allow the user to follow the control system's operation.

Seizure entrainment with polarizing low frequency electric fields in a chronic animal epilepsy model

PubMed Central

Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

2009-01-01

Neural activity can be modulated by applying a polarizing low frequency (≪ 100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5–25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson’s harmonic F-test, with 45/132 stimulated seizures in 4 animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in 3 of 4 animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording. PMID:19602730

East Coast fever as a continued constraint to livestock improvement in Tanzania: a case study.

PubMed

Kambarage, D M

1995-08-01

An investigation was carried out into the cause of deaths in a recently established dairy farm with 211 animals. Clinical examination revealed that 14 out of 15 sick animals were depressed, pyrexic, anorexic and had variable degrees of respiratory distress and enlarged lymph nodes. These clinical signs were suggestive of East Coast fever (ECF). This was confirmed on positive demonstration of piroplasms and macroschizonts in blood and lymph node smears respectively, and on post-mortem examination. Parasites were also demonstrated in smears taken from 5 other animals which were pyrexic and had enlarged lymph nodes. Epidemiological investigation revealed that the occurrence of the disease was associated with contact with tick-infested pastures and unsatisfactory tick control due to improper dipping of the herd. The use of pasture by pastoral cattle which are rarely dipped also increased tick infestation. It is concluded that, unless effective disease control is applied ECF will continue to be a major killer disease of cattle in Tanzania.

Using 3D computer simulations to enhance ophthalmic training.

PubMed

Glittenberg, C; Binder, S

2006-01-01

To develop more effective methods of demonstrating and teaching complex topics in ophthalmology with the use of computer aided three-dimensional (3D) animation and interactive multimedia technologies. We created 3D animations and interactive computer programmes demonstrating the neuroophthalmological nature of the oculomotor system, including the anatomy, physiology and pathophysiology of the extra-ocular eye muscles and the oculomotor cranial nerves, as well as pupillary symptoms of neurological diseases. At the University of Vienna we compared their teaching effectiveness to conventional teaching methods in a comparative study involving 100 medical students, a multiple choice exam and a survey. The comparative study showed that our students achieved significantly better test results (80%) than the control group (63%) (diff. = 17 +/- 5%, p = 0.004). The survey showed a positive reaction to the software and a strong preference to have more subjects and techniques demonstrated in this fashion. Three-dimensional computer animation technology can significantly increase the quality and efficiency of the education and demonstration of complex topics in ophthalmology.

[Determination of various toxic minerals in spiruline algae of different origins, and evaluation of long-term toxicity in the rat of a lot of spiruline algae of Mexican origin].

PubMed

Boudène, C; Collas, E; Jenkins, C

1975-01-01

A detailed analytical study made on samples of Spirulines algae of various origins showed that these microorganisms may present an important telluric contamination, especially demonstrated by high levels of fluorine and arsenic they contain. A long term animal experimentation has been achieved with Spirula Maxima, obtained from the Sosa Texcoco solar evaporator. A diet contained in total proteins 25 p. 100 of dried atomized algae and was given for 75 weeks to Wistar rats. All along the experiment, the animals submitted to that diet showed no difference with control animals fed with caseine. The increase in weight was comparable for control animals and male experimented animals; a slight decrease in weight has been observed for females fed with algae up to the 30th week. At the end of the experiment, a normal frequency of tumours was noted on experimented animals. The cumulative potentiality of certain mineral toxicants, has been evaluated, when abnormal high levels of them have been detected in the Spirulines samples. The fed animals have been killed at definite times all along the experiment and the metals dosed in the body. Such a cumulative potency has been demonstrated for arsenic. On the contrary, in the case of fluorine, even particular dosages in the femoral bone could not show any significant cumulation of that toxicant, comparing with control animals. In conclusion, the authors have not noted any evident toxicity related to the samples of Spirulines tested in rats, whatever these algae were the only source of proteins in the diet. They hope anyway that the exact origin of contamination of these algaes by these metals will be better known to prevent the variations in the composition of industrial samples of Spirulines according to these metals for instance.

Development and Training of a Neural Controller for Hind Leg Walking in a Dog Robot

PubMed Central

Hunt, Alexander; Szczecinski, Nicholas; Quinn, Roger

2017-01-01

Animals dynamically adapt to varying terrain and small perturbations with remarkable ease. These adaptations arise from complex interactions between the environment and biomechanical and neural components of the animal's body and nervous system. Research into mammalian locomotion has resulted in several neural and neuro-mechanical models, some of which have been tested in simulation, but few “synthetic nervous systems” have been implemented in physical hardware models of animal systems. One reason is that the implementation into a physical system is not straightforward. For example, it is difficult to make robotic actuators and sensors that model those in the animal. Therefore, even if the sensorimotor circuits were known in great detail, those parameters would not be applicable and new parameter values must be found for the network in the robotic model of the animal. This manuscript demonstrates an automatic method for setting parameter values in a synthetic nervous system composed of non-spiking leaky integrator neuron models. This method works by first using a model of the system to determine required motor neuron activations to produce stable walking. Parameters in the neural system are then tuned systematically such that it produces similar activations to the desired pattern determined using expected sensory feedback. We demonstrate that the developed method successfully produces adaptive locomotion in the rear legs of a dog-like robot actuated by artificial muscles. Furthermore, the results support the validity of current models of mammalian locomotion. This research will serve as a basis for testing more complex locomotion controllers and for testing specific sensory pathways and biomechanical designs. Additionally, the developed method can be used to automatically adapt the neural controller for different mechanical designs such that it could be used to control different robotic systems. PMID:28420977

Effects of Animal-Assisted Activities with Guinea Pigs in the Primary School Classroom

PubMed Central

O’Haire, Marguerite E.; McKenzie, Samantha J.; McCune, Sandra; Slaughter, Virginia

2013-01-01

This study investigated the effects of a classroom-based animal-assisted activities (AAA) program with guinea pigs on the social functioning of primary school children. We hypothesized that participants in the experimental condition (n = 64), compared with a waitlist control group (n = 64), would demonstrate improvements in social functioning following the program. Parents and teachers used the Social Skills Rating System (SSRS) to evaluate the social skills and problem behaviors of 128 participating children (age range = 4.8 to 12.7 years) before and after an 8-week period. Teachers also rated academic competence at both time points. Children who participated in the AAA program demonstrated significantly greater improvements in social functioning than their control group peers, as defined by greater increases in social skills (teacher SSRS) and decreases in problem behaviors (parent and teacher SSRS). There were no significant differences between the groups in academic competence. AAA participants demonstrated significant increases in social skills and decreases in problem behaviors from pre- to post-program on the teacher version of the SSRS. Control group participants did not show significant changes on these measures. These findings suggest that an AAA program with guinea pigs may be a feasible addition to the primary school classroom in order to improve social functioning. Further component analysis will be necessary to determine whether the animal is the active ingredient in AAA programs of this nature. PMID:24265514

21 CFR 812.35 - Supplemental applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... control procedures of § 820.30, preclinical/animal testing, peer reviewed published literature, or other... the verification and validation testing, as appropriate, demonstrated that the design outputs met the...

21 CFR 812.35 - Supplemental applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... control procedures of § 820.30, preclinical/animal testing, peer reviewed published literature, or other... the verification and validation testing, as appropriate, demonstrated that the design outputs met the...

21 CFR 812.35 - Supplemental applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... control procedures of § 820.30, preclinical/animal testing, peer reviewed published literature, or other... the verification and validation testing, as appropriate, demonstrated that the design outputs met the...

21 CFR 812.35 - Supplemental applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... control procedures of § 820.30, preclinical/animal testing, peer reviewed published literature, or other... the verification and validation testing, as appropriate, demonstrated that the design outputs met the...

A turtle cognition research demonstration enhances visitor engagement and keeper-animal relationships.

PubMed

Alba, Andrew C; Leighty, Katherine A; Pittman Courte, Victoria L; Grand, Alison P; Bettinger, Tamara L

2017-07-01

Environmental enrichment techniques present animals with cognitive challenges while providing them opportunities to make choices and exert control over their environment. In this way, cognitive research and training is enriching to animals and can be used as a form of enrichment in zoos and aquariums. Cognitive research demonstrations also provide an opportunity to enhance visitor experience, as well as foster interactions between animals and keepers. We investigated how cognitive research sessions involving eastern box turtles (Terrapene carolina carolina) at Disney's Animal Kingdom ® impacted both the rate of visitors coming to the exhibit and the amount of time they spent engaged. Further, we used a questionnaire to assess the impact of keeper participation in these sessions on their relationships with and perceptions of the turtles. While visitation rate to the exhibit was not impacted, cognitive research sessions held visitor attention for longer than keeper interpretation or at times during which no keepers or researchers were present. We also found that keepers that had worked with the turtles for longer and keepers that regularly participated in cognitive research sessions reported stronger bonds with the turtles. Our research suggests that use of cognitive research and training demonstrations for guest viewing in zoos and aquariums may enhance visitor learning opportunities by increasing the amount of time they spend at the exhibit. Our study also provides evidence that participation in such demonstrations by zoo and aquarium professionals can be related to improved keeper-animal bonds, potentially resulting in better husbandry and enhanced animal welfare. © 2017 Wiley Periodicals, Inc.

Brucellosis in low-income and middle-income countries

PubMed Central

Rubach, Matthew P.; Halliday, Jo E.B.; Cleaveland, Sarah; Crump, John A.

2014-01-01

Purpose of review Human brucellosis is a neglected, underrecognized infection of widespread geographic distribution. It causes acute febrile illness and a potentially debilitating chronic infection in humans, and livestock infection has substantial socioeconomic impact. This review describes new information regarding the epidemiology of brucellosis in the developing world and advances in diagnosis and treatment. Recent findings The highest recorded incidence of human brucellosis occurs in the Middle East and Central Asia. Fever etiology studies demonstrate brucellosis as a cause of undifferentiated febrile illness in the developing world. Brucellosis is a rare cause of fever among returning travelers, but is more common among travelers returning from the Middle East and North Africa. Sensitive and specific rapid diagnostic tests appropriate for resource-limited settings have been validated. Randomized controlled trials demonstrate that optimal treatment for human brucellosis consists of doxycycline and an aminoglycoside. Decreasing the burden of human brucellosis requires control of animal brucellosis, but evidence to inform the design of control programs in the developing world is needed. Summary Brucellosis causes substantial morbidity in human and animal populations. While improvements in diagnostic options for resource-limited settings and stronger evidence for optimal therapy should enhance identification and treatment of human brucellosis, prevention of human disease through control in animals remains paramount. PMID:23963260

Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

PubMed

Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

2012-11-10

Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

Changes in the sialylation and sulfation of secreted thyrotropin in congenital hypothyroidism

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

Gyves, P.W.; Gesundheit, N.; Thotakura, N.R.

1990-05-01

The authors have examined the oligosaccharide structure of secreted thyrotropin (TSH) in perinatal and mature rats with congenital primary hypothyroidism. Rat pituitaries from euthyroid control animals and those rendered hypothyroid by methimazole treatment were incubated with ({sup 3}H)glucosamine in vitro. Secreted TSH was purified, and oligosaccharides were enzymatically released and characterized by anion-exchange HPLC. In perinatal hypothyroid animals compared with control animals, oligosaccharides from TSH {alpha} and {beta} subunits contained more species with three or more negative charges. Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negativemore » charge. In mature hypothyroid 9-week-old animals compared with control animals, changes were less pronounced, suggesting that endocrine regulation of oligosaccharide structure is dependent upon the maturational state of the animal. Together, these data provide direct evidence and characterization of specific changes in the structure of a secreted pituitary glycoprotein hormone occurring as a result of in vivo endocrine alterations during early development. Moreover, they provide a potential structural basis to explain the delayed clearance of both TSH and the gonadotropins with end-organ deficiency, which may have important implications for the in vivo biological activities of these hormones.« less

Recommendation for a non-animal alternative to rat caries testing.

PubMed

Featherstone, John D B; Stookey, George K; Kaminski, Michael A; Faller, Robert V

2011-10-01

As a requirement of the Food & Drug Administration's final monograph on "Anticaries drug products for over-the-counter human use", the toothpaste industry has been conducting animal caries tests on every fluoride-containing toothpaste introduced into the U.S. market since 1996. The practice of testing in animals, although required by law, is in stark conflict with the corporate policy of many U.S. and global toothpaste manufacturers, in which, if possible, alternatives to animal testing are utilized. A provision does exist within the regulation which allows the use of an alternative method to demonstrate efficacy. However, to take advantage of this provision, a petition must be submitted to the FDA and in this petition data demonstrating the alternative provides results of "equivalent accuracy" must be included. After many years of research, model development and model comparisons, we have identified one particular laboratory model that demonstrated excellent correlation with the currently accepted animal caries models. This model, known as the Featherstone pH cycling model, is discussed in this paper. The Featherstone pH cycling model has been shown to produce results of equivalent accuracy to the animal caries model by: (1) demonstrating a clinically relevant fluoride dose response similar to that shown in the animal caries model (including 1100 ppm F, 250 ppm F and placebo); (2) demonstrating similar results to the animal caries model for clinically proven dentifrice formulations relative to positive and negative controls; (3) demonstrating discriminating ability in strong agreement with the animal caries model for differentiating between a dentifrice formulation with attenuated fluoride activity and a USP standard; and (4) providing a clinically relevant representation of the caries process, as demonstrated by orthodontic banding studies. In addition, the model sufficiently addresses both salivary and abrasive/anticalculus agent interference concerns. For more than 50 years, fluoride has been the first defense in the fight against dental caries. The clinical effectiveness of fluoride is well accepted and documented extensively in the literature. The mechanism through which fluoride provides its benefit is very straightforward and well understood. The proposed laboratory model effectively simulates the effect of the caries process and has been shown to demonstrate equivalent accuracy to animal caries. This indicates that there are strong scientific grounds for the use of this model as an alternative to the animal caries test. Based on the strength of the data and the correlations noted between the two models, we recommend that the scientific community and the toothpaste industry broadly accept the Featherstone laboratory pH cycling model as an appropriate alternative to animal testing, particularly for ionic fluoride based dentifrices.

Coping with parvovirus infections in mice: health surveillance and control.

PubMed

Janus, Lydia M; Bleich, Andre

2012-01-01

Parvoviruses of mice, minute virus of mice (MVM) and mouse parvovirus (MPV), are challenging pathogens to eradicate from laboratory animal facilities. Due to the impediment on rodent-based research, recent studies have focused on the assessment of re-derivation techniques and parvoviral potential to induce persistent infections. Summarizing recent data, this review gives an overview on studies associated with parvoviral impact on research, diagnostic methods, parvoviral persistence and re-derivation techniques, demonstrating the complex nature of parvovirus infection in mice and unfolding the challenge of controlling parvovirus infections in laboratory animal facilities.

Applications of Java and Vector Graphics to Astrophysical Visualization

NASA Astrophysics Data System (ADS)

Edirisinghe, D.; Budiardja, R.; Chae, K.; Edirisinghe, G.; Lingerfelt, E.; Guidry, M.

2002-12-01

We describe a series of projects utilizing the portability of Java programming coupled with the compact nature of vector graphics (SVG and SWF formats) for setup and control of calculations, local and collaborative visualization, and interactive 2D and 3D animation presentations in astrophysics. Through a set of examples, we demonstrate how such an approach can allow efficient and user-friendly control of calculations in compiled languages such as Fortran 90 or C++ through portable graphical interfaces written in Java, and how the output of such calculations can be packaged in vector-based animation having interactive controls and extremely high visual quality, but very low bandwidth requirements.

The Effect of Disgust and Fear Modeling on Children’s Disgust and Fear for Animals

PubMed Central

2014-01-01

Disgust is a protective emotion associated with certain types of animal fears. Given that a primary function of disgust is to protect against harm, increasing children’s disgust-related beliefs for animals may affect how threatening they think animals are and their avoidance of them. One way that children’s disgust beliefs for animals might change is via vicarious learning: by observing others responding to the animal with disgust. In Experiment 1, children (ages 7–10 years) were presented with images of novel animals together with adult faces expressing disgust. Children’s fear beliefs and avoidance preferences increased for these disgust-paired animals compared with unpaired control animals. Experiment 2 used the same procedure and compared disgust vicarious learning with vicarious learning with fear faces. Children’s fear beliefs and avoidance preferences for animals again increased as a result of disgust vicarious learning, and animals seen with disgust or fear faces were also rated more disgusting than control animals. The relationship between increased fear beliefs and avoidance preferences for animals was mediated by disgust for the animals. The experiments demonstrate that children can learn to believe that animals are disgusting and threatening after observing an adult responding with disgust toward them. The findings also suggest a bidirectional relationship between fear and disgust with fear-related vicarious learning leading to increased disgust for animals and disgust-related vicarious learning leading to increased fear and avoidance. PMID:24955571

Testing of Safety-Critical Software Embedded in an Artificial Heart

NASA Astrophysics Data System (ADS)

Cha, Sungdeok; Jeong, Sehun; Yoo, Junbeom; Kim, Young-Gab

Software is being used more frequently to control medical devices such as artificial heart or robotic surgery system. While much of software safety issues in such systems are similar to other safety-critical systems (e.g., nuclear power plants), domain-specific properties may warrant development of customized techniques to demonstrate fitness of the system on patients. In this paper, we report results of a preliminary analysis done on software controlling a Hybrid Ventricular Assist Device (H-VAD) developed by Korea Artificial Organ Centre (KAOC). It is a state-of-the-art artificial heart which completed animal testing phase. We performed software testing in in-vitro experiments and animal experiments. An abnormal behaviour, never detected during extensive in-vitro analysis and animal testing, was found.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

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.

Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration

PubMed Central

Jacobs, Lloydine; Vo, Nam; Coehlo, J. Paulo; Dong, Qing; Bechara, Bernard; Woods, Barrett; Hempen, Eric; Hartman, Robert; Preuss, Harry; Balk, Judith; Kang, James; Sowa, Gwendolyn

2013-01-01

Study Design Laboratory based controlled in vivo study Objective To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration Summary of Background Data Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses. Results The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix. Conclusions These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these findings. PMID:23324939

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy

PubMed Central

Tar, Moses; Cabrales, Pedro; Mahantesh, Navarti; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel; Davies, Kelvin P.

2014-01-01

Introduction Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to PDE5 inhibitors, which act downstream of CN-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. Aim To determine if topically applied NO-releasing nanoparticles (NO-np) can elicit erections in a rat model of RP and demonstrate that the mechanism is through increased blood flow. Methods 26 Sprague–Dawley rats underwent bilateral transection of the CN. One week later NO-np were applied topically to the penile shaft in DMSO-gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty-np. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-np on blood flow was determined using a hamster dorsal window chamber. Main Outcome Measures Animals were investigated for spontaneous erections, onset and duration of erectile response and basal ICP/BP ratio. Microcirculatory blood-flow was determined through arteriolar and venular diameter and blood flow. Results Eight of ten animals treated with NO-np suspended in DMSO-gel had significant increases in basal ICP/BP, and six out of these ten animals demonstrated spontaneous erections of approximately one minute duration. Onset of spontaneous erections ranged from 5–37 minutes and occurred for at least 45 minutes. Similar results were observed with NO-np applied in coconut oil. No erectile response was observed in control animal models treated with empty-np. The hamster dorsal window chamber demonstrated NO-np applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Conclusions Topically applied NO-np induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that the NO-np would be useful in penile rehabilitation of patients following RP. PMID:25302850

Spatial but not object memory impairments in children with fetal alcohol syndrome.

PubMed

Uecker, A; Nadel, L

1998-07-01

Behavioral dissociations on tests of cognitive abilities are powerful tools that can help define the neuropsychology of developmentally disabling conditions. Animals gestationally exposed to alcohol demonstrate spatial (place) but not object (cue) memory impairments. Whether children with fetal alcohol syndrome demonstrate a similar dissociation has received little attention. In this experiment, 30 Native American children, 15 previously identified with fetal alcohol syndrome and 15 control children, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. As in animal models, children with fetal alcohol syndrome demonstrated a spatial but not an object memory impairment. A possible role for the hippocampus was discussed.

Nematophagous fungi for biological control of gastrointestinal nematodes in domestic animals.

PubMed

Braga, Fabio Ribeiro; de Araújo, Jackson Victor

2014-01-01

Several studies have been conducted using fungi in the biological control of domestic animals and humans. In this respect, a large amount of research has been undertaken to understand the particularities of each fungus used. These fungi have been demonstrated to act on all classes of helminthes. Therefore, they should not only be called nematophagous but also helmintophagous. Evidence of enzymatic action has also revealed their mechanism of action, as well as potential metabolites that could be synthesized as bioactive molecules. Cultural barriers to the use of fungi should be broken down, since the impact on the environment is minimal. In this context, much is already known about the mechanism of interaction of these organisms with their 'targets'. Recent research has pointed to the search for substances derived from nematophagous fungi that have demonstrated their ovicidal and/or larvicidal activity, thus being a global premise to be studied further. Crude extracts derived from nematophagous fungi of predator and ovicidal groups reduce the amount of larvae of gastrointestinal nematodes and prevent the hatching of their eggs, since they have been demonstrated to act with extracellular proteases and other enzymes. Furthermore, the activity of these enzymes has begun to be explored regarding their possible interaction with the exoskeleton of arthropods, which could emerge as an alternative method of tick control. Finally, it should be clear that nematophagous fungi in general are 'old friends' that are ready to the 'fight with our old enemies', the gastrointestinal helminth parasites harmful to human and animal health.

Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity.

PubMed

Rus, Florentina; Flatt, Thomas; Tong, Mei; Aggarwal, Kamna; Okuda, Kendi; Kleino, Anni; Yates, Elisabeth; Tatar, Marc; Silverman, Neal

2013-05-29

Throughout the animal kingdom, steroid hormones have been implicated in the defense against microbial infection, but how these systemic signals control immunity is unclear. Here, we show that the steroid hormone ecdysone controls the expression of the pattern recognition receptor PGRP-LC in Drosophila, thereby tightly regulating innate immune recognition and defense against bacterial infection. We identify a group of steroid-regulated transcription factors as well as two GATA transcription factors that act as repressors and activators of the immune response and are required for the proper hormonal control of PGRP-LC expression. Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals.

Nifedipine-induced gingival overgrowth in rats: brief review and experimental study.

PubMed

Fu, E; Nieh, S; Hsiao, C T; Hsieh, Y D; Wikesjö, U M; Shen, E C

1998-07-01

The first case report of gingival overgrowth induced by nifedipine (NIF), a calcium-beta blocker, was in 1984. However, the association between gingival alterations and the drug therapy of sodium diphenyl hydantoinate was initially described in 1939. The purpose of the experimental study was to examine the effect of NIF on gingival morphology in an animal model. Forty-five male Sprague-Dawley rats were randomly divided into 3 groups. Animals in each group daily received NIF in dimethyl sulfoxide by gastric feeding at a dosage of 0 (control), 30, or 50 mg/kg body weight for 9 weeks. Gingival gross morphology was assessed tri-weekly from stone models obtained from the mandibular incisal region. Animals were sacrificed at the end of study and tissue blocks were processed for histopathologic and histometric evaluation. Histometric analysis was performed at 5 selected tissue levels. Macro- and microscopic significantly increased gingival dimensions were demonstrated in NIF-treated animals compared to control. Although a fibrovascular tissue was observed in the tooth-gingiva interface for both NIF-treated and control animals, it was thicker and appeared earlier in NIF-treated animals. The results of the present study suggest that gingival overgrowth can be induced by NIF in rats and that the gingival overgrowth appears dose dependent.

Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: A pilot study.

PubMed

da Costa, Anaelle; Prehaud, Christophe; Khou, Cecile; Pardigon, Nathalie; Saulnier, Aure; Nougarede, Nolwenn; Lafon, Monique

2018-05-01

Live attenuated vaccines have proved to be mostly valuable in the prevention of infectious diseases in humans, especially in developing countries. The safety and potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing, must be proven before being administrated to humans. For now, the tests used to control vaccine safety largely involve animal testing. For live viral vaccines, regulations require suppliers to demonstrate the absence of neurovirulence in animals, principally in non-human primates and mice. In a search to reduce the use of animals and embracing the 3Rs principles (Replacement, Reduction, Refinement in the use of laboratory animals), we developed a new Blood-Brain Barrier Minibrain (BBB-Minibrain) in cellulo device to evaluate the neuroinvasiveness/neurovirulence of live Yellow Fever virus (YFV) vaccines. A pilot study was performed using the features of two distinct YFV strains, with the ultimate goal of proposing a companion test to characterize YFV neurovirulence. Here, we demonstrate that the BBB-Minibrain model is a promising alternative to consider for future replacement of YFV vaccine in vivo neurovirulence testing (see graphical abstract). Copyright © 2018. Published by Elsevier Ltd.

Social behavior impairment in offspring exposed to maternal seizures in utero.

PubMed

Novaes, Gisane Faria; Amado, Debora; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

2012-06-01

Human and animal models have demonstrated that maternal seizures in utero could be deleterious to the development of the offspring. This study focused on the social behavior of offspring exposed to seizures in utero. A pilocarpine model of temporal lobe epilepsy was induced in female Wistar rats that were mated after the first spontaneous seizure. Early after birth, pups from an epileptic mother were reared by a control mother. To evaluate the influence of the adoption process, two other groups were added: rat pups from control mothers cross-fostered with other control mothers, and rat pups reared by their birth mother. Animals exposed to seizures in utero showed impaired social behavior with no signs of anxiety-like behavior. This study demonstrated that epileptic seizures during pregnancy could be harmful to brain development and may increase the risk of developing neurodevelopmental disorders. The mechanisms underlying the abnormalities of social behavior are not well understood, and further studies in this field are warranted.

Wound-healing activity of Morinda citrifolia fruit juice on diabetes-induced rats.

PubMed

Nayak, B S; Isitor, G N; Maxwell, A; Bhogadi, V; Ramdath, D D

2007-02-01

Morinda citrifolia L. is a traditional Polynesian medicinal plant which is apparently useful for bowel disorders, skin inflammation, infection, mouth ulcers and wound healing. This study aimed to evaluate the wound-healing activity of Morinda citrifolia fruit juice in streptozotocin-induced diabetic rats. An excision wound model was used. The animals were weight-matched and placed into three groups (n = 6 per group). Group 1 animals served as normal controls, while animals in groups 2 and 3 served as diabetic controls and experimental diabetic animals respectively. All animals were anaesthetised and a full-thickness excision wound (circular area of 300 mm2 and 2 mm deep) was created. Group 3 animals were given the juice of Morinda citrifolia fruit (100 ml per kilogram of body weight) in their drinking water for 10 days. Wound area measurements were taken on days 1, 5 and 11. Blood samples were collected simultaneously for glucose measurement. Granulation tissue that had formed on the wound was excised on day 11 and processed for histological and biochemical analysis. The wound area of the Morinda citrifolia-treated group reduced by 73% (p < 0.001) when compared with the diabetic controls (63%). Significant increases in the weight of granulation tissue (p < 0.001) and hydroxyproline content (p < 0.00 1, 92.16 +/- 4.02) were observed. The protein content was moderately high. Histological studies showed that collagen was laid down faster in the experimental diabetic animals than in the normal control and diabetic control groups. Fasting blood glucose values in the diabetic experimental group had reduced by 29% (p < 0.00 1) compared with the diabetic control animals. There was a good correlation between the wound contraction rate and blood glucose values. This study demonstrates that the juice of Morinda citrifolia fruit significantly reduces blood sugar levels and hastens wound healing in diabetic rats.

The animacy advantage for free-recall performance is not attributable to greater mental arousal.

PubMed

Popp, Earl Y; Serra, Michael J

2018-01-01

People often demonstrate better memory for animate concepts (e.g., lion and sailor) than for inanimate concepts (e.g., hammer and mountain). Researchers have attributed this effect to an adaptive memory mechanism that favours information relevant for survival, including information about living things. In the present experiment, we examined the hypothesis that people demonstrate better free-recall performance for animate than inanimate words because animate words tend to be associated with greater mental arousal than inanimate words, a factor that was not controlled for in previous experiments on this topic. To this end, we matched animate and inanimate word lists on mental arousal (and several other factors), and compared participants' free-recall performance for the two word types. We were able to replicate past findings that participants' free-recall of animate words exceeds their free-recall of inanimate words, but we found no support for the possibility that the effect stems from differences in mental arousal between animate and inanimate concepts, as this effect maintained even when the word lists were matched on mental arousal. The present results therefore indicate that mental arousal cannot explain the effects of animacy on free-recall performance.

Development of porcine model of chronic tachycardia-induced cardiomyopathy.

PubMed

Paslawska, Urszula; Gajek, Jacek; Kiczak, Liliana; Noszczyk-Nowak, Agnieszka; Skrzypczak, Piotr; Bania, Jacek; Tomaszek, Alicja; Zacharski, Maciej; Sambor, Izabela; Dziegiel, Piotr; Zysko, Dorota; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr

2011-11-17

There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Biphasic alterations in serotonin-1B (5-HT1B) receptor function during abstinence from extended cocaine self-administration.

PubMed

O'Dell, Laura E; Manzardo, Ann M; Polis, Ilham; Stouffer, David G; Parsons, Loren H

2006-12-01

Alterations in 5-HT1B receptor function during cocaine abstinence were evaluated in rats given either limited- or extended access (LA and EA, respectively) to cocaine self-administration. The locomotor response to the 5-HT1B/1A agonist RU24969 was significantly reduced in cocaine-experienced animals relative to cocaine-naïve controls following 6 h of abstinence but became sensitized over the subsequent 14 days of abstinence. Both the early phase subsensitivity and later phase supersensivity to RU 24969-induced activity were greater in EA versus LA animals. Intra-nucleus accumbens administration of the 5-HT1B agonist CP 93, 129 produced significantly greater increases in dialysate dopamine levels in EA versus control animals following 14 days of abstinence. However, there was no difference between EA and cocaine-naïve control animals in the augmentation of cocaine-induced increases in nucleus accumbens DA produced by intra-VTA CP 93, 129. Collectively these findings demonstrate that 5-HT1B receptor function is persistently altered by cocaine self-administration.

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.

Effect of 16-Day Spaceflight on the Morphology of Thick-Toed Geckos (Pachydactylus Bibronii Smith, 1846)

NASA Technical Reports Server (NTRS)

Gulimova, V. I.; Nikitin, V. B.; Asadchikov, V. E.; Buzmakov, A. V.; Okshtein, I. L.; Almeida, E. A. C.; Ilyin, E. A.; Tairbekov, M. G.; Saveliev, S. V.

2006-01-01

There are grounds to believe that space flown experiments on thick-toed geckos may help solve the problem of floatation of vertebrates in microgravity. Geckos of this species carry on the lower surface of their toes numerous setae, which allow them to remain attached to any surfaces regardless of the gravitational effects. Experiments were performed on 5 animals in each of the following groups: flight, basal, synchronous and laboratory controls. 32 hours after a 16- day flight the animals were euthanazed and examined using traditional histology and X-ray microtomography. Body mass losses were 10% in the flight animals, 7.4% in the synchronous controls, and 12.3% in the laboratory controls. Since the flight and synchronous animals were kept at 15-19 C, whereas the laboratory controls - at 26-28 C, it can be inferred that environmental temperatures impacted animal metabolism no less than flight induced stress. Blood tests of the flown animals showed a 12% decrease of erythrocytes and a 40% decrease of dark-nuclear granulocytes, with the number of light-nuclear granulocytes remaining unchanged. In the small intestine the number of goblet cells increased allowing them to occupy a large portion of the cyptal surface. Enhanced secretion was accompanied by the appearance of dead intestinal cells in the lumen. Clusters of degraded hepatocytes were found at the liver edges of flight animals. Signs of liver involution were similar to the changes produced by alcohol consumption but did not spread to its central part. In the heart, insignificant hypertrophy and excessive blood supply that still remained within the physiological norm were detected. No significant changes were found in the pancreas, lungs, nervous systems or the snouts of the flown animals, but the volume of their gallbladders was greater than in controls. The epithelium of toe pads of the flight animals became thinner. Histological examination of the humerus did not demonstrate significant mineral losses. However, X-ray microtomography showed changes in the trabecular structure in the subepyphyseal zone of bones in flight animals compared to the controls. In summary, all the changes detected in the flight animals were adaptive. Therefore, geckos of this species can be used as an animal model for morphological studies in longer-duration space flights.

Frontal Traumatic Brain Injury in Rats Causes Long-Lasting Impairments in Impulse Control That Are Differentially Sensitive to Pharmacotherapeutics and Associated with Chronic Neuroinflammation.

PubMed

Vonder Haar, Cole; Lam, Frederick C W; Adams, Wendy K; Riparip, Lara-Kirstie; Kaur, Sukhbir; Muthukrishna, Michael; Rosi, Susanna; Winstanley, Catharine A

2016-11-16

Traumatic brain injury (TBI) affects millions yearly, and is increasingly associated with chronic neuropsychiatric symptoms. We assessed the long-term effects of different bilateral frontal controlled cortical impact injury severities (mild, moderate, and severe) on the five-choice serial reaction time task, a paradigm with relatively independent measurements of attention, motor impulsivity, and motivation. Moderately- and severely injured animals exhibited impairments across all cognitive domains that were still evident 14 weeks postinjury, while mild-injured animals only demonstrated persistent deficits in impulse control. However, recovery of function varied considerably between subjects such that some showed no impairment ("TBI-resilient"), some demonstrated initial deficits that recovered ("TBI-vulnerable"), and some never recovered ("chronically-impaired"). Three clinically relevant treatments for impulse-control or TBI, amphetamine, atomoxetine, and amantadine, were assessed for efficacy in treating injury-induced deficits. Susceptibility to TBI affected the response to pharmacological challenge with amphetamine. Whereas sham and TBI-resilient animals showed characteristic impairments in impulse control at higher doses, amphetamine had the opposite effect in chronically impaired rats, improving task performance. In contrast, atomoxetine and amantadine reduced premature responding but increased omissions, suggesting psychomotor slowing. Analysis of brain tissue revealed that generalized neuroinflammation was associated with impulsivity even when accounting for the degree of brain damage. This is one of the first studies to characterize psychiatric-like symptoms in experimental TBI. Our data highlight the importance of testing pharmacotherapies in TBI models in order to predict efficacy, and suggest that neuroinflammation may represent a treatment target for impulse control problems following injury.

A randomized triple blind trial to assess the effect of an anthelmintic programme for working equids in Morocco

PubMed Central

2011-01-01

Background Gastro-intestinal parasitism has been identified as a significant cause of disease in working equids in many countries. This randomized triple-blind trial was designed to assess the impact of an anthelmintic treatment programme (using oral ivermectin and fenbendazole) comparing treated and placebo control populations of working donkeys, mules and horses in field conditions in Morocco. In particular, we assessed animal body weight and condition score, together with a questionnaire-based owner evaluation of number of subjective animal health parameters. Faecal worm egg count was also measured. Results 239 animals completed the full study, 130 in the treatment group and 109 in the control group. Although the average animal weight increased during the study, this change was not significantly different between the two groups. Animals in the treatment group had a significantly lower strongyle worm egg count and increased in body condition score compared to animals in the control group at each examination during the study period. Owners of animals in the treatment group reported improvement in health and work ability and a beneficial effect on pruritus during the early period of the study. These differences in owner perception between treatment groups had disappeared in the latter stages of the study. Conclusion This study demonstrated that a routine anthelmintic treatment programme of three treatments annually can have a significant effect on faecal worm egg count. There may be beneficial consequences for the animal health and productivity. Further research on other populations of working equids in different environments would facilitate the objective planning of effective parasite control strategies for specific situations and provide better understanding of the likely clinical benefits of such programmes. PMID:21208398

Anti cancerous efficacy of Ayurvedic milk extract of Semecarpus anacardium nuts on hepatocellular carcinoma in Wistar rats.

PubMed

Joseph, Joice P; Raval, Sunant K; Sadariya, Kamlesh A; Jhala, Mayur; Kumar, Pranay

2013-01-01

The objective of the study was to determine the anticancerous efficacy of Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of rats were used for the study. Group I served as water control. Hepatocellular carcinoma (HCC) was induced in groups II, III and IV animals using N-nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for 13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma control. Group-III animals were treated with Ayurvedic milk extract of Semecarpus anacardium nuts at dose mentioned in Ashtangahridaya, an authentic book of Ayurveda for 49 days and group-IV animals were treated with doxorubicin as reference drug at dose of 1mg/kg twice a week for 7 weeks. Group V animals were kept as drug (SA nut milk extract) control for studying the effect of nut milk extract on normal rats. After 154 days of experiment, all animals were subjected to screening for HCC by estimation of liver enzymes, HCC marker (alpha-2 macroglobulin) and histopathology. Both liver enzymes and HCC marker were increased in hepatocellular carcinoma control along with neoplastic changes in liver and were decreased in Semecarpus anacardium nut milk extract treated group. The Ayurvedic drug showed positive correlation with the action of doxorubicin. This study demonstrated the efficacy of Semecarpus anacardium nut milk extract for the treatment of hepatocellular carcinoma either alone or along with chemotherapy.

Stars Cant Spin Out of Control Artist Animation

NASA Image and Video Library

2006-07-24

This artist concept demonstrates how a dusty planet-forming disk can slow down a whirling young star, essentially saving the star from spinning itself to death. Evidence for this phenomenon comes from NASA Spitzer Space Telescope.

Creatine supplementation and glycemic control: a systematic review.

PubMed

Pinto, Camila Lemos; Botelho, Patrícia Borges; Pimentel, Gustavo Duarte; Campos-Ferraz, Patrícia Lopes; Mota, João Felipe

2016-09-01

The focus of this review is the effects of creatine supplementation with or without exercise on glucose metabolism. A comprehensive examination of the past 16 years of study within the field provided a distillation of key data. Both in animal and human studies, creatine supplementation together with exercise training demonstrated greater beneficial effects on glucose metabolism; creatine supplementation itself demonstrated positive results in only a few of the studies. In the animal studies, the effects of creatine supplementation on glucose metabolism were even more distinct, and caution is needed in extrapolating these data to different species, especially to humans. Regarding human studies, considering the samples characteristics, the findings cannot be extrapolated to patients who have poorer glycemic control, are older, are on a different pharmacological treatment (e.g., exogenous insulin therapy) or are physically inactive. Thus, creatine supplementation is a possible nutritional therapy adjuvant with hypoglycemic effects, particularly when used in conjunction with exercise.

9 CFR 2.3 - Demonstration of compliance with standards and regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Demonstration of compliance with standards and regulations. 2.3 Section 2.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.3 Demonstration of compliance...

9 CFR 2.3 - Demonstration of compliance with standards and regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Demonstration of compliance with standards and regulations. 2.3 Section 2.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.3 Demonstration of compliance...

9 CFR 2.3 - Demonstration of compliance with standards and regulations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Demonstration of compliance with standards and regulations. 2.3 Section 2.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.3 Demonstration of compliance...

9 CFR 2.3 - Demonstration of compliance with standards and regulations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Demonstration of compliance with standards and regulations. 2.3 Section 2.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.3 Demonstration of compliance...

9 CFR 2.3 - Demonstration of compliance with standards and regulations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Demonstration of compliance with standards and regulations. 2.3 Section 2.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.3 Demonstration of compliance...

78 FR 63477 - Guidance for Industry on Active Controls in Studies To Demonstrate Effectiveness of a New Animal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0419... controls and have a basic understanding of statistical principles. DATES: Submit either electronic or... the Agency's current thinking on the topic. It does not create or confer any rights for or on any...

In vivo recording of aerodynamic force with an aerodynamic force platform: from drones to birds.

PubMed

Lentink, David; Haselsteiner, Andreas F; Ingersoll, Rivers

2015-03-06

Flapping wings enable flying animals and biomimetic robots to generate elevated aerodynamic forces. Measurements that demonstrate this capability are based on experiments with tethered robots and animals, and indirect force calculations based on measured kinematics or airflow during free flight. Remarkably, there exists no method to measure these forces directly during free flight. Such in vivo recordings in freely behaving animals are essential to better understand the precise aerodynamic function of their flapping wings, in particular during the downstroke versus upstroke. Here, we demonstrate a new aerodynamic force platform (AFP) for non-intrusive aerodynamic force measurement in freely flying animals and robots. The platform encloses the animal or object that generates fluid force with a physical control surface, which mechanically integrates the net aerodynamic force that is transferred to the earth. Using a straightforward analytical solution of the Navier-Stokes equation, we verified that the method is accurate. We subsequently validated the method with a quadcopter that is suspended in the AFP and generates unsteady thrust profiles. These independent measurements confirm that the AFP is indeed accurate. We demonstrate the effectiveness of the AFP by studying aerodynamic weight support of a freely flying bird in vivo. These measurements confirm earlier findings based on kinematics and flow measurements, which suggest that the avian downstroke, not the upstroke, is primarily responsible for body weight support during take-off and landing.

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

PubMed

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

2011-01-01

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

A review on prevalence, control measure, and tolerance of Tanzania Shorthorn Zebu cattle to East Coast fever in Tanzania.

PubMed

Laisser, E L K; Chenyambuga, S W; Karimuribo, E D; Msalya, G; Kipanyula, M J; Mwilawa, A J; Mdegela, R H; Kusiluka, L J M

2017-04-01

In Tanzania, control of East Coast fever (ECF) has predominantly relied on tick control using acaricides and chemotherapy, little on ECF vaccination, and very little on dissemination regarding animal immunization. In this paper, the prevalence, control measure, and tolerance of Tanzania Shorthorn Zebu (TSHZ) cattle to ECF are reviewed. In addition, the opportunities available for reducing the use of acaricides for the benefit of the farmers in terms of reduction of costs of purchasing acaricides and environmental pollution are described. The tick distribution and epidemiological factors for ECF such as the agro-ecological zones (AEZ), livestock production systems (LPS), strain, and age of the animals are also described. These factors influence the epidemiology of ECF and the distribution of TSHZ strains in different geographic locations of Tanzania. We have further showed that there is a tendency of farmers to select among the strains of TSHZ for animals which can tolerate ticks and ECF and crossbreed them with their local strains with the aim of benefiting from the inherent characteristics of the most tolerant strains. Generally, many strains of TSHZ cattle are tolerant to tick infestation and ECF infection and can be bred to respond to the needs of the people. In this review paper, we recommend that in future, ECF epidemiological studies should account for factors such as livestock production system, agro-climate, breed of animal, tick control strategy, and the dynamic interactions between them. In conclusion, we have demonstrated that an integrated control method involving use of acaricides, immunization, and ECF-tolerant/-resistant animals is required.

Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

NASA Astrophysics Data System (ADS)

Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

2017-04-01

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ɛ-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model.

PubMed

Al-Ghobashy, Medhat A; ElMeshad, Aliaa N; Abdelsalam, Rania M; Nooh, Mohammed M; Al-Shorbagy, Muhammad; Laible, Götz

2017-04-20

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ε-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

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.

Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats.

PubMed

Napimoga, Marcelo H; Benatti, Bruno B; Lima, Flavia O; Alves, Polyanna M; Campos, Alline C; Pena-Dos-Santos, Diego R; Severino, Fernando P; Cunha, Fernando Q; Guimarães, Francisco S

2009-02-01

Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties. In the present study we tested the effects of CBD in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying these effects. Periodontal disease was induced by a ligature placed around the mandible first molars of each animal. Male Wistar rats were divided into 3 groups: control animals; ligature-induced animals treated with vehicle and ligature-induced animals treated with CBD (5 mg/kg, daily). Thirty days after the induction of periodontal disease the animals were sacrificed and mandibles and gingival tissues removed for further analysis. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappaB ligand RANKL/RANK. Moreover, gingival tissues from the CBD-treated group showed decreased neutrophil migration (MPO assay) associated with lower interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha production. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats.

Ethanol modifies the effect of handling stress on gene expression: problems in the analysis of two-way gene expression studies in mouse brain.

PubMed

Rulten, Stuart L; Ripley, Tamzin L; Manerakis, Ektor; Stephens, David N; Mayne, Lynne V

2006-08-02

Studies analysing the effects of acute treatments on animal behaviour and brain biochemistry frequently use pairwise comparisons between sham-treated and -untreated animals. In this study, we analyse expression of tPA, Grik2, Smarca2 and the transcription factor, Sp1, in mouse cerebellum following acute ethanol treatment. Expression is compared to saline-injected and -untreated control animals. We demonstrate that acute i.p. injection of saline may alter gene expression in a gene-specific manner and that ethanol may modify the effects of sham treatment on gene expression, as well as inducing specific effects independent of any handling related stress. In addition to demonstrating the complexity of gene expression in response to physical and environmental stress, this work raises questions on the interpretation and validity of studies relying on pairwise comparisons.

Mapping Resting-State Brain Networks in Conscious Animals

PubMed Central

Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

2010-01-01

In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

Avian-specific real-time PCR assay for authenticity control in farm animal feeds and pet foods.

PubMed

Pegels, Nicolette; González, Isabel; García, Teresa; Martín, Rosario

2014-01-01

A highly sensitive TaqMan real-time PCR assay targeting the mitochondrial 12S rRNA gene was developed for detection of an avian-specific DNA fragment (68bp) in farm animal and pet feeds. The specificity of the assay was verified against a wide representation of animal and plant species. Applicability assessment of the avian real-time PCR was conducted through representative analysis of two types of compound feeds: industrial farm animal feeds (n=60) subjected to extreme temperatures, and commercial dog and cat feeds (n=210). Results obtained demonstrated the suitability of the real-time PCR assay to detect the presence of low percentages of highly processed avian material in the feed samples analysed. Although quantification results were well reproducible under the experimental conditions tested, an accurate estimation of the target content in feeds is impossible in practice. Nevertheless, the method may be useful as an alternative tool for traceability purposes within the framework of feed control. Copyright © 2013 Elsevier Ltd. All rights reserved.

Testosterone regulates erectile function and Vcsa1 expression in the corpora of rats.

PubMed

Chua, Rowena G; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E; Melman, Arnold; Davies, Kelvin P

2009-05-06

Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4 ng/ml to <0.04 ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2 mg in 100ml sesame oil every 4 days for 2 weeks) restored average levels of testosterone to 2 ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls.

Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus).

PubMed

Demas, Gregory E; Polacek, Kelly M; Durazzo, Alfredo; Jasnow, Aaron M

2004-12-01

Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.

Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

PubMed

Artico, Marco; Riganò, Rachele; Buttari, Brigitta; Profumo, Elisabetta; Ionta, Brunella; Bosco, Sandro; Rasile, Manuela; Bianchi, Enrica; Bruno, Moira; Fumagalli, Lorenzo

2011-04-01

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

Anti-coccidial activity of the ethanol extract of Tribulus terrestris fruits on Eimeria tenella

PubMed Central

Hong, Sunhwa; Moon, Mi-Na; Im, Eun-Kyung; Won, Jum-Soon; Yoo, Ji-Hyun

2018-01-01

Anti-coccidial effects of the fruits of Tribulus terrestris (Tribuli fructus) ethanol extract (TTE) were studied with animal experiment following per oral administration with Eimeria (E.) tenella. This experiment was performed on the 3-day-old chicks (n=30). The animals were divided with 3 groups; TFE 15mg per animal+infected (n=10), TTE untreated+infected (n=10) and non-infected control (n=10). Animals were administrated with or without TTE during 1 week, and then inoculated with E. tenella. The anti-coccidial activity were evaluated with oocysts shedding numbers in stools, body weights changes and food intake changes. The TTE-inoclated animals revealed significantly decreased stool oocysts numbers (P<0.05) when compared to the TTE untreated animals. Also, TTE-treated animals showed more increased body weight gains (P<0.05) than the TTE untreated animals. These results demonstrate that TTE produce anticoccidial activities against E. tenella. TTE could be a promising treatment for the coccidiosis. PMID:29628976

Anti-coccidial activity of the ethanol extract of Tribulus terrestris fruits on Eimeria tenella.

PubMed

Hong, Sunhwa; Moon, Mi-Na; Im, Eun-Kyung; Won, Jum-Soon; Yoo, Ji-Hyun; Kim, Okjin

2018-03-01

Anti-coccidial effects of the fruits of Tribulus terrestris (Tribuli fructus) ethanol extract (TTE) were studied with animal experiment following per oral administration with Eimeria ( E .) tenella . This experiment was performed on the 3-day-old chicks (n=30). The animals were divided with 3 groups; TFE 15mg per animal+infected (n=10), TTE untreated+infected (n=10) and non-infected control (n=10). Animals were administrated with or without TTE during 1 week, and then inoculated with E. tenella . The anti-coccidial activity were evaluated with oocysts shedding numbers in stools, body weights changes and food intake changes. The TTE-inoclated animals revealed significantly decreased stool oocysts numbers ( P <0.05) when compared to the TTE untreated animals. Also, TTE-treated animals showed more increased body weight gains ( P <0.05) than the TTE untreated animals. These results demonstrate that TTE produce anticoccidial activities against E. tenella . TTE could be a promising treatment for the coccidiosis.

THE ABSCOPAL EFFECT OF X IRRADIATION ON BONE GROWTH IN RATS

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

Pappas, A.M.; Cohen, J.

1963-06-01

The abscopal effect of irradiation (that which is evident at a distance from the irradiated volume but within the same organism) was investigated in rats. It was possible to demonstrate the effects on growth locally and abscopally when x-ray doses of 400 and 800 r were delivered to the lower extremity and when 800 r was delivered to the knee alone. A distinction between abscopal effects after local irradiation and systemic effects after whole-body irradiation is discussed. The weights of control and irradiated animals were similar for the first 21 days, during which period they did not exhibit any untowardmore » effects of irradiation. However, after 21 days there was a decrease in weight gain, which persisted until the 72nd day. Group A (controls) was the heaviest group, with a mean weight of 412 g. Group B (800 r to the left hind extremity) had a mean weight of 378. Group C (400 r to the left hind extremity) and Group D (800 r to the left knee) exhibited mean weights of 391 and 394 g, respectively. Roentgenographic measurements revealed that all animals receiving irradiation had retardation in the growth of the irradiated tibiae, which were shorter than both the control and the contralateral (unirradiated) tibiae. Only the animals that had received 800 r to their leff hind extremity showed significant differences in the lengths of their unirradiated bones compared with the bones of the control animals of Group A, that is, a significant abscopal growth retardation. Although the abscopal effect appeared to be associated with the volume of tissue irradiated, the way this effect is mediated is not known. The weight gains of the animals demonstrated a strong association between decrease in weight gain, the volume of tissue irradiated, and the dose administered. The impaired weight gsin roughly paralleled the abscopal retardation of bone growth. The animals which received the highest dose of irradiation, 800 r, to the largest volume of tissue, 10% of the body volume, revealed the greatest deviation from the control group. It is concluded that irradiation effects in animals are composites of the responses of the whole organism to the injury, of the responses of local tissues, and vessels at their level of tissue organization, and of the responses of individual cells. All of these responses may be interdependent. The evidence indicates that a systemic inhibition of all bone growth and weight gain occurs when a sufficient volume of tissue is irradiated at a sufficiently high dosage. (BBB)« less

Parasitological surveillance in a rat (Rattus norvegicus) colony in São Paulo Zoo animal house

PubMed

Chagas, Carolina Romeiro Fernandes; Gonzalez, Irys Hany Lima; Favoretto, Samantha Mesquita; Ramos, Patrícia Locosque

Rattus norvegicus (Mammalia: Rodentia) is a widespread and synanthropic rodent, broadly used in medical experiments. It can also be used for feeding captive animals in zoos. Parasitological surveys are important to guarantee the health of both the animals and the staff responsible for their management. The aim of this study was to identify intestinal parasites of Rattus norvegicus offered as food to captive animals from São Paulo Zoo, and demonstrate the importance of sanitary hurdling, disease control and biosecurity. The identified protozoan parasites were Eimeria sp., Entamoeba sp., Spironucleus sp., Giardia sp., Tritrichomonas sp., Chilomastix sp., unidentified cysts and non-sporulated coccidians oocysts (Isospora/Eimeria). The following helminths were found: Syphacia muris, Rodentolepis nana and Aspiculuris tetraptera.

Does accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) ensure greater compliance with animal welfare laws?

PubMed

Goodman, Justin R; Chandna, Alka; Borch, Casey

2015-01-01

Accreditation of nonhuman animal research facilities by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) is widely considered the "gold standard" of commitment to the well being of nonhuman animals used in research. AAALAC-accredited facilities receive preferential treatment from funding agencies and are viewed favorably by the general public. Thus, it bears investigating how well these facilities comply with U.S. animal research regulations. In this study, the incidences of noncompliance with the Animal Welfare Act (AWA) at AAALAC-accredited facilities were evaluated and compared to those at nonaccredited institutions during a period of 2 years. The analysis revealed that AAALAC-accredited facilities were frequently cited for AWA noncompliance items (NCIs). Controlling for the number of animals at each facility, AAALAC-accredited sites had significantly more AWA NCIs on average compared with nonaccredited sites. AAALAC-accredited sites also had more NCIs related to improper veterinary care, personnel qualifications, and animal husbandry. These results demonstrate that AAALAC accreditation does not improve compliance with regulations governing the treatment of animals in laboratories.

The Interaction of Ethanol Ingestion and Social Interaction with an Intoxicated Peer on the Odor-Mediated Response to the Drug in Adolescent Rats.

PubMed

Eade, Amber M; Youngentob, Lisa M; Youngentob, Steven L

2016-04-01

Using a social transmission of food preference paradigm in rats, we previously demonstrated that ethanol (EtOH) exposure during adolescence, as either an observer (interaction with an intoxicated conspecific) or demonstrator (intragastric infusion with EtOH), altered the reflexive odor-mediated responses to the drug. The 2 modes of exposure were equivalent in the magnitude of their effects. Human adolescents, however, are likely to experience the drug in a social setting as both an EtOH observer and demonstrator. That is, both interacting with an intoxicated peer and experiencing EtOH's postingestive consequences in conjunction with hematogenic olfaction. Therefore, we tested whether combined adolescent exposure as both an observer and demonstrator differed from either form of individual experience. Beginning on postnatal day (P) 29, naïve rats received EtOH or water exposures in a social interaction paradigm as either an observer, a demonstrator, or combined experience (where each animal in the interaction was, itself, an observer and demonstrator). Exposures occurred 4 times, once every 48 hours. On P37, the reflexive behavioral response to EtOH odor was tested, using whole-body plethysmography. The odor-mediated responses of adolescent EtOH observers, demonstrators, and combined exposure animals all significantly differed from controls. Compared to controls, however, the magnitude of the behavioral effect was greatest in the combined exposure animals. Moreover, combined exposure as both an EtOH observer and demonstrator significantly differed from either form of individual EtOH experience. EtOH's component chemosensory qualities are known to be central contributors to its acceptance and increases in the acceptability of EtOH's odor, resulting from a social transmission experience, are predictive of enhanced EtOH avidity in adolescence. Our findings demonstrate that combined exposure as an observer and demonstrator, within a socially relevant framework, may represent a higher risk scenario for increased EtOH avidity in adolescence (and by extension adult persistence) as compared to the individual effects of direct ingestion or social experience with the drug. Copyright © 2016 by the Research Society on Alcoholism.

Modeling, Control, and Estimation of Flexible, Aerodynamic Structures

NASA Astrophysics Data System (ADS)

Ray, Cody W.

Engineers have long been inspired by nature’s flyers. Such animals navigate complex environments gracefully and efficiently by using a variety of evolutionary adaptations for high-performance flight. Biologists have discovered a variety of sensory adaptations that provide flow state feedback and allow flying animals to feel their way through flight. A specialized skeletal wing structure and plethora of robust, adaptable sensory systems together allow nature’s flyers to adapt to myriad flight conditions and regimes. In this work, motivated by biology and the successes of bio-inspired, engineered aerial vehicles, linear quadratic control of a flexible, morphing wing design is investigated, helping to pave the way for truly autonomous, mission-adaptive craft. The proposed control algorithm is demonstrated to morph a wing into desired positions. Furthermore, motivated specifically by the sensory adaptations organisms possess, this work transitions to an investigation of aircraft wing load identification using structural response as measured by distributed sensors. A novel, recursive estimation algorithm is utilized to recursively solve the inverse problem of load identification, providing both wing structural and aerodynamic states for use in a feedback control, mission-adaptive framework. The recursive load identification algorithm is demonstrated to provide accurate load estimate in both simulation and experiment.

Gait control in a soft robot by sensing interactions with the environment using self-deformation.

PubMed

Umedachi, Takuya; Kano, Takeshi; Ishiguro, Akio; Trimmer, Barry A

2016-12-01

All animals use mechanosensors to help them move in complex and changing environments. With few exceptions, these sensors are embedded in soft tissues that deform in normal use such that sensory feedback results from the interaction of an animal with its environment. Useful information about the environment is expected to be embedded in the mechanical responses of the tissues during movements. To explore how such sensory information can be used to control movements, we have developed a soft-bodied crawling robot inspired by a highly tractable animal model, the tobacco hornworm Manduca sexta . This robot uses deformations of its body to detect changes in friction force on a substrate. This information is used to provide local sensory feedback for coupled oscillators that control the robot's locomotion. The validity of the control strategy is demonstrated with both simulation and a highly deformable three-dimensionally printed soft robot. The results show that very simple oscillators are able to generate propagating waves and crawling/inching locomotion through the interplay of deformation in different body parts in a fully decentralized manner. Additionally, we confirmed numerically and experimentally that the gait pattern can switch depending on the surface contact points. These results are expected to help in the design of adaptable, robust locomotion control systems for soft robots and also suggest testable hypotheses about how soft animals use sensory feedback.

Gait control in a soft robot by sensing interactions with the environment using self-deformation

PubMed Central

Ishiguro, Akio; Trimmer, Barry A.

2016-01-01

All animals use mechanosensors to help them move in complex and changing environments. With few exceptions, these sensors are embedded in soft tissues that deform in normal use such that sensory feedback results from the interaction of an animal with its environment. Useful information about the environment is expected to be embedded in the mechanical responses of the tissues during movements. To explore how such sensory information can be used to control movements, we have developed a soft-bodied crawling robot inspired by a highly tractable animal model, the tobacco hornworm Manduca sexta. This robot uses deformations of its body to detect changes in friction force on a substrate. This information is used to provide local sensory feedback for coupled oscillators that control the robot's locomotion. The validity of the control strategy is demonstrated with both simulation and a highly deformable three-dimensionally printed soft robot. The results show that very simple oscillators are able to generate propagating waves and crawling/inching locomotion through the interplay of deformation in different body parts in a fully decentralized manner. Additionally, we confirmed numerically and experimentally that the gait pattern can switch depending on the surface contact points. These results are expected to help in the design of adaptable, robust locomotion control systems for soft robots and also suggest testable hypotheses about how soft animals use sensory feedback. PMID:28083114

Neuroprotective properties of curcumin in toxin-base animal models of Parkinson's disease: a systematic experiment literatures review.

PubMed

Wang, Xin-Shi; Zhang, Zeng-Rui; Zhang, Man-Man; Sun, Miao-Xuan; Wang, Wen-Wen; Xie, Cheng-Long

2017-08-17

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective actions of curcumin have been documented for experimental therapy in Parkinson's disease (PD). In this study, we used a systematic review to comprehensively assess the efficacy of curcumin in experimental PD. Using electronic and manual search for the literatures, we identified studies describing the efficacy of curcumin in animal models of PD. We identified 13 studies with a total of 298 animals describing the efficacy of curcumin in animal models of PD. The methodological quality of all preclinical trials is ranged from 2 to 5. The majority of the experiment studies demonstrated that curcumin was more significantly neuroprotection effective than control groups for treating PD. Among them, five studies indicated that curcumin had an anti-inflammatory effect in the PD animal models (p < 0.05). Meanwhile, four studies showed the antioxidant capability of curcumin, by which it protected substantia nigra neurons and improved striatal dopamine levels. Furthermore, two studies in this review displayed that curcumin treatment was also effective in reducing neuronal apoptosis and improving functional outcome in animal models of PD. Most of the preclinical studies demonstrated the positive findings while one study reported that curcumin had no beneficial effects against Mn-induced disruption of hippocampal metal and neurotransmitter homeostasis. The results demonstrated a marked efficacy of curcumin in experimental model of PD, suggesting curcumin probably a candidate neuroprotective drug for human PD patients.

AnimatLab: a 3D graphics environment for neuromechanical simulations.

PubMed

Cofer, David; Cymbalyuk, Gennady; Reid, James; Zhu, Ying; Heitler, William J; Edwards, Donald H

2010-03-30

The nervous systems of animals evolved to exert dynamic control of behavior in response to the needs of the animal and changing signals from the environment. To understand the mechanisms of dynamic control requires a means of predicting how individual neural and body elements will interact to produce the performance of the entire system. AnimatLab is a software tool that provides an approach to this problem through computer simulation. AnimatLab enables a computational model of an animal's body to be constructed from simple building blocks, situated in a virtual 3D world subject to the laws of physics, and controlled by the activity of a multicellular, multicompartment neural circuit. Sensor receptors on the body surface and inside the body respond to external and internal signals and then excite central neurons, while motor neurons activate Hill muscle models that span the joints and generate movement. AnimatLab provides a common neuromechanical simulation environment in which to construct and test models of any skeletal animal, vertebrate or invertebrate. The use of AnimatLab is demonstrated in a neuromechanical simulation of human arm flexion and the myotactic and contact-withdrawal reflexes. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

Desjardins, G.C.; Beaudet, A.; Brawer, J.R.

The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioidmore » binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.« less

The benefits of 'One Health' for pastoralists in Africa.

PubMed

Greter, Helena; Jean-Richard, Vreni; Crump, Lisa; Béchir, Mahamat; Alfaroukh, Idriss O; Schelling, Esther; Bonfoh, Bassirou; Zinsstag, Jakob

2014-04-23

'One health' is particularly suited to serve mobile pastoralists. Dinka pastoralists in Sudan inspired Calvin Schwabe to coin the term 'one medicine', indicating that there is no difference in paradigm between human and veterinary medicine. Our contemporary definition of 'one health' is any added value in terms of improved health of humans and animals or financial savings or environmental services resulting from a closer cooperation of human and animal health sectors. Here we present a summary of 'one health' studies with mobile pastoralists in Africa which were done in research partnership, demonstrating such an added value. Initial joint human and animal health studies revealed higher livestock vaccination coverage than in the pastoralist community, leading to joint animal and human vaccination intervention studies which demonstrated a better access to primary health care services for pastoralists in Chad. Further simultaneous animal and human serological studies showed that camel breeding was associated with human Q-fever seropositivity. In Borana communities in Ethiopia, human cases of Mycobacterium bovis infection could be related to strains isolated from cattle. A challenge remained with regard to how to assess vaccination coverage in mobile populations. With the advent of mobile phones, health and demographic surveillance could be established for mobile pastoralists and their animals. This presents vast possibilities for surveillance and control of human and animal diseases. Pastoralists prefer a 'one health' approach and therefore contribute toward the validation of this concept by showing real added value of the cooperation between human and animal health services.

Computer-task testing of rhesus monkeys (Macaca mulatta) in the social milieu.

PubMed

Washburn, D A; Harper, S; Rumbaugh, D M

1994-07-01

Previous research has demonstrated that a behavior and performance testing paradigm, in which rhesus monkeys (Macaca mulatta) manipulate a joystick to respond to computer-generated stimuli, provides environmental enrichment and supports the psychological well-being of captive research animals. The present study was designed to determine whether computer-task activity would be affected by pair-housing animals that had previously been tested only in their single-animal home cages. No differences were observed in productivity or performance levels as a function of housing condition, even when the animals were required to "self-identify" prior to performing each trial. The data indicate that cognitive challenge and control are as preferred by the animals as social opportunities, and that, together with comfort/health considerations, each must be addressed for the assurance of psychological well-being.

Enzymatic recontouring of auricular cartilage in a rabbit model.

PubMed

Massengill, Phillip L; Goco, Paulino E; Norlund, L Layne; Muir-Padilla, Jeanne

2005-01-01

To evaluate the effectiveness of contouring auricular cartilage in a rabbit model using biologically active enzymes injected subcutaneously. The first phase determined the most effective volume and concentration required to affect the cartilage. To accomplish this task, we used ex vivo rabbit ears from a slaughterhouse. In the second phase, we injected 1 mL of hyaluronidase (150 U per milliliter of isotonic sodium chloride solution [saline]), elastase (1 mg per milliliter of saline), or saline into the ears of live rabbits. The study took place at the Madigan Army Medical Center (Tacoma, Wash), and included 10 animals. In each rabbit, we injected the test compound in one ear and saline in the other ear (control). We injected hyaluronidase in 5 ears and elastase in 5 ears. After injection, the ears were contoured and splinted for 4 weeks. In the third phase, we changed the injection pathway in 5 animals. At 4 weeks, 4 (80%) of the 5 ears injected with hyaluronidase showed full response and 1 (20%) had a partial response. Of the 5 ears injected with elastase, 4 (80%) showed a full response while 1 (20%) demonstrated a partial response. There was a response in all 10 of the ears injected with a test compound. Of the 10 control ears, 3 (30%) showed a partial response. At 6 weeks, approximately 6 (30%) of the ears had maintained contour demonstrating a full response. The difference between the test ears and the control ears was statistically significant (P = .006). Compared with the control ears, the results were statistically significant for elastase (P = .004) and hyaluronidase (P = .02). Overall, both agents demonstrated a subjective and objective response compared with control ears. This study demonstrates that bioactive enzymes and splinting can be effective in correcting ear deformities in a rabbit model.

KISS1 can be used as a novel target for developing a DNA immunocastration vaccine in ram lambs.

PubMed

Han, Yanguo; Liu, Guiqiong; Jiang, Xunping; Ijaz, Nabeel; Tesema, Birhanu; Xie, Guangyue

2015-02-04

KISS1 gene-encoding kisspeptins are critical for the onset of puberty and control of adult fertility. This study investigated whether KISS1 can be used as a novel target for immunocastration. Human KISS1 was fused with the HBsAg-S gene for constructing an antibiotic-free recombinant plasmid pKS-asd that coded for 31.168 kDa target fusion protein. Six male Hu sheep lambs were divided into two equal groups, treatment and control. The vaccine (1mg/ram lamb) prepared in saline solution was injected into lambs at weeks 0, 3 and 6 of the experiment, respectively. Vaccine efficacy was evaluated in terms of KISS1-specific IgG antibody response, serum testosterone levels, scrotal circumference, testicular weight, length and breadth, extent of testicular tissue damage, and sexual behaviour changes. The specific anti-KISS1 antibody titre in vaccinated animals was significantly higher than that in controls (p<0.05). In addition, vaccinated animals showed lower serum testosterone level, testicular weight and length and smaller scrotal circumference than those in controls (p<0.05). Spermatogenesis of seminiferous tubules in vaccinated animals was suppressed; sexual behaviours in vaccinated animals were significantly lower (p<0.05) than those in controls. In conclusion, the immunization against KISS1 in this DNA vaccine induced a strong antibody response and resulted in the suppression of gonadal function and sexual behaviour in animals, demonstrating that KISS1 can be used as a novel target for developing a DNA immunocastration vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Tonsillar PolyICLC/AT-2 SIV Therapeutic Vaccine Maintains Low Viremia Following Antiretroviral Therapy Cessation

PubMed Central

Vagenas, Panagiotis; Aravantinou, Meropi; Williams, Vennansha G.; Jasny, Edith; Piatak, Michael; Lifson, Jeffrey D.; Salazar, Andres M.; Blanchard, James L.; Gettie, Agegnehu; Robbiani, Melissa

2010-01-01

Background HIV-infected individuals rely on antiretroviral therapy (ART) to control viral replication. Despite abundant demonstrable benefits, the multiple limitations of ART point to the potential advantages of therapeutic vaccination approaches that could provide sustained host control of viral replication after discontinuation of ART. We provide evidence from a non-human primate model that a therapeutic vaccine applied to the tonsils can maintain low viral loads after cessation of ART. Methodology/Principal Findings Animals received 40 weeks of ART initiated 9 weeks after rectal SIVmac239 infection. During ART, animals were vaccinated (or not) with AT-2 inactivated SIVmac239 using CpG-C ISS-ODN (C274) or polyICLC as adjuvants. PolyICLC/AT-2 SIV vaccinated animals maintained viral loads <3×103 copies/ml for up to 16 weeks post-ART, whereas the C274/AT-2 SIV vaccinated and non-vaccinated animals' viremia ranged between 1×104–4×105 copies/ml (p<0.03). Neutralizing Ab activity in plasma was increased by polyICLC/AT-2 tonsillar vaccination under ART, compared to controls (p<0.03). Subsequent vaccination of all animals with polyICLC/AT-2 SIV in the absence of ART did not alter viral loads. Other immune parameters measured in blood and tissues were comparable between groups. Conclusions/Significance These results provide support for the potential benefit of mucosally delivered vaccines in therapeutic immunization strategies for control of AIDS virus infection. PMID:20877632

Decentralized control mechanism underlying interlimb coordination of millipedes.

PubMed

Kano, Takeshi; Sakai, Kazuhiko; Yasui, Kotaro; Owaki, Dai; Ishiguro, Akio

2017-04-04

Legged animals exhibit adaptive and resilient locomotion through interlimb coordination. The long-term goal of this study is to clarify the relationship between the number of legs and the inherent decentralized control mechanism for interlimb coordination. As a preliminary step, the study focuses on millipedes as they represent the species with the greatest number of legs among various animal species. A decentralized control mechanism involving local force feedback was proposed based on the qualitative findings of behavioural experiments in which responses to the removal of part of the terrain and leg amputation were observed. The proposed mechanism was implemented in a developed millipede-like robot to demonstrate that the robot can adapt to the removal of the part of the terrain and leg amputation in a manner similar to that in behavioural experiments.

Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis?

PubMed

Murnaghan, Mark; Li, Gang; Marsh, David R

2006-11-01

Approximately 5% to 10% of fractures may result in delayed union or nonunion. The results of research done over the past three decades have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has an inhibitory effect on fracture repair, but the exact mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID-induced nonunions. This hypothesis was investigated in a randomized placebo-controlled trial of the NSAID rofecoxib with use of a murine femoral fracture model. Two hundred and forty mice were randomized to receive either the nonsteroidal anti-inflammatory drug rofecoxib (5 mg/kg orally) in a 0.5% methylcellulose solution (the NSAID group) or the 0.5% methylcellulose solution only (the control group). Two hundred and thirty-five of the 240 mice underwent surgery to induce an open transverse middiaphyseal femoral fracture, which was then treated with use of a custom-made external fixator. Five additional animals underwent sham surgery with no fracture induced. Outcomes measures included radiographic assessment, histologic analysis, biomechanical testing, and use of laser Doppler flowmetry to assess blood flow across the fracture gap. Radiography revealed similar healing patterns in both groups; however, at the later stages (day 32), the NSAID group had poorer healing. Histological analysis demonstrated that the control animals healed quicker (at days 24 and 32) and had more callus and less fibrous tissue (at days 8 and 32) than the NSAID animals did. Biomechanical testing found that the control animals were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however, the NSAID group exhibited a lower median flow from day 4 onward (significant at days 4, 16, and 24). Positive correlations were demonstrated between both histological and radiographic assessments of healing and increasing blood flow. NSAID-treated animals exhibited lower blood flow and poorer healing by all parameters. Regression analysis, however, demonstrated that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow. Following the development of a novel method of analyzing functional vascularity across a fracture gap, we have demonstrated that the cyclooxygenase-2 (COX-2) inhibitor rofecoxib has a significant negative effect on blood flow across the fracture gap as well as an inhibiting effect on fracture repair. COX-2 inhibitors are marketed as having low side-effect profiles. We propose that these drugs should be used with caution in all patients following osseous trauma and, in particular, after injuries that may already predispose a fracture to a delayed union due to osseous, vascular, or patient-related factors.

Adaptations of the aging animal to exercise: role of daily supplementation with melatonin.

PubMed

Mendes, Caroline; Lopes, Ana Maria de Souza; do Amaral, Fernanda Gaspar; Peliciari-Garcia, Rodrigo A; Turati, Ariane de Oliveira; Hirabara, Sandro M; Scialfa Falcão, Julieta H; Cipolla-Neto, José

2013-10-01

The pineal gland, through melatonin, seems to be of fundamental importance in determining the metabolic adaptations of adipose and muscle tissues to physical training. Evidence shows that pinealectomized animals fail to develop adaptive metabolic changes in response to aerobic exercise and therefore do not exhibit the same performance as control-trained animals. The known prominent reduction in melatonin synthesis in aging animals led us to investigate the metabolic adaptations to physical training in aged animals with and without daily melatonin replacement. Male Wistar rats were assigned to four groups: sedentary control (SC), trained control (TC), sedentary treated with melatonin (SM), and trained treated with melatonin (TM). Melatonin supplementation lasted 16 wk, and the animals were subjected to exercise during the last 8 wk of the experiment. After euthanasia, samples of liver, muscle, and adipose tissues were collected for analysis. Trained animals treated with melatonin presented better results in the following parameters: glucose tolerance, physical capacity, citrate synthase activity, hepatic and muscular glycogen content, body weight, protein expression of phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and protein kinase activated by adenosine monophosphate (AMPK) in the liver, as well as the protein expression of the glucose transporter type 4 (GLUT4) and AMPK in the muscle. In conclusion, these results demonstrate that melatonin supplementation in aging animals is of great importance for the required metabolic adaptations induced by aerobic exercise. Adequate levels of circulating melatonin are, therefore, necessary to improve energetic metabolism efficiency, reducing body weight and increasing insulin sensitivity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Wireless powering and data telemetry for biomedical implants.

PubMed

Young, Darrin J

2009-01-01

Wireless powering and data telemetry techniques for two biomedical implant studies based on (1) wireless in vivo EMG sensor for intelligent prosthetic control and (2) adaptively RF powered implantable bio-sensing microsystem for real-time genetically engineered mice monitoring are presented. Inductive-coupling-based RF powering and passive data telemetry is effective for wireless in vivo EMG sensing, where the internal and external RF coils are positioned with a small separation distance and fixed orientation. Adaptively controlled RF powering and active data transmission are critical for mobile implant application such as real-time physiological monitoring of untethered laboratory animals. Animal implant studies have been successfully completed to demonstrate the wireless and batteryless in vivo sensing capabilities.

Insularity and the determinants of lizard population density.

PubMed

Buckley, Lauren B; Jetz, Walter

2007-06-01

The relative effects of resource availability and partitioning on animal population density are unresolved yet central to ecology and conservation. Species-depauperate islands offer an intriguing test case. Across 643 lizard populations from around the world, local abundances are one order of magnitude higher on islands than on mainlands, even when controlled for resource availability. On mainlands, predator and competitor richness only weakly correlate with lizard densities. On islands, sharp reductions in predator and competitor richness are the dominant drivers of lizard abundance. Our results demonstrate the dramatic effect insularity has on the interplay between biotic and abiotic control of animal abundances and the heightened sensitivity of island communities to species' losses and gains.

The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

PubMed

Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

2012-07-01

Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

Targeted delivery of an antisense oligonucleotide in the retina: uptake, distribution, stability, and effect.

PubMed

Rakoczy, P E; Lai, M C; Watson, M; Seydel, U; Constable, I

1996-01-01

In this article, we describe the preliminary results of the development of an animal model that will enable us to study the effect of photoreceptor-derived debris accumulation on the normal function of the retina in vivo. An antisense oligonucleotide (Cat 5), saline, and two control oligonucleotides were injected into the vitreous of 7-week-old RCS-rdy+ rats. The uptake, distribution, and persistence of the antisense oligonucleotide in the retina was demonstrated by fluorescent confocal microscopy, and the stability of the oligonucleotide was shown by GeneScan analysis using a fluorescein-labeled derivative of Cat 5 (Cat 5F). The accumulation of photoreceptor-derived debris was monitored by the number of undigested phagosomes in the RPE layer by light microscopy. Following intravitreal injection of Cat 5F, penetration of the oligonucleotide was observed in the ganglion cell layer in 2 hours and in the photoreceptor and pigment epithelial layers 3 days later. However, at 7, 28, and 56 days postinjection, only the RPE layer had significant amounts of Cat 5F present. Using GeneScan analysis, it was demonstrated that the fluorescein-labeled oligonucleotide present in the RPE layer was not degraded and it retained its original 19-mer length. There was no statistically significant difference in the number of phagosomes found in the RPE layer of control uninjected, saline-injected, and two sense and two antisense oligonucleotides-injected animals at 7 and 28 days postinjection. In contrast, the number of phagosomes was significantly higher (p < 0.001) in the RPE layer of Cat 5 antisense oligonucleotide-injected animals at 7 and 28 days postinjection. This difference, however, disappeared by 56 days postinjection. The inner nuclear layers of the retina of control and experimental animals were not affected by the injections.

Compensation for Unconstrained Catheter Shaft Motion in Cardiac Catheters

PubMed Central

Degirmenci, Alperen; Loschak, Paul M.; Tschabrunn, Cory M.; Anter, Elad; Howe, Robert D.

2016-01-01

Cardiac catheterization with ultrasound (US) imaging catheters provides real time US imaging from within the heart, but manually navigating a four degree of freedom (DOF) imaging catheter is difficult and requires extensive training. Existing work has demonstrated robotic catheter steering in constrained bench top environments. Closed-loop control in an unconstrained setting, such as patient vasculature, remains a significant challenge due to friction, backlash, and physiological disturbances. In this paper we present a new method for closed-loop control of the catheter tip that can accurately and robustly steer 4-DOF cardiac catheters and other flexible manipulators despite these effects. The performance of the system is demonstrated in a vasculature phantom and an in vivo porcine animal model. During bench top studies the robotic system converged to the desired US imager pose with sub-millimeter and sub-degree-level accuracy. During animal trials the system achieved 2.0 mm and 0.65° accuracy. Accurate and robust robotic navigation of flexible manipulators will enable enhanced visualization and treatment during procedures. PMID:27525170

Limited awareness of animal influenza prevention and control among Dai Lue smallholder farmers in Southwest China.

PubMed

Zhao, Xiang; Davey, Gareth

2017-10-01

Awareness of animal influenza and its prevention and control is important for ensuring livestock health, production and welfare. In China, a country stereotyped as a major source of emerging zoonotic infectious diseases, research on the public understanding of animal influenza is limited to the Han, the main ethnic group. The present qualitative study in Southwest China investigated awareness of animal influenza among the Dai, an ethnic minority. The participants (15 men and 10 women, ages 18-83) were smallholder farmers of pigs and poultry in rural areas of Jinghong, Xishuangbanna, Yunnan Province. A mixture of interviews and group discussions took place in homes and villages. The participants were asked about their knowledge of avian influenza (H7N9), swine influenza (H1N1), precautions taken to protect against influenza, procedures when animals were sick and perceived risk of animal influenza. The data were analysed following coding and thematic analysis. The findings demonstrated a limited understanding of animal health and welfare among participants. Specifically, they were largely unaware of animal influenza (H7N9, H1N1) including its causes, symptoms, prevention and treatment. The farmers were also uninformed of the risks they faced and unknowingly engaged in behaviours which increased direct or indirect exposure to infected animals, a risk factor for human infection. They also reported poor usage of veterinary services. In order to guarantee the health, welfare and production of their livestock, immediate action is needed to enable Dai smallholder farmers to prevent and respond to animal influenza effectively and timely.

Research and demonstration to improve air quality for the U.S. animal feeding operations in the 21st century - a critical review.

PubMed

Ni, Ji-Qin

2015-05-01

There was an increasing interest in reducing production and emission of air pollutants to improve air quality for animal feeding operations (AFOs) in the U.S. in the 21st century. Research was focused on identification, quantification, characterization, and modeling of air pollutions; effects of emissions; and methodologies and technologies for scientific research and pollution control. Mitigation effects were on pre-excretion, pre-release, pre-emission, and post-emission. More emphasis was given on reducing pollutant emissions than improving indoor air quality. Research and demonstrations were generally continuation and improvement of previous efforts. Most demonstrated technologies were still in a limited scale of application. Future efforts are needed in many fundamental and applied research areas. Advancement in instrumentation, computer technology, and biological sciences and genetic engineering is critical to bring major changes in this area. Development in research and demonstration will depend on the actual political, economic, and environmental situations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Progress Report: Transportable Gasifier for On-Farm Disposal ...

EPA Pesticide Factsheets

Report A prototype transportable gasifier intended to process a minimum of 25 tons per day of animal mortalities (scalable to 200 tons per day) was built as part of an interagency effort involving the U.S. Environmental Protection Agency, the Department of Homeland Security, the U.S. Department of Agriculture, and the Department of Defense as well as the State of North Carolina. This effort is intended to demonstrate the feasibility of gasification for disposal of contaminated carcasses and to identify technical challenges and improvements that will simplify, improve, and enhance the gasifier system as a mobile response tool. Initial testing of the prototype in 2008 and 2010 demonstrated partial success by meeting the transportability and rapid deployment requirements. However, the throughput of animal carcasses was approximately 1/3 of the intended design capacity. Modifications have been made to the fuel system, burner system, feed system, control system, power distribution, and ash handling system to increase its operating capacity to the rated design throughput. Further testing will be performed to demonstrate the throughput as well as to demonstrate the ability of the unit to operate around the clock for an extended period of time. This report gives a status update on the progress of the project. Purpose is to give an update on the Transportable Animal Carcass Gasifier.

Handedness helps homing in swimming and flying animals.

PubMed

Bandyopadhyay, Promode R; Leinhos, Henry A; Hellum, Aren M

2013-01-01

Swimming and flying animals rely on their ability to home on mobile targets. In some fish, physiological handedness and homing correlate, and dolphins exhibit handedness in their listening response. Here, we explore theoretically whether the actuators, sensors, and controllers in these animals follow similar laws of self-regulation, and how handedness affects homing. We find that the acoustic sensor (combined hydrophone-accelerometer) response maps are similar to fin force maps-modeled by Stuart-Landau oscillators-allowing localization by transitional vortex-propelled animals. The planar trajectories of bats in a room filled with obstacles are approximately reproduced by the states of a pair of strong and weak olivo-cerebellar oscillators. The stereoscopy of handedness reduces ambiguity near a mobile target, resulting in accelerated homing compared to even-handedness. Our results demonstrate how vortex-propelled animals may be localizing each other and circumventing obstacles in changing environments. Handedness could be useful in time-critical robot-assisted rescues in hazardous environments.

Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats

PubMed Central

Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

2017-01-01

ABSTRACT High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats. PMID:28785736

Effect of High Fructose Corn Syrup (HFCS) Intake on the Female Reproductive Organs and Lipid Accumulation in Adult Rats.

PubMed

Ko, Eun-Ah; Kim, Hye-Ri; Kim, Yong-Bin; Kim, Hee-Su; Lee, Sung-Ho

2017-06-01

High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.

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.

An insect with selective control of egg coloration.

PubMed

Abram, Paul K; Guerra-Grenier, Eric; Després-Einspenner, Marie-Lyne; Ito, Shosuke; Wakamatsu, Kazumasa; Boivin, Guy; Brodeur, Jacques

2015-08-03

The color and patterning of animal eggs has important consequences for offspring survival. There are examples of between-species and polymorphic differences in egg coloration in birds and amphibians [1-3], as well as cases of birds and insects whose nutritional status or age can cause within-individual variation in egg pigmentation [4-6]. However, no studies to date have demonstrated that individual animals can selectively control the color of their eggs. Here, we show that individual females of the predatory stink bug Podisus maculiventris can control the pigmentation of their eggs during oviposition, as a response to environmental conditions. The color of egg masses produced by individual females can range from pale yellow to dark black/brown. Females tend to lay darker eggs, which are more resistant to UV radiation, on the upper surface of leaves where UV exposure is highest in nature. Conversely, they lay lighter eggs on the undersides of leaves. However, egg color is not determined by the intensity of UV radiation falling on the surface where they are laid. Rather, female stink bugs appear to use a visual assessment of oviposition substrate reflectance to determine egg color. Unexpectedly, biochemical analyses revealed that the egg pigment is not melanin, the most ubiquitous light-absorbing pigment in animals. Our study offers the first example of an animal able to selectively control the color of its eggs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The epidemiology of animal bite, scratch, and other potential rabies exposures, Louisiana.

PubMed

Balsamo, Gary A; Ratard, Raoult; Claudet, Amanda

2009-01-01

The authors conducted a review of 318 investigative reports of animal exposures recorded from November 2004 through April 2008. These reports were gathered as components of the rabies surveillance program in Louisiana. The reports were recorded by employees of the Louisiana Office of Public Health. Results were summarized and analyzed using the Centers for Disease Control and Prevention's (CDC) EpiInfo statistical software. The most common victims were children, most often exposed to a pet that was familiar. In children victimized by pets, males were much more likely to be involved. Children most often suffered injuries to the head and upper torso. Exposures to bats and skunks characterized the greatest risks for rabies transmission, but potential for exposure to rabies from pet species remained a reality. Pit bull type dogs were most frequently involved in dog bite exposures. Requests for animal rabies testing peak in the summer months. The increased risk to children demonstrates a need for public education, animal control programs, and evaluation of risk from certain breeds. Promotion of rabies vaccine compliance is of utmost importance to public health.

Metabolic Design of Corynebacterium glutamicum for Production of l-Cysteine with Consideration of Sulfur-Supplemented Animal Feed.

PubMed

Joo, Young-Chul; Hyeon, Jeong Eun; Han, Sung Ok

2017-06-14

l-Cysteine is a valuable sulfur-containing amino acid widely used as a nutrition supplement in industrial food production, agriculture, and animal feed. However, this amino acid is mostly produced by acid hydrolysis and extraction from human or animal hairs. In this study, we constructed recombinant Corynebacterium glutamicum strains that overexpress combinatorial genes for l-cysteine production. The aims of this work were to investigate the effect of the combined overexpression of serine acetyltransferase (CysE), O-acetylserine sulfhydrylase (CysK), and the transcriptional regulator CysR on l-cysteine production. The CysR-overexpressing strain accumulated approximately 2.7-fold more intracellular sulfide than the control strain (empty pMT-tac vector). Moreover, in the resulting CysEKR recombinant strain, combinatorial overexpression of genes involved in l-cysteine production successfully enhanced its production by approximately 3.0-fold relative to that in the control strain. This study demonstrates a biotechnological model for the production of animal feed supplements such as l-cysteine using metabolically engineered C. glutamicum.

Testosterone Regulates Erectile Function and Vcsa1 Expression in the Corpora of Rats

PubMed Central

Chua, Rowena G.; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E.; Melman, Arnold; Davies, Kelvin P.

2009-01-01

Summary Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4ng/ml to <0.04ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2mg in 100ml sesame oil every 4 days for two weeks) restored average levels of testosterone to 2ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls. PMID:19428993

Interleukin-15 receptor blockade in non-human primate kidney transplantation.

PubMed

Haustein, Silke; Kwun, Jean; Fechner, John; Kayaoglu, Ayhan; Faure, Jean-Pierre; Roenneburg, Drew; Torrealba, Jose; Knechtle, Stuart J

2010-04-27

Interleukin (IL)-15 is a chemotactic factor to T cells. It induces proliferation and promotes survival of activated T cells. IL-15 receptor blockade in mouse cardiac and islet allotransplant models has led to long-term engraftment and a regulatory T-cell environment. This study investigated the efficacy of IL-15 receptor blockade using Mut-IL-15/Fc in an outbred non-human primate model of renal allotransplantation. Male cynomolgus macaque donor-recipient pairs were selected based on ABO typing, major histocompatibility complex class I typing, and carboxy-fluorescein diacetate succinimidyl ester-based mixed lymphocyte responses. Once animals were assigned to one of six treatment groups, they underwent renal transplantation and bilateral native nephrectomy. Serum creatinine level was monitored twice weekly and as indicated, and protocol biopsies were performed. Rejection was defined as a increase in serum creatinine to 1.5 mg/dL or higher and was confirmed histologically. Complete blood counts and flow cytometric analyses were performed periodically posttransplant; pharmacokinetic parameters of Mut-IL-15/Fc were assessed. Compared with control animals, Mut-IL-15/Fc-treated animals did not demonstrate increased graft survival despite adequate serum levels of Mut-IL-15/Fc. Flow cytometric analysis of white blood cell subgroups demonstrated a decrease in CD8 T-cell and natural killer cell numbers, although this did not reach statistical significance. Interestingly, two animals receiving Mut-IL-15/Fc developed infectious complications, but no infection was seen in control animals. Renal pathology varied widely. Peritransplant IL-15 receptor blockade does not prolong allograft survival in non-human primate renal transplantation; however, it reduces the number of CD8 T cells and natural killer cells in the peripheral blood.

The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

PubMed Central

Yang, Hongli; Ren, Ruojin; Lockwood, Howard; Williams, Galen; Libertiaux, Vincent; Downs, Crawford; Gardiner, Stuart K.; Burgoyne, Claude F.

2015-01-01

Purpose To characterize optic nerve head (ONH) connective tissue change within 21 monkey experimental glaucoma (EG) eyes, so as to identify its principal components. Methods Animals were imaged three to five times at baseline then every 2 weeks following chronic unilateral IOP elevation, and euthanized early through end-stage confocal scanning laser tomographic change. Optic nerve heads were serial-sectioned, three-dimensionally (3D) reconstructed, delineated, and quantified. Overall EG versus control eye differences were assessed by general estimating equations (GEE). Significant, animal-specific, EG eye change was required to exceed the maximum physiologic intereye differences in six healthy animals. Results Overall EG eye change was significant (P < 0.0026) and animal-specific EG eye change most frequent, for five phenomena (number of EG eyes and range of animal-specific change): posterior laminar deformation (21, −29 to −437 μm), laminar thickening (11, 20–73 μm) and thinning (3, −23 to −31 μm), scleral canal expansion (17, 20–139 μm), outward anterior (16, −16 to −124 μm) and posterior (17, −22 to −279 μm) laminar insertion migration, and peripapillary scleral bowing (11, 21–77 μm). Experimental glaucoma versus control eye laminar thickness differences were bimodal in behavior, being thickened in most EG eyes demonstrating the least deformation and less thickened or thinned in most EG eyes demonstrating the greatest deformation. Conclusions Our postmortem studies retrospectively identify five connective tissue components of ONH “cupping” in monkey EG which serve as targets for longitudinally staging and phenotyping ONH connective tissue alteration within all forms of monkey and human optic neuropathy. PMID:26641545

Control of Groundwater Pollution from Animal Feeding Operations: A Farm-Level Dynamic Model for Policy Analysis

NASA Astrophysics Data System (ADS)

Wang, J.; Baerenklau, K.

2012-12-01

Consolidation in livestock production generates higher farm incomes due to economies of scale, but it also brings waste disposal problems. Over-application of animal waste on adjacent land produces adverse environmental and health effects, including groundwater nitrate pollution. The situation is particularly noticeable in California. In respond to this increasingly severe problem, EPA published a type of command-and-control regulation for concentrated animal feeding operations (CAFOs) in 2003. The key component of the regulation is its nutrient management plans (NMPs), which intend to limit the land application rates of animal waste. Although previous studies provide a full perspective on potential economic impacts for CAFOs to meet nutrient standards, their models are static and fail to reflect changes in management practices other than spreading manure on additional land and changing cropping patterns. We develop a dynamic environmental-economic modeling framework for representative CAFOs. The framework incorporates four models (i.e., animal model, crop model, hydrologic model, and economic model) that include various components such as herd management, manure handling system, crop rotation, water sources, irrigation system, waste disposal options, and pollutant emissions. We also include the dynamics of soil characteristics in the rootzone as well as the spatial heterogeneity of the irrigation system. The operator maximizes discounted total farm profit over multiple periods subject to environmental regulations. Decision rules from the dynamic optimization problem demonstrate best management practices for CAFOs to improve their economic and environmental performance. Results from policy simulations suggest that direct quantity restrictions of emission or incentive-based emission policies are much more cost-effective than the standard approach of limiting the amount of animal waste that may be applied to fields (as shown in the figure below); reason being, policies targeting intermediate pollution and final pollution create incentives for the operator to examine the effects of other management practices to reduce pollution in addition to controlling the polluting inputs. Incentive-based mechanisms are slightly more cost-effective than quantity controls when seasonal emissions fluctuate. Our approach demonstrates the importance of taking into account the spatial & temporal dynamics in the rootzone and the integrated effects of water, nitrogen, and salinity on crop yield and nitrate emissions. It also highlights the significant role the environment can play in pollution control and the potential benefits from designing policies that acknowledge this role.oss of Total Net Farm Income Under Alternative Policies

Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia in rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Krausz, Michael M; Lurie, Michael; Hirsh, Mark; Coran, Arnold G; Shiloni, Eitan

2004-12-01

The objective of this study was to evaluate the effects of lipopolysaccharide (LPS) endotoxemia and enteral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis in rat. Male Sprague-Dawley rats, weighing 250-280 g, were divided into three experimental groups: control rats, LPS rats treated with lipopolysaccharide given ip at a dose of 10 mg/kg every 24 h (two injections), and LPS-ARG rats treated with enteral arginine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined on day 3 following the first LPS injection. LPS rats demonstrated a significant decrease in bowel weight in duodenum, mucosal weight in duodenum, jejunum, and ileum, mucosal DNA and protein in jejunum and ileum, and villus height in jejunum and ileum compared to control animals. LPS rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in jejunum and ileum compared to control rats. LPS-ARG animals demonstrated greater duodenal bowel weight, duodenal and ileal mucosal weight, ileal mucosal DNA and protein, ileal villus height, and jejunal and ileal cell proliferation index compared to LPS animals. LPS endotoxemia impairs the integrity of the gastrointestinal mucosa in rat. Decreased cell proliferation and increased apoptosis may be considered the main mechanisms responsible for the decreased cell mass. Enteral arginine administration decreases the mucosal injury caused by lipopolysaccharide.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

PubMed

Jiang, Shichao; Wang, Wei; Yan, Hede; Fan, Cunyi

2013-06-04

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy.

PubMed

Tar, Moses; Cabrales, Pedro; Navati, Mahantesh; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam J; Friedman, Joel; Davies, Kelvin P

2014-12-01

Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to phosphodiesterase 5 inhibitors, which act downstream of cavernous nerve (CN)-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. This study aimed to determine if topically applied NO-releasing nanoparticles (NO-NPs) could elicit erections in a rat model of RP through increased blood flow. Twenty-six Sprague Dawley rats underwent bilateral transection of the CN. One week later, NO-NPs were applied topically to the penile shaft in dimethylsulfoxide (DMSO) gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty NPs. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-NPs on blood flow was determined using a hamster dorsal window chamber. Animals were investigated for spontaneous erections, onset and duration of erectile response, and basal ICP/BP ratio. Microcirculatory blood flow was determined through measurements of arteriolar and venular diameter and red blood cell velocity. Eight of 10 animals treated with NO-NPs suspended in DMSO gel had significant increases in basal ICP/BP, and 6 out of these 10 animals demonstrated spontaneous erections of approximately 1 minute in duration. Time to onset of spontaneous erections ranged from 5 to 37 minutes, and they occurred for at least 45 minutes. Similar results were observed with NO-NPs applied in coconut oil. No erectile response was observed in control animal models treated with empty NPs. The hamster dorsal window chamber experiment demonstrated that NO-NPs applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Topically applied NO-NPs induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that NO-NPs would be useful in penile rehabilitation of patients following RP. © 2014 International Society for Sexual Medicine.

Obsessive-compulsive disorder: Insights from animal models☆

PubMed Central

Szechtman, Henry; Ahmari, Susanne E.; Beninger, Richard J.; Eilam, David; Harvey, Brian H.; Edemann-Callesen, Henriette; Winter, Christine

2017-01-01

Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. PMID:27168347

Mutually opposing forces during locomotion can eliminate the tradeoff between maneuverability and stability

NASA Astrophysics Data System (ADS)

Cowan, Noah; Sefati, Shahin; Neveln, Izaak; Roth, Eatai; Mitchell, Terence; Snyder, James; Maciver, Malcolm; Fortune, Eric

A surprising feature of animal locomotion is that organisms typically produce substantial forces in directions other than what is necessary to move the animal through its environment, such as perpendicular to, or counter to, the direction of travel. The effect of these forces has been difficult to observe because they are often mutually opposing and therefore cancel out. Using a combination of robotic physical modeling, computational modeling, and biological experiments, we discovered that these forces serve an important role: to simplify and enhance the control of locomotion. Specifically, we examined a well-suited model system, the glass knifefish Eigenmannia virescens, which produces mutually opposing forces during a hovering behavior. By systematically varying the locomotor parameters of our biomimetic robot, and measuring the resulting forces and kinematics, we demonstrated that the production and differential control of mutually opposing forces is a strategy that generates passive stabilization while simultaneously enhancing maneuverability. Mutually opposing forces during locomotion are widespread across animal taxa, and these results indicate that such forces can eliminate the tradeoff between stability and maneuverability, thereby simplifying robotic and neural control.

Practical training on porcine hearts enhances students' knowledge of human cardiac anatomy.

PubMed

Musumeci, Giuseppe; Loreto, Carla; Mazzone, Venera; Szychlinska, Marta Anna; Castrogiovanni, Paola; Castorina, Sergio

2014-05-01

Historically, cadavers have been used for the study of anatomy. Nowadays, the territorial and legal limitations of this approach have led to the introduction of alternative teaching methods such as the use of practical exercise consisting of dissection and observation of animal organs. The aim of this study was to evaluate the use of practical training on animal organs compared with the traditional method of anatomy teaching, based on the dissection of human cadavers. In this study, we seek to demonstrate the usefulness of practical exercise on animal organs. This practical training was held a week after the series of lectures, thus leaving time for the students to learn and understand the topics discussed. Immediately after the lecture, all of the students completed a preliminary test to assess the immediate effect of the lecture. Immediately before the practical exercise, both control and experimental groups completed a second test to assess the effectiveness of personal study. Immediately after practical training, a third test was completed by the experimental group and the control group (no practical activity on animal organs) to highlight the added value of hands-on practice in addition to the lecture. Data obtained from statistical analysis showed a p<0.05 (control group vs. experimental group) only for the third test as expected, highlighting significant differences in anatomy learning between control and experimental groups. Thus, the results of this study emphasize the utility of practical training on animal organs in learning and understanding anatomy, considering the limitations of the use of cadavers. Copyright © 2014 Elsevier GmbH. All rights reserved.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

PubMed Central

Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J

2016-01-01

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257

The effect of a fenbendazole treatment on cyst excretion and weight gain in calves experimentally infected with Giardia duodenalis.

PubMed

Geurden, Thomas; Vandenhoute, Els; Pohle, Herbert; Casaert, Stijn; De Wilde, Nathalie; Vercruysse, Jozef; Claerebout, Edwin

2010-04-19

A total of 28 Holstein-Friesian calves were experimentally infected with 10(5)Giardia duodenalis cysts. Eleven days later, all animals were allocated into two groups of 14 animals each, based on the average pre-treatment cyst counts. Treatment was randomly assigned to one of the two groups, and all animals in the treatment group received a daily oral dosage of 15mg fenbendazole per kg bodyweight during 3 consecutive days. The calves in the control group received a placebo (water). From 3 days after treatment onwards, cyst excretion was determined three times a week during 4 consecutive weeks. The faecal consistency and general health were recorded on a daily basis, and all animals were weighed prior to treatment and weekly thereafter. At the end of the experimental period, there was a significant (P<0.001) reduction (98%) of the cumulative cyst excretion. There were no significant differences in general health between both groups, but faecal consistency was significantly lower (P<0.002) in the control group compared to the treatment group, although none of the animals displayed overt gastro-intestinal symptoms. Prior to treatment the weight did not differ between both experimental groups. At the end of the 4-week experimental period however, the animals in the treatment group gained on average 2.86kg (=102g per day) more than the animals in the control group (P<0.031). This study demonstrates for the first time a significant difference in weight gain between fenbendazole treated and untreated calves experimentally infected with G. duodenalis, although additional data need to confirm the need for treatment in natural conditions.

Transition by head-on collision: mechanically mediated manoeuvres in cockroaches and small robots.

PubMed

Jayaram, Kaushik; Mongeau, Jean-Michel; Mohapatra, Anand; Birkmeyer, Paul; Fearing, Ronald S; Full, Robert J

2018-02-01

Exceptional performance is often considered to be elegant and free of 'errors' or missteps. During the most extreme escape behaviours, neural control can approach or exceed its operating limits in response time and bandwidth. Here we show that small, rapid running cockroaches with robust exoskeletons select head-on collisions with obstacles to maintain the fastest escape speeds possible to transition up a vertical wall. Instead of avoidance, animals use their passive body shape and compliance to negotiate challenging environments. Cockroaches running at over 1 m or 50 body lengths per second transition from the floor to a vertical wall within 75 ms by using their head like an automobile bumper, mechanically mediating the manoeuvre. Inspired by the animal's behaviour, we demonstrate a passive, high-speed, mechanically mediated vertical transitions with a small, palm-sized legged robot. By creating a collision model for animal and human materials, we suggest a size dependence favouring mechanical mediation below 1 kg that we term the 'Haldane limit'. Relying on the mechanical control offered by soft exoskeletons represents a paradigm shift for understanding the control of small animals and the next generation of running, climbing and flying robots where the use of the body can off-load the demand for rapid sensing and actuation. © 2018 The Authors.

Transition by head-on collision: mechanically mediated manoeuvres in cockroaches and small robots

PubMed Central

Mongeau, Jean-Michel; Mohapatra, Anand; Birkmeyer, Paul; Fearing, Ronald S.; Full, Robert J.

2018-01-01

Exceptional performance is often considered to be elegant and free of ‘errors’ or missteps. During the most extreme escape behaviours, neural control can approach or exceed its operating limits in response time and bandwidth. Here we show that small, rapid running cockroaches with robust exoskeletons select head-on collisions with obstacles to maintain the fastest escape speeds possible to transition up a vertical wall. Instead of avoidance, animals use their passive body shape and compliance to negotiate challenging environments. Cockroaches running at over 1 m or 50 body lengths per second transition from the floor to a vertical wall within 75 ms by using their head like an automobile bumper, mechanically mediating the manoeuvre. Inspired by the animal's behaviour, we demonstrate a passive, high-speed, mechanically mediated vertical transitions with a small, palm-sized legged robot. By creating a collision model for animal and human materials, we suggest a size dependence favouring mechanical mediation below 1 kg that we term the ‘Haldane limit’. Relying on the mechanical control offered by soft exoskeletons represents a paradigm shift for understanding the control of small animals and the next generation of running, climbing and flying robots where the use of the body can off-load the demand for rapid sensing and actuation. PMID:29445036

Health and reproductive profiles of malaria antigen-producing transgenic goats derived by somatic cell nuclear transfer.

PubMed

Behboodi, E; Ayres, S L; Memili, E; O'Coin, M; Chen, L H; Reggio, B C; Landry, A M; Gavin, W G; Meade, H M; Godke, R A; Echelard, Y

2005-01-01

Nuclear transfer (NT) using transfected primary cells is an efficient approach for the generation of transgenic goats. However, reprogramming abnormalities associated with this process might result in compromised animals. We examined the health, reproductive performance, and milk production of four transgenic does derived from somatic cell NT. Goats were derived from two fetal cell lines, each transfected with a transgene expressing a different version of the MSP-1(42) malaria antigen, either glycosylated or non-glycosylated. Two female kids were produced per cell line. Health and growth of these NT animals were monitored and compared with four age-matched control does. There were no differences in birth and weaning weights between NT and control animals. The NT does were bred and produced a total of nine kids. The control does delivered five kids. The NT does expressing the glycosylated antigen lactated only briefly, probably as a result of over-expression of the MSP-1(42) protein. However, NT does expressing the non-glycosylated antigen had normal milk yields and produced the recombinant protein. These data demonstrated that the production of healthy transgenic founder goats by somatic cell NT is readily achievable and that these animals can be used successfully for the production of a candidate Malaria vaccine.

[Depressive-like state and sleep in laboratory mice].

PubMed

Strekalova, T V; Cespuglio, R; Koval'zon, V M

2008-01-01

In order to induce the state of anhedonia, a key symptom of depression, mice were subjected to a one-month stress procedure comprised of various stressors. Anhedonic state was defined by a reduction of preference for sucrose solution over tap water. Conventional cortical and neck-muscle electrodes were implanted to control and stressed animals under chloral-hydrate anesthesia. After a two-week recovery and habituation period, mice from chronically stressed group were re-subjected to five-day stress, and the anhedonic state was verified. As not all the stressed mice displayed a decrease in sucrose preference, animals were divided in two groups: stressed-non-anhedonic and stressed-anhedonic animals. Seven-day continuous polygraphic recording was carried out in animals from both stressed groups and the control group in recording chambers under conditions of 12/12-hour light/dark schedule. The anhedonic mice demonstrated a significant advanced shift in circadian distribution of paradoxical sleep and increased amount of paradoxical sleep during the light period. In the course of the dark period, the anhedonic group showed a slight but significant decrease in total amount of slow-wave sleep as compared to the non-anhedonic and control groups. The results suggest that the changes in sleep structure documented in the model of anhedonia are similar to those described for human depression.

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Detection of lipomannan in cattle infected with bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

Early and rapid detection of bovine tuberculosis (bTB) is critical to controlling the spread of this disease in cattle and other animals. In this study, we demonstrate the development of an immunoassay for the direct detection of the bovine bTB biomarker, lipomannan (LM) in serum using a waveguide-...

Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication.

PubMed

Ivanova, Juliana; Gluhcheva, Yordanka; Dimova, Donika; Pavlova, Ekaterina; Arpadjan, Sonja

2016-01-01

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs. Copyright © 2015 Elsevier GmbH. All rights reserved.

Calbindins decreased after space flight

NASA Technical Reports Server (NTRS)

Sergeev, I. N.; Rhoten, W. B.; Carney, M. D.

1996-01-01

Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins may contribute to the disorders of Ca2+ metabolism induced by space flight.

Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity.

PubMed

Awadalla, Eatemad A

2012-07-01

Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ+VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat. Copyright © 2010 Elsevier GmbH. All rights reserved.

Adapting astronomical source detection software to help detect animals in thermal images obtained by unmanned aerial systems

NASA Astrophysics Data System (ADS)

Longmore, S. N.; Collins, R. P.; Pfeifer, S.; Fox, S. E.; Mulero-Pazmany, M.; Bezombes, F.; Goodwind, A.; de Juan Ovelar, M.; Knapen, J. H.; Wich, S. A.

2017-02-01

In this paper we describe an unmanned aerial system equipped with a thermal-infrared camera and software pipeline that we have developed to monitor animal populations for conservation purposes. Taking a multi-disciplinary approach to tackle this problem, we use freely available astronomical source detection software and the associated expertise of astronomers, to efficiently and reliably detect humans and animals in aerial thermal-infrared footage. Combining this astronomical detection software with existing machine learning algorithms into a single, automated, end-to-end pipeline, we test the software using aerial video footage taken in a controlled, field-like environment. We demonstrate that the pipeline works reliably and describe how it can be used to estimate the completeness of different observational datasets to objects of a given type as a function of height, observing conditions etc. - a crucial step in converting video footage to scientifically useful information such as the spatial distribution and density of different animal species. Finally, having demonstrated the potential utility of the system, we describe the steps we are taking to adapt the system for work in the field, in particular systematic monitoring of endangered species at National Parks around the world.

Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty.

PubMed

Tu, Duong D; Chung, Yeun Goo; Gil, Eun Seok; Seth, Abhishek; Franck, Debra; Cristofaro, Vivian; Sullivan, Maryrose P; Di Vizio, Dolores; Gomez, Pablo; Adam, Rosalyn M; Kaplan, David L; Estrada, Carlos R; Mauney, Joshua R

2013-11-01

Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm(2)) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth.In addition, animals augmented with both matrix configurations displayed increases in bladder compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to growth-related elevations observed in non-surgical controls (354%) [corrected]. Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair. © 2013 Elsevier Ltd. All rights reserved.

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

PubMed

Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

PubMed

Johnson, B J; Bruno, J P

1995-02-01

A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

Differences in Active Avoidance Conditioning in Male and Female Rats with Experimental Anxiety-Depressive Disorder.

PubMed

Khlebnikova, N N; Krupina, N A; Kushnareva, E Yu; Orlova, I N

2015-07-01

Using rat model of experimental anxiety-depressive disorder caused by postnatal administration of methionyl-2(S)-cyanopyrrolidine, an inhibitor of dipeptidyl peptidase IV, we compared conditioned active avoidance response and memory retention in males and females. In experimental males and females, conditioning was impaired in comparison with the control. In experimental groups, females were worse learners than males, while in control groups, females were better learners than males. Memory retention in experimental animals did not differ from that in controls 24 h after learning. Two months after learning, control females demonstrated better retention than control males.

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.

Tinnitus-provoking salicylate treatment triggers social impairments in mice.

PubMed

Guitton, Matthieu J

2009-09-01

Tinnitus (perception of sound in silence) strongly affects the quality of life of sufferers. Tinnitus sufferers and their relatives frequently complain about major social impairments. However, it is not known whether this impairment directly results from the occurrence of tinnitus or is the indirect expression of a preexisting psychological vulnerability. Using the well-characterized animal model of salicylate-induced tinnitus, we investigate in mice whether the occurrence of tinnitus can trigger social impairments. Experiments were performed on 32 male Balb/C mice. Tinnitus was induced in mice using salicylate treatment. Social behavior was assessed in experimental and control animals using social interaction paradigm. Interaction time, number of social events, and number of nonsocial events were assessed in all animals. We demonstrate for the first time that treatment known to induce tinnitus triggers complex social impairments in mice. While salicylate-treated animals present a massive decrease in their overall social interactions compared to control untreated animals, they also display a paradoxal increase in the number of conspecific followings. Tinnitus can thus trigger a complex set of modifications of behavior, which will not only find their expression at the individual level, but also at the social level. Our results suggest that tinnitus can directly be a cause of psychosocial impairment in human and have strong implications for the clinical management of tinnitus sufferers.

Intra- and extracellular dehydration-induced thirst-related behavior in an amphibian.

PubMed

Taylor, K; Mayer, L P; Propper, C R

The behavioral response to dehydration is critical to an animal's survival. Because of their permeable skin, amphibians are particularly sensitive to dehydrating conditions. We tested the hypothesis that different forms of dehydration induce water absorption response (WR) behavior in the desert spadefoot toad, Scaphiopus couchii. First, we determined the behavioral response to intracellular dehydration by treating fully hydrated toads with increasing concentrations of hypertonic solutions of NaCl or sucrose via intraperitoneal injection (i.p.). Animals that were treated to induce intracellular dehydration with either solute exhibited a significant increase in WR behavior compared to vehicle-treated controls. To distinguish that the response was a result of an increased osmotic gradient between the intra- and extracellular compartments, we treated fully hydrated animals i.p. with urea, which freely passes into the intracellular compartment and increases overall animal osmolarity. Urea treatment did not induce WR behavior. To determine the response to extracellular dehydration, the blood volume of fully hydrated toads was reduced via cardiac puncture, and the WR behavior was measured. Animals who had a reduction in blood volume exhibited a significant increase in WR behavior compared to sham-punctured controls. Our results are the first to demonstrate that multiple forms of dehydration can induce thirst-related behavior in amphibians.

Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease.

PubMed

Anway, Matthew D; Skinner, Michael K

2008-04-01

The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.

Transgenerational Effects of the Endocrine Disruptor Vinclozolin on the Prostate Transcriptome and Adult Onset Disease

PubMed Central

Anway, Matthew D.; Skinner, Michael K.

2018-01-01

PURPOSE The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. METHODS Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. RESULTS Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1–F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). CONCLUSIONS The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease. PMID:18220299

Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

PubMed Central

Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M.; Sarafandi, Alia A.; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H.; Walsh, Thomas J.

2004-01-01

PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring β-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 μg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis. PMID:15388459

Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

PubMed

Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

2004-10-01

PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P

Dosage-Dependent Antifungal Efficacy of V-Echinocandin (LY303366) against Experimental Fluconazole-Resistant Oropharyngeal and Esophageal Candidiasis

PubMed Central

Petraitis, Vidmantas; Petraitiene, Ruta; Groll, Andreas H.; Sein, Tin; Schaufele, Robert L.; Lyman, Caron A.; Francesconi, Andrea; Bacher, John; Piscitelli, Stephen C.; Walsh, Thomas J.

2001-01-01

V-echinocandin (VER-002; LY303366) is a semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1, 3)-β-d-glucan synthase. We studied the antifungal efficacy, the concentrations in saliva and tissue, and the safety of VER-002 at escalating dosages against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant Candida albicans in immunocompromised rabbits. Study groups consisted of untreated controls, animals treated with VER-002 at 1, 2.5, and 5 mg/kg of body weight/day intravenously (i.v.), animals treated with fluconazole at 2 mg/kg/day i.v., or animals treated with amphotericin B at 0.3 mg/kg/day. VER-002-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, esophagus, stomach, and duodenum in comparison to that for untreated controls. VER-002 also was superior to amphotericin B and fluconazole in clearing the organism from all sites studied. These in vivo findings are consistent with the results of in vitro time-kill assays, which demonstrated that VER-002 has concentration-dependent fungicidal activity. Esophageal tissue VER-002 concentrations were dosage proportional and exceeded the MIC at all dosages. Echinocandin concentrations in saliva were greater than or equal to the MICs at all dosages. There was no elevation of serum hepatic transaminase, alkaline phosphatase, bilirubin, potassium, or creatinine levels in VER-002-treated rabbits. In summary, the echinocandin VER-002 was well tolerated, penetrated the esophagus and salivary glands, and demonstrated dosage-dependent antifungal activity against fluconazole-resistant esophageal candidiasis in immunocompromised rabbits. PMID:11158743

Improvement of Endurance Based on Muscle Fiber-Type Composition by Treatment with Dietary Apple Polyphenols in Rats.

PubMed

Mizunoya, Wataru; Miyahara, Hideo; Okamoto, Shinpei; Akahoshi, Mariko; Suzuki, Takahiro; Do, Mai-Khoi Q; Ohtsubo, Hideaki; Komiya, Yusuke; Lan, Mu; Waga, Toshiaki; Iwata, Akira; Nakazato, Koichi; Ikeuchi, Yoshihide; Anderson, Judy E; Tatsumi, Ryuichi

2015-01-01

A recent study demonstrated a positive effect of apple polyphenol (APP) intake on muscle endurance of young-adult animals. While an enhancement of lipid metabolism may be responsible, in part, for the improvement, the contributing mechanisms still need clarification. Here we show that an 8-week intake of 5% (w/w) APP in the diet, up-regulates two features related to fiber type: the ratio of myosin heavy chain (MyHC) type IIx/IIb and myoglobin protein expression in plantaris muscle of 9-week-old male Fischer F344 rats compared to pair-fed controls (P < 0.05). Results were demonstrated by our SDS-PAGE system specialized for MyHC isoform separation and western blotting of whole muscles. Animal-growth profiles (food intake, body-weight gain, and internal-organ weights) did not differ between the control and 5% APP-fed animals (n = 9/group). Findings may account for the increase in fatigue resistance of lower hind limb muscles, as evidenced by a slower decline in the maximum isometric planter-flexion torque generated by a 100-s train of electrical stimulation of the tibial nerve. Additionally, the fatigue resistance was lower after 8 weeks of a 0.5% APP diet than after 5% APP, supporting an APP-dose dependency of the shift in fiber-type composition. Therefore, the present study highlights a promising contribution of dietary APP intake to increasing endurance based on fiber-type composition in rat muscle. Results may help in developing a novel strategy for application in animal sciences, and human sports and age-related health sciences.

Evaluation of an internet-based animated preparatory video for children undergoing non-sedated MRI.

PubMed

McGlashan, Hannah L; Dineen, Rob A; Szeszak, Sofia; Whitehouse, William P; Chow, Gabriel; Love, Andrew; Langmack, Gill; Wharrad, Heather

2018-05-10

We evaluate the value of an internet-based educational animated video designed to prepare children for MRI scans, and whether this video reduces scan-related anxiety in children with a neurological disorder, and healthy controls. Participants completed a pre- and post-scan questionnaire evaluating participant online viewing behaviour, understanding of the MRI procedure, anxiety regarding the MRI, impact of animation in preparing the child and whether the child's expectation of the MRI scan matched their experience. 21 children were recruited (12 healthy controls) ranging in age from 6.5 to 11.5 years. The animation was successfully accessed by participants on a range of digital devices and had high levels of approval. Children who viewed the animation had a good understanding of the MRI procedure and low anxiety levels prior to the scan, and reported that their expectations broadly matched the real-life MRI experience. Children reported that the animation positively impacted on their preparation with similar ratings before and after the scan, and the impact on preparation was rated greater by younger children. There were no group differences between healthy children and those with the neurological disorder for ratings of anxiety, impact on preparation and expectation of the experience. This evaluation demonstrates accessibility, acceptability and relevance of internet-based educational animation for typically developing children, and children with a neurodisability aged 6 to 11 years, with positive impact on preparation for MRI. Advances in knowledge: The internet-based educational animation provides a widely accessible tool to support preparation of children for non-sedated MRI.

Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

PubMed Central

Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

2015-01-01

There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1h sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to non-stressed controls in an overnight sucrose test, while 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously ‘resilient’ animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta expression in limbic brain areas. While all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared to food deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. PMID:25914924

Real-time physics-based 3D biped character animation using an inverted pendulum model.

PubMed

Tsai, Yao-Yang; Lin, Wen-Chieh; Cheng, Kuangyou B; Lee, Jehee; Lee, Tong-Yee

2010-01-01

We present a physics-based approach to generate 3D biped character animation that can react to dynamical environments in real time. Our approach utilizes an inverted pendulum model to online adjust the desired motion trajectory from the input motion capture data. This online adjustment produces a physically plausible motion trajectory adapted to dynamic environments, which is then used as the desired motion for the motion controllers to track in dynamics simulation. Rather than using Proportional-Derivative controllers whose parameters usually cannot be easily set, our motion tracking adopts a velocity-driven method which computes joint torques based on the desired joint angular velocities. Physically correct full-body motion of the 3D character is computed in dynamics simulation using the computed torques and dynamical model of the character. Our experiments demonstrate that tracking motion capture data with real-time response animation can be achieved easily. In addition, physically plausible motion style editing, automatic motion transition, and motion adaptation to different limb sizes can also be generated without difficulty.

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Right Ventricular Longitudinal Strain Is Depressed in a Bovine Model of Pulmonary Hypertension.

PubMed

Bartels, Karsten; Brown, R Dale; Fox, Daniel L; Bull, Todd M; Neary, Joseph M; Dorosz, Jennifer L; Fonseca, Brian M; Stenmark, Kurt R

2016-05-01

Pulmonary hypertension and resulting right ventricular (RV) dysfunction are associated with significant perioperative morbidity and mortality. Although echocardiography permits real-time, noninvasive assessment of RV function, objective and comparative measures are underdeveloped, and appropriate animal models to study their utility are lacking. Longitudinal strain analysis is a novel echocardiographic method to quantify RV performance. Herein, we hypothesized that peak RV longitudinal strain would worsen in a bovine model of pulmonary hypertension compared with control animals. Newborn Holstein calves were randomly chosen for induction of pulmonary hypertension versus control conditions. Pulmonary hypertension was induced by exposing animals to 14 days of hypoxia (equivalent to 4570 m above sea level or 430 mm Hg barometric pressure). Control animals were kept at ambient pressure/normoxia. At the end of the intervention, transthoracic echocardiography was performed in awake calves. Longitudinal wall strain was analyzed from modified apical 4-chamber views focused on the RV. Comparisons between measurements in hypoxic versus nonhypoxic conditions were performed using Student t test for independent samples and unequal variances. After 14 days at normoxic versus hypoxic conditions, 15 calves were examined with echocardiography. Pulmonary hypertension was confirmed by right heart catheterization and associated with reduced RV systolic function. Mean systolic strain measurements were compared in normoxia-exposed animals (n = 8) and hypoxia-exposed animals (n = 7). Peak global systolic longitudinal RV strain after hypoxia worsened compared to normoxia (-10.5% vs -16.1%, P = 0.0031). Peak RV free wall strain also worsened after hypoxia compared to normoxia (-9.6% vs -17.3%, P = 0.0031). Findings from strain analysis were confirmed by measurement of tricuspid annular peak systolic excursion. Peak longitudinal RV strain detected worsened RV function in animals with hypoxia-induced pulmonary hypertension compared with control animals. This relationship was demonstrated in the transthoracic echocardiographic 4-chamber view independently for the RV free wall and for the combination of the free and septal walls. This innovative model of bovine pulmonary hypertension may prove useful to compare different monitoring technologies for the assessment of early events of RV dysfunction. Further studies linking novel RV imaging applications with mechanistic and therapeutic approaches are needed.

Animation-assisted CPRII program as a reminder tool in achieving effective one-person-CPR performance.

PubMed

Choa, Minhong; Cho, Junho; Choi, Young Hwan; Kim, Seungho; Sung, Ji Min; Chung, Hyun Soo

2009-06-01

The objective of this study is to compare the skill retention of two groups of lay persons, six months after their last CPR training. The intervention group was provided with animation-assisted CPRII (AA-CPRII) instruction on their cellular phones, and the control group had nothing but what they learned from their previous training. This study was a single blind randomized controlled trial. The participants' last CPR trainings were held at least six months ago. We revised our CPR animation for on-site CPR instruction content emphasizing importance of chest compression. Participants were randomized into two groups, the AA-CPRII group (n=42) and the control group (n=38). Both groups performed three cycles of CPR and their performances were video recorded. These video clips were assessed by three evaluators using a checklist. The psychomotor skills were evaluated using the ResusciAnne SkillReporter. Using the 30-point scoring checklist, the AA-CPRII group had a significantly better score compared to the control group (p<0.001). Psychomotor skills evaluated with the AA-CPRII group demonstrated better performance in hand positioning (p=0.025), compression depth (p=0.035) and compression rate (p<0.001) than the control group. The AA-CPRII group resulted in better checklist scores, including chest compression rate, depth and hand positioning. Animation-assisted CPR could be used as a reminder tool in achieving effective one-person-CPR performance. By installing the CPR instruction on cellular phones and having taught them CPR with it during the training enabled participants to perform better CPR.

Vaccination as a potential means to prevent plague in black-footed ferrets: Progress and continuing challenges

USGS Publications Warehouse

Rocke, Tonie E.; Nol, Pauline; Marinari, Paul E.; Kreeger, J.S.; Smith, Susan R.; Andrews, G.P.; Friedlander, A.W.

2006-01-01

This study was conducted to further assess the feasibility of vaccinating black-footed ferrets (Mustela nigripes) against plague (caused by the bacterium Yersinia pestis). On days 0 and 28, 17 postreproductive ferrets were immunized by subcutaneous injection with a recombinant fusion protein containing F1 and V antigens from Y. pestis. Another 17 animals received a placebo by the same route. Two weeks after the second immunization, mean antibody titers to Y. pestis F1 and V antigens were measured and found to be significantly higher in vaccinates than their preimmunization values (P < 0.0001) and significantly higher than the control values (P < 0.0001). Six months postimmunization, 16 vaccinates and eight controls were challenged with approximately 8,000 colony forming units of virulent plague by subcutaneous inoculation. Eleven of 16 vaccinates (69 percent) survived with no ill effects whereas all eight control animals died within 3a??6 days. Two months later, the 11 surviving vaccinates were challenged again by ingestion of a plague-infected mouse. None of the animals showed any ill effects and all survived. In contrast, seven control ferrets fed infected mice died within 2a??4 days, including one animal that did not actually ingest the mouse but was likely exposed to it. This study demonstrates that immunization of ferrets with the recombinant F1-V fusion protein can induce significant antibody responses and reduce their susceptibility to plague infection.

The economics of animal welfare.

PubMed

Gibson, T J; Jackson, E L

2017-04-01

This paper examines four examples of animal welfare issues, demonstrating the interactions between welfare and economic principles. Welfare issues associated with purebred companion animals are examined in terms of predicted inherited diseases, highlighting the power of supply and demand in perpetuating traits in pets that compromise their well-being. The livestock industry is presented from the point of view of pig production and the impact that a major disease (pleurisy) has on production and the animals' welfare. The authors investigate the conflicting and complementary demands of animal welfare and economic gains during the transport and slaughter of livestock and poultry. Finally, wildlife species are considered in terms of their prevalence as pests, and the different types of economic analysis that have been conducted to understand the losses caused by these organisms. Also included in this example are decisions made about cost effectiveness and opportunity costs, and regulatory and financial barriers to the development of humane control agents. In conclusion, animal welfare is illustrated as a central factor in the benefits that humans enjoy from the role played by animals in society. There are, however, tradeoffs between optimal animal welfare and meeting the needs of modern human society.

Considerations in video playback design: using optic flow analysis to examine motion characteristics of live and computer-generated animation sequences.

PubMed

Woo, Kevin L; Rieucau, Guillaume

2008-07-01

The increasing use of the video playback technique in behavioural ecology reveals a growing need to ensure better control of the visual stimuli that focal animals experience. Technological advances now allow researchers to develop computer-generated animations instead of using video sequences of live-acting demonstrators. However, care must be taken to match the motion characteristics (speed and velocity) of the animation to the original video source. Here, we presented a tool based on the use of an optic flow analysis program to measure the resemblance of motion characteristics of computer-generated animations compared to videos of live-acting animals. We examined three distinct displays (tail-flick (TF), push-up body rock (PUBR), and slow arm wave (SAW)) exhibited by animations of Jacky dragons (Amphibolurus muricatus) that were compared to the original video sequences of live lizards. We found no significant differences between the motion characteristics of videos and animations across all three displays. Our results showed that our animations are similar the speed and velocity features of each display. Researchers need to ensure that similar motion characteristics in animation and video stimuli are represented, and this feature is a critical component in the future success of the video playback technique.

Neuromechanics: an integrative approach for understanding motor control.

PubMed

Nishikawa, Kiisa; Biewener, Andrew A; Aerts, Peter; Ahn, Anna N; Chiel, Hillel J; Daley, Monica A; Daniel, Thomas L; Full, Robert J; Hale, Melina E; Hedrick, Tyson L; Lappin, A Kristopher; Nichols, T Richard; Quinn, Roger D; Satterlie, Richard A; Szymik, Brett

2007-07-01

Neuromechanics seeks to understand how muscles, sense organs, motor pattern generators, and brain interact to produce coordinated movement, not only in complex terrain but also when confronted with unexpected perturbations. Applications of neuromechanics include ameliorating human health problems (including prosthesis design and restoration of movement following brain or spinal cord injury), as well as the design, actuation and control of mobile robots. In animals, coordinated movement emerges from the interplay among descending output from the central nervous system, sensory input from body and environment, muscle dynamics, and the emergent dynamics of the whole animal. The inevitable coupling between neural information processing and the emergent mechanical behavior of animals is a central theme of neuromechanics. Fundamentally, motor control involves a series of transformations of information, from brain and spinal cord to muscles to body, and back to brain. The control problem revolves around the specific transfer functions that describe each transformation. The transfer functions depend on the rules of organization and operation that determine the dynamic behavior of each subsystem (i.e., central processing, force generation, emergent dynamics, and sensory processing). In this review, we (1) consider the contributions of muscles, (2) sensory processing, and (3) central networks to motor control, (4) provide examples to illustrate the interplay among brain, muscles, sense organs and the environment in the control of movement, and (5) describe advances in both robotics and neuromechanics that have emerged from application of biological principles in robotic design. Taken together, these studies demonstrate that (1) intrinsic properties of muscle contribute to dynamic stability and control of movement, particularly immediately after perturbations; (2) proprioceptive feedback reinforces these intrinsic self-stabilizing properties of muscle; (3) control systems must contend with inevitable time delays that can simplify or complicate control; and (4) like most animals under a variety of circumstances, some robots use a trial and error process to tune central feedforward control to emergent body dynamics.

Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults: a randomized, placebo-controlled clinical trial

USDA-ARS?s Scientific Manuscript database

Background: In vitro studies have shown Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and anti-hypertensive properties. Objective: To exa...

Experimental Concussion

PubMed Central

Brown, W. Jann; Yoshida, N.; Canty, T.; Verity, M. Anthony

1972-01-01

Ultrastructural and biochemical alterations were studied in the brainstem reticular formation of animals in which transient coma had been induced by controlled blows to the head. After a period of 7-10 days, animals that did not show obvious injury were artificially respired and sacrificed by perfusion with buffered formalin and glutaraldehyde. Histochemistry and light microscopy revealed chromatolysis of 10-15% of the neurons of pertinent segments of the nucleus giganto cellularis. There was much PAS-positive, diastase-sensitive material in the associated neuropil. Electron miscroscopy of the region confirmed the polysaccharide accumulation in dendrites, presynaptic boutons and preterminal axons. Similar material was found in some astrocytes. A longitudinal microchemical investigation with suitable controls of glycogen concentration in the brainstem demonstrated peak values at 5-7 days after concussion. No significant change in phosphorylase activity was demonstrated. The significance of glycogen accumulation in postconcussive injury and possible mechanisms for its accumulation in relation to changes in electrolyte balance and alterations in Kreb's cycle intermediates are discussed. ImagesFig 9Fig 10Fig 1Fig 2Fig 3Fig 11Fig 4Fig 5Fig 6Fig 7Fig 8 PMID:5045878

Mass vaccination as a complementary tool in the control of a severe outbreak of bovine brucellosis due to Brucella abortus in Extremadura, Spain.

PubMed

Sanz, Cristina; Sáez, José Luis; Alvarez, Julio; Cortés, María; Pereira, Gema; Reyes, Aurelia; Rubio, Félix; Martín, Javier; García, Nerea; Domínguez, Lucas; Hermoso-de-Mendoza, María; Hermoso-de-Mendoza, Javier

2010-11-01

We report the evolution of an outbreak of bovine brucellosis (Brucella abortus) in the region of Extremadura (Spain) involving more than 1000 herds and nearly 40,000 animals. S19 vaccination of young cattle combined with a test and slaughter strategy did not result in a rapid decrease in herd prevalence and animal incidence; these parameters showed a constant decreasing trend only when a combination of restriction of cattle movements, increased test frequency, S19 vaccination and mass RB51 vaccination (with yearly revaccinations) were applied to all susceptible populations. These measures were applied for 5 years; abortions following RB51 vaccination of pregnant cows were limited to the first inoculation and the involvement of the vaccine strain could only be demonstrated in 78 out of 897 abortions. Our results demonstrate the usefulness - and lack of significant side effects - of RB51 mass vaccination as a complementary tool to control bovine brucellosis outbreaks in areas where the disease cannot be contained using more conservative approaches. Copyright © 2010 Elsevier B.V. All rights reserved.

Plasma-Generating Glucose Monitor Accuracy Demonstrated in an Animal Model

PubMed Central

Magarian, Peggy; Sterling, Bernhard

2009-01-01

Introduction Four randomized controlled trials have compared mortality and morbidity of tight glycemic control versus conventional glucose for intensive care unit (ICU) patients. Two trials showed a positive outcome. However, one single-center trial and a large multicenter trial had negative results. The positive trials used accurate portable lab analyzers. The negative trial allowed the use of meters. The portable analyzer measures in filtered plasma, minimizing the interference effects. OptiScan Biomedical Corporation is developing a continuous glucose monitor using centrifuged plasma and mid-infrared spectroscopy for use in ICU medicine. The OptiScanner draws approximately 0.1 ml of blood every 15 min and creates a centrifuged plasma sample. Internal quality control minimizes sample preparation error. Interference adjustment using this technique has been presented at the Society of Critical Care Medicine in separate studies since 2006. Method A good laboratory practice study was conducted on three Yorkshire pigs using a central venous catheter over 6 h while performing a glucose challenge. Matching Yellow Springs Instrument glucose readings were obtained. Results Some 95.7% of the predicted values were in the Clarke Error Grid A zone and 4.3% in the B zone. Of those in the B zone, all were within 3.3% of the A zone boundaries. The coefficient of determination (R2) was 0.993. The coefficient of variance was 5.02%. Animal necropsy and blood panels demonstrated safety. Conclusion The OptiScanner investigational device performed safely and accurately in an animal model. Human studies using the device will begin soon. PMID:20144396

Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation.

PubMed

Mehaffey, James H; Money, Dustin; Charles, Eric J; Schubert, Sarah; Piñeros, Angela Fernandez; Wu, Di; Bontha, Sai Vineela; Hawkins, Robert; Teman, Nicholas R; Laubach, Victor E; Mas, Valeria R; Tribble, Curtis G; Maluf, Daniel G; Sharma, Ashish K; Yang, Zequan; Kron, Irving L; Roeser, Mark E

2018-01-25

We tested the hypothesis that systemic administration of an A2AR agonist will reduce multiorgan IRI in a porcine model of ECPR. Advances in ECPR have decreased mortality after cardiac arrest; however, subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI has been reported with the use of an A2AR agonist. Adult swine underwent 20 minutes of circulatory arrest, induced by ventricular fibrillation, followed by 6 hours of reperfusion with ECPR. Animals were randomized to vehicle control, low-dose A2AR agonist, or high-dose A2AR agonist. A perfusion specialist using a goal-directed resuscitation protocol managed all the animals during the reperfusion period. Hourly blood, urine, and tissue samples were collected. Biochemical and microarray analyses were performed to identify differential inflammatory markers and gene expression between groups. Both the treatment groups demonstrated significantly higher percent reduction from peak lactate after reperfusion compared with vehicle controls. Control animals required significantly more fluid, epinephrine, and higher final pump flow while having lower urine output than both the treatment groups. The treatment groups had lower urine NGAL, an early marker of kidney injury (P = 0.01), lower plasma aspartate aminotransferase, and reduced rate of troponin rise (P = 0.01). Pro-inflammatory cytokines were lower while anti-inflammatory cytokines were significantly higher in the treatment groups. Using a novel and clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated that a selective A2AR agonist significantly attenuated systemic IRI and warrants clinical investigation.

Assessment of gliosis around moveable implants in the brain

PubMed Central

Stice, Paula

2010-01-01

Repositioning microelectrodes post-implantation is emerging as a promising approach to achieve long-term reliability in single neuronal recordings. The main goal of this study was to (a) assess glial reaction in response to movement of microelectrodes in the brain post-implantation and (b) determine an optimal window of time post-implantation when movement of microelectrodes within the brain would result in minimal glial reaction. Eleven Sprague-Dawley rats were implanted with two microelectrodes each that could be moved in vivo post-implantation. Three cohorts were investigated: (1) microelectrode moved at day 2 (n = 4 animals), (2) microelectrode moved at day 14 (n = 5 animals) and (3) microelectrode moved at day 28 (n = 2 animals). Histological evaluation was performed in cohorts 1–3 at four-week post-movement (30 days, 42 days and 56 days post-implantation, respectively). In addition, five control animals were implanted with microelectrodes that were not moved. Control animals were implanted for (1) 30 days (n = 1), (2) 42 days (n = 2) and (3) 56 days (n = 2) prior to histological evaluation. Quantitative assessment of glial fibrillary acidic protein (GFAP) around the tip of the microelectrodes demonstrated that GFAP levels were similar around microelectrodes moved at day 2 when compared to the 30-day controls. However, GFAP expression levels around microelectrode tips that moved at day 14 and day 28 were significantly less than those around control microelectrodes implanted for 42 and 56 days, respectively. Therefore, we conclude that moving microelectrodes after implantation is a viable strategy that does not result in any additional damage to brain tissue. Further, moving the microelectrode downwards after 14 days of implantation may actually reduce the levels of GFAP expression around the tips of the microelectrodes in the long term. PMID:19556680

[Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25-35) antibody production in mice].

PubMed

Bobkova, N V; Gruden', M A; Samokhin, A N; Medvinskaia, N I; Morozova-Roch, L; Uudasheva, T A; Ostrovskaia, R U; Seredinin, S B

2005-01-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.

Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice.

PubMed

Turnbull, Isaiah R; Ghosh, Sarbani; Fuchs, Anja; Hilliard, Julia; Davis, Christopher G; Bochicchio, Grant V; Southard, Robert E

2016-05-01

Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8-month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8-10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham-pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24  h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8-10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response.

A silicon central pattern generator controls locomotion in vivo.

PubMed

Vogelstein, R J; Tenore, F; Guevremont, L; Etienne-Cummings, R; Mushahwar, V K

2008-09-01

We present a neuromorphic silicon chip that emulates the activity of the biological spinal central pattern generator (CPG) and creates locomotor patterns to support walking. The chip implements ten integrate-and-fire silicon neurons and 190 programmable digital-to-analog converters that act as synapses. This architecture allows for each neuron to make synaptic connections to any of the other neurons as well as to any of eight external input signals and one tonic bias input. The chip's functionality is confirmed by a series of experiments in which it controls the motor output of a paralyzed animal in real-time and enables it to walk along a three-meter platform. The walking is controlled under closed-loop conditions with the aide of sensory feedback that is recorded from the animal's legs and fed into the silicon CPG. Although we and others have previously described biomimetic silicon locomotor control systems for robots, this is the first demonstration of a neuromorphic device that can replace some functions of the central nervous system in vivo.

Dissecting and Culturing Animal Cap Explants.

PubMed

Dingwell, Kevin S; Smith, James C

2018-05-16

The animal cap explant is a simple but adaptable tool available to developmental biologists. The use of animal cap explants in demonstrating the presence of mesoderm-inducting activity in the Xenopus embryo vegetal pole is one of many elegant examples of their worth. Animal caps respond to a range of growth factors (e.g., Wnts, FGF, TGF-β), making them especially useful for studying signal transduction pathways and gene regulatory networks. Explants are also suitable for examining cell behavior and have provided key insights into the molecular mechanisms controlling vertebrate morphogenesis. In this protocol, we outline two methods to isolate animal cap explants from Xenopus laevis , both of which can be applied easily to Xenopus tropicalis The first method is a standard manual method that can be used in any laboratory equipped with a standard dissecting microscope. For labs planning on dissecting large numbers of explants on a regular basis, a second, high throughput method is described that uses a specialized microcautery surgical instrument. © 2018 Cold Spring Harbor Laboratory Press.

Low-oxygen waters limited habitable space for early animals.

PubMed

Tostevin, R; Wood, R A; Shields, G A; Poulton, S W; Guilbaud, R; Bowyer, F; Penny, A M; He, T; Curtis, A; Hoffmann, K H; Clarkson, M O

2016-09-23

The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems.

Handedness helps homing in swimming and flying animals

PubMed Central

Bandyopadhyay, Promode R.; Leinhos, Henry A.; Hellum, Aren M.

2013-01-01

Swimming and flying animals rely on their ability to home on mobile targets. In some fish, physiological handedness and homing correlate, and dolphins exhibit handedness in their listening response. Here, we explore theoretically whether the actuators, sensors, and controllers in these animals follow similar laws of self-regulation, and how handedness affects homing. We find that the acoustic sensor (combined hydrophone-accelerometer) response maps are similar to fin force maps—modeled by Stuart-Landau oscillators—allowing localization by transitional vortex-propelled animals. The planar trajectories of bats in a room filled with obstacles are approximately reproduced by the states of a pair of strong and weak olivo-cerebellar oscillators. The stereoscopy of handedness reduces ambiguity near a mobile target, resulting in accelerated homing compared to even-handedness. Our results demonstrate how vortex-propelled animals may be localizing each other and circumventing obstacles in changing environments. Handedness could be useful in time-critical robot-assisted rescues in hazardous environments. PMID:23350035

Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia.

PubMed

Bercker, Sven; Bert, Bettina; Bittigau, Petra; Felderhoff-Müser, Ursula; Bührer, Christoph; Ikonomidou, Chrysanthy; Weise, Mirjam; Kaisers, Udo X; Kerner, Thoralf

2009-08-01

Propofol and sevoflurane are commonly used drugs in pediatric anesthesia. Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. Newborn Wistar rats were treated with repeated intraperitoneal injections of propofol or sevoflurane inhalation and compared to controls. Brains were examined histopathologically using the De Olmos cupric silver staining. Additionally, a summation score of the density of apoptotic cells was calculated for every brain. Spatial memory learning was assessed by the Morris Water Maze (MWM) test and the hole board test, performed in 7 weeks old animals who underwent the same anesthetic procedure. Brains of propofol-treated animals showed a significant higher neurodegenerative summation score (24,345) when compared to controls (15,872) and to sevoflurane-treated animals (18,870). Treated animals also demonstrated persistent learning deficits in the hole board test, whereas the MWM test revealed no differences between both groups. Among other substances acting via GABAA agonism and/or NMDA antagonism propofol induced neurodegeneration in newborn rat brains whereas a sevoflurane based anesthesia did not. The significance of these results for clinical anesthesia has not been completely elucidated. Future studies have to focus on the detection of safe anesthetic strategies for the developing brain.

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

Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV) type 1 protects against HSV-2 genital disease in guinea pigs

PubMed Central

2010-01-01

Background CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs. Results Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p < 0.0001). Immunization significantly reduced the amount and duration of viral shedding and provided complete protection against neurological symptoms, while 90% of mock-immunized animals succumbed due to the severity of disease. Importantly, immunized animals showed no signs of recurrent disease or viral shedding during a 60-days observation period after recovery from primary infection, and carried 50-fold less latent viral DNA load in their dorsal root ganglia than the surviving mock-vaccinated controls (p < 0.0001). Conclusions Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection. PMID:20525279

Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.

PubMed

Saladino, R; Garcia, C; Thompson, C; Hammer, B; Parsonnet, J; Novitsky, T; Siber, G; Fleisher, G

1994-02-01

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal-Assisted Therapy for Post-traumatic Stress Disorder: Lessons from "Case Reports" in Media Stories.

PubMed

Altschuler, Eric L

2018-01-01

Post-traumatic stress disorder (PTSD) can follow war trauma, sexual abuse, other traumas, and even be experienced by commanders for the PTSD of their subordinates. Medications and counseling are sometimes not effective, so new treatments are needed. Some years ago, I suggested that animal-assisted therapy (AAT) (pet therapy) might be beneficial for PTSD. A large randomized controlled trial is underway of canine-assisted therapy for PTSD. Randomized controlled trials are most useful in assessing the efficacy of a medical intervention as these trials control for known and unknown biases. However, due to their very nature and rigorous requirements, knowledge gained from randomized controlled trials may need to be supplemented from other kinds of studies. Here, I note that media reports of AAT for PTSD may effectively function as case reports and suggest further studies: For PTSD, these demonstrate that (1) AAT can be dramatically effective in improving PTSD symptoms; (2) there is the potential for benefit from AAT by multiple different animals besides canines for PTSD; and (3) AAT may have a role in preventing suicide in patients with PTSD. © Association of Military Surgeons of the United States 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Optimizing a Male Reproductive Aging Mouse Model by d-Galactose Injection

PubMed Central

Liao, Chun-Hou; Chen, Bing-Huei; Chiang, Han-Sun; Chen, Chiu-Wei; Chen, Mei-Feng; Ke, Chih-Chun; Wang, Ya-Yun; Lin, Wei-Ning; Wang, Chi-Chung; Lin, Ying-Hung

2016-01-01

The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8–10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies or maintaining nuclear integration (e.g., cylicin, basic protein of sperm head cytoskeleton 2 (Cylc2), casein kinase 2, alpha prime interacting protein (Csnka2ip) and katanin p80 (WD40-containing) subunit B1 (Katnb1)). These results indicate that d-gal-injected mice are suitable for investigating male reproductive aging. PMID:26771610

Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test.

PubMed

Salloum, R H; Sandridge, S; Patton, D J; Stillitano, G; Dawson, G; Niforatos, J; Santiago, L; Kaltenbach, J A

2016-01-01

In recent years, there has been increasing use of the gap detection reflex test to demonstrate induction of tinnitus in animals. Animals with tinnitus show weakened gap detection ability for background noise that matches the pitch of the tinnitus. The usual explanation is that the tinnitus 'fills in the gap'. It has recently been shown, however, that tinnitus is commonly associated with hyperacusis-like enhancements of the acoustic startle response, a change which might potentially alter responses in the gap detection test. We hypothesized that such enhancements could lead to an apparent reduction of gap suppression, resembling that caused by tinnitus, by altering responses to the startle stimulus or the background noise. To test this hypothesis, we compared gap detection abilities in 3 subsets of noise-exposed animals with those in unexposed controls. The results showed that exposed animals demonstrated altered gap detection abilities, but these alterations were sometimes explained as consequences of hyper-responsiveness to either the startle stimulus or to the background noise. Two of the three subsets of animals studied, however, displayed weakened gap detection abilities that could not be explained by enhanced responses to these stimuli or by reduced sound sensitivity or a reduction of temporal processing speed, consistent with the induction of tinnitus. These results demonstrate that not only hearing loss but also changes in sensitivity to background noise or to startle stimuli are potential confounds that, when present, can underlie changes in gap detection irrespective of tinnitus. We discuss how such confounds can be recognized and how they can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

The consistency approach for quality control of vaccines - a strategy to improve quality control and implement 3Rs.

PubMed

De Mattia, Fabrizio; Chapsal, Jean-Michel; Descamps, Johan; Halder, Marlies; Jarrett, Nicholas; Kross, Imke; Mortiaux, Frederic; Ponsar, Cecile; Redhead, Keith; McKelvie, Jo; Hendriksen, Coenraad

2011-01-01

Current batch release testing of established vaccines emphasizes quality control of the final product and is often characterized by extensive use of animals. This report summarises the discussions of a joint ECVAM/EPAA workshop on the applicability of the consistency approach for routine release of human and veterinary vaccines and its potential to reduce animal use. The consistency approach is based upon thorough characterization of the vaccine during development and the principle that the quality of subsequent batches is the consequence of the strict application of a quality system and of a consistent production of batches. The concept of consistency of production is state-of-the-art for new-generation vaccines, where batch release is mainly based on non-animal methods. There is now the opportunity to introduce the approach into established vaccine production, where it has the potential to replace in vivo tests with non-animal tests designed to demonstrate batch quality while maintaining the highest quality standards. The report indicates how this approach may be further developed for application to established human and veterinary vaccines and emphasizes the continuing need for co-ordination and harmonization. It also gives recommendations for work to be undertaken in order to encourage acceptance and implementation of the consistency approach. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

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

Rinaldo, J.E.; English, D.; Levine, J.

1988-02-01

Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

A Longitudinal Motor Characterisation of the HdhQ111 Mouse Model of Huntington's Disease.

PubMed

Yhnell, Emma; Dunnett, Stephen B; Brooks, Simon P

2016-05-31

Huntington's disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms. Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice. An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function. A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery. The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation.

In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury.

PubMed Central

Hines, J. E.; Johnson, S. J.; Burt, A. D.

1993-01-01

We investigated the response of macrophages and perisinusoidal (Ito) cells (PSCs) during the development of secondary biliary cirrhosis after ligation and division of the common bile duct. Liver tissue was obtained from three groups of male Wistar rats: 1) untreated controls (n = 3); 2) common bile duct-ligated (CBDL) animals (n = 15); and 3) sham-operated controls (n = 15). Material from animal groups 2 and 3 was obtained on days 3, 7, 14, 21, and 28 after operation; in all animals 5-bromo-2-deoxyuridine was administered intraperitoneally before death. Monocytes and macrophages were detected using the monoclonal antibody ED1 and tissue macrophages using the antibody ED2. Cell proliferation within the macrophage population was demonstrated by double labeling for ED2 and incorporated 5-bromo-2-deoxyuridine. PSCs were demonstrated in tissue sections by immunolocalization of desmin; proliferating PSCs were identified by double labeling for desmin and incorporated 5-bromo-2-deoxyuridine. Evidence of phenotypic modulation of PSCs was sought using anti-alpha-smooth muscle actin (alpha-SMA) antibody. Increased numbers of ED1- and ED2-positive cells were seen in CBDL animals at all time points. Local proliferation of macrophages could be identified and reached a peak at day 3, thereafter falling toward control values. Compared with those of controls, livers of CBDL animals showed increased numbers of desmin-positive PSCs in periportal zones from day 3 on, reaching a peak at day 14 (127.8 +/- 10.99 cells/0.635 mm2) and followed by a plateau. PSC proliferation peaked at days 3 and 7 (labeling indices 11.2% and 11.2%, respectively) and thereafter fell toward control values; no expansion of the PSC population was seen in sham-operated rats. Increased alpha-SMA-positive cells were also noted from day 3, with a peak at day 21 (231.1 +/- 11.52 cells/0.635 mm2) and followed by a plateau. En face labeling experiments in days 14, 21, and 28 CBDL animals showed cells co-expressing alpha-SMA and desmin and cells expressing alpha-SMA alone. These results indicate that in response to chronic cholestatic liver injury, PSCs proliferate and undergo phenotypic modulation toward "myofibroblast-like" cells. The kinetics of the response are similar to those of the ED2-positive cell population in keeping with a hypothesis that PSC proliferation and activation may be mediated by factors released by macrophages in response to various forms of liver injury. We conclude that the responses of macrophages and PSCs to cholestatic injury are similar to those after toxin-induced hepatocyte necrosis. Images Figure 2 Figure 4 Figure 5 Figure 6 PMID:8434646

[Effects of hypothalamic microinjections of 6-hydroxydopamine (6-OHDA) on estral cycle and morphology of the genital tract in the female rat (author's transl)].

PubMed

Sala, M A; Oteui, J T; Benedetti, W I

1975-01-01

To determine whether central catecholaminergic pathways are involved in the neural contral of gonadotrophin secretion, they were interrupted at the hypothalamic level by microinjections of 6-hydroxydopamine (6-OHDA). The effects on ovulation, estral cycle and ovarian and uterine histology were studied. Microinjections of 50 mug of 6-OHDA hydrobromyde were made bilaterally into the anterolateral hypothalamus in a group of rats. Another group was injected with 25 mug of 6-OHDA, while a control group recieved an equivalent volume (5 mul) of saline with ascorbic acid. Animals injected with 50 mug of 6-OHDA showed blockade of ovulation, vaginal cytology characteristics of persistent estrous, polyfollicular ovaries and enlarged uteri with hypertrophic endometrial glands. In the group injected with 25 mug, similiar effects were demonstrated, but the number of affected animals was smaller than that in the 50 mug group. Control animals dit not show modifications, either in estral cycle or in ovarian and uterine histology. These results suggest that 6-OHDA injected into the anterolateral hypothalmus interferes with catecholaminergic pathways that participate in the neural control of ovulation.

Assessment of the anti-protozoal activity of crude Carica papaya seed extract against Trypanosoma cruzi.

PubMed

Jiménez-Coello, Matilde; Guzman-Marín, Eugenia; Ortega-Pacheco, Antonio; Perez-Gutiérrez, Salud; Acosta-Viana, Karla Y

2013-10-11

In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage).

Universal computing by DNA origami robots in a living animal

PubMed Central

Levner, Daniel; Ittah, Shmulik; Abu-Horowitz, Almogit; Bachelet, Ido

2014-01-01

Biological systems are collections of discrete molecular objects that move around and collide with each other. Cells carry out elaborate processes by precisely controlling these collisions, but developing artificial machines that can interface with and control such interactions remains a significant challenge. DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems1-3, logic circuits4-6 and robotics7-9. The molecule also naturally interfaces with living systems, and different forms of DNA-based biocomputing have previously been demonstrated10-13. Here we show that DNA origami14-16 can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other17-18 in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof-of-principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT, and a half adder). Following an ex vivo prototyping phase, we successfully employed the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets the cells of the animal. PMID:24705510

Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot.

PubMed

Sarode, Bhagyesh R; Kover, Karen; Tong, Pei Y; Zhang, Chaoying; Friedman, Simon H

2016-11-07

In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans-cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas.

The Effect of Elevated Intra-Abdominal Pressure on TLR4 Signaling in Intestinal Mucosa and on Intestinal Bacterial Translocation in a Rat.

PubMed

Strier, Adam; Kravarusic, Dragan; Coran, Arnold G; Srugo, Isaac; Bitterman, Nir; Dorfman, Tatiana; Pollak, Yulia; Matter, Ibrahim; Sukhotnik, Igor

2017-02-01

Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model. Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes. Rats were sacrificed 24 hours later. BT to mesenteric lymph nodes, liver, portal vein blood, and peripheral blood was determined at sacrifice. TLR4-related gene and protein expression (TLR-4; myeloid differentiation factor 88 [Myd88] and TNF-α receptor-associated factor 6 [TRAF6]) expression were determined using real-time PCR, western blotting, and immunohistochemistry. Thirty percent of sham rats developed BT in the mesenteric lymph nodes (level I) and 20% of control rats developed BT in the liver and portal vein (level II). abdominal compartment syndrome (ACS) rats demonstrated an 80% BT in the lymph nodes (Level I) and 40% BT in the liver and portal vein (Level II). Elevated BT was accompanied by a significant increase in TLR-4 immunostaining in jejunum (51%) and ileum (35.9%), and in a number of TRAF6-positive cells in jejunum (2.1%) and ileum (24.01%) compared to control animals. ACS rats demonstrated a significant increase in TLR4 and MYD88 protein levels compared to control animals. Twenty-four hours after the induction of elevated IAP in a rat model, increased BT rates were associated with increased TLR4 signaling in intestinal mucosa.

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

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

PubMed

Koko, Kiavash R; McCauley, Brian M; Gaughan, John P; Nolan, Ryan S; Fromer, Marc W; Hagaman, Ashleigh L R; Choron, Rachel L; Brown, Spencer A; Hazelton, Joshua P

2017-07-01

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05). These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model. This is basic science research based on a large animal model, level V.

Medial Entorhinal Grid Cells and Head Direction Cells Rotate with a T-Maze More Often During Less Recently Experienced Rotations

PubMed Central

Gupta, Kishan; Beer, Nathan J.; Keller, Lauren A.; Hasselmo, Michael E.

2014-01-01

Prior studies of head direction (HD) cells indicate strong landmark control over the preferred firing direction of these cells, with few studies exhibiting shifts away from local reference frames over time. We recorded spiking activity of grid and HD cells in the medial entorhinal cortex of rats, testing correlations of local environmental cues with the spatial tuning curves of these cells' firing fields as animals performed continuous spatial alternation on a T-maze that shared the boundaries of an open-field arena. The environment was rotated into configurations the animal had either seen or not seen in the past recording week. Tuning curves of both cell types demonstrated commensurate shifts of tuning with T-maze rotations during less recent rotations, more so than recent rotations. This strongly suggests that animals are shifting their reference frame away from the local environmental cues over time, learning to use a different reference frame more likely reliant on distal or idiothetic cues. In addition, grid fields demonstrated varying levels of “fragmentation” on the T-maze. The propensity for fragmentation does not depend on grid spacing and grid score, nor animal trajectory, indicating the cognitive treatment of environmental subcompartments is likely driven by task demands. PMID:23382518

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Griko, Yuri V.; Rask, Jon C.; Raychev, Raycho

2017-01-01

As the world's space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organism's self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as "pathfinders," which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes. In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Griko, Yuri V.; Rask, Jon C.; Raychev, Raycho

2017-01-01

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

Cellular responses to various levels of sustained delivery of testosterone in the ventral prostate.

PubMed

Cavett, W; Tucci, M; Cason, Z; Lemos, L; England, B; Tsao, A; Benghuzzi, H

1997-01-01

The objective of this study was to evaluate the effect of various dosages of testosterone (T) delivered in a sustained manner by means of tricalcium phosphate-lysine (TCPL) delivery system on morphological changes of prostatic tissue using adult male rats as a model. In this experiment, adult male rats (250-300 g BW) were randomly divided into five equal groups (n = 8). Rats in group I, II, and III were castrated and implanted subcutaneously with TCPL loaded with three different dosages (10, 100 and 200 mg T, respectively) of T. Rats in group IV were castrated and implanted with sharm TCPL capsules, and rats in group V served as intact unimplanted controls. Surgical aseptic techniques were performed according to standard laboratory procedures. At the end of 4 and 12 weeks post implantation, four animals from each group were sacrificed and the prostate tissues were collected, weighted, and embedded for histo-pathological evaluations. Data collected from this study have shown that exogenous intake of T delivered in a sustained manner for twelve weeks induced several pathophysiological conditions in ventral prostatic tissue in comparison to the control and sham operated groups. This phenomenon was found to be directly proportional to the dose or the level of sustained delivery. The results demonstrated that the use of 10 mg filled TCPL implants decreased the total mass weight of ventral prostate. Light microscopic evaluation of this group (Group I) revealed a cellular adaptation through an atrophy in the epithelium component. Cytopathological observations such as low cuboidal and thin glands, pleomorphism, and occasional presence of connective tissue stroma were detected. In contrast, ventral prostate collected from animals implanted with TCPL filled with 200 mg T (Group III) showed a significant increase in weights of the wet prostatic tissues in comparison to all groups. Histopathological evaluations demonstrated the following. (i) prostatic hypertrophy alone, or in conjunction with hyperplasia of the epithelial cells, (ii) less connective tissue stroma in comparison to the control group, (iii) occasional involvement of mitotic figures, and (iv) increased angiogenesis. No significant change was observed in those animals implanted with TCPL capsules containing 100 mg T compared to the intact control animals.

Evidence for Emergency Vaccination Having Played a Crucial Role to Control the 1965/66 Foot-and-Mouth Disease Outbreak in Switzerland

PubMed Central

Zingg, Dana; Häsler, Stephan; Schuepbach-Regula, Gertraud; Schwermer, Heinzpeter; Dürr, Salome

2015-01-01

Foot-and-mouth disease (FMD) is a highly contagious disease that caused several large outbreaks in Europe in the last century. The last important outbreak in Switzerland took place in 1965/66 and affected more than 900 premises and more than 50,000 animals were slaughtered. Large-scale emergency vaccination of the cattle and pig population has been applied to control the epidemic. In recent years, many studies have used infectious disease models to assess the impact of different disease control measures, including models developed for diseases exotic for the specific region of interest. Often, the absence of real outbreak data makes a validation of such models impossible. This study aimed to evaluate whether a spatial, stochastic simulation model (the Davis Animal Disease Simulation model) can predict the course of a Swiss FMD epidemic based on the available historic input data on population structure, contact rates, epidemiology of the virus, and quality of the vaccine. In addition, the potential outcome of the 1965/66 FMD epidemic without application of vaccination was investigated. Comparing the model outcomes to reality, only the largest 10% of the simulated outbreaks approximated the number of animals being culled. However, the simulation model highly overestimated the number of culled premises. While the outbreak duration could not be well reproduced by the model compared to the 1965/66 epidemic, it was able to accurately estimate the size of the area infected. Without application of vaccination, the model predicted a much higher mean number of culled animals than with vaccination, demonstrating that vaccination was likely crucial in disease control for the Swiss FMD outbreak in 1965/66. The study demonstrated the feasibility to analyze historical outbreak data with modern analytical tools. However, it also confirmed that predicted epidemics from a most carefully parameterized model cannot integrate all eventualities of a real epidemic. Therefore, decision makers need to be aware that infectious disease models are useful tools to support the decision-making process but their results are not equal valuable as real observations and should always be interpreted with caution. PMID:26697436

Effect of 3D animation videos over 2D video projections in periodontal health education among dental students.

PubMed

Dhulipalla, Ravindranath; Marella, Yamuna; Katuri, Kishore Kumar; Nagamani, Penupothu; Talada, Kishore; Kakarlapudi, Anusha

2015-01-01

There is limited evidence about the distinguished effect of 3D oral health education videos over conventional 2 dimensional projections in improving oral health knowledge. This randomized controlled trial was done to test the effect of 3 dimensional oral health educational videos among first year dental students. 80 first year dental students were enrolled and divided into two groups (test and control). In the test group, 3D animation and in the control group, regular 2D video projections pertaining to periodontal anatomy, etiology, presenting conditions, preventive measures and treatment of periodontal problems were shown. Effect of 3D animation was evaluated by using a questionnaire consisting of 10 multiple choice questions given to all participants at baseline, immediately after and 1month after the intervention. Clinical parameters like Plaque Index (PI), Gingival Bleeding Index (GBI), and Oral Hygiene Index Simplified (OHI-S) were measured at baseline and 1 month follow up. A significant difference in the post intervention knowledge scores was found between the groups as assessed by unpaired t-test (p<0.001) at baseline, immediate and after 1 month. At baseline, all the clinical parameters in the both the groups were similar and showed a significant reduction (p<0.001)p after 1 month, whereas no significant difference was noticed post intervention between the groups. 3D animation videos are more effective over 2D videos in periodontal disease education and knowledge recall. The application of 3D animation results also demonstrate a better visual comprehension for students and greater health care outcomes.

Chemomodulatory Potential of Flaxseed Oil Against DMBA/Croton Oil-Induced Skin Carcinogenesis in Mice.

PubMed

Sharma, Jyoti; Singh, Ritu; Goyal, P K

2016-09-01

The present study was conducted to evaluate the potential of flaxseed oil to prevent chemically induced skin cancer in mice. Cancer was induced on 2-stage skin carcinogenesis model by single topical application of 7,12 dimethylbenz [a]anthracene (DMBA), as, initiator, and two weeks later it was promoted by croton oil treatment thrice a week on the dorsal surface of mice for 16 weeks. Flaxseed oil (FSO; 100µL/animal/d) was orally administered 1 week before and 1 week after DMBA application (Peri-initiation stage). The animals of the FSO-administered group showed a significant reduction in tumor incidence (76.67%), cumulative number of tumors (37), tumor yield (3.7), and tumor burden (4.81) when compared with the carcinogen-treated control animals. Biochemical parameters in skin and liver tissue such as LPO and phase I enzymes were significantly (P < .01) reduced in the FSO-treated experimental group, whereas the phase II enzymes (GST, DT-diaphorase) and antioxidant parameters (GSH, GPx, SOD, catalase, and vitamin C) exhibited a significant (P < .01) elevation when compared with the animals of the carcinogen-treated control group. Histopathological alterations in the carcinogen-treated control animals were also observed in the form of epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and tumors, whereas these were found to be reduced after FSO administration. The results of the present study demonstrate that the oral administration of FSO has the potential to modulate the levels of LPO, antioxidants, and detoxification enzymes in the DMBA-croton oil-induced skin carcinogenesis in mice. © The Author(s) 2015.

Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

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

Green, Damian J.; Shadman, Mazyar; Jones, Jon C.

Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls).more » In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.« less

Development of shampoo, soap and ointment formulated by green synthesised silver nanoparticles functionalised with antimicrobial plants oils in veterinary dermatology: treatment and prevention strategies.

PubMed

Bansod, Sunita Dashrath; Bawaskar, Manisha Subrashrao; Gade, Aniket Krishnarao; Rai, Mahendra Kumar

2015-08-01

Many scientists have focused their research on the role of nanotechnology for the control of human pathogens, but there are also many topical pathogens present in animals, which infect animals and transfer to humans. Topical therapy is extremely important for the management of dermatological condition in animals. Therefore, the present study aims to evaluate the efficacy of biogenic silver nanoparticles (AgNPs) in combination with herbal oils against animal skin infections which may be responsible for causing infections in human beings. Here, the authors synthesised and characterised the AgNPs from Azadirachta indica. The oils were extracted from medicinal plants including Cymbopogon citratus, Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the antifungal and antibacterial activity of plant oils along with AgNPs were evaluated. An excision wound model was used for the study of wound healing activity in rabbits. AgNPs functionalised oil has demonstrated remarkable antimicrobial activity against pathogens present on the skin of animals. The nano-functionalised antimicrobial oils were used in the formulation of shampoo, soap and ointment for veterinary dermatology. Antimicrobial products of plant origin with AgNPs are valuable, safe and have a specific role in controlling diseases. The authors believe that this approach will be a good alternative therapy to solve the continuous antibiotic resistance developed by many bacterial pathogens and will be utilised in various animal contacting areas in medicine.

An outbreak of Shiga toxin-producing Escherichia coli serogroup O157 linked to a lamb-feeding event.

PubMed

Rowell, S; King, C; Jenkins, C; Dallman, T J; Decraene, V; Lamden, K; Howard, A; Featherstone, C A; Cleary, P

2016-09-01

Fifteen confirmed cases and 15 possible cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 21/28 were linked to direct contact with lambs at a 'Lambing Live' event in the North West of England between 29 March and 21 April 2014. Twenty-one (70%) of the cases were female, 23 (77%) were children aged <16 years, of whom 14 (46%) were in the 0-5 years age group. Five children developed haemolytic uraemic syndrome. Multilocus variable number tandem repeat analysis (MLVA) profiles on 14 human cases were indistinguishable, and 6/10 animal isolates had a MLVA profile identical to the outbreak profile. Whole-genome sequencing analysis revealed that all isolates, both human and animal, fell within a 5-single nucleotide polymorphism cluster indicating the isolates belonged to the same point source. On inspection of the premises, extensive and uncontrolled physical contact between visitors and animals was occuring within the animal pens and during bottle-feeding. Public areas were visibly contaminated with animal faeces. Information to visitors, and the infection control awareness demonstrated by staff, was inadequate. Managing the risk to visitors of STEC O157 infection at animal petting events and open farms requires implementation of stringent control measures by the operator, as outlined in the industry code of practice. Enforcement action is sometimes required to prevent high-risk activities taking place at both permanent and temporary attractions.

Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

PubMed

Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

2017-08-17

Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P < 0.01). This reduction was even higher if only extra-pulmonary infection was considered (17% and 68%, respectively; P < 0.001). This trial demonstrates that BCG vaccination of goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

THE EFFECT OF X-RAY IRRADIATION ON THE COURSE OF VACCINAL PROCESS CAUSED BY THE ADMINISTRATION OF LIVING BRUCELLOSIS VACCINE TO ANIMALS (in Russian)

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

Shevtsova, Z.V.

1959-10-01

Investigations were conducted on white rats irradiated at doses of 300 to 600 r and guinea pigs irradiated at doses of 150 to 250 r. It appeared that immunizition with vaccinal brucella culture it the height of radiation sickness increases the death rate of the irradiated animals. As demonstrated by bacteriological examination, development of generalized vaccinal process in the irradiated and immunized animals pursued the same course as in the immunized non- irradiated animals. This procoss was manifested in the dissemination of brucella vaccinal strain in various organs. However the irradiated animals become cleared of the vaccinal culture at amore » somewhat slower rate than in the non-irradiated ones. in guinea pigs, irradiated privious to vaccination there was a slower formation of agglutinins with lower titre than in control non-irradiated animals. Opsonic phagocytic blood index was somewhat lower only in the animals irradiated 24 hours previous to the vaccination. When irradiating white rats 24 hours or 10 days in advance or 24 hours after the vaccination, a delay in the agglutinin production has been observed during the first days following the vaccination. (auth)« less

Lied Animal Shelter Animal campus Renewable Energy Demonstration Project

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

Randy Spitzmesser, AIA

2005-11-22

The Animal Shelter campus plan includes a new adoption center coupled with a dog adoption park, a wellness/veterinary technician education center, a show arena, and an addition to the existing shelter that will accommodate all animal control and sheltering for the Las Vegas Valley. The new facility will provide a sophisticated and innovative presentation of the animals to be adopted in an attempt to improve the public's perception of shelter animals. Additionally, the Regional Animal Campus will be a ''green building'', embodying a design intent on balancing environmental responsiveness, resource efficiency and cultural and community sensitivity. Designing an energy-efficient buildingmore » helps reduce pollution from burning fossil fuels, reduce disturbance of natural habitats for the harvesting of resources and minimizes global warming. The project will be a leader in the use of renewable energy by relying on photovoltaic panels, wind turbines, and solar collectors to produce a portion of the project's energy needs The building will operate more efficiently in comparison to a typical shelter through the use of monitoring and specialized cooling/heating equipment. Windows bringing in natural daylight will reduce the center's demand for electricity.« less

Histomorphometric Study of New Bone Formation Comparing Defect Healing with Three Bone Grafting Materials: The Effect of Osteoporosis on Graft Consolidation.

PubMed

Zhang, Qiao; Jing, Dai; Zhang, Yufeng; Miron, Richard J

Bone grafting materials are frequently utilized in oral surgery and periodontology to fill bone defects and augment lost or missing bone. The purpose of this study was to compare new bone formation in bone defects created in both normal and osteoporotic animals loaded with three types of bone grafts from different origins. Forty-eight female Wistar rats were equally divided into control normal and ovariectomized animals. Bilateral 2.5-mm femur defects were created and filled with an equal weight of (1) natural bone mineral (NBM, BioOss) of bovine origin, (2) demineralized freeze-dried bone allograft (DFDBA, LifeNet), or (3) biphasic calcium phosphate (BCP, Vivoss). Following 3 and 6 weeks of healing, hematoxylin and eosin and TRAP staining was performed to determine new bone formation, material degradation, and osteoclast activity. All bone substitutes demonstrated osteoconductive potential at 3 and 6 weeks with higher osteoclast numbers observed in all ovariectomized animals. NBM displayed continual new bone formation with little to no sign of particle degradation, even in osteoporotic animals. DFDBA particles showed similar levels of new bone formation but rapid particle degradation rates with lower levels of mineralized tissue. BCP bone grafts demonstrated significantly higher new bone formation when compared with both NBM and DFDBA particles; however, the material was associated with higher osteoclast activity and particle degradation. Interestingly, in osteoporotic animals, BCP displayed synergistically and markedly more rapid rates of particle degradation. Recent modifications to synthetically fabricated materials were shown to be equally or more osteopromotive than NBM and DFDBA. However, the current BCP utilized demonstrated much faster resorption properties in osteoporotic animals associated with a decrease in total bone volume when compared with the slowly/nonresorbing NBM. The results from this study point to the clinical relevance of minimizing fast-resorbing bone grafting materials in osteoporotic phenotypes due to the higher osteoclastic activity and greater material resorption.

Past and Ongoing Tsetse and Animal Trypanosomiasis Control Operations in Five African Countries: A Systematic Review

PubMed Central

Holt, Hannah R.; Selby, Richard; Guitian, Javier

2016-01-01

Background Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a mere 1.3% of the tsetse infested area. Although extensive trypanosomiasis and tsetse (T&T) control operations have been running since the beginning of the 20th century, Animal African Trypanosomiasis is still a major constraint of livestock production in sub-Saharan Africa. Methodology/Principal Findings We performed a systematic review of the existing literature describing T&T control programmes conducted in a selection of five African countries, namely Burkina Faso, Cameroon, Ethiopia, Uganda and Zambia, between 1980 and 2015. Sixty-eight documents were eventually selected from those identified by the database search. This was supplemented with information gathered through semi-structured interviews conducted with twelve key informants recruited in the study countries and selected based on their experience and knowledge of T&T control. The combined information from these two sources was used to describe the inputs, processes and outcomes from 23 major T&T control programmes implemented in the study countries. Although there were some data gaps, involvement of the target communities and sustainability of the control activities were identified as the two main issues faced by these programmes. Further, there was a lack of evaluation of these control programmes, as well as a lack of a standardised methodology to conduct such evaluations. Conclusions/Significance Past experiences demonstrated that coordinated and sustained control activities require careful planning, and evidence of successes, failures and setbacks from past control programmes represent a mine of information. As there is a lack of evaluation of these programmes, these data have not been fully exploited for the design, analyses and justification of future control programmes. PMID:28027299

Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

Effects of cocoa-enriched diet on orofacial pain in a murine model.

PubMed

Bowden, L N; Rohrs, E L; Omoto, K; Durham, P L; Holliday, L S; Morris, A D; Allen, K D; Caudle, R M; Neubert, J K

2017-06-01

To investigate and discuss the effects of cocoa on orofacial pain. The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changing their food from the standard chow to a cocoa-enriched or control-equivalent diet. Male rats fed the cocoa diet had a significantly higher operant pain index when tested at 37°C as compared to control diet-fed animals. Female rats on the cocoa diet had a significantly higher pain index when tested at 18°C and 44°C, as compared to animals fed the control diet. Capsaicin-induced pain was inhibited, with cocoa-diet male rats having a significantly higher pain index than control-diet male rats and cocoa-diet female rats at both 37°C and 44°C. Cocoa-diet female rats had a significantly higher pain index at 44°C than control-diet females. Mechanical sensitivity was affected following capsaicin cream, with a significantly decreased tolerated bottle distance in both cocoa- and control-diet animals, but there was no difference between cocoa- and control-diet groups. Using the OPAD operant system, we demonstrated that a diet rich in cocoa was effective in inhibiting neurogenic inflammatory pain in rats. This has implications for the use of novel alternative therapies such as diet modification for pain control. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques

PubMed Central

Lee, Kim M.; Chiu, Kevin B.; Didier, Peter J.; Baker, Kate C.; MacLean, Andrew G.

2015-01-01

The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2 mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. PMID:26191654

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

PubMed

Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

2015-11-01

The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

THE LYMPHOCYTE RESPONSE TO PRIMARY MOLONEY SARCOMA VIRUS TUMORS IN BALB/c MICE

PubMed Central

Lamon, E. W.; Wigzell, H.; Klein, E.; Andersson, B.; Skurzak, H. M.

1973-01-01

Adult BALB/c mice were injected with Moloney sarcoma virus (MSV) after which the animals' lymphocytes were examined for activity against Moloney leukemia virus (MLV) antigen-bearing target cells at 5-day intervals for 30 days. Lymphocytes from these animals and appropriately matched controls were fractionated into B cell-deficient (primarily T cells) and T cell-deficient (primarily B cells) subpopulations. Macrophages were removed using iron powder and magnetism. The unfractionated lymphocytes, T cells, and non-T cells were then tested in microcytotoxicity tests. Antigen-specific activity was found in the unfractionated lymphocytes from animals that had not yet developed palpable tumors and from regressor animals. The T cells were active just before tumor development and just after regression; however, by day 30 after virus infection (8–10 days after regression) the T cell subpopulation was much less active. The non-T cell subpopulation was also active before tumor development and soon after regression. However, this activity continued to rise after regression and was highest at 30 days. At day 15 (peak tumor size) neither subpopulation was active. The activity was demonstrated to be specific for the MLV-determined cell surface antigen by testing on control target cells that were MLV antigen negative and by comparison of the inhibitory effects with lymphocytes immune to a nonpertinent antigen as well as normal lymphocytes. The non-T cells were tested for activity before and after removal of macrophages with iron powder and magnetism. Such cells were significantly more active after removal of the macrophages. These data demonstrate specific T cell and non-T cell activity in microcytotoxicity tests with a tumor-specific system and strongly suggest that the non-T cell activity described herein is a B cell function. PMID:4709269

Target-Selectivity of Parvalbumin-Positive Interneurons in Layer II of Medial Entorhinal Cortex in Normal and Epileptic Animals

PubMed Central

Armstrong, Caren; Wang, Jessica; Lee, Soo Yeun; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2015-01-01

The medial entorhinal cortex layer II (MEClayerII) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII. However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII. However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII. Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. PMID:26663222

Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

PubMed

Armstrong, Caren; Wang, Jessica; Yeun Lee, Soo; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2016-06-01

The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The effectiveness of humane teaching methods in veterinary education.

PubMed

Knight, Andrew

2007-01-01

Animal use resulting in harm or death has historically played an integral role in veterinary education, in disciplines such as surgery, physiology, biochemistry, anatomy, pharmacology, and parasitology. However, many non-harmful alternatives now exist, including computer simulations, high quality videos, ''ethically-sourced cadavers'' such as from animals euthanased for medical reasons, preserved specimens, models and surgical simulators, non-invasive self-experimentation, and supervised clinical experiences. Veterinary students seeking to use such methods often face strong opposition from faculty members, who usually cite concerns about their teaching efficacy. Consequently, studies of veterinary students were reviewed comparing learning outcomes generated by non-harmful teaching methods with those achieved by harmful animal use. Of eleven published from 1989 to 2006, nine assessed surgical training--historically the discipline involving greatest harmful animal use. 45.5% (5/11) demonstrated superior learning outcomes using more humane alternatives. Another 45.5% (5/11) demonstrated equivalent learning outcomes, and 9.1% (1/11) demonstrated inferior learning outcomes. Twenty one studies of non-veterinary students in related academic disciplines were also published from 1968 to 2004. 38.1% (8/21) demonstrated superior, 52.4% (11/21) demonstrated equivalent, and 9.5% (2/21) demonstrated inferior learning outcomes using humane alternatives. Twenty nine papers in which comparison with harmful animal use did not occur illustrated additional benefits of humane teaching methods in veterinary education, including: time and cost savings, enhanced potential for customisation and repeatability of the learning exercise, increased student confidence and satisfaction, increased compliance with animal use legislation, elimination of objections to the use of purpose-killed animals, and integration of clinical perspectives and ethics early in the curriculum. The evidence demonstrates that veterinary educators can best serve their students and animals, while minimising financial and time burdens, by introducing well-designed teaching methods not reliant on harmful animal use.

Neuroendocrine and physiological regulation of intake with particular reference to domesticated ruminant animals.

PubMed

Roche, John R; Blache, Dominique; Kay, Jane K; Miller, Dale R; Sheahan, Angela J; Miller, David W

2008-12-01

The central nervous system undertakes the homeostatic role of sensing nutrient intake and body reserves, integrating the information, and regulating energy intake and/or energy expenditure. Few tasks regulated by the brain hold greater survival value, particularly important in farmed ruminant species, where the demands of pregnancy, lactation and/or growth are not easily met by often bulky plant-based and sometimes nutrient-sparse diets. Information regarding metabolic state can be transmitted to the appetite control centres of the brain by a diverse array of signals, such as stimulation of the vagus nerve, or metabolic 'feedback' factors derived from the pituitary gland, adipose tissue, stomach/abomasum, intestine, pancreas and/or muscle. These signals act directly on the neurons located in the arcuate nucleus of the medio-basal hypothalamus, a key integration, and hunger (orexigenic) and satiety (anorexigenic) control centre of the brain. Interest in human obesity and associated disorders has fuelled considerable research effort in this area, resulting in increased understanding of chronic and acute factors influencing feed intake. In recent years, research has demonstrated that these results have relevance to animal production, with genetic selection for production found to affect orexigenic hormones, feeding found to reduce the concentration of acute controllers of orexigenic signals, and exogenous administration of orexigenic hormones (i.e. growth hormone or ghrelin) reportedly increasing DM intake in ruminant animals as well as single-stomached species. The current state of knowledge on factors influencing the hypothalamic orexigenic and anorexigenic control centres is reviewed, particularly as it relates to domesticated ruminant animals, and potential avenues for future research are identified.

28 CFR 36.302 - Modifications in policies, practices, or procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... service animal from the premises if: (i) The animal is out of control and the animal's handler does not take effective action to control it; or (ii) The animal is not housebroken. (3) If an animal is... accommodations without having the service animal on the premises. (4) Animal under handler's control. A service...

Mental imagery boosts music compositional creativity.

PubMed

Wong, Sarah Shi Hui; Lim, Stephen Wee Hun

2017-01-01

We empirically investigated the effect of mental imagery on young children's music compositional creativity. Children aged 5 to 8 years participated in two music composition sessions. In the control session, participants based their composition on a motif that they had created using a sequence of letter names. In the mental imagery session, participants were given a picture of an animal and instructed to imagine the animal's sounds and movements, before incorporating what they had imagined into their composition. Six expert judges independently rated all music compositions on creativity based on subjective criteria (consensual assessment). Reliability analyses indicated that the expert judges demonstrated a high level of agreement in their ratings. The mental imagery compositions received significantly higher creativity ratings by the expert judges than did the control compositions. These results provide evidence for the effectiveness of mental imagery in enhancing young children's music compositional creativity.

Real-time animation software for customized training to use motor prosthetic systems.

PubMed

Davoodi, Rahman; Loeb, Gerald E

2012-03-01

Research on control of human movement and development of tools for restoration and rehabilitation of movement after spinal cord injury and amputation can benefit greatly from software tools for creating precisely timed animation sequences of human movement. Despite their ability to create sophisticated animation and high quality rendering, existing animation software are not adapted for application to neural prostheses and rehabilitation of human movement. We have developed a software tool known as MSMS (MusculoSkeletal Modeling Software) that can be used to develop models of human or prosthetic limbs and the objects with which they interact and to animate their movement using motion data from a variety of offline and online sources. The motion data can be read from a motion file containing synthesized motion data or recordings from a motion capture system. Alternatively, motion data can be streamed online from a real-time motion capture system, a physics-based simulation program, or any program that can produce real-time motion data. Further, animation sequences of daily life activities can be constructed using the intuitive user interface of Microsoft's PowerPoint software. The latter allows expert and nonexpert users alike to assemble primitive movements into a complex motion sequence with precise timing by simply arranging the order of the slides and editing their properties in PowerPoint. The resulting motion sequence can be played back in an open-loop manner for demonstration and training or in closed-loop virtual reality environments where the timing and speed of animation depends on user inputs. These versatile animation utilities can be used in any application that requires precisely timed animations but they are particularly suited for research and rehabilitation of movement disorders. MSMS's modeling and animation tools are routinely used in a number of research laboratories around the country to study the control of movement and to develop and test neural prostheses for patients with paralysis or amputations.

Microfilaricidal efficacy of a single administration of Advocate(®) (Bayer Animal Health) in dogs naturally infected with Dirofilaria immitis or Dirofilaria repens.

PubMed

Frangipane di Regalbono, Antonio; Di Cesare, Angela; Traversa, Donato; Simonato, Giulia; Poser, Helen; Danesi, Patrizia; Furnari, Carmelo; Russi, Ilaria; Raele, Donato Antonio; Crisi, Paolo; Pampurini, Fabrizio; Pietrobelli, Mario

2016-08-15

The present study evaluated the microfilaricidal efficacy of a single application of the spot-on containing imidacloprid 10%/moxidectin 2.5% (Advocate(®), Bayer Animal Health) in dogs naturally infected either by Dirofilaria immitis or Dirofilaria repens. Dogs living in north-eastern and central-southern Italy, endemic for D. immitis and D. repens respectively, were randomly screened. Sixteen animals, eight infected with D. immitis and eight with D. repens, and fulfilling inclusion criteria were enrolled. Dogs infected with D. immitis received an adulticide treatment prior to the study and Advocate(®) 3 weeks after. The animals were divided in blocks of two (1:1, T1:T2) animals each, where Day 0 (D0) had an interval of 15days to compare T2 vs. T1 dogs during the first fortnight of examination (i.e. T2 dogs acted as control animals at each examination). At baseline (Days -15 and 0 for T2 and T1 dogs, respectively) the animals had a range of microfilaraemia of 180-99.700mff/ml (D. immitis) and 60-750 mff/ml (D. repens). All animals received a topical administration of Advocate(®) at D0 and were examined for microfilariae with microscopic and molecular tests at D15, D30, D60 and D90. All animals scored negative for mff at the first control post-treatment and throughout the study, with the exception of two D. immitis- infected animals that had a 2 mff/ml count at D15, and then become negative from Day 30 onwards. No adverse events were observed. The present study demonstrates the safety and the high microfilaricidal efficacy (99.97% and 100% for D. immitis and D. repens, respectively) of a single dose of moxidectin contained in Advocate(®) in naturally infected dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

Vestibulo-Sympathetic Responses

PubMed Central

Yates, Bill J; Bolton, Philip S.; Macefield, Vaughan G.

2014-01-01

Evidence accumulated over 30 years, from experiments on animals and human subjects, has conclusively demonstrated that inputs from the vestibular otolith organs contribute to the control of blood pressure during movement and changes in posture. This review considers the effects of gravity on the body axis, and the consequences of postural changes on blood distribution in the body. It then separately considers findings collected in experiments on animals and human subjects demonstrating that the vestibular system regulates blood distribution in the body during movement. Vestibulosympathetic reflexes differ from responses triggered by unloading of cardiovascular receptors such as baroreceptors and cardiopulmonary receptors, as they can be elicited before a change in blood distribution occurs in the body. Dissimilarities in the expression of vestibulosympathetic reflexes in humans and animals are also described. In particular, there is evidence from experiments in animals, but not humans, that vestibulosympathetic reflexes are patterned, and differ between body regions. Results from neurophysiological and neuroanatomical studies in animals are discussed that identify the neurons that mediate vestibulosympathetic responses, which include cells in the caudal aspect of the vestibular nucleus complex, interneurons in the lateral medullary reticular formation, and bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Recent findings showing that cognition can modify the gain of vestibulosympathetic responses are also presented, and neural pathways that could mediate adaptive plasticity in the responses are proposed, including connections of the posterior cerebellar vermis with the vestibular nuclei and brainstem nuclei that regulate blood pressure. PMID:24715571

Effects of classroom animal-assisted activities on social functioning in children with autism spectrum disorder.

PubMed

O'Haire, Marguerite E; McKenzie, Samantha J; McCune, Sandra; Slaughter, Virginia

2014-03-01

The objective of this study was to implement and evaluate a classroom-based Animal-Assisted Activities (AAA) program on social functioning in children with autism spectrum disorder (ASD). This was a multisite, control-to-intervention design study. The study was conducted in 41 classrooms in 15 schools in Brisbane, Australia. Sixty-four (64) 5- to 12-year-old children diagnosed with ASD comprised the study group. The AAA program consisted of 8 weeks of animal exposure in the school classroom in addition to 16 20-minute animal-interaction sessions. Teacher- and parent-reported child behavior and social functioning were assessed through standardized instruments at three time points: upon study entry (Time 1), after an 8-week waiting period during the week prior to the AAA program (Time 2), and during the week following the 8-week AAA program (Time 3). Significant improvements were identified in social functioning, including increases in social approach behaviors and social skills, and decreases in social withdrawal behaviors, from before to after the AAA program, but not during the waitlist period. Over half of parents also reported that participants demonstrated an increased interest in attending school during the program. Results demonstrate the feasibility and potential efficacy of a new classroom-based Animal-Assisted Activities model, which may provide a relatively simple and cost-effective means of helping educators and families to improve the social functioning of children with ASD.

A combined behavioral and morphological study on the effects of fetal asphyxia on the nigrostriatal dopaminergic system in adult rats.

PubMed

Strackx, E; Van den Hove, D L A; Steinbusch, H P; Steinbusch, H W M; Vles, J S H; Blanco, C E; Gavilanes, A W D

2008-06-01

Fetal asphyxic insults in the brain are known to be associated with developmental neurological problems like neuromotor disorders. However, little is known about the long-term consequences of fetal asphyxia (FA). For that reason, the present study investigated the long-term effects of FA on motor behavior and dopaminergic circuitry. FA was induced at embryonic day 17 by 75-minute clamping of the uterine circulation. SHAM animals underwent the same procedure except for the clamping. This was followed by full-term vaginal delivery of animals in all groups (FA, SHAM and untreated controls). At 6 months, basal and amphetamine-induced locomotor activity was measured during open field testing. Brain sections were stained for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). TH-positive cells and GFAP-positive cells in substantia nigra pars compacta (SN(C)) and striatum were counted using design-based stereology. Moreover, TH-immunoreactivity in the striatum was assessed by grey value measurements. Behavioral analysis demonstrated that SHAM and FA showed less basal and amphetamine-induced activity than controls. Histochemically, FA decreased the number of TH-positive neurons in the SN(C) and lowered TH-positive in the striatum. Furthermore, more GFAP-positive cells were found in the SN(C) and striatum in FA than in either control and SHAM groups. Additionally, FA animals showed ventriculomegaly associated with smaller white matter as well as grey matter volumes. The data show that FA was associated with deficits in both dopamine-related motor behavior and biochemistry. These alterations were associated with nigrostriatal astrogliosis. The present study demonstrates the sensitivity of the dopaminergic system towards FA.

Controlled release of vancomycin from thin sol-gel films on implant surfaces successfully controls osteomyelitis.

PubMed

Adams, Christopher S; Antoci, Valentin; Harrison, Gerald; Patal, Payal; Freeman, Terry A; Shapiro, Irving M; Parvizi, Javad; Hickok, Noreen J; Radin, Shula; Ducheyne, Paul

2009-06-01

Peri-prosthetic infection remains a serious complication of joint replacement surgery. Herein, we demonstrate that a vancomycin-containing sol-gel film on Ti alloy rods can successfully treat bacterial infections in an animal model. The vancomycin-containing sol-gel films exhibited predictable release kinetics, while significantly inhibiting S. aureus adhesion. When evaluated in a rat osteomyelitis model, microbiological analysis indicated that the vancomycin-containing sol-gel film caused a profound decrease in S. aureus number. Radiologically, while the control side showed extensive bone degradation, including abscesses and an extensive periosteal reaction, rods coated with the vancomycin-containing sol-gel film resulted in minimal signs of infection. MicroCT analysis confirmed the radiological results, while demonstrating that the vancomycin-containing sol-gel film significantly protected dense bone from resorption and minimized remodeling. These results clearly demonstrate that this novel thin sol-gel technology can be used for the targeted delivery of antibiotics for the treatment of periprosthetic as well as other bone infections. Copyright 2008 Orthopaedic Research Society

Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.

PubMed

Harata, G; He, F; Hiruta, N; Kawase, M; Kubota, A; Hiramatsu, M; Yausi, H

2010-06-01

To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0.05). The YAC-1 cell-killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0.01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)-1 beta, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)-1 (P < 0.01). These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell-mediated immune responses following up-regulation of lung natural killer (NK) cell activation. We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.

Aversive pavlovian responses affect human instrumental motor performance.

PubMed

Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

2012-01-01

IN NEUROSCIENCE AND PSYCHOLOGY, AN INFLUENTIAL PERSPECTIVE DISTINGUISHES BETWEEN TWO KINDS OF BEHAVIORAL CONTROL: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology.

Aversive Pavlovian Responses Affect Human Instrumental Motor Performance

PubMed Central

Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

2012-01-01

In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioral control: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology. PMID:23060738

Parasitism and calfhood diseases.

PubMed

Herlich, H; Douvres, F W

1977-02-01

That animals can and do acquire an effective immunity against helminth parasites has been demonstrated extensively experimentally, and the fact that domestic animals such as cattle, sheep, and horses become adults while maintaining good health in spite of constant exposure to reinfection long has suggested that immunity must be important to such survival. Although our attempts to date to vaccinate calves against helminth parasites have either failed or been unsatisfactory because of the pathosis induced by the experimental vaccines, the results are not surprising or discouraging. In contrast to the long history of immunization research on bacterial and viral diseases, only within a relatively short time have serious efforts been directed at exploiting hostal immunity for prevention and control of helminthic diseases. Unlike the comparatively simple structures of viruses and bacteria, helminths are complex multicellular animals with vast arrays of antigens and complicated physiological and immunological interactions with their hosts. Much more fundamental information on helminth-bovine interactions, on helminth antigens, and on cattle antibody systems must be developed before progress on control of cattle helminths by vaccination can be meaningful.

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat.

PubMed

Sukhotnik, Igor; Helou, Habib; Mogilner, Jorge; Lurie, Michael; Bernsteyn, Aleksander; Coran, Arnold G; Shiloni, Eitan

2005-03-01

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia-reperfusion (IR) in the rat. Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.

Late ophthalmological complications after total body irradiation in non-human primates

NASA Technical Reports Server (NTRS)

Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.;

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

PubMed

Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

2017-03-01

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 * and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T 2 * and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T 2 * values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Mobility experiments with microrobots for minimally invasive intraocular surgery.

PubMed

Ullrich, Franziska; Bergeles, Christos; Pokki, Juho; Ergeneman, Olgac; Erni, Sandro; Chatzipirpiridis, George; Pané, Salvador; Framme, Carsten; Nelson, Bradley J

2013-04-23

To investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye. A system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments. The developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye. Intravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

50 CFR 30.11 - Control of feral animals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Control of feral animals. 30.11 Section 30... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.11 Control of feral animals. (a) Feral animals, including horses, burros, cattle, swine, sheep, goats...

50 CFR 30.11 - Control of feral animals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Control of feral animals. 30.11 Section 30... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.11 Control of feral animals. (a) Feral animals, including horses, burros, cattle, swine, sheep, goats...

50 CFR 30.11 - Control of feral animals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Control of feral animals. 30.11 Section 30... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.11 Control of feral animals. (a) Feral animals, including horses, burros, cattle, swine, sheep, goats...

50 CFR 30.11 - Control of feral animals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Control of feral animals. 30.11 Section 30... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.11 Control of feral animals. (a) Feral animals, including horses, burros, cattle, swine, sheep, goats...

50 CFR 30.11 - Control of feral animals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Control of feral animals. 30.11 Section 30... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.11 Control of feral animals. (a) Feral animals, including horses, burros, cattle, swine, sheep, goats...

Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

PubMed

Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

Neuromodulation of the lumbar spinal locomotor circuit.

PubMed

AuYong, Nicholas; Lu, Daniel C

2014-01-01

The lumbar spinal cord contains the necessary circuitry to independently drive locomotor behaviors. This function is retained following spinal cord injury (SCI) and is amenable to rehabilitation. Although the effectiveness of task-specific training and pharmacologic modulation has been repeatedly demonstrated in animal studies, results from human studies are less striking. Recently, lumbar epidural stimulation (EDS) along with locomotor training was shown to restore weight-bearing function and lower-extremity voluntary control in a chronic, motor-complete human SCI subject. Related animal studies incorporating EDS as part of the therapeutic regiment are also encouraging. EDS is emerging as a promising neuromodulatory tool for SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

[Application of paramunity inducers in small animal practice].

PubMed

Proksch, A L; Hartmann, K

2016-01-01

Paramunity inducers have been used to treat small animals for decades. Paramunity inducers are based on attenuated and inactivated poxviruses (avipox virus and parapox virus). Their applications include both therapeutic and prophylactic use in various diseases. Despite their wide and variable use, only a very small number of placebo-controlled studies has been published. Positive effects in preventing kitten mortality and in treating feline stomatitis have been reported, however, no statistically significant effect of their therapeutic use in canine parvovirus infection, feline leukemia infection virus infection or canine papillomavirus infection could be demonstrated. For these infectious diseases, paramunity inducers do not appear to be effective.

Adaptive Immunity Restricts Replication of Novel Murine Astroviruses

PubMed Central

Yokoyama, Christine C.; Loh, Joy; Zhao, Guoyan; Stappenbeck, Thaddeus S.; Wang, David; Huang, Henry V.

2012-01-01

The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a lack of a small-animal model of disease. Using shotgun sequencing and a custom analysis pipeline, we identified two novel astroviruses capable of infecting research mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis revealed the presence of at least two additional viruses (MuAstV STL3 and STL4), suggestive of a diverse population of murine astroviruses in research mice. Complete genomic characterization and subsequent phylogenetic analysis showed that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely members of a new mamastrovirus genogroup. Using Rag1−/− mice deficient in B and T cells, we demonstrate that adaptive immunity is required to control MuAstV infection. Furthermore, using Stat1−/− mice deficient in innate signaling, we demonstrate a role for the innate immune response in the control of MuAstV replication. Our results demonstrate that MuAstV STL permits the study of the mechanisms of astrovirus infection and host-pathogen interactions in a genetically manipulable small-animal model. Finally, we detected MuAstV in commercially available mice, suggesting that these viruses may be present in academic and commercial research mouse facilities, with possible implications for interpretation of data generated in current mouse models of disease. PMID:22951832

Hepatic glucocorticoid receptor antagonism is sufficient to reduce elevated hepatic glucose output and improve glucose control in animal models of type 2 diabetes.

PubMed

Jacobson, Peer B; von Geldern, Thomas W; Ohman, Lars; Osterland, Marie; Wang, Jiahong; Zinker, Bradley; Wilcox, Denise; Nguyen, Phong T; Mika, Amanda; Fung, Steven; Fey, Thomas; Goos-Nilsson, Annika; Grynfarb, Marlena; Barkhem, Tomas; Marsh, Kennan; Beno, David W A; Nga-Nguyen, Bach; Kym, Philip R; Link, James T; Tu, Noah; Edgerton, Dale S; Cherrington, Alan; Efendic, Suad; Lane, Benjamin C; Opgenorth, Terry J

2005-07-01

Glucocorticoids amplify endogenous glucose production in type 2 diabetes by increasing hepatic glucose output. Systemic glucocorticoid blockade lowers glucose levels in type 2 diabetes, but with several adverse consequences. It has been proposed, but never demonstrated, that a liver-selective glucocorticoid receptor antagonist (LSGRA) would be sufficient to reduce hepatic glucose output (HGO) and restore glucose control to type 2 diabetic patients with minimal systemic side effects. A-348441 [(3b,5b,7a,12a)-7,12-dihydroxy-3-{2-[{4-[(11b,17b)-17-hydroxy-3-oxo-17-prop-1-ynylestra-4,9-dien-11-yl] phenyl}(methyl)amino]ethoxy}cholan-24-oic acid] represents the first LSGRA with significant antidiabetic activity. A-348441 antagonizes glucocorticoid-up-regulated hepatic genes, normalizes postprandial glucose in diabetic mice, and demonstrates synergistic effects on blood glucose in these animals when coadministered with an insulin sensitizer. In insulin-resistant Zucker fa/fa rats and fasted conscious normal dogs, A-348441 reduces HGO with no acute effect on peripheral glucose uptake. A-348441 has no effect on the hypothalamic pituitary adrenal axis or on other measured glucocorticoid-induced extrahepatic responses. Overall, A-348441 demonstrates that an LSGRA is sufficient to reduce elevated HGO and normalize blood glucose and may provide a new therapeutic approach for the treatment of type 2 diabetes.

Trichoderma virens as a biocontrol of Toxocara canis: In vivo evaluation.

PubMed

de Souza Maia Filho, Fernando; da Silva Fonseca, Anelise Oliveira; Persici, Beatriz Maroneze; de Souza Silveira, Julia; Braga, Caroline Quintana; Pötter, Luciana; de Avila Botton, Sônia; Brayer Pereira, Daniela Isabel

Microorganisms have been widely studied as biological control agents of parasites of medical and veterinary importance. Coprophagous arthropods, bacteria and fungi are among the different organisms evaluated as potential biological control agents. Nematophagous fungi capture and digest the free forms of nematodes in the soil. Due to its zoonotic potential, Toxocara canis have been brought to the attention of researchers. The aim of the present study was to determine whether the administration of embryonated T. canis eggs exposed to the nematophagous fungus Trichoderma virens reduces parasite infection in experimental animals. Embryonated T. canis eggs were exposed to T. virens mycelium for 15 days at 25°C. Subsequently, 100 fungus-exposed eggs were orally administered to 20 Swiss mice. As a positive control, another 20 mice received 100 embryonated eggs that were not exposed to the fungus. After 48h, the animals were killed, and heart, lungs and liver were harvested for the recovery of larvae. The organs of the animals that received embryonated T. canis eggs exposed to the fungus showed a lower mean larval recovery when compared with the animals that received embryonated eggs without fungus exposure (p<0.05). The exposure of T. canis eggs to T. virens reduces the experimental infection, demonstrating the potential of this nematophagous fungus as a biocontrol agent. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Testing optimal foraging theory in a penguin-krill system.

PubMed

Watanabe, Yuuki Y; Ito, Motohiro; Takahashi, Akinori

2014-03-22

Food is heterogeneously distributed in nature, and understanding how animals search for and exploit food patches is a fundamental challenge in ecology. The classic marginal value theorem (MVT) formulates optimal patch residence time in response to patch quality. The MVT was generally proved in controlled animal experiments; however, owing to the technical difficulties in recording foraging behaviour in the wild, it has been inadequately examined in natural predator-prey systems, especially those in the three-dimensional marine environment. Using animal-borne accelerometers and video cameras, we collected a rare dataset in which the behaviour of a marine predator (penguin) was recorded simultaneously with the capture timings of mobile, patchily distributed prey (krill). We provide qualitative support for the MVT by showing that (i) krill capture rate diminished with time in each dive, as assumed in the MVT, and (ii) dive duration (or patch residence time, controlled for dive depth) increased with short-term, dive-scale krill capture rate, but decreased with long-term, bout-scale krill capture rate, as predicted from the MVT. Our results demonstrate that a single environmental factor (i.e. patch quality) can have opposite effects on animal behaviour depending on the time scale, emphasizing the importance of multi-scale approaches in understanding complex foraging strategies.

Toxicological safety assessment of genetically modified Bacillus thuringiensis with additional N-acyl homoserine lactonase gene.

PubMed

Peng, Donghai; Zhou, Chenfei; Chen, Shouwen; Ruan, Lifang; Yu, Ziniu; Sun, Ming

2008-01-01

The aim of the present study is to evaluate the toxicology safety to mammals of a genetically modified (GM) Bacillus thuringiensis with an additional N-acyl homoserine lactones gene (aiiA), which possesses insecticidal activity together with restraint of bacterial pathogenicity and is intended for use as a multifunctional biopesticide. Safety assessments included an acute oral toxicity test and 28-d animal feeding study in Wistar rats, primary eye and dermal irritation in Zealand White rabbits, and delayed contact hypersensitivity in guinea pigs. Tests were conducted using spray-dried powder preparation. This GM product showed toxicity neither in oral acute toxicity test nor in 28-d animal feeding test at a dose of 5,000 mg/kg body weight. During the animal feeding test, there were no significant differences in growth, food and water consumption, hematology, blood biochemical indices, organ weights, and histopathology finding between rats in controls and tested groups. Tested animals in primary eye and dermal irritation and delayed contact hypersensitivity test were also devoid of any toxicity compared to controls. All the above results demonstrated that the GM based multifunctional B. thuringiensis has low toxicity and low eye and dermal irritation and would not cause hypersensitivity to laboratory mammals and therefore could be regarded as safe for use as a pesticide.

Changes in antigen-presenting cell function in the spleen and lymph nodes of ultraviolet-irradiated mice

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

Gurish, M.F.; Lynch, D.H.; Daynes, R.A.

1982-03-01

It has been previously reported that mice exposed to ultraviolet (UV) radiation exhibit a decrease in splenic antigen-presenting cell (APC) function. The results presented here confirm this observation and further demonstrate that animals exposed daily to UV for extended periods of time (5 weeks instead of 6 days) no longer exhibit this depressed capability. In spite of the depression in splenic APC activity found in 6-day UV-irradiated mice, lymph node APC function from these same animals was elevated compared with that found in the lymph nodes from normal animals. Lymph node APC activity in animals that were splenectomized prior tomore » the UV irradiation, however, was not enhanced over controls. Treatment of animals with a chemical irritant (turpentine) also caused a depression in splenic APC function without modifying lymph node activity. Collectively, our findings suggest that the observed decrease in splenic APC activity, found after the first week of UV exposures, may be attributable to the migration of splenic APC to peripheral lymphoid tissue which drain the site of epidermal inflammation.« less

The need for randomization in animal trials: an overview of systematic reviews.

PubMed

Hirst, Jennifer A; Howick, Jeremy; Aronson, Jeffrey K; Roberts, Nia; Perera, Rafael; Koshiaris, Constantinos; Heneghan, Carl

2014-01-01

Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition. We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment. Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective. Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior

PubMed Central

Burke, Mary V; Small, Dana M

2017-01-01

Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning. PMID:29619405

An Experimental Aneurysm Model: a Training Model for Neurointerventionalists

PubMed Central

Grunwald, I.Q.; Romeike, B.; Eymann, R.; Roth, C.; Struffert, T.; Reith, W.

2006-01-01

Summary Reproducible animal models not only facilitate the pre-clinical assessment of aneurysm therapy but can also help in training for interventional procedures. The objective of this study was to find an animal model that can be used to test different endovascular occlusion techniques. Aneurysms in the right common carotid artery were created in 35 NZW rabbits by distal ligation and intraluminal elastase infusion. A total of 27 aneurysms were occluded by endovascular embolization with GDC-Coils. The time needed for placement of the microcatheter into the aneurysm by a professional interventionalist, a semi-professional interventionalist and a trainee was measured. The percentage of occlusion (occlusion rate) of the aneurysms was determined angiographically after embolization and again three months later, followed by a histological examination. Aneurysms of 2-6 mm size were reliably created in all 35 animals; mean size was 3.0 mm in height and 5.5 mm in diameter. Occlusion was achieved in 27 animals. Five animals from the group of 35 were initially planned as a control group with no embolization. We added to the control group one animal whose aneurysm could not be occluded endovascularly because of partial thrombosis and small size of the aneurysm. The angiographically determined mean occlusion rate was 89.5% ± 11.3% standard deviation. Histological evaluation of the six aneurysms of the control group showed that they remained patent. Aneurysms that underwent embolization showed organized thrombus formation with no signs of recanalization. Two animals died from anaesthesia related or embolic complications. The time needed by the professional did not significantly decrease, after a little practice the trainee was nearly as quick as the professional. The beginner showed extensive progress, reducing the time for catheter placement by more than 50%. This paper describes the angiographic and histopathologic findings and also demonstrates possible methods for training in interventional procedures. Animal models will play a vital part in the training of future interventionalists. This model has the capability of testing different embolization devices (GDC, Onyx®) and methods. Histologic long-term prognosis and the physical effect of the coils can be evaluated with this model. PMID:20569546

Exercise alters myostatin protein expression in sedentary and exercised streptozotocin-diabetic rats.

PubMed

Bassi, Daniela; Bueno, Patricia de Godoy; Nonaka, Keico Okino; Selistre-Araujo, Heloisa Sobreiro; Leal, Angela Merice de Oliveira

2015-04-01

The aim of this study was to analyze the effect of exercise on the pattern of muscle myostatin (MSTN) protein expression in two important metabolic disorders, i.e., obesity and diabetes mellitus. MSTN, is a negative regulator of skeletal muscle mass. We evaluated the effect of exercise on MSTN protein expression in diabetes mellitus and high fat diet-induced obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia in both diabetic and obese animals. The expression of precursor and processed protein forms of MSTN and the weight of gastrocnemius muscle did not vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius muscle weight in sedentary animals. However, gastrocnemius muscle weight increased in diabetic exercised animals. Both the precursor and processed forms of muscle MSTN protein were significantly higher in sedentary diabetic rats than in control rats. The precursor form was significantly lower in diabetic exercised animals than in diabetic sedentary animals. However, the processed form did not change. These results demonstrate that exercise can modulate the muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be involved in energy homeostasis.

Corridors affect plants, animals, and their interactions in fragmented landscapes

PubMed Central

Tewksbury, Joshua J.; Levey, Douglas J.; Haddad, Nick M.; Sargent, Sarah; Orrock, John L.; Weldon, Aimee; Danielson, Brent J.; Brinkerhoff, Jory; Damschen, Ellen I.; Townsend, Patricia

2002-01-01

Among the most popular strategies for maintaining populations of both plants and animals in fragmented landscapes is to connect isolated patches with thin strips of habitat, called corridors. Corridors are thought to increase the exchange of individuals between habitat patches, promoting genetic exchange and reducing population fluctuations. Empirical studies addressing the effects of corridors have either been small in scale or have ignored confounding effects of increased habitat area created by the presence of a corridor. These methodological difficulties, coupled with a paucity of studies examining the effects of corridors on plants and plant–animal interactions, have sparked debate over the purported value of corridors in conservation planning. We report results of a large-scale experiment that directly address this debate. In eight large-scale experimental landscapes that control for patch area and test alternative mechanisms of corridor function, we demonstrate that corridors not only increase the exchange of animals between patches, but also facilitate two key plant–animal interactions: pollination and seed dispersal. Our results show that the beneficial effects of corridors extend beyond the area they add, and suggest that increased plant and animal movement through corridors will have positive impacts on plant populations and community interactions in fragmented landscapes. PMID:12239344

Predictability and hierarchy in Drosophila behavior.

PubMed

Berman, Gordon J; Bialek, William; Shaevitz, Joshua W

2016-10-18

Even the simplest of animals exhibit behavioral sequences with complex temporal dynamics. Prominent among the proposed organizing principles for these dynamics has been the idea of a hierarchy, wherein the movements an animal makes can be understood as a set of nested subclusters. Although this type of organization holds potential advantages in terms of motion control and neural circuitry, measurements demonstrating this for an animal's entire behavioral repertoire have been limited in scope and temporal complexity. Here, we use a recently developed unsupervised technique to discover and track the occurrence of all stereotyped behaviors performed by fruit flies moving in a shallow arena. Calculating the optimally predictive representation of the fly's future behaviors, we show that fly behavior exhibits multiple time scales and is organized into a hierarchical structure that is indicative of its underlying behavioral programs and its changing internal states.

Synthetic Sex Pheromone Attracts the Leishmaniasis Vector Lutzomyia longipalpis (Diptera: Psychodidae) to Traps in the Field

PubMed Central

Bray, D. P.; Bandi, K. K.; Brazil, R. P.; Oliveira, A. G.; Hamilton, J.G.C.

2011-01-01

Improving vector control remains a key goal in reducing the world’s burden of infectious diseases. More cost-effective approaches to vector control are urgently needed, particularly as vaccines are unavailable and treatment is prohibitively expensive. The causative agent of AVL, Leishmania chagasi, Cunha and Chagas (Kinetoplastida: Trypanosomatidae) is transmitted between animal and human hosts by blood-feeding female sand flies, attracted to mating aggregations formed on or above host animals by male-produced sex pheromones. Our results demonstrate the potential of using synthetic pheromones to control populations of Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae), the sand fly vector of one of the world’s most important neglected diseases, American visceral leishmaniasis (AVL). We showed that a synthetic pheromone, (±)-9-methylgermacrene-B, produced from a low-cost plant intermediate, attracted females in the laboratory. Then by formulating dispensers that released this pheromone at a rate similar to that released by aggregating males, we were able to attract flies of both sexes to traps in the field. These dispensers worked equally well when deployed with mechanical light traps and inexpensive sticky traps. If deployed effectively, pheromone-based traps could be used to decrease AVL transmission rates through specific targeting and reduction of L. longipalpis populations. This is the first study to show attraction of a human disease-transmitting insect to a synthetic pheromone in the field, demonstrating the general applicability of this novel approach for developing new tools for use in vector control. PMID:19496409

Effect of 3D animation videos over 2D video projections in periodontal health education among dental students

PubMed Central

Dhulipalla, Ravindranath; Marella, Yamuna; Katuri, Kishore Kumar; Nagamani, Penupothu; Talada, Kishore; Kakarlapudi, Anusha

2015-01-01

Background: There is limited evidence about the distinguished effect of 3D oral health education videos over conventional 2 dimensional projections in improving oral health knowledge. This randomized controlled trial was done to test the effect of 3 dimensional oral health educational videos among first year dental students. Materials and Methods: 80 first year dental students were enrolled and divided into two groups (test and control). In the test group, 3D animation and in the control group, regular 2D video projections pertaining to periodontal anatomy, etiology, presenting conditions, preventive measures and treatment of periodontal problems were shown. Effect of 3D animation was evaluated by using a questionnaire consisting of 10 multiple choice questions given to all participants at baseline, immediately after and 1month after the intervention. Clinical parameters like Plaque Index (PI), Gingival Bleeding Index (GBI), and Oral Hygiene Index Simplified (OHI-S) were measured at baseline and 1 month follow up. Results: A significant difference in the post intervention knowledge scores was found between the groups as assessed by unpaired t-test (p<0.001) at baseline, immediate and after 1 month. At baseline, all the clinical parameters in the both the groups were similar and showed a significant reduction (p<0.001)p after 1 month, whereas no significant difference was noticed post intervention between the groups. Conclusion: 3D animation videos are more effective over 2D videos in periodontal disease education and knowledge recall. The application of 3D animation results also demonstrate a better visual comprehension for students and greater health care outcomes. PMID:26759805

An Arbitrary Waveform Wearable Neuro-stimulator System for Neurophysiology Research on Freely Behaving Animals.

PubMed

Samani, Mohsen Mosayebi; Mahnam, Amin; Hosseini, Nasrin

2014-04-01

Portable wireless neuro-stimulators have been developed to facilitate long-term cognitive and behavioral studies on the central nervous system in freely moving animals. These stimulators can provide precisely controllable input(s) to the nervous system, without distracting the animal attention with cables connected to its body. In this study, a low power backpack neuro-stimulator was developed for animal brain researches that can provides arbitrary stimulus waveforms for the stimulation, while it is small and light weight to be used for small animals including rats. The system consists of a controller that uses an RF link to program and activate a small and light microprocessor-based stimulator. A Howland current source was implemented to produce precise current controlled arbitrary waveform stimulations. The system was optimized for ultra-low power consumption and small size. The stimulator was first tested for its electrical specifications. Then its performance was evaluated in a rat experiment when electrical stimulation of medial longitudinal fasciculus induced circling behavior. The stimulator is capable of delivering programmed stimulations up to ± 2 mA with adjusting steps of 1 μA, accuracy of 0.7% and compliance of 6 V. The stimulator is 15 mm × 20 mm × 40 mm in size, weights 13.5 g without battery and consumes a total power of only 5.l mW. In the experiment, the rat could easily carry the stimulator and demonstrated the circling behavior for 0.1 ms current pulses of above 400 μA. The developed system has a competitive size and weight, whereas providing a wide range of operation and the flexibility of generating arbitrary stimulation patterns ideal for long-term experiments in the field of cognitive and neuroscience research.

Effects of perinatal asphyxia on cell proliferation and neuronal phenotype evaluated with organotypic hippocampal cultures.

PubMed

Morales, P; Reyes, P; Klawitter, V; Huaiquín, P; Bustamante, D; Fiedler, J; Herrera-Marschitz, M

2005-01-01

The present report summarizes studies combining an in vivo and in vitro approach, where asphyxia is induced in vivo at delivery time of Wistar rats, and the long term effects on hippocampus neurocircuitry are investigated in vitro with organotypic cultures plated at postnatal day seven. The cultures preserved hippocampus layering and regional subdivisions shown in vivo, and only few dying cells were observed when assayed with a viability test at day in vitro 27. When properly fixed, cultures from asphyxia-exposed animals showed a decreased amount of microtubule-associated protein-2 immunocytochemically positive cells (approximately 30%), as compared with that from controls. The decrease in microtubule-associated protein-2 immunocytochemistry was particularly prominent in Ammon's horn 1 and dentate gyrus regions (approximately 40%). 5-Bromo-2'deoxyuridine labeling revealed a two-fold increase in cellular proliferation in cultures from asphyxia-exposed, compared with that from control animals. Furthermore, confocal microscopy and quantification using the optical disector technique demonstrated that in cultures from asphyxia-exposed animals approximately 30% of 5-bromo-2'deoxyuridine-positive cells were also positive to microtubule-associated protein-2, a marker for neuronal phenotype. That proportion was approximately 20% in cultures from control animals. Glial fibrillary acidic protein-immunocytochemistry and Fast Red nuclear staining revealed that the core of the hippocampus culture was surrounded by a well-developed network of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein-processes providing an apparent protective shield around the hippocampus. That shield was less developed in cultures from asphyxia-exposed animals. The increased mitotic activity observed in this study suggests a compensatory mechanism for the long-term impairment induced by perinatal asphyxia, although it is not clear yet if that mechanism leads to neurogenesis, astrogliogenesis, or to further apoptosis.

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

PubMed

Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

Immunization with Eimeria ninakohlyakimovae-live attenuated oocysts protect goat kids from clinical coccidiosis.

PubMed

Ruiz, Antonio; Muñoz, María Carmen; Molina, José Manuel; Hermosilla, Carlos; Andrada, Marisa; Lara, Pedro; Bordón, Elisa; Pérez, Davinia; López, Adassa María; Matos, Lorena; Guedes, Aránzazu Carmen; Falcón, Soraya; Falcón, Yaiza; Martín, Sergio; Taubert, Anja

2014-01-17

Caprine coccidiosis, affecting mainly young goat kids around the weaning period, is worldwide the most important disease in the goat industry. Control of caprine coccidiosis is increasingly hampered by resistances developed against coccidiostatic drugs leading to an enhanced need for anticoccidial vaccines. In the current study we conducted an oral immunization trial with live attenuated sporulated Eimeria ninakohlyakimovae oocysts. Sporulated E. ninakohlyakimovae oocysts were attenuated by X-irradiation technique. The experimental design included a total of 18 goat kids divided into the following groups: (i) animals immunized with attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-irradiated homologous oocysts (group 1); (ii) animals infected with non-attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-attenuated homologous oocysts (group 2); (iii) animals primary-infected with untreated E. ninakohlyakimovae oocysts at 8 weeks of age (control of the challenge infection, group 3); (iv) non-infected control animals (group 4). Goat kids immunized with live attenuated E. ninakohlyakimovae oocysts (group 1) excreted significantly less oocysts in the faeces (95.3% reduction) than kids infected with non-attenuated ones (group 2). Furthermore, immunization with live but attenuated oocysts resulted in ameliorated clinical coccidiosis compared to goat kids infected with untreated oocysts (group 2) and resulted in equally reduced signs of coccidiosis after challenge infection compared to acquired immunity driven by non-attenuated oocysts. Overall, the present study demonstrates for the first time that live attenuated E. ninakohlyakimovae oocysts orally administered showed almost no pathogenicity but enough immunogenicity in terms of immunoprotection. Importantly, vaccinated animals still shed low amounts of oocysts, guaranteeing environmental contamination and consecutive booster infections to sustain ongoing immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

Pilot study of the antifibrotic effects of the multikinase inhibitor pacritinib in a mouse model of liver fibrosis.

PubMed

Al-Fayoumi, Suliman; Hashiguchi, Taishi; Shirakata, Yuka; Mascarenhas, John; Singer, Jack W

2018-01-01

Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients. In two Phase III clinical trials, pacritinib, however, demonstrated improvements in platelet counts and hemoglobin and reductions in transfusion burden in some patients with baseline cytopenias, suggesting it may improve bone-marrow function. Unlike ruxolitinib, pacritinib suppresses signaling through IRAK1, a key control point for inflammatory and fibrotic signaling. To investigate potential antifibrotic effects of pacritinib in an animal model of liver fibrosis relevant to the observed course of human disease. Pacritinib, negative control (vehicle), and positive control (the angiotensin 2-receptor antagonist and PPARγ partial agonist telmisartan) were assessed in the murine Stelic animal model, which mimics the clinically observed progression from hepatic steatosis to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Histopathological analysis used hematoxylin and eosin staining. Body and liver weight changes, nonalcoholic fatty-liver disease activity scores, and plasma cytokeratin 18 fragment levels (a biomarker of hepatic necrosis) were measured. Pacritinib-treated mice had significantly ( P <0.01) reduced fibrotic areas in liver compared to vehicle control and significantly ( P <0.05) lower levels of CK18. The antifibrotic effect of pacritinib was comparable to that of telmisartan, but without significant effects on fat accumulation. These results, the first to demonstrate hepatic antifibrotic effects for pacritinib in an animal model of liver disease, provide preliminary support for potential clinical applications of pacritinib in fibrotic diseases other than myelofibrosis.

The effect of low-intensity laser therapy on wound healing in Streptozotocin-induced diabetic rats

NASA Astrophysics Data System (ADS)

Rabelo, Sylvia B.; Villaverde, Antonio G. J. B.; Salgado, Miguel A. C.; Melo, Milene d. S.; Nicolau, Renata A.; Pacheco, Marcos T. T.

2004-10-01

Diabetes Mellitus is a condition that results in a delay of the wound healing process, that is associated with an insufficient production of collagen, a decrease of the amount of collagen fibrils and deficient blood flow in the wound area. It is sugested that Low Intensity Laser Therapy acts by improving wound healing in normal organisms, accelerating tissue regeneration. The aim of this work was to investigate the biostimulatory effect of the HeNe laser irradiation, at 632.8 nm, on wound healing in 15 male rats suffering from diabetes induced by Streptozotocin, compared to 15 control diabetic animals. Irradiation parameters were: laser power of 15mW, exposition time of 17 s., irradiated area of 0.025 cm2 and laser energy density of 10 J/cm2. Full-thickness skin squared samples, with 5 mm of non-injured tissue around the wound, were obtained at 4, 7 and 15 days after wounding procedure (5 treated and 5 control animals each time). The histopathologic analysis performed by haematoxylin-cosin staining. Results suggested that the irradiation of diabetic rats was efficient for wound healing. Treated group presented better quality of the wound tissues by the macroscopic observation than control group and the microscopic analysis demonstrated that treated animals had better histopathologic evaluation than non treated.

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

PubMed Central

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-01-01

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model. PMID:19638223

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet.

PubMed

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-07-28

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

Hypogammaglobulinaemia in nephrotic rats is attributable to hypercatabolism of IgG.

PubMed Central

Beaman, M; Oldfield, S; MacLennan, I C; Michael, J; Adu, D

1988-01-01

The effect of the nephrotic syndrome induced by puromycin aminonucleoside (PA) in rats on specific antibody responses to 2,4 dinitrophenyl (DNP) conjugated to either spider crab haemocyanin (MSH), a T cell-dependent antigen, or hydroxyethyl starch (HES), a T cell-independent type 2 antigen were studied. The serum IgG anti-DNP levels following immunization with both antigens were reduced in nephrotic animals compared with controls while IgM anti-DNP antibody titres were higher. The half-life of IgG anti-DNP antibodies passively transferred into non-immunized nephrotic rats was markedly reduced while the half-life of anti-DNP antibodies of the IgM class was comparable to that in controls. Low serum IgG and elevated IgM levels were seen in nephrotic animals compared to controls. Antibody-forming cells specific for DNP were demonstrated by immunohistology on rat spleens and the numbers of both IgG and IgM-producing cells were found to be significantly increased (P less than 0.05) in nephrotic animals in response to both DNP-HES and DNP-MSH. These data indicate that in nephrotic rats the alteration seen in the serum immunoglobulin levels is not attributable to reduced antibody production but increased catabolism of serum IgG antibodies. PMID:3233791

The neglected zoonoses--the case for integrated control and advocacy.

PubMed

Welburn, S C; Beange, I; Ducrotoy, M J; Okello, A L

2015-05-01

The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries, but remain major causes of ill-health and mortality across Africa, Asia, and Latin America. This neglect is, in part, a consequence of under-reporting, resulting in an underestimation of their global burden that downgrades their relevance to policy-makers and funding agencies. Increasing awareness about the causes of NZDs and how they can be prevented could reduce the incidence of many endemic zoonoses. Addressing NZDs by targeting the animal reservoir can deliver a double benefit, as enhanced animal health means a reduced risk of infection for humans, as well as improved livelihoods through increased animal productivity. Advocacy for NZD control is increasing, but with it comes a growing awareness that NZD control demands activities both in the short term and over a long period of time. Moreover, despite the promise of cheap, effective vaccines or other control tools, these endemic diseases will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. NZD intervention costs can seem high when compared with the public health benefits alone, but these costs are easily outweighed when a full cross-sector analysis is carried out and monetary/non-monetary benefits--particularly regarding the livestock sector--are taken into account. Public-private partnerships have recently provided advocacy for human disease control, and could prove equally effective in addressing endemic zoonoses through harnessing social impact investments. Evidence of the disease burdens imposed on communities by the NZDs and demonstration of the cost-effectiveness of integrated control can strengthen the case for a One Health approach to endemic zoonotic disease control. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2.

PubMed

Quintin-Colonna, F; Devauchelle, P; Fradelizi, D; Mourot, B; Faure, T; Kourilsky, P; Roth, C; Mehtali, M

1996-12-01

The production of human interleukin-2 (hIL-2) local to the tumor site by engineered histoincompatible cells has been shown in various murine models to promote a strong immune response leading to tumor growth inhibition or rejection. To assess whether this strategy would be similarly applicable for treatment of primary neoplastic cells, two naturally occurring tumors were used as preclinical models; the highly metastatic melanoma of the dog and the low metastatic fibrosarcoma of the cat. We demonstrate that both cats and dogs when treated by tumor surgery, radiotherapy and repeated local injections of xenogeneic Vero cells secreting high levels of hIL-2 relapse less frequently and survive longer than control animals treated by surgery and radiotherapy alone. Local secretion of hIL-2 by the xenogeneic cells is shown to be necessary for the induction of an optimal antitumor effect. Moreover, the safety of the procedure was demonstrated in both animal models and through extensive toxicological analysis performed in rats. These results confirm for the first time to our knowledge the safety and therapeutic potential of a gene transfer strategy in animals with spontaneous metastatic and nonmetastatic tumors.

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

Delayed finger tapping and cognitive responses in preterm-born male teenagers with mild spastic diplegia.

PubMed

Gao, Fei; Mei, Xi; Chen, Andrew C N

2015-02-01

Information on fine motor and basic cognitive functions in spastic diplegia is sparse in the literature. The aim of this study was to investigate index finger's tapping speed and cognitive functions in categorization and old/new recognition of pictures in patients with mild spastic diplegia. Fifteen preterm-born male teenagers with mild spastic diplegia and 15 healthy male teenagers participated in this study. Finger-tapping tests and cognitive tests were performed on all participants. Outcomes were compared between the two groups. In the finger-tapping tests, the tapping speed was significantly slower in patients than in controls. In the tests of tapping one key persistently and tapping two keys alternately, the reaction time gaps between the left and right digits were larger in patients than in controls. In the categorization tests, the accuracies and reaction times for animal/plant and girl face pictures, but not for boy face pictures, were significantly worse in patients than in controls. In the recognition tests, the accuracies for old/new, animal/plant, and boy/girl face pictures were significantly lower in patients than in controls. The reaction times for old/new, animal/plant, and new face pictures, but not for old face pictures, were significantly longer in patients compared with controls. Our results demonstrate delayed finger tapping and cognitive responses in preterm-born male teenagers with mild spastic diplegia. Our experimental paradigm is sensitive for the study of fine motor and cognitive functions between patients and healthy controls. Copyright © 2015 Elsevier Inc. All rights reserved.

Protecting cows in small holder farms in East Africa from tsetse flies by mimicking the odor profile of a non-host bovid

PubMed Central

Orindi, Benedict O.; Mbahin, Norber; Muasa, Peter N.; Mbuvi, David M.; Muya, Caroline M.; Pickett, John A.; Borgemeister, Christian W.

2017-01-01

Background For the first time, differential attraction of pathogen vectors to vertebrate animals is investigated for novel repellents which when applied to preferred host animals turn them into non-hosts thereby providing a new paradigm for innovative vector control. For effectively controlling tsetse flies (Glossina spp.), vectors of African trypanosomosis, causing nagana, repellents more powerful than plant derived, from a non-host animal the waterbuck, Kobus ellipsiprymnus defassa, have recently been identified. Here we investigate these repellents in the field to protect cattle from nagana by making cattle as unattractive as the buck. Methodology/Principal findings To dispense the waterbuck repellents comprising guaiacol, geranylacetone, pentanoic acid and δ-octalactone, (patent application) we developed an innovative collar-mounted release system for individual cattle. We tested protecting cattle, under natural tsetse challenge, from tsetse transmitted nagana in a large field trial comprising 1,100 cattle with repellent collars in Kenya for 24 months. The collars provided substantial protection to livestock from trypanosome infection by reducing disease levels >80%. Protected cattle were healthier, showed significantly reduced disease levels, higher packed cell volume and significantly increased weight. Collars >60% reduced trypanocide use, 72.7% increase in ownership of oxen per household and enhanced traction power (protected animals ploughed 66% more land than unprotected). Land under cultivation increased by 73.4%. Increase in traction power of protected animals reduced by 69.1% acres tilled by hand per household per ploughing season. Improved food security and household income from very high acceptance of collars (99%) motivated the farmers to form a registered community based organization promoting collars for integrated tsetse control and their commercialization. Conclusion/Significance Clear demonstration that repellents from un-preferred hosts prevent contact between host and vector, thereby preventing disease transmission: a new paradigm for vector control. Evidence that deploying water buck repellents converts cattle into non-hosts for tsetse flies—‘cows in waterbuck clothing’. PMID:29040267

Genetic factors controlling wool shedding in a composite Easycare sheep flock.

PubMed

Matika, O; Bishop, S C; Pong-Wong, R; Riggio, V; Headon, D J

2013-12-01

Historically, sheep have been selectively bred for desirable traits including wool characteristics. However, recent moves towards extensive farming and reduced farm labour have seen a renewed interest in Easycare breeds. The aim of this study was to quantify the underlying genetic architecture of wool shedding in an Easycare flock. Wool shedding scores were collected from 565 pedigreed commercial Easycare sheep from 2002 to 2010. The wool scoring system was based on a 10-point (0-9) scale, with score 0 for animals retaining full fleece and 9 for those completely shedding. DNA was sampled from 200 animals of which 48 with extreme phenotypes were genotyped using a 50-k SNP chip. Three genetic analyses were performed: heritability analysis, complex segregation analysis to test for a major gene hypothesis and a genome-wide association study to map regions in the genome affecting the trait. Phenotypes were treated as a continuous or binary variable and categories. High estimates of heritability (0.80 when treated as a continuous, 0.65-0.75 as binary and 0.75 as categories) for shedding were obtained from linear mixed model analyses. Complex segregation analysis gave similar estimates (0.80 ± 0.06) to those above with additional evidence for a major gene with dominance effects. Mixed model association analyses identified four significant (P < 0.05) SNPs. Further analyses of these four SNPs in all 200 animals revealed that one of the SNPs displayed dominance effects similar to those obtained from the complex segregation analyses. In summary, we found strong genetic control for wool shedding, demonstrated the possibility of a single putative dominant gene controlling this trait and identified four SNPs that may be in partial linkage disequilibrium with gene(s) controlling shedding. © 2013 University of Edinburgh, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Scientific uses and technical implementation of a variable gravity centrifuge on Space Station Freedom

NASA Technical Reports Server (NTRS)

Johnson, C. C.; Hargens, A. R.

1990-01-01

The potential need and science requirements for a centrifuge to be designed and flown on Space Station Freedom are discussed, with a focus on a design concept for a centrifuge developed at NASA Ames. Applications identified for the centrifuge include fundamental studies in which gravity is a variable under experimental control, the need to provide a 1-g control, attempts to discover the threshold value of gravitation force for psychological response, and an effort to determine the effects of intermittent hypergravity. Science requirements specify the largest possible diameter at approximately 2.5 m, gravity levels ranging from 0.01 to 2 g, a nominal ramp-up rate of 0.01 g/sec, and life support for plants and animals. Ground-based studies using rats and squirrel monkeys on small-diameter centrifuges have demonstrated that animals can adapt to centrifugation at gravity gradients higher than those normally used in ground-based hypergravity studies.

Predatory behavior inTupinambis teguixin (Sauria: Teiidae). I. Tongue-flicking responses to chemical food stimuli.

PubMed

Yanosky, A A; Iriart, D E; Mercolli, C

1993-02-01

Black tegu lizards (Tupinambis teguixin) have the ability to detect food odors and discriminate between them and nonfood odors. This was tested by offering chemical stimuli on cotton-tipped applicators to the animals. Stimuli were from two plant and two animal species known to be principal items in these lizards' diets, demineralized water as an odorless control, and eaude-cologne as an odorous control lacking feeding or social importance. Tongueflick attack score, latency to attack, preattack tongue-flicks, and number of attacks were analyzed. The results clearly demonstrated that this species responds to chemical food stimuli, but does not respond to odorless nonfood stimuli. Responses differed among food types. There were no sex differences. These results are in agreement with the prediction that lizards having forked tongues and an active foraging mode rely on chemical cues for feeding.

Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

PubMed Central

Takahashi, Aki; Nagayasu, Kazuki; Nishitani, Naoya; Kaneko, Shuji; Koide, Tsuyoshi

2014-01-01

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. PMID:24740241

The functions of sound production in the lined seahorse, Hippocampus erectus, and effects of loud ambient noise on its behavior and physiology in captive environments

NASA Astrophysics Data System (ADS)

Anderson, Paul August

Loud noise in aquaria represents a cacophonous environment for captive fishes. I tested the effects of loud noise on acoustic communication, feeding behavior, courtship behavior, and the stress response of the lined seahorse, Hippocampus erectus. Total Root Mean Square (RMS) power of ambient noise to which seahorses are exposed in captivity varies widely but averages 126.1 +/- 0.8 deciBels with reference to one micropascal (dB re: 1 muPa) at the middle of the water column and 133.7 +/- 1.1 dB at the tank bottom, whereas ambient noise in the wild averages 119.6 +/- 3.5 dB. Hearing sensitivity of H. erectus, measured from auditory evoked potentials, demonstrated maximum spectrum-level sensitivities of 105.0 +/- 1.5 dB and 3.5 x 10-3 + 7.6 x 10-4 m/s2 at 200 Hz; which is characteristic of hearing generalists. H. erectus produces acoustic clicks with mean peak spectrum-level amplitudes of 94.3 +/- 0.9 dB at 232 +/- 16 Hz and 1.5 x 10 -3 +/- 1.9 x 10-4 m/s2 at 265 +/- 22 Hz. Frequency matching of clicks to best hearing sensitivity, and estimates of audition of broadband signals suggest that seahorses may hear conspecific clicks, especially in terms of particle motion. Behavioral investigations revealed that clicking did not improve prey capture proficiency. However, animals clicked more often as time progressed in a courtship sequence, and mates performed more courtship behaviors with control animals than with muted animals, lending additional evidence to the role of clicking as an acoustic signal during courtship. Despite loud noise and the role of clicking in communication, masking of the acoustic signal was not demonstrated. Seahorses exposed to loud noise in aquaria for one month demonstrated physiological, chronic stress responses: reduced weight and body condition, and increased heterophil to lymphocyte ratio. Behavioral alterations were characterized by greater mean and variance of activity among animals housed in loud tanks in the first week, followed by habituation. By week four, animals in loud tanks demonstrated variable performance of clicking and piping, putative distress behaviors. Despite the physiological stress response, animals in loud tanks did not reduce feeding response or courtship behavior, suggesting allostasis.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PubMed

Garcia, Camila Araújo Bernardino; Catalão, Carlos Henrique Rocha; Machado, Hélio Rubens; Júnior, Ivair Matias; Romeiro, Thais Helena; Peixoto-Santos, José Eduardo; Santos, Marcelo Volpon; da Silva Lopes, Luiza

2017-03-01

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Germ-line induction of the Caenorhabditis elegans vulva

PubMed Central

Thompson, Beth E.; Lamont, Liana B.; Kimble, Judith

2006-01-01

Development of the Caenorhabditis elegans vulva serves as a paradigm for intercellular signaling during animal development. In wild-type animals, the somatic gonadal anchor cell generates the LIN-3/EGF ligand to induce vulval fates in the underlying hypodermis, whereas FBF, FOG-1, and FOG-3 control germ-line development. Here we report that FBF functions redundantly with FOG-1 and FOG-3 to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have multiple vulvae, the Muv phenotype. The fog; fbf Muv phenotype is generated by aberrant induction of vulval precursor cells (VPCs): in wild-type animals, three VPCs are induced to form a single vulva, but, in fog; fbf mutants, four or five VPCs are typically induced, resulting in ectopic vulvae. Laser ablation experiments and mosaic analyses demonstrate that the germ line is critical for the fog; fbf Muv phenotype. Consistent with that site of action, we detect FBF and FOG-1 in the germ line but not in the VPCs. The simplest interpretation is that FOG-1, FOG-3, and FBF act in the germ line to influence vulval fates. The LIN-3/EGF ligand may be the germ-line signal to the VPCs: the fog; fbf Muv phenotype depends on LIN-3 activity, and the lin-3 3′ UTR possesses an FBF binding element. Our findings reveal new insights into germ line-to-soma signals and the role of PUF proteins in animal development. PMID:16407099

Effectiveness of a Glycylcycline Antibiotic for Reducing the Pathogenicity of Superantigen-Producing Methicillin-Resistant Staphylococcus aureus in Burn Wounds

PubMed Central

Nosanov, Lauren B.; Jo, Daniel Y.; Randad, Pranay R.; Moffatt, Lauren T.; Carney, Bonnie C.; Ortiz, Rachel T.

2017-01-01

Objective: Burn-injured patients are highly susceptible to infectious complications, which are often associated with increased morbidity and mortality. Rates of antibiotic resistance have increased, and resistant species such as methicillin-resistant Staphylococcus aureus provide additional challenges in the form of virulence factors. Proteins can disrupt local healing, leading to systemic immune disruption. To optimize outcomes, treatments that reduce pathogenicity must be identified. This study aims to compare a glycylcycline antibiotic—tigecycline—with clindamycin for effectiveness in treating superantigenic methicillin-resistant Staphylococcus aureus in burn wounds. Methods: Sprague-Dawley rats received paired 2 × 2-cm burn wounds, which were subsequently inoculated with known virulence factor–producing methicillin-resistant Staphylococcus aureus or media alone on postinjury day 1. Infected animals received twice-daily tigecycline (high or low dose), twice-daily clindamycin (high or low dose), or saline alone (positive controls). Daily sampling and imaging assessments were performed. Results: Bacterial counts and toxin levels were reduced significantly in antibiotic-treated groups relative to positive controls (P < .001). Results from day 7 showed measurable toxin levels in clindamycin-treated, but not tigecycline-treated, wounds. Imaging analysis revealed a return of wound perfusion in tigecycline-treated animals similar to the sham animals. Transcript analysis using polymerase chain reaction and polymerase chain reaction arrays demonstrated downregulation of gene expression in antibiotic-treated animals as compared with positive controls. Conclusions: Overall, this study supports the use of tigecycline in the treatment of methicillin-resistant Staphylococcus aureus–infected burn wounds. While both protein synthesis inhibitors are effective, tigecycline appears to be superior in controlling toxin levels, enabling better wound healing. PMID:28943993

Effectiveness of a Glycylcycline Antibiotic for Reducing the Pathogenicity of Superantigen-Producing Methicillin-Resistant Staphylococcus aureus in Burn Wounds.

PubMed

Nosanov, Lauren B; Jo, Daniel Y; Randad, Pranay R; Moffatt, Lauren T; Carney, Bonnie C; Ortiz, Rachel T; Shupp, Jeffrey W

2017-01-01

Objective : Burn-injured patients are highly susceptible to infectious complications, which are often associated with increased morbidity and mortality. Rates of antibiotic resistance have increased, and resistant species such as methicillin-resistant Staphylococcus aureus provide additional challenges in the form of virulence factors. Proteins can disrupt local healing, leading to systemic immune disruption. To optimize outcomes, treatments that reduce pathogenicity must be identified. This study aims to compare a glycylcycline antibiotic-tigecycline-with clindamycin for effectiveness in treating superantigenic methicillin-resistant Staphylococcus aureus in burn wounds. Methods : Sprague-Dawley rats received paired 2 × 2-cm burn wounds, which were subsequently inoculated with known virulence factor-producing methicillin-resistant Staphylococcus aureus or media alone on postinjury day 1. Infected animals received twice-daily tigecycline (high or low dose), twice-daily clindamycin (high or low dose), or saline alone (positive controls). Daily sampling and imaging assessments were performed. Results : Bacterial counts and toxin levels were reduced significantly in antibiotic-treated groups relative to positive controls ( P < .001). Results from day 7 showed measurable toxin levels in clindamycin-treated, but not tigecycline-treated, wounds. Imaging analysis revealed a return of wound perfusion in tigecycline-treated animals similar to the sham animals. Transcript analysis using polymerase chain reaction and polymerase chain reaction arrays demonstrated downregulation of gene expression in antibiotic-treated animals as compared with positive controls. Conclusions : Overall, this study supports the use of tigecycline in the treatment of methicillin-resistant Staphylococcus aureus -infected burn wounds. While both protein synthesis inhibitors are effective, tigecycline appears to be superior in controlling toxin levels, enabling better wound healing.

50 CFR 31.14 - Official animal control operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Official animal control operations. 31.14... Reduction and Disposal § 31.14 Official animal control operations. (a) Animal species which are surplus or...) Animal species which are damaging or destroying Federal property within a wildlife refuge area may be...

50 CFR 31.14 - Official animal control operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Official animal control operations. 31.14... Reduction and Disposal § 31.14 Official animal control operations. (a) Animal species which are surplus or...) Animal species which are damaging or destroying Federal property within a wildlife refuge area may be...

50 CFR 31.14 - Official animal control operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Official animal control operations. 31.14... Reduction and Disposal § 31.14 Official animal control operations. (a) Animal species which are surplus or...) Animal species which are damaging or destroying Federal property within a wildlife refuge area may be...

50 CFR 31.14 - Official animal control operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Official animal control operations. 31.14... Reduction and Disposal § 31.14 Official animal control operations. (a) Animal species which are surplus or...) Animal species which are damaging or destroying Federal property within a wildlife refuge area may be...

50 CFR 31.14 - Official animal control operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Official animal control operations. 31.14... Reduction and Disposal § 31.14 Official animal control operations. (a) Animal species which are surplus or...) Animal species which are damaging or destroying Federal property within a wildlife refuge area may be...

A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil

PubMed Central

Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Kurucz, Andrea; Kertész, Attila; Takacs, Akos; Posa, Aniko; Kiss, Rita; Szilvassy, Zoltan; Juhasz, Bela

2017-01-01

Right-sided heart failure—often caused by elevated pulmonary arterial pressure—is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease. In this present investigation, PAH was induced by a single dose of monocrotaline (MCT) injection in Sprague-Dawley rats, and animals were divided into 4 treatment groups as follows: I. healthy control animals (Control group); II. pulmonary hypertensive rats (PAH group); III. pulmonary hypertensive rats + daily sildenafil treatment (Sildenafil group); and IV. pulmonary hypertensive rats + Wild garlic liophylisate-enriched chow (WGLL group), for 8 weeks. Echocardiographic measurements were obtained on the 0 and 8 weeks with fundamental and Doppler imaging. Isolated working heart method was used to determinate cardiac functions ex vivo after thoracotomy on the 8th week. Histological analyses were carried out on excised lung samples, and Western blot technique was used to determine Phosphodiesterase type 5 enzyme (PDE5) expression in both myocardial and pulmonary tissues. Our data demonstrate that right ventricle function measured by echocardiography was deteriorated in PAH animals compared to controls, which was counteracted by AU treatment. Isolated working heart measurements showed elevated aortic flow in WGLL group compared to PAH animals. Histological analysis revealed dramatic increase in medial wall thickness of pulmonary arteries harvested from PAH animals, but arteries of animals in sildenafil- and WGLL-treated groups showed physiological status. Our results suggest that bioactive compounds in Allium ursinum could have beneficial effects in pulmonary hypertension. PMID:28677661

Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research.

PubMed

Ding, Ming; Cheng, Liming; Bollen, Peter; Schwarz, Peter; Overgaard, Søren

2010-02-15

Glucocorticoid with low calcium and phosphorus intake induces osteopenia in cancellous bone of sheep. To validate a large animal model for spine fusion and biomaterial research. A variety of ovariectomized animals has been used to study osteoporosis. Most experimental spine fusions were based on normal animals, and there is a great need for suitable large animal models with adequate bone size that closely resemble osteoporosis in humans. Eighteen female skeletal mature sheep were randomly allocated into 3 groups, 6 each. Group 1 (GC-1) received prednisolone (GC) treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (GC-2) received the same treatment as GC-1 for 7 months followed by 3 months without treatment. Group 3 was left untreated and served as the controls. All sheep received restricted diet with low calcium and phosphorus during experiment. After killing the animals, cancellous bone specimens from the vertebra, femurs, and tibias were micro-CT scanned and tested mechanically. Serum biomarkers were determined. In lumbar vertebra, the GC treatment resulted in significant decrease of cancellous bone volume fraction and trabecular thickness, and bone strength. However, the microarchitecture and bone strength of GC-2 recovered to a similar level of the controls. A similar trend of microarchitectural changes was also observed in the distal femur and proximal tibia of both GC treated sheep. The bone formation marker serum-osteocalcin was largely reduced in GC-1 compared to the controls, but recovered with a rebound increase at month 10 in GC-2. The current investigation demonstrates that the changes in microarchitecture and mechanical properties were comparable with those observed in humans after long-term GC treatment. A prolonged GC treatment is needed for a long-term observation to keep osteopenic bone. This model resembles long-term glucocorticoid treated osteoporotic model, and is useful in preclinical studies.

Simulating vasogenic brain edema using chronic VEGF infusion

PubMed Central

Piazza, Martin; Munasinghe, Jeeva; Murayi, Roger; Edwards, Nancy; Montgomery, Blake; Walbridge, Stuart; Merrill, Marsha; Chittiboina, Prashant

2017-01-01

OBJECTIVE To study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings. METHODS Male Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2–20 μg/ml). Following a preinfusion phase (4–6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 μl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12–24, 24–36, 48–72, and 120–144 hours. Rat brains were then collected and histological analysis was performed. RESULTS Control animals and animals infused with 2 μg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74–42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120–144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions. CONCLUSIONS The results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE. PMID:28059647

Calorie restriction inhibits relapse behaviour and preference for alcohol within a two-bottle free choice paradigm in the alcohol preferring (iP) rat.

PubMed

Guccione, Lisa; Djouma, Elvan; Penman, Jim; Paolini, Antonio G

2013-02-17

Among its many beneficial effects, calorie restriction (CR) has also been found to reduce anxiety related behavior in the rodent. With heightened levels of stress and anxiety implicated as a key precipitating factor of relapse and alcohol addiction, it was found that a 25% CR in addition to inducing anxiolytic effects also had the capacity to reduce intake of alcohol and inhibit relapse within a model of operant self-administration. The aim of this study was to investigate if a 25% CR would also display similar effects in a two-bottle free choice paradigm, whereby 24 h ad libitum access to both 10% ethanol and water is provided. All animals were initially tested on the elevated plus maze (EPM) and open field test prior to commencing the two-bottle free choice paradigm. Differences between control and CR25% animals demonstrated the anxiolytic effects of CR, with the CR25% group displaying greater percentage of open arm/total arm duration and open arm/total arm entries in the EPM. During the acquisition phase of the two-bottle free choice paradigm, CR25% animals showed a reduced intake of 10% ethanol in ml/kg, in comparison to the control group. Whilst control animals displayed a strong preference for 10% ethanol, the CR25% group consumed both 10% ethanol and water equally with no differences found in total fluid intake between groups. Similarly this was also the case following forced deprivation. In addition to reduced intake and lack of preference for 10% ethanol, CR 25% animals unlike controls failed to display a typical alcohol deprivation effect following abstinence. Taken collectively the results of this study suggest that CR may act as a protective factor against addiction and relapse in the alcohol preferring (iP) rat. In addition, given CR25% animals did not display a preference for 10% ethanol, results also suggest that CR may be altering the hedonic impact of ethanol within this group. Copyright © 2012 Elsevier Inc. All rights reserved.

Immunological studies in cattle exposed to polybrominated biphenyls

PubMed Central

Kateley, John R.; Bazzell, S. J.

1978-01-01

The intactness of the immune system in cattle exposed to polybrominated biphenyls (PBBs) has been investigated by using several immunoassays. Eighty-seven animals have been studied, 35 control animals (not exposed to PBBs) and 52 animals exposed to PBBs (0.02–30 ppm/g fat equivalent). The immunoassays included a complete blood count, identification of peripheral blood T and B lymphocyte subpopulations, serum immunoglobulin levels (IgG, IgM, and IgA), the in vitro response to lymphocytes to phytolectins (PHA, Con A, PWM), the antibody response to Keyhole limpet hemocyanin (KLH), the cell-mediated response to PPD, and determination of autoantibodies and/or immunosuppressive serum factors. For control and PBB-exposed cattle, there was no statistical difference between the number of circulating erythrocytes or leukocytes, the hematocrit, or hemoglobin content; the percentage or number of T and B lymphocytes; the isotope incorporation index (DNA synthesis) of lymphocytes in response to mitogens; the concentrations of serum immunoglobulins IgG, IgM, or IgA; the mean peak titer to KLH; or in vivo or in vitro immune response to PPD. Additional evaluation of cattle with tissue levels of PBB greater than 3 ppm/g tissue for hematological and immunological parameters revealed no statistical difference from control animals. Other experiments were performed to evaluate serum from cattle exposed to PBBs for autoantibodies to smooth muscle, mitochondrial or nuclear antigens. No evidence for autoantibodies was observed. Further studies were done to examine the cytotoxic and/or immunosuppressive activity of sera from PBB-exposed animals. In these studies, the blastogenic response of lymphocytes from control cattle and humans were evaluated in the presence and absence of serum from animals exposed to PBBs (> 3 ppm/g tissue). No evidence for either a cytotoxic or an immunosuppressive influence of such sera was demonstrable. Our studies indicate that PBB, at the levels studied, does not alter or interfere with lymphocyte surface antigens, the complex nuclear and cytoplasmic events required for mitosis and cell division, or the biological events required for antibody formation and cell-mediated immune reactions. Further, PBB exposure at the levels studied does not predispose cattle to autoantibody production or leucotoxic serum factors. PMID:210004

Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis.

PubMed Central

Vanin, E F; Kaloss, M; Broscius, C; Nienhuis, A W

1994-01-01

Rapidly progressive T-cell lymphomas were observed in 3 of 10 rhesus monkeys several months after autologous transplantation of enriched bone marrow stem cells that had been transduced with a retroviral vector preparation containing replication-competent virus (R. E. Donahue, S. W. Kessler, D. Bodice, K. McDonagh, C. Dunbar, S. Goodman, B. Agricola, E. Byrne, M. Raffeld, R. Moen, J. Bacher, K. M. Zsebo, and A. W. Nienhuis, J. Exp. Med. 176:1124-1135, 1992). The animals with lymphoma appeared to be tolerant to retroviral antigens in that their sera lacked antibodies reactive with viral proteins and contained 10(4) to 10(5) infectious virus particles per ml. By molecular cloning and DNA sequencing, we have now demonstrated that the serum from one of the monkeys contained a replication-competent retrovirus that arose by recombination between vector and packaging encoding sequences (vector/helper [V/H] recombinant) in the producer clone used for transduction of bone marrow stem cells. Southern blot analysis demonstrated 14 or 25 copies of this genome per cell where present in two animals. The genome of a second replication-competent virus was also recovered by molecular cloning; it arose by recombination involving the genome of the V/H recombinant and endogenous murine retroviral genomes in the producer clone. Twelve copies of this amphotropic virus/mink cell focus-forming virus genome were present in tumor DNA of one animal, but it was not found in tumor DNA of the other two animals with lymphoma. Southern blot analysis of DNA from various tissues demonstrated common insertion site bands in several samples of tumor DNA from one animal, suggesting clonal origin of the lymphoma. Our data are most consistent with a pathogenic mechanism in which chronic productive retroviral infection allowed insertional mutagenesis of critical growth control genes, leading to cell transformation and clonal tumor evolution. Images PMID:8207799

Feasibility of the runt cow for in vivo testing of a spinal interbody prosthesis with preliminary results.

PubMed

Buttermann, Glenn R; Mendenhall, H Vincent

2012-04-01

The optimal lumbar spinal disc prosthesis has yet to be developed. Failures of clinical device studies may be minimized by appropriate large animal preclinical studies. The lumbar spine of the mature "runt" cow, Corrientes breed, has been shown to have a number of desirable characteristics to the human. This study assessed the feasibility of the "runt" cow for in vivo testing of human-sized lumbar interbody implants and the ability to perform common analyses of explants. Eight cows (four experimental and four controls) were compared. The experimental animals had transosseous implantation of the disc prosthesis at L4-L5, and their spines were harvested at four or six months. They were evaluated for the ease of surgical access and healing, motion segment mobility, ability to remove the implant nondestructively, and microradiography and histomorphology. All animals had successful implantation. All explantations were performed without alteration to the devices. All animals had surgical healing and intended device motion, and histology found device stability by demonstrating bone ingrowth into the device's porous plates. There was a significant 46% increase in the amount of trabecular bone adjacent to the implants. The mature runt cow allows for implantation of human-sized interbody and intrabody spinal prostheses. This animal model allowed for macro- and histological analysis of the implant and surrounding tissues. In vivo stability was demonstrated for the disc prosthesis while also allowing for evaluation of intended mobility. Additionally, this is the first study to suggest increased bone density supporting an interbody prosthesis.

An improved, rapid competitive ELISA using a novel conserved 3B epitope for the detection of serum antibodies to foot-and-mouth disease virus.

PubMed

Chung, Chungwon J; Clavijo, Alfonso; Bounpheng, Mangkey A; Uddowla, Sabena; Sayed, Abu; Dancho, Brooke; Olesen, Ian C; Pacheco, Juan; Kamicker, Barbara J; Brake, David A; Bandaranayaka-Mudiyanselage, Carey L; Lee, Stephen S; Rai, Devendra K; Rieder, Elizabeth

2018-06-01

The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed animals, resulting in significant costs because of loss of trade and recovery from disease. We developed a sensitive, specific, and rapid competitive ELISA (cELISA) to detect serum antibodies to FMDV. The cELISA utilized a monoclonal blocking antibody specific for a highly conserved FMDV nonstructural 3B epitope, a recombinant mutant FMDV 3ABC coating protein, and optimized format variables including serum incubation for 90 min at 20-25°C. Samples from 16 animals experimentally infected with one FMDV serotype (A, O, Asia, or SAT-1) demonstrated early detection capacity beginning 7 d post-inoculation. All samples from 55 vesicular stomatitis virus antibody-positive cattle and 44 samples from cloven-hoofed animals affected by non-FMD vesicular diseases were negative in the cELISA, demonstrating 100% analytical specificity. The diagnostic sensitivity was 100% against sera from 128 cattle infected with isolates of all FMDV serotypes, emphasizing serotype-agnostic results. Diagnostic specificities of U.S. cattle ( n = 1135) and swine ( n = 207) sera were 99.4% and 100%, respectively. High repeatability and reproducibility were demonstrated with 3.1% coefficient of variation in percent inhibition data and 100% agreement using 2 kit lots and 400 negative control serum samples, with no difference between bench and biosafety cabinet operation. Negative results from vaccinated, uninfected cattle, pig, and sheep sera confirmed the DIVA (differentiate infected from vaccinated animals) capability. This rapid (<3 h), select agent-free assay with high sensitivity and specificity, DIVA capability, and room temperature processing capability will serve as a useful tool in FMDV surveillance, emergency preparedness, response, and outbreak recovery programs.

Specific immune response genes of the guinea pig. II. Relationship between the poly-L-lysine gene and the genes controlling immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine in random-bred Hartley guinea pigs.

PubMed

Bluestein, H G; Green, I; Benacerraf, B

1971-08-01

The ability of guinea pigs to make immune responses to GA, a linear random copolymer of L-glutamic acid and L-alanine, GT, a random linear copolymer of L-glutamic acid and L-tyrosine, and PLL, a linear homopolymer of L-lysine, is controlled by different autosomal dominant genes specific for each of those polymers. We have investigated the relationship between the PLL gene and the GA and GT immune response genes by simultaneously immunizing random-bred Hartley strain guinea pigs with GA and PLL, GT and PLL, or GA and GT. In most Hartley guinea pigs the ability to respond immunologically to GA and to PLL is inherited together; that is, most animals responding to GA respond to PLL and vice versa. However, a few animals respond to either GA or to PLL but not both, demonstrating that the GA and PLL immune response genes are not identical but linked in most Hartley animals. Conversely, when simultaneously immunized with GT and PLL, most Hartley guinea pigs respond to either PLL or GT but not both, indicating that GT and PLL responsiveness tends to segregate away from each other. Thus, the GT and PLL immune response genes also are not inherited independently but, rather, behave as alleles or pseudoalleles. Similar results are observed when Hartley guinea pigs are simultaneously immunized with GA and GT. The ability to respond to GA segregates away from the ability to respond to GT. Our studies demonstrated that the specific immune response genes thus far identified in guinea pigs controlling the ability to respond to GA, GT, and PLL, respectively, are found on the same chromosome. In most Hartley animals, the GA and PLL immune response genes are often linked, i.e. occur on the same chromosome strand, and tend to behave as alleles or pseudoalleles to the GT immune response gene.

Metronidazole for the treatment of Tritrichomonas foetus in bulls.

PubMed

Love, David; Fajt, Virginia R; Hairgrove, Thomas; Jones, Meredyth; Thompson, James A

2017-04-14

Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Results from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovine Tritrichomonas foetus. The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior to treatment was negative for Tritrichomonas foetus culture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treat Tritrichomonas foetus in bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls. The study demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in vivo with metronidazole. The current status of metronidazole is that the Animal Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in food-producing animals. Veterinarians and regulators should consider approaches that might lead to permitting the legal use of metronidazole in bulls.

Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

USGS Publications Warehouse

Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E.

2011-01-01

Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

Clinical and research searching on the wild side: exploring the veterinary literature

PubMed Central

Alpi, Kristine M.; Stringer, Elizabeth; DeVoe, Ryan S.; Stoskopf, Michael

2009-01-01

Zoological medicine furthers the health and well-being of captive and free-ranging wild animals. Effective information retrieval of the zoological medicine literature demands searching multiple databases, conference proceedings, and organization websites using a wide variety of keywords and controlled vocabulary. Veterinarians, residents, students, and the librarians who serve them must have patience for multiple search iterations to capture the majority of the available knowledge. The complexities of thorough literature searches are more difficult for nondomestic animal clinical cases and research reviews as demonstrated by three search requests involving poisonous snakes, a gorilla, and spiders. Expanding and better disseminating the knowledgebase of zoological medicine will make veterinary searching easier. PMID:19626142

Effects of GSM modulated radio-frequency electromagnetic radiation on permeability of blood-brain barrier in male & female rats.

PubMed

Sırav, Bahriye; Seyhan, Nesrin

2016-09-01

With the increased use of mobile phones, their biological and health effects have become more important. Usage of mobile phones near the head increases the possibility of effects on brain tissue. This study was designed to investigate the possible effects of pulse modulated 900MHz and 1800MHz radio-frequency radiation on the permeability of blood-brain barrier of rats. Study was performed with 6 groups of young adult male and female wistar albino rats. The permeability of blood-brain barrier to intravenously injected evans blue dye was quantitatively examined for both control and radio-frequency radiarion exposed groups. For male groups; Evans blue content in the whole brain was found to be 0.08±0.01mg% in the control, 0.13±0.03mg% in 900MHz exposed and 0.26±0.05mg% in 1800MHz exposed animals. In both male radio-frequency radiation exposed groups, the permeability of blood-brain barrier found to be increased with respect to the controls (p<0.01). 1800MHz pulse modulated radio-frequency radiation exposure was found more effective on the male animals (p<0.01). For female groups; dye contents in the whole brains were 0.14±0.01mg% in the control, 0.24±0.03mg% in 900MHz exposed and 0.14±0.02mg% in 1800MHz exposed animals. No statistical variance found between the control and 1800MHz exposed animals (p>0.01). However 900MHz pulse modulated radio-frequency exposure was found effective on the permeability of blood-brain barrier of female animals. Results have shown that 20min pulse modulated radio-frequency radiation exposure of 900MHz and 1800MHz induces an effect and increases the permeability of blood-brain barrier of male rats. For females, 900MHz was found effective and it could be concluded that this result may due to the physiological differences between female and male animals. The results of this study suggest that mobile phone radation could lead to increase the permeability of blood-brain barrier under non-thermal exposure levels. More studies are needed to demonstrate the mechanisms of that breakdown. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of alprazolam on capture stress-related serum cortisol responses in Korean raccoon dogs (Nyctereutes procyonoides koreensis)

PubMed Central

Kim, Sun-A; Lee, So-Yeong; Kimura, Junpei

2011-01-01

The purpose of this study was to evaluate the effect of alprazolam on the stress that Korean raccoon dogs (Nyctereutes procyonoides koreensis) may experience while caught in a live trap by measuring their serum cortisol response. The animals were placed in a live trap with or without being pretreated with oral doses of alprazolam. In both groups, pre-trap blood samples were initially collected without anesthesia before the animals were positioned in the live trap; then post-trap blood samples were collected after the animals had remained in the live trap for 2 h. Changes in cortisol levels were observed using a chemiluminescent immunoassay. The level of cortisol increased in the control group and decreased in the alprazolam-pretreatment group (p < 0.05). In this study, we demonstrated that alprazolam pretreatment reduced stress during live trap capture. PMID:21368571

Effects of alprazolam on capture stress-related serum cortisol responses in Korean raccoon dogs (Nyctereutes procyonoides koreensis).

PubMed

Kim, Sun-A; Lee, So-Yeong; Kimura, Junpei; Shin, Nam-Shik

2011-03-01

The purpose of this study was to evaluate the effect of alprazolam on the stress that Korean raccoon dogs (Nyctereutes procyonoides koreensis) may experience while caught in a live trap by measuring their serum cortisol response. The animals were placed in a live trap with or without being pretreated with oral doses of alprazolam. In both groups, pre-trap blood samples were initially collected without anesthesia before the animals were positioned in the live trap; then post-trap blood samples were collected after the animals had remained in the live trap for 2 h. Changes in cortisol levels were observed using a chemiluminescent immunoassay. The level of cortisol increased in the control group and decreased in the alprazolam-pretreatment group (p < 0.05). In this study, we demonstrated that alprazolam pretreatment reduced stress during live trap capture.

ANABOLIC-ANDROGENIC STEROID DEPENDENCE? INSIGHTS FROM ANIMALS AND HUMANS

PubMed Central

Wood, Ruth I.

2008-01-01

Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. PMID:18275992

Premetazoan origin of the Hippo signaling pathway

PubMed Central

Sebé-Pedrós, Arnau; Zheng, Yonggang; Ruiz-Trillo, Iñaki; Pan, Duojia

2012-01-01

Summary Non-aggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in non-bilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the co-activator Yorkie and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism pre-dating the origin of Metazoa. PMID:22832104

Perception and selection of macrophyte detrital falls by the bathyal echinoid Stylocidaris lineata

NASA Astrophysics Data System (ADS)

Young, C. M.; Tyler, P. A.; Emson, R. H.; Gage, J. D.

1993-07-01

Many deep-sea animals are known to exploit patchy food resources such as animal carcasses and sunken plant remains, but the mechanisms by which such foods are located remain generally unknown. The bathyal echinoid Stylocidaris lineata is an omnivorous deposit feeder that ingests sediment, dead animal remains, seagrass blades, and macroalgae such as Sargassum spp. Using a submersible, we investigated the ability of urchins to locate and exploit large falls of detritus. Individuals quickly arrived at packets of Thalassia testudinum and Sargassum spp. placed on the bottom, and they preferred these food items significantly over inert controls. However, the echinoids demonstrated no significant tendency to move toward the scent of upstream T. testudinum, either in situ or in laboratory flume experiments. Individuals moved at net speeds up to 30 m day -1. The existing evidence suggests that S. lineata locate food by chance encounter, not distant chemoreception.

Hepatic blood flow measurement III. Total hepatic blood flow measured by ICG clearance and electromagnetic flowmeters in a canine septic shock model.

PubMed Central

Nxumalo, J L; Teranaka, M; Schenk, W G

1978-01-01

The validity of the ICG clearance method for the measurement of THBF in abnormal circulatory states remains questionable. In this study THBF measured by this method is compared with the electromagnetic flow technique in a canine spetic model. Good correlation is demonstrated between the two in normal control animals. However, in the septic animals the ICG underestimated the electromagnetic flow result by 20%. This is true in both the high and the low cardiac output septic shock pictures that emerge. In the septic animals, the total hepatic blood flow as measured by the ICG was almost equal to the portal vein flow alone measured by the electromagnetic flowmeters suggesting that this was the quantity it was measuring in this abnormal state. Pathophysiologic mechanisms that may explain the discrepancy are given. PMID:637587

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters

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

Ellender, M.; Hodgson, A.; Wood, K.L.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with [sup 57]CO. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of [sup 57]CO at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and [sup 57]Comore » activity of the washings. The subsequent fractional clearance rate of [sup 57]Co from lavaged animals was not significantly different from that in a group of untreated control animals. 30 refs., 2 figs., 2 tabs.« less

DoD Pest Management Program

DTIC Science & Technology

2008-05-29

Plant Health Inspection Service / Animal Damage Control Memorandum of Agreement on Animal Damage Control, April 19905 (am) Army Regulation 40-905...Services shall manage vertebrate pests in accordance with the DoD-USDA/Animal and Plant Health Inspection Service / Animal Damage Control MOA (Reference

Prevalence of Hydatid Cysts in Livestock Animals in Xinjiang, China

PubMed Central

Qingling, Meng; Guanglei, Wang; Xinquan, Zhu; Tianli, Liu; Xuemei, Song; Jinsheng, Zhang; Huisheng, Wang; Kuojun, Cai; Chuangfu, Chen

2014-01-01

Hydatid worms, hosted by humans and animals, impose serious human health risk and cause significant livestock production loss. To better understand the disease infection status in Xinjiang, China, we investigated the disease epidemics in 4 livestock animals, i.e., cattle, sheep (both sheep and goat), camels, and horses, slaughtered at the abattoirs in Urumqi, Yining, Tacheng, and Altay areas. The results showed that the animals were infected at different rates, in the order of sheep (9.8%), cattle (8.4%), camels (6.8%), and horses (4.3%). The infection rates were found to be different between the abattoirs in various regions even for the same animals. For sheep, the rates increased significantly as the animals grew older. It was 1.9% before 1 year of age and increased to 8.2% in the age of 1-2 years, and further increased to 12.3% when the animals were 3-4 years old, and reached 17.2% when they were 5-6 year old. Sheep older than 6 years had an infection rate of 19.5%. This study demonstrates that the 4 livestock animals in the pastoral areas in Xinjiang were infected by the parasites to various extend. This study is the first systematic investigation of the hydatid worms in various livestock animals in Xinjiang, China, which provides epidemiological information about the infection of hydatid worms in livestock, and is valuable in developing strategies for prevention and control of the hydatid disease. PMID:25031478

A preclinical model of CD38-pretargeted radioimmunotherapy for plasma cell malignancies.

PubMed

Green, Damian J; Orgun, Nural N; Jones, Jon C; Hylarides, Mark D; Pagel, John M; Hamlin, Donald K; Wilbur, D S; Lin, Yukang; Fisher, Darrell R; Kenoyer, Aimee L; Frayo, Shani L; Gopal, Ajay K; Orozco, Johnnie J; Gooley, Theodore A; Wood, Brent L; Bensinger, William I; Press, Oliver W

2014-02-15

The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. (90)Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals. ©2013 AACR.

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota

PubMed Central

Liehr, Martin; Mereu, Alessandro; Pastor, Jose Javier; Quintela, Jose Carlos; Staats, Stefanie; Rimbach, Gerald; Ipharraguerre, Ignacio Rodolfo

2017-01-01

Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function. PMID:28346507

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

PubMed

Lakhera, Abhijeet; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

2015-06-01

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats

PubMed Central

Lakhera, Abhijeet; Bansal, Divya; Dubey, Nazneen

2015-01-01

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components. PMID:27486367

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

PubMed Central

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

2011-01-01

Background Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares “resting” CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Methods Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8–14.6 mg/kg/hr). Three resting H215O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4 mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI = 3.04/2100/785 msec, flip angle=13 degrees). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. Results When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. Conclusions “Resting” CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine’s propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation. PMID:18801644

Granulocyte colony-stimulating factor (G-CSF) production in hemorrhagic shock requires both the ischemic and resuscitation phase.

PubMed

Hierholzer, C; Kelly, E; Billiar, T R; Tweardy, D J

1997-01-01

Granulocyte colony-stimulating factor (G-CSF) is the cytokine that is critical for polymorphonuclear neutrophilic granulocyte (PMN) production as well as being a potent agonist of PMN activation. We have recently reported that in the lung and the liver of rats resuscitated after hemorrhagic shock (HS) G-CSF mRNA expression is induced. It is not known if both phases of HS, the ischemic and the reperfusion phase, are required for G-CSF mRNA induction. The present study was designed to test the hypothesis that the upregulation of G-CSF mRNA expression is the consequence of HS followed by resuscitation and that ischemia alone is insufficient to induce G-CSF mRNA expression in the affected organs. Male Sprague-Dawley rats were subjected to resuscitated and unresuscitated shock protocols of varying severity. Control animals were subjected to anesthesia and all surgical preparations except for hemorrhage. Lungs and livers were isolated and their RNA extracted. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that G-CSF mRNA was induced in the lung and liver of shock animals above the level observed in control animals. Upregulation of G-CSF mRNA relative to controls occurred only in animals undergoing resuscitated HS and not in ones subjected to unresuscitated HS. These results indicate that G-CSF production specific for the hemorrhage component of shock is dependent on resuscitation. As a consequence, the production of this cytokine may be decreased through modifications in the resuscitation protocols.

Effect of methamphetamine exposure and cross-fostering on cognitive function in adult male rats.

PubMed

Hrubá, Lenka; Schutová, Barbora; Pometlová, Marie; Rokyta, Richard; Slamberová, Romana

2010-03-17

The aim of our study was to examine the effect of prenatal methamphetamine (MA) exposure and cross-fostering on cognitive functions of adult male rats tested in Morris water maze (MWM). Rat mothers were exposed daily to injection of MA (5mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Females without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised 4 pups of her own and 8 pups from the mothers with the other two treatments. Four types of tests were used: (1) Place navigation test (Learning), (2) Probe test (Probe), (3) Retention memory test (Memory) and (4) Visible platform task. Our results demonstrate that the prenatal exposure to MA does not impact learning and memory, while postnatal exposure to MA shows impairments in cognition. In the test of learning, all animals fostered to MA-treated dams had longer latencies, bigger search error and used lower spatial strategies than the animals fostered to control or saline-treated mother, regardless of prenatal exposure. Regardless of postnatal exposure, the animals prenatally exposed to saline swam faster in all the tests than the animals prenatally exposed to MA and controls, respectively. This study indicates that postnatal but not prenatal exposure to MA affects learning in adult male rats. However, it is still not clear whether these impairments are due to a direct effect of MA on neuronal structure or due to an indirect effect of MA mediated by impaired maternal care. Copyright 2009 Elsevier B.V. All rights reserved.

The efficacy of eprinomectin extended-release injection against naturally acquired nematode parasites of cattle, with special regard to inhibited fourth-stage Ostertagia larvae.

PubMed

Hunter, J S; Yoon, S; Yazwinski, T A; Williams, J C; Rehbein, S

2013-03-01

The efficacy of eprinomectin in an extended-release injection (ERI) formulation in the treatment of cattle harboring naturally acquired nematode populations (including inhibited nematodes) was evaluated. Five studies were conducted under a similar protocol in the USA, the UK, and in Germany. All study animals were infected by grazing naturally contaminated pastures. The adequacy of pasture infectivity was confirmed by examining tracer calves prior to allocation and treatment of the study animals. The cattle were of various breeds or crosses, weighing 79-491 kg, and aged approximately 6-15 months. In each study, 20 animals were infected by grazing, and then removed from pasture and housed in a manner to preclude further nematode infections for 8-16 days until treatment. Animals were blocked based on descending pre-treatment body weight and randomly allocated to one of two treatments: ERI vehicle (control) at 1 mL/50 kg body weight or eprinomectin 5% (w/v) ERI at 1 mL/50 kg body weight (1.0 mg eprinomectin/kg). Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. For parasite recovery and count, all study animals were humanely euthanized 14/15 days after treatment. Cattle treated with eprinomectin ERI had significantly (p<0.05) fewer of the following nematodes than the controls with overall reduction of parasite counts of ≥94%: adult Dictyocaulus viviparus, Capillaria spp., Cooperia oncophora, Cooperia pectinata, Cooperia punctata, Cooperia surnabada, Haemonchus placei, Nematodirus helvetianus, Oesophagostomum radiatum, Ostertagia lyrata, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Trichuris discolor, Trichuris skrjabini, and Trichuris spp.; developing fourth-stage larvae of Ostertagia spp. and Trichostrongylus spp.; and inhibited fourth-stage larvae of Cooperia spp., Haemonchus spp., Nematodirus spp., Oesophagostomum spp., Ostertagia spp., and Trichostrongylus spp. Animal treatments were well accepted, with no adverse reactions to treatment observed in any study animals. The results of this series of controlled studies demonstrated high therapeutic efficacy and acceptability of eprinomectin ERI against pulmonary nematodes and a wide range of gastrointestinal parasitic infections, including inhibited gastrointestinal nematodes, in cattle. Copyright © 2012. Published by Elsevier B.V.

Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control.

PubMed

Spetea, Mariana

2013-01-01

Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major health problem, and an adequate management requires understanding of both peripheral and central components, with more attention drawn to the former. Intense experimental and clinical research activities resulted in important knowledge on the mechanisms and functions of the endogenous opioid system located in the periphery. This review describes the occurrence and distribution of endogenous opioids and their receptors in the musculoskeletal system, and their role in pain control in musculoskeletal disorders, such as rheumatoid arthritis and osteoarthritis. Using different techniques, including immunohistochemistry, electron microscopy or radioimmunoassay, expression of enkephalins, dynorphin, β-endorphin, and endomorphins was demonstrated in musculoskeletal tissues of animals and humans. Localization of opioid peptides was found in synovial membrane, periosteum, bone and bone marrow, loose connective tissue, the paratenon and musculotendinous junction of the achilles tendon. Animal and human studies have also demonstrated expression of µ, δ and κ opioid receptor proteins in musculoskeletal tissues using radioligand binding assays, autoradiography, electrophysiology, immunohistochemistry and Western blotting. Opioid receptor gene expression was reported based on polymerase chain reaction and in situ hybridization techniques. Combining morphological and quantitative approaches, important evidence that the musculoskeletal apparatus is equipped with a peripheral opioid system is provided. Demonstration of the occurrence of an endogenous opioid system in bone and joint tissues represents an essential step for defining novel pharmacological strategies to attain peripheral control of pain in musculoskeletal disorders.

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

PubMed Central

Escombe, A. Roderick; Moore, David A. J; Gilman, Robert H; Navincopa, Marcos; Ticona, Eduardo; Mitchell, Bailey; Noakes, Catherine; Martínez, Carlos; Sheen, Patricia; Ramirez, Rocio; Quino, Willi; Gonzalez, Armando; Friedland, Jon S; Evans, Carlton A

2009-01-01

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings. PMID:19296717

Comparison of strategies for substantiating freedom from scrapie in a sheep flock.

PubMed

Durand, Benoit; Martinez, Marie-José; Calavas, Didier; Ducrot, Christian

2009-04-30

The public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led European animal health authorities to launch large screening and genetic selection programmes. If demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. In this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapie. Classical approaches, based on surveys designed to detect disease presence, do not account for scrapie specificities: the genetic variations of susceptibility and the absence of live diagnostic test routinely available. Adapting these approaches leads to a paradoxical situation in which a greater amount of testing is needed to substantiate disease freedom in genetically resistant flocks than in susceptible flocks, whereas probability of disease freedom is a priori higher in the former than in the latter. The goal of this study was to propose, evaluate and compare several qualification strategies for demonstrating a flock is free from scrapie. A probabilistic framework was defined that accounts for scrapie specificities and allows solving the preceding paradox. Six qualification strategies were defined that combine genotyping data, diagnostic tests results and flock pedigree. These were compared in two types of simulated flocks: resistant and susceptible flocks. Two strategies allowed demonstrating disease freedom in several years, for the majority of simulated flocks: a strategy in which all the flock animals are genotyped, and a strategy in which only founders animals are genotyped, the flock pedigree being known. In both cases, diagnostic tests are performed on culled animals. The less costly strategy varied according to the genetic context (resistant or susceptible) and to the relative costs of a genotyping exam and of a diagnostic test. This work demonstrates that combining data sources allows substantiating a flock is free from scrapie within a reasonable time frame. Qualification schemes could thus be a useful tool for voluntary or mandatory scrapie control programmes. However, there is no general strategy that would always minimize the costs and choice of the strategy should be adapted to local genetic conditions.

The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

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

Nekvasil, N.; Baggio, C.

Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressuremore » than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.« less

Immunotherapy of acute radiation syndromes with antiradiation gamma G globulin.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav; Casey, Rachael; Jones, Jeffrey; Kedar, Prasad

Introduction: If an immunotherapy treatment approach to treatment of acute radiation syndromes (ARS) were to be developed; consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants- SRD) by specific antiradiation antibodies. To accomplish this objective, irradiated animals were injected with a preparation of antiradiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-indeced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic and enterotoxic) characteristics as well as specific antigenic properties that combined with the direct physiochemical direct radiation damage, induce the development of many of the pathological processes associated with ARS. We tested several specific hyperimmune IgG preparations against these radiation toxins and observed that their toxic properties were neutralized by specific antiradiation IgGs. Material and Methods: Rabbits were inoculated with SRD radiation toxins to induce hyperimmune serum. The hyperimmune serum was pooled from several animals, purified, and concentrated. Enzyme-linked immunosorbent assays of the hyperimmune serum revealed high titers of IgG with specific binding to radiation toxins. The antiradiation IgG preparation was injected into laboratory animals one hour before and three hours after irradiation, and was evaluated for its ability to protect inoculated animals against the development of acute radiation syndromes. Results: Animals that were inoculated with specific antiradiation antibodies before receiving lethal irradiation at LD 100/30 exhibited 60-75% survival rate at 30 days, whereas all control animals expired by 30 days following exposure. These inoculated animals also exhibited markedly reduced clinical symptoms of ARS, even those that did not survive irradiation. Discussion: The results of our experiments demonstrate that rabbit hyperimmune serum directed against SRD toxins afford significant, albeit incomplete, protection against high doses of radiation. In comparison, the mortality rate of irradiated control animals was 100% in the same time period. The mortality rates of hyperimmune serum-treated animals varied in different groups of animals and different forms of ARS; however, significant radioprotection was observed in each group treated with IgGs activated against specific radiation toxins.

Effects of inhalation exposure to SRC-II heavy and middle distillates

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

Springer, D.L.; Miller, R.A.; Weimer, W.C.

1984-11-01

To expand the data base on potential health effects of coal liquefaction materials, we have performed studies with both solvent refined coal (SRC)-II heavy distillate (HD) and middle distillate (MD). Weight gain for exposed animals was less than that of controls and was dose-related, ranging from no significant difference for animals in the low-exposure group to failure to gain in the high-dose animals. Liver weights increased significantly over controls, and thymus weights decreased for animals sacrificed at 5 and 13 weeks. After both exposure periods, there were significant treatment-related decreases in erythrocyte parameters and in certain types of white bloodmore » cells (WBC). Bone marrow cellularity, and numbers of megakaryocytes consistently decreased, suggesting that bone marrow is a target tissue for high-boiling coal liquids. Microscopic evaluation of tissue indicated exposure-related changes is listed. In contrast to the reported mutagenic and carcinogenic effects observed for the high-boiling coal liquids, middle-boiling-range materials lacked such activity in these assays. These data demonstrate a great deal of similarity in the kinds of effects observed following exposure to middle- and high-boiling-range coal liquids. However, the significance of changes in organ weights and peripheral blood parameters are not always readily apparent following a subchronic study. Because of this, we exposed animals to HD in a manner similar to that for the subchronic experiment and have followed these animals throughout their lives for the development of adverse effects such as reduced longevity and the appearance of tumors. Results from this study will be available for mice in FY 1985 and for rats in FY 1986.« less

Nocturnal illumination maintains reproductive function and simulates the period-lengthening effect of constant light in the mature male Djungarian hamster (Phodopus sungorus)

NASA Technical Reports Server (NTRS)

Ferraro, J. S.

1990-01-01

Mature male Djungarian hamsters (Phodopus sungorus) were placed in individual light-tight, sound attenuated chambers and exposed to one of four lighting conditions for a duration of approximately seven weeks. The four lighting conditions were: constant light (LL); constant dark (DD); feedback lighting (LDFB; a condition that illuminates the cage in response to locomotor activity); or a feedback lighting neighbor control (LDFB NC; the animal receives the same light pattern as a paired animal in feedback lighting, but has no control over it). Exposure of hamsters to LL or LDFB produced significantly and similarly longer free-running periods of the locomotor activity rhythm than exposure of animals to DD. Hamsters exposed to LDFB NC did not free-run or entrain, but rather displayed "relative coordination". The paired testes and sex accessory glands weights suggest that in the Djungarian hamster, LL and LDFB exposed animals maintained reproductive function, whereas DD exposed animals did not. Animals exposed to LDFB NC had intermediate paired testes weights. Since several previous studies have demonstrated that short pulses of light, which are coincident with the subjective night, are photostimulatory, it is not surprising that LDFB maintained reproductive function in the mature Djungarian hamster. Feedback lighting, however, has been shown to be an insufficient stimulus to maintain reproductive function of mature male and female Syrian hamsters, and to the reproductive maturation of immature Djungarian hamsters. The results suggest that there may be slight, but significant differences in the way these two species interpret photoperiod, as well as a developmental change in the photoperiodic response of Djungarian hamsters.

The effects of a moderate and high dose of vitamin C on wound healing in a controlled guinea pig model.

PubMed

Silverstein, R J; Landsman, A S

1999-01-01

The purpose of this pilot study was to investigate the effect of vitamin C on wound healing in a controlled animal study. Twenty male guinea pigs were divided into two groups and were maintained on one of two commercially prepared diets: 1) supplemented with a moderate dose of vitamin C, or 2) supplemented with a high dose of vitamin C. After 6 weeks, a dorsal incision was made on the back of each of the animals. The incision was closed by primary intention as the animals continued on their respective diets until they were sacrificed. At the time of testing, either 10 days or 21 days postoperatively, the animals' skin was excised around the original incision using a metal template. A second skin sample was excised from each animal from an area adjacent to the original skin incision. This was done in order to determine the breaking force of the intact unaffected skin. Tension studies were performed to measure and compare the integrity and strength of the healing incisions. Biopsies were also sent for histopathologic analysis. The study presented here focused on whether or not increases in dietary vitamin C may improve the strength of a skin wound postoperatively. Although the sample size was small, the data suggest that a trend may exist in which increased vitamin C intake prior to and after surgery may result in faster recovery of skin integrity and strength across the wound. Although the difference between the groups is not statistically significant, the data clearly indicate that the animals receiving the higher dose of vitamin C demonstrated greater wound integrity than those receiving the moderate dose of the vitamin.

Ten-year oral toxicity study with Norlestrin in rhesus monkeys.

PubMed

Fitzgerald, J; de la Iglesia, F; Goldenthal, E I

1982-12-01

The long term effects of the oral contraceptive, Norlestrin, were evaluated in sexually mature female rhesus (Macaca mulatta) monkeys over a 10 year period. Norlestrin, a combination of norethindrone acetate and ethinylestradiol (50:1) was given orally on a continuous cyclic regimen of 21 d of dosing followed by 7 d without treatment. Groups of 16 monkeys each received the drug at dose levels of 0.05, 0.51, and 2.55 mg/kg representing multiples of 1, 10, and 50 times the human dose, respectively. A comparable group of 16 animals remained untreated and served as controls. Selected clinical and laboratory parameters were monitored throughout the study and all animals were necropsied and evaluated for gross and histopathologic changes. All dose levels were well tolerated and survival was not affected. There were no consistent treatment-related alterations in coagulation or other clinical laboratory parameters. Ophthalmologically, macular pigmentary anomalies were observed in all groups. Treatment-associated pathologic findings, representing exaggerated pharmacological responses with superimposed senile changes, including ovarian and uterine atrophy and dilatation of acini and ducts in the mammary gland. Periodic vaginal cytologic examination and mammary gland palpation did not demonstrate drug related changes. A small number of neoplasms was seen in all groups and a granulosa cell carcinoma of the ovary occurred in a control animal. The benign tumors consisted of three cutaneous papillomas: one in a low dose and one in a high dose animal, a uterine leiomyoma in one high dose animal, and a pancreatic duct adenoma in one low dose animal. The results of this study indicate that Norlestrin had no significant toxic manifestations or tumorigenic potential when administered on a cyclic regimen to female rhesus monkeys at levels up to 50 times the human dose for ten yr.

DNA authentication of animal-derived concentrated Chinese medicine granules.

PubMed

Jiang, Li-Li; Lo, Yat-Tung; Chen, Wei-Ting; Shaw, Pang-Chui

2016-09-10

Concentrated Chinese medicine granules (CCMG) offer patients a convenient option for traditional therapy. However with morphological and microscopic characteristics lost, it is difficult to authenticate and control the quality of these medicinal products. This study is the first to examine the feasibility of using DNA techniques to authenticate animal-derived CCMG, which has so far lacking of effective means for authentication. Primers targeting amplicons of different sizes were designed to determine the presence of PCR-amplifiable DNA fragments in two types of CCMG, namely Zaocys and Scorpio. Species-specific primers were designed to differentiate the genuine drugs from their adulterants. The specificity of the designed primers was evaluated in crude drugs (including genuine and adulterant) and CCMG. Results showed that by using species-specific primers, DNA fragments of less than 200bp could be isolated from the CCMG and the concerned source materials. This study demonstrated the presence of small size DNA in animal-derived CCMG and the DNA is effective in species identification. The work has extended the application of DNA techniques in herbal medicine and this approach may be further developed for quality control and regulatory compliance in the CCMG industry. Copyright © 2016 Elsevier B.V. All rights reserved.

Active touch sensing

PubMed Central

Prescott, Tony J.; Diamond, Mathew E.; Wing, Alan M.

2011-01-01

Active sensing systems are purposive and information-seeking sensory systems. Active sensing usually entails sensor movement, but more fundamentally, it involves control of the sensor apparatus, in whatever manner best suits the task, so as to maximize information gain. In animals, active sensing is perhaps most evident in the modality of touch. In this theme issue, we look at active touch across a broad range of species from insects, terrestrial and marine mammals, through to humans. In addition to analysing natural touch, we also consider how engineering is beginning to exploit physical analogues of these biological systems so as to endow robots with rich tactile sensing capabilities. The different contributions show not only the varieties of active touch—antennae, whiskers and fingertips—but also their commonalities. They explore how active touch sensing has evolved in different animal lineages, how it serves to provide rapid and reliable cues for controlling ongoing behaviour, and even how it can disintegrate when our brains begin to fail. They demonstrate that research on active touch offers a means both to understand this essential and primary sensory modality, and to investigate how animals, including man, combine movement with sensing so as to make sense of, and act effectively in, the world. PMID:21969680

Does preoperative electrical stimulation of the skin alter the healing process?

PubMed

Borba, Graziela C; Hochman, Bernardo; Liebano, Richard E; Enokihara, Milvia M S S; Ferreira, Lydia M

2011-04-01

In vitro studies have demonstrated that electrical current may affect fibroblast proliferation and synthesis of collagen fibers. In humans, the application of electrical current by positioning the positive electrode on skin wounds resulted in thinner hypertrophic scars. The aim of this study was to evaluate the effects of preoperative electrical stimulation on cutaneous wound healing in rats. Forty rats were divided into two groups of 20 animals each. In the control group, an incision was made on the back of the animals. In the stimulation group, a preoperative electrical stimulation was applied using a rectangular pulse current at a frequency of 7.7 Hz, and intensity of 8 mA, for 30 min, with the positive electrode placed on the back of the animal, and the negative electrode placed on the abdominal wall. Following, an incision was made on their back. Biopsy was carried out on postoperative day 7 and 14, and histologic analysis was performed. The number of newly formed vessels, fibroblasts, and type III collagen fibers in the stimulation group on postoperative day 7 were greater than those in the control group. Preoperative positive-polarity electrical stimulation positively affects angiogenesis and fibroblast proliferation. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

Expression of animal anti-apoptotic gene Ced-9 enhances tolerance during Glycine max L.-Bradyrhizobium japonicum interaction under saline stress but reduces nodule formation.

PubMed

Robert, Germán; Muñoz, Nacira; Melchiorre, Mariana; Sánchez, Federico; Lascano, Ramiro

2014-01-01

The mechanisms by which the expression of animal cell death suppressors in economically important plants conferred enhanced stress tolerance are not fully understood. In the present work, the effect of expression of animal antiapoptotic gene Ced-9 in soybean hairy roots was evaluated under root hairs and hairy roots death-inducing stress conditions given by i) Bradyrhizobium japonicum inoculation in presence of 50 mM NaCl, and ii) severe salt stress (150 mM NaCl), for 30 min and 3 h, respectively. We have determined that root hairs death induced by inoculation in presence of 50 mM NaCl showed characteristics of ordered process, with increased ROS generation, MDA and ATP levels, whereas the cell death induced by 150 mM NaCl treatment showed non-ordered or necrotic-like characteristics. The expression of Ced-9 inhibited or at least delayed root hairs death under these treatments. Hairy roots expressing Ced-9 had better homeostasis maintenance, preventing potassium release; increasing the ATP levels and controlling the oxidative damage avoiding the increase of reactive oxygen species production. Even when our results demonstrate a positive effect of animal cell death suppressors in plant cell ionic and redox homeostasis under cell death-inducing conditions, its expression, contrary to expectations, drastically inhibited nodule formation even under control conditions.

Viability of ligaments after freezing: an experimental study in a rabbit model.

PubMed

Frank, C; Edwards, P; McDonald, D; Bodie, D; Sabiston, P

1988-01-01

Our purpose in this study was to assess ligament fibroblast viability after freezing by quantifying the subsequent ability of fibroblasts to synthesize collagen in vitro. Both medial collateral ligament (MCL) complexes from 40 adolescent rabbits were studied. Collagen production was determined by in vitro incubation of ligaments in 3H-proline (a collagen precursor) and subsequent analysis of 3H-hydroxyproline (a marker of newly synthesized collagen). Autoradiographs determined the distributions of ligament cell activity. All right MCL complexes served as fresh controls, providing a baseline of collagen production. Each left MCL was assigned to an experimental group and was either incubated fresh (10 animals); "killed" by drying, multiple freeze thawing, or cycloheximide (six animals); or slowly frozen at -70 degrees C without cryoprotection (24 animals). Collagen production of rapidly thawed ligaments was studied by proline incubation at 1 day, 9 days, or 6 weeks after freezing and was compared with that of contralateral fresh controls. Results demonstrate that some cells in the substance of these rabbit ligaments retained the ability to synthesize collagen in vitro after being frozen for up to 6 weeks. Mean collagen production of frozen ligaments was decreased, but tests of mean and median values as well as ratios were statistically similar to fresh contralateral ligaments in all animals. This postfreezing ligament cell survival and collagen production after -70 degrees C storage may have implications for ligament transplantation.

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

PubMed

Hurlbut, B J; Lubar, J F; Switzer, R; Dougherty, J; Eisenstadt, M L

1987-01-01

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

Comparing the Effect of Animal-Rearing Education in Japan with Conventional Animal-Assisted Education

PubMed Central

Nakajima, Yuka

2017-01-01

An increasing number of teachers are introducing animals into their class so that pupils foster cognitive, physiological, and social skills through their interaction with animals. Along with such an educational style termed animal-assisted education (AAE), Japanese formal education has also utilized animals for education. Japanese animal-rearing education is unique regarding the following two points: (1) it takes the form of “education through assisting animals” rather than “animals assisting education” and (2) animal rearing is embedded in formal education. While conventional AAE expects the benefit from the social support of animals, Japanese animal-rearing education expects benefit from nurturing and caring for animals. The present study aims to identify effective methods for using animals for education by highlighting the benefits of Japanese animal-rearing education. An overview of Japanese animal-rearing education is followed by a critical review of empirical studies of conventional AAE and Japanese animal-rearing education. Despite the differences in the educational styles, it was found that both systems commonly help children adapt to school. Additionally, conventional AAE were effective in enhancing cognitive and athletic ability of students and foster social skills, while Japanese animal-rearing education enhanced academic knowledge and skills and cultivated sympathy for animals and other people. Furthermore, it was demonstrated that the experience of raising animals affects children’s development for a long time even after children stop raising animals. In order to determine the effect of animal presence at school, however, more empirical studies with various viewpoints are necessary for both styles of education. Concerning Japanese animal-rearing education, the effects of the differences such as the amount of exposure to animals, developmental stage or character of individual children, the types of animals need to be controlled for a more sophisticated examination. Empirical studies show that preadolescence is one of the periods in which animal rearing has the greatest impact on children’s development. It is suggested that through the program of raising school animals, conventional AAE obtains more a variety of effects in their interaction with animals. PMID:28638823

Sustainable improvement of animal health care by systematic quality risk management according to the HACCP concept.

PubMed

Noordhuizen, J P; Welpelo, H J

1996-12-01

This paper addresses the principles of the Hazard Analysis Critical Control Point (HACCP) concept as applied to animal health management strategy. Characteristics of the concept were analysed and compared with those of current animal health care strategies for disease risk identification and herd health management, insurance, and certification. HACCP is a hybrid strategy of quality control at both production process and product level. Animal health is considered a particular quality feature. We show that process control (expressed in terms of controlling both general and specific disease risk factors) and product control (expressed in terms of testing animals or animal products for specific disease agents) could form the basis for improving animal health. We conclude that HACCP provides ample opportunity for preventive health action and risk management at a relatively low cost in terms of labour, finance and documentation expenditure, at both the farm and sector level. Epidemiological field studies are currently needed to identify critical control points and to design HACCP procedures for livestock producers. In the long run, HACCP based animal health care can be further developed into a quality control systems approach to cover all aspects that are related, either directly or indirectly, to animal health.

Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

PubMed

Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

2015-11-01

Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxicity and Metabolism of Layered Double Hydroxide Intercalated with Levodopa in a Parkinson’s Disease Model

PubMed Central

Kura, Aminu Umar; Ain, Nooraini Mohd; Hussein, Mohd Zobir; Fakurazi, Sharida; Hussein-Al-Ali, Samer Hasan

2014-01-01

Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 μg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment. PMID:24722565

Historical evidence for nature disconnection in a 70-year time series of Disney animated films.

PubMed

Prévot-Julliard, Anne-Caroline; Julliard, Romain; Clayton, Susan

2015-08-01

The assumed ongoing disconnection between humans and nature in Western societies represents a profoundly challenging conservation issue. Here, we demonstrate one manifestation of this nature disconnection, via an examination of the representation of natural settings in a 70-year time series of Disney animated films. We found that natural settings are increasingly less present as a representation of outdoor environments in these films. Moreover, these drawn natural settings tend to be more and more human controlled and are less and less complex in terms of the biodiversity they depict. These results demonstrate the increasing nature disconnection of the filmmaking teams, which we consider as a proxy of the Western relation to nature. Additionally, because nature experience of children is partly based on movies, the depleted representation of biodiversity in outdoor environments of Disney films may amplify the current disconnection from nature for children. This reduction in exposure to nature may hinder the implementation of biodiversity conservation measures. © The Author(s) 2014.

Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (NexGard Spectra(®), Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs.

PubMed

Beugnet, Frederic; Crafford, Dionne; de Vos, Christa; Kok, Dawid; Larsen, Diane; Fourie, Josephus

2016-08-15

The nematode Spirocerca lupi (Rudolphi, 1809) is widely distributed but mostly occurs sporadically with stable populations only in certain geographic areas. This helminth mainly infects dogs and wild canids. Primary pathology relates to migration of third stage larvae (L3) damaging the thoracic aorta and establishment of adults in nodules in the oesophagus. The objective of the present study was to evaluate the efficacy of milbemycin oxime in combination with afoxolaner (NexGard Spectra(®), Merial), administered monthly, in preventing establishment of adult worms after experimental infection. Two groups consisting of eight animals each were experimentally infected with 15 L3 on Days -28, -14 and -2, respectively (45 L3 per animal in total). Group 1 dogs served as untreated (negative) control, whereas animals in group 2 were treated with NexGard Spectra(®) at a minimum dose of 0.5mg/kg milbemycin oxime on Day 0 and from then onwards every 28 days up to Day 140 (six treatment occasions). Endoscopy was performed on Day 112 and for some animals also Day 140. Necropsy for worm recovery and nodule/lesion scoring was performed on Day 168. All eight animals in the control group (group 1) presented with 1-3 nodules and worm counts ranging from 9 to 41. Six animals in the NexGard Spectra(®) group presented with 1-4 nodules and worm counts ranging from 1 to 5. Significantly (p<0.05) fewer worms were collected from treated animals in the treated group (geometric mean 1.7) versus the negative control group (geometric mean 22.0) with 92.3% efficacy calculated. There was no significant (p>0.05) difference between groups with reference to number of nodules in the oesophagus. However, nodules in the control group were significantly (p<0.05) larger than those in the treated group. Number and size of lesions in the dorsal aorta did not differ statistically between groups 1 and 2. Because NexGard Spectra(®) was administered 28 days after onset of inoculation, migrating and developing L3 caused damage to the aorta wall of animals in the treated group. Milbemycin oxime (administered as NexGard Spectra(®)) demonstrated effectiveness in reducing infection with adult Spirocerca lupi worms in the oesophagus. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The Effect of Gentle Handling on Depressive-Like Behavior in Adult Male Mice: Considerations for Human and Rodent Interactions in the Laboratory

PubMed Central

Lane, Christina; Torres, Julio; Flinn, Jane

2018-01-01

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being. A factor that is often overlooked is handling and how researchers interact with their animals. Researchers, lab assistants, and husbandry staff in animal facilities may use inconsistent handling methods when interacting with rodents, but humans should be considered a part of the animal's social environment. This study examined the effects of different handling techniques on depressive-like behavior, measured by the Porsolt forced swim test, in adult C57BL/6J male mice. The same two researchers handled the mice in a gentle, aggressive, or minimal (control) fashion over approximately two weeks prior to testing. The results demonstrated a beneficial effect of gentle handling: gentle handling reduced swimming immobility in the forced swim test compared to mice that were aggressively or minimally handled. We argue that gentle handling, rather than methodical handling, can foster a better relationship between the handlers and rodents. Although handling is not standardized across labs, consistent gentle handling allows for less challenging behavioral testing, better data collection, and overall improved animal welfare. PMID:29692869

The Effect of Gentle Handling on Depressive-Like Behavior in Adult Male Mice: Considerations for Human and Rodent Interactions in the Laboratory.

PubMed

Neely, Caroline; Lane, Christina; Torres, Julio; Flinn, Jane

2018-01-01

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being. A factor that is often overlooked is handling and how researchers interact with their animals. Researchers, lab assistants, and husbandry staff in animal facilities may use inconsistent handling methods when interacting with rodents, but humans should be considered a part of the animal's social environment. This study examined the effects of different handling techniques on depressive-like behavior, measured by the Porsolt forced swim test, in adult C57BL/6J male mice. The same two researchers handled the mice in a gentle, aggressive, or minimal (control) fashion over approximately two weeks prior to testing. The results demonstrated a beneficial effect of gentle handling: gentle handling reduced swimming immobility in the forced swim test compared to mice that were aggressively or minimally handled. We argue that gentle handling, rather than methodical handling, can foster a better relationship between the handlers and rodents. Although handling is not standardized across labs, consistent gentle handling allows for less challenging behavioral testing, better data collection, and overall improved animal welfare.

Investigating Empathy-Like Responding to Conspecifics’ Distress in Pet Dogs

PubMed Central

Quervel-Chaumette, Mylene; Faerber, Viola; Faragó, Tamás; Marshall-Pescini, Sarah; Range, Friederike

2016-01-01

Empathy covers a wide range of phenomena varying according to the degree of cognitive complexity involved; ranging from emotional contagion, defined as the sharing of others’ emotional states, to sympathetic concern requiring animals to have an appraisal of the others’ situation and showing concern-like behaviors. While most studies have investigated how animals reacted in response to conspecifics’ distress, dogs so far have mainly been targeted to examine cross-species empathic responses. To investigate whether dogs would respond with empathy-like behavior also to conspecifics, we adopted a playback method using conspecifics’ vocalizations (whines) recorded during a distressful event as well as control sounds. Our subjects were first exposed to a playback phase where they were subjected either to a control sound, a familiar whine (from their familiar partner) or a stranger whine stimulus (from a stranger dog), and then a reunion phase where the familiar partner entered the room. When exposed to whines, dogs showed a higher behavioral alertness and exhibited more stress-related behaviors compared to when exposed to acoustically similar control sounds. Moreover, they demonstrated more comfort-offering behaviors toward their familiar partners following whine playbacks than after control stimuli. Furthermore, when looking at the first session, this comfort offering was biased towards the familiar partner when subjects were previously exposed to the familiar compared to the stranger whines. Finally, familiar whine stimuli tended to maintain higher cortisol levels while stranger whines did not. To our knowledge, these results are the first to suggest that dogs can experience and demonstrate “empathic-like” responses to conspecifics’ distress-calls. PMID:27124485

Newly designed "pieced" stent in a rabbit model of benign esophageal stricture.

PubMed

Liu, Jin; Shang, Liang; Liu, Ji-Yong; Qin, Cheng-Yong

2015-07-28

To investigate a newly designed stent and its dilatation effect in a rabbit model of benign esophageal stricture. Thirty-four New Zealand white rabbits underwent a corrosive injury in the middle esophagus for esophageal stricture formation. Thirty rabbits with a successful formation of esophageal strictures were randomly allocated into two groups. The control group (n = 15) was implanted with a conventional stent, and the study group (n = 15) was implanted with a detachable "pieced" stent. The study stent (30 mm in length, 10 mm in diameter) was composed of three covered metallic pieces connected by surgical suture lines. The stent was collapsed by pulling the suture lines out of the mesh. Two weeks after stricture formation, endoscopic placement of a conventional stent or the new stent was performed. Endoscopic extraction was carried out four weeks later. The extraction rate, ease of extraction, migration, complications, and survival were evaluated. Stent migration occurred in 3/15 (20%) animals in the control group and 2/15 (13%) animals in the study group; the difference between the two groups was not statistically significant. At the end of four weeks, the remaining stents were successfully extracted with the endoscope in 100% (11/11) of the animals in the study group, and 60% (6/10) of the animals in the control group; this difference was statistically significant (P < 0.05). There was no difference in the mean number of follow-up days between the control and study groups (25.33 vs 25.85). Minor bleeding was reported in five cases in the study group and four in the control group. There were no severe complications directly associated with stent implantation or extraction in either of the two groups. In this experimental protocol of benign esophageal strictures, the novel "pieced" stent demonstrated a superior removal rate with a similar migration rate compared to a conventional stent.

Adverse metabolic effects of a hypercaloric, high-fat diet in rodents precede observable changes in body weight.

PubMed

McDonald, Sarah D; Pesarchuk, Eric; Don-Wauchope, Andrew; El Zimaity, Hala; Holloway, Alison C

2011-09-01

Although a high-fat diet (HFD) is recognized as an important contributor to obesity, human research is limited by confounders such as income, whereas animal research has typically examined diet during specific developmental periods rather than throughout the lifespan. We hypothesized that the use of an HFD in short-term studies as has been commonly done in animals does not adequately reflect the lifelong dietary patterns seen frequently in humans with consequent metabolic disturbances. We examined the impact of HFD from weaning until 39 weeks (middle age) on the metabolism of male rats. At 7, 26, and 39 weeks, glucose tolerance tests were performed, a subset of animals was euthanized, and serum and tissues were collected. After 4 weeks, preceding increased body weight, HFD animals had increased intra-abdominal fat, triglycerides, and hyperglycemia. Hyperinsulinemia was insufficient to maintain normoglycemia, and beta cell mass and glucagon-like peptide 1 decreased over time in HFD and control animals. Despite lacking significant lipid abnormalities, nonalcoholic fatty liver disease was evident by 39 weeks. Our HFD model demonstrated that significant metabolic abnormalities may go undetected by current standard screening such as weighing and biochemistry. Copyright © 2011 Elsevier Inc. All rights reserved.

Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint

PubMed Central

Zopf, David A.; Flanagan, Colleen L.; Wheeler, Matthew; Hollister, Scott J.; Green, Glenn E.

2015-01-01

Importance The study demonstrates an application for 3-dimensional (3D) printing that may serve as an effective intervention for severe tracheobronchomalacia. Objective A novel 3D printed, bioresorbable airway splint is tested for efficacy in extending survival in an animal model of severe, life-threatening tracheobronchomalacia. Participants Evaluation of an external airway splint for severe, life-threatening tracheobronchomalacia in a porcine animal model. Setting Multi-institutional and multidisciplinary collaboration between biomedical engineering laboratories and an academic animal surgery center. Interventions Experimental analysis of a 3D printed, bioresorbable airway splint is assessed in a porcine animal model of life-threatening tracheobronchomalacia. The open-cylindrical, bellow shaped porous polycaprolactone splint is placed externally and designed to suspend the underlying collapsed airway. Control animals (n=3) undergoing tracheal cartilage division and inner tracheal lumen dissociation and experimental animals (n=3) receiving the same model with overlying placement of the newly developed airway splint were evaluated. Main Outcomes and Measures An animal model for severe, life-threatening tracheobronchomalacia is proposed. Complete or near complete tracheal lumen collapse was observed in each animal with resolution of symptoms in all of the experimental animals after splint placement. Using our severe tracheobronchomalacia animal model, survival was significantly longer in duration in the experimental group receiving the airway splint after model creation when compared to model creation alone (p = 0.0495). Mortality in the experimental group was related to infection. Conclusions A multidisciplinary effort producing a CAD/CAM, bioresorbable tracheobronchial splint was tested in a porcine model of severe tracheomalacia and was found to extend survival. PMID:24232078

The Analysis of a Diet for the Human Being and the Companion Animal using Big Data in 2016

PubMed Central

Kang, Hye Won

2017-01-01

The purpose of this study was to investigate the diet tendencies of human and companion animals using big data analysis. The keyword data of human diet and companion animals' diet were collected from the portal site Naver from January 1, 2016 until December 31, 2016 and collected data were analyzed by simple frequency analysis, N-gram analysis, keyword network analysis and seasonality analysis. In terms of human, the word exercise had the highest frequency through simple frequency analysis, whereas diet menu most frequently appeared in the N-gram analysis. companion animals, the term dog had the highest frequency in simple frequency analysis, whereas diet method was most frequent through N-gram analysis. Keyword network analysis for human indicated 4 groups: diet group, exercise group, commercial diet food group, and commercial diet program group. However, the keyword network analysis for companion animals indicated 3 groups: diet group, exercise group, and professional medical help group. The analysis of seasonality showed that the interest in diet for both human and companion animals increased steadily since February of 2016 and reached its peak in July. In conclusion, diets of human and companion animals showed similar tendencies, particularly having higher preference for dietary control over other methods. The diets of companion animals are determined by the choice of their owners as effective diet method for owners are usually applied to the companion animals. Therefore, it is necessary to have empirical demonstration of whether correlation of obesity between human being and the companion animals exist. PMID:29124046

The Analysis of a Diet for the Human Being and the Companion Animal using Big Data in 2016.

PubMed

Jung, Eun-Jin; Kim, Young-Suk; Choi, Jung-Wa; Kang, Hye Won; Chang, Un-Jae

2017-10-01

The purpose of this study was to investigate the diet tendencies of human and companion animals using big data analysis. The keyword data of human diet and companion animals' diet were collected from the portal site Naver from January 1, 2016 until December 31, 2016 and collected data were analyzed by simple frequency analysis, N-gram analysis, keyword network analysis and seasonality analysis. In terms of human, the word exercise had the highest frequency through simple frequency analysis, whereas diet menu most frequently appeared in the N-gram analysis. companion animals, the term dog had the highest frequency in simple frequency analysis, whereas diet method was most frequent through N-gram analysis. Keyword network analysis for human indicated 4 groups: diet group, exercise group, commercial diet food group, and commercial diet program group. However, the keyword network analysis for companion animals indicated 3 groups: diet group, exercise group, and professional medical help group. The analysis of seasonality showed that the interest in diet for both human and companion animals increased steadily since February of 2016 and reached its peak in July. In conclusion, diets of human and companion animals showed similar tendencies, particularly having higher preference for dietary control over other methods. The diets of companion animals are determined by the choice of their owners as effective diet method for owners are usually applied to the companion animals. Therefore, it is necessary to have empirical demonstration of whether correlation of obesity between human being and the companion animals exist.

Does cross-fostering modify the prenatal effect of methamphetamine on learning of adult male rats?

PubMed

Hrubá, L; Schutová, B; Pometlová, M; Slamberová, R

2009-01-01

Our previous studies demonstrated that methamphetamine administered during gestation and lactation periods impairs maternal behavior, alters the functional development of rat pups and affects behavior in adulthood. The aim of our study was to investigate the effect of prenatal methamphetamine exposure and cross-fostering on learning tested in Morris water maze (MWM) in adult male rats. Mothers were daily exposed to injection of methamphetamine (MA) (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups of mother with the opposite treatment. Based on the prenatal and postnatal treatments 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in MWM. Two types of tests were used: (1) "Place navigation test" (Learning) and (2) "Probe test" (Probe). In the test of learning, all animals fostered by methamphetamine-treated dams had longer latencies and trajectories, and bigger search error than the animals fostered by saline-treated control mother, regardless of prenatal exposure. Further, the animals prenatally exposed to methamphetamine swam slower than the animals prenatally exposed to saline, regardless of postnatal exposure in the test of learning and in the Probe test. Our results showed that neither prenatal nor postnatal methamphetamine exposure affected the Probe test. Our results showed that prenatal exposure to methamphetamine at dose of 5 mg/kg does not impair learning in the MWM, while postnatal exposure to methamphetamine from mothers' breastmilk and maternal care of mother exposed to methamphetamine impairs learning of adult male rats. On the other hand, the maternal care of control mothers does not impair learning of rat pups prenatally exposed to methamphetamine. The present study demonstrates that cross-fostering may affect learning in adulthood.

Evaluation of Biochemical, Hematological and Parasitological Parameters of Protein-Deficient Hamsters Infected with Ancylostoma ceylanicum

PubMed Central

Pacanaro, Carina P.; Dias, Sílvia R.; Serafim, Luciana R.; Costa, Mariana P.; Aguilar, Edenil; Paes, Paulo R.; Alvarez-Leite, Jacqueline I.; Rabelo, Élida M.

2014-01-01

Background Hookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model. Methodology/Principal Findings Hamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as “malnourished”) and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool. Conclusions In this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection. PMID:25254370

Evaluation of the reversal of multidrug resistance by MDR1 ribonucleic acid interference in a human colon cancer model using a Renilla luciferase reporter gene and coelenterazine.

PubMed

Jeon, Yong Hyun; Bae, Seon-ae; Lee, Yong Jin; Lee, You La; Lee, Sang-Woo; Yoon, Ghil-Suk; Ahn, Byeong-Cheol; Ha, Jeoung-Hee; Lee, Jaetae

2010-12-01

The reversal effect of multidrug resistance (MDR1) gene expression by adenoviral vector-mediated MDR1 ribonucleic acid interference was assessed in a human colon cancer animal model using bioluminescent imaging with Renilla luciferase (Rluc) gene and coelenterazine, a substrate for Rluc or MDR1 gene expression. A fluorescent microscopic examination demonstrated an increased green fluorescent protein signal in Ad-shMDR1- (recombinant adenovirus that coexpressed MDR1 small hairpin ribonucleic acid [shRNA] and green fluorescent protein) infected HCT-15/Rluc cells in a virus dose-dependent manner. Concurrently, with an increasing administered virus dose (0, 15, 30, 60, and 120 multiplicity of infection), Rluc activity was significantly increased in Ad-shMDR1-infected HCT-15/Rluc cells in a virus dose-dependent manner. In vivo bioluminescent imaging showed about 7.5-fold higher signal intensity in Ad-shMDR1-infected tumors than in control tumors (p < .05). Immunohistologic analysis demonstrated marked reduction of P-glycoprotein expression in infected tumor but not in control tumor. In conclusion, the reversal of MDR1 gene expression by MDR1 shRNA was successfully evaluated by bioluminescence imaging with Rluc activity using an in vivo animal model with a multidrug resistance cancer xenograft.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

PubMed

Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

2017-03-30

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

Seasonal effects of heat shock on bacterial populations, including artificial Vibrio parahaemolyticus exposure, in the Pacific oyster, Crassostrea gigas.

PubMed

Aagesen, Alisha M; Häse, Claudia C

2014-04-01

During the warmer summer months, oysters are conditioned to spawn, resulting in massive physiological efforts for gamete production. Moreover, the higher temperatures during the summer typically result in increased bacteria populations in oysters. We hypothesized that these animals are under multiple stresses that lead to possible immune system impairments during the summer months that can possibly lead to death. Here we show that in the summer and the fall animals exposed to a short heat stress respond similarly, resulting in a general trend of more bacteria being found in heat shocked animals than their non-heat shocked counterparts. We also show that naturally occurring bacterial populations are effected by a heat shock. In addition, oysters artificially contaminated with Vibrio parahaemolyticus were also affected by a heat shock. Heat shocked animals contained higher concentrations of V. parahaemolyticus in their tissues and hemolymph than control animals and this was consistent for animals examined during summer and fall. Finally, oyster hemocyte interactions with V. parahaemolyticus differed based on the time of the year. Overall, these findings demonstrate that seasonal changes and/or a short heat shock is sufficient to impact bacterial retention, particularly V. parahaemolyticus, in oysters and this line of research might lead to important considerations for animal harvesting procedures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Examination of epithelial tissue cytokine response to natural peste des petits ruminants virus (PPRV) infection in sheep and goats by immunohistochemistry.

PubMed

Atmaca, H T; Kul, O

2012-01-01

In this study, we aimed to evaluate expression of IL-4, IL-10, TNF-α, IFN-γ and iNOS in lingual, buccal mucosa and lung epithelial tissue using immunoperoxidase technique and to compare with the tissues of control animals. The tissues used in the study were collected from 17 PPRV-affected and 5 healthy sheep and goats. In PPRV positive animals, the lungs, lingual and buccal mucosa had significantly higher iNOS, IFN-γ and TNF-α expressions compared to control group animals. There was no significant difference between PPRV positive and control groups for IL-4 and IL-10 expressions of epithelial tissues. In conclusion, the epithelial tissues infected by PPRV showed significant iNOS, IFN-γ and TNF-α expressions and they might play an important role in the initiation and regulation of cytokine response, as they take place in the first host barrier to be in contact with PPRV. It is suggested that the more epithelial damage produced by PPRV the more cytokine response may result in the infected epithelial cells. The first demonstration of iNOS expression and epithelial cytokine response to PPRV in natural cases is important because it may contribute to an early initiation of systemic immunity against PPRV infection, in addition to direct elimination of the virus during the initial epithelial phase of the infection.

Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13)C]pyruvate.

PubMed

Josan, Sonal; Billingsley, Kelvin; Orduna, Juan; Park, Jae Mo; Luong, Richard; Yu, Liqing; Hurd, Ralph; Pfefferbaum, Adolf; Spielman, Daniel; Mayer, Dirk

2015-12-01

To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13)C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13)C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13)C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

A novel conduit-based coaptation device for primary nerve repair.

PubMed

Bamba, Ravinder; Riley, D Colton; Kelm, Nathaniel D; Cardwell, Nancy; Pollins, Alonda C; Afshari, Ashkan; Nguyen, Lyly; Dortch, Richard D; Thayer, Wesley P

2018-06-01

Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device. The conduit-based device group was compared to a control group of rats that underwent a standard end-to-end microsurgical repair of the sciatic nerve. Animals underwent behavioral assessments at weekly intervals post-operatively using the sciatic functional index (SFI) test. Animals were sacrificed at four weeks to obtain motor axon counts from immunohistochemistry. A sub-group of animals were sacrificed immediately post repair to obtain MRI images. SFI scores were superior in rats which received conduit-based repairs compared to the control group. Motor axon counts distal to the injury in the device group at four weeks were statistically superior to the control group. MRI tractography was used to demonstrate repair of two nerves using the novel conduit device. A conduit-based nerve coaptation device avoids sutures at the nerve repair site and leads to improved outcomes in a rat model. Conduit-based nerve repair devices have the potential to standardize nerve repairs while improving outcomes.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus

PubMed Central

Zawaski, Janice A.; Sahnoune, Iman

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT. PMID:27242931

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

PubMed

Rodgers, Shaefali P; Zawaski, Janice A; Sahnoune, Iman; Leasure, J Leigh; Gaber, M Waleed

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

PubMed

Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

2013-06-01

This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.

PubMed

Xu, Huanbin; Andersson, Anne-Marie; Ragonnaud, Emeline; Boilesen, Ditte; Tolver, Anders; Jensen, Benjamin Anderschou Holbech; Blanchard, James L; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Veazey, Ronald S; Holst, Peter Johannes

2017-04-01

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[General characteristics of an experiment to study the ontogeny of rats on board the Kosmos-1514 biosatellite].

PubMed

Serova, L V; Denisova, L A; Apanasenko, Z I; Briantseva, L A; Chel'naia, N A

1985-01-01

Ten female Wistar rats were exposed to zero-g during 5 days, i. e., from gestation day 13 to day 18. After recovery the flight animals showed a significant delay in weight gain, thymus involution, decreased liver weight, hemoglobin concentration. Nevertheless, their reproductive function did not differ from that of the controls: the rate of preimplantation and total fetal mortality as well as the number of live fetuses were very similar in the experimental and control animals. The flight group showed a slight decline of fetal weight and water content. The size of the litters produced by the flight and control rats was identical but the mortality rate of those former during the first 7 days after birth was significantly higher. This experiment has demonstrated that the mammalian fetus exposed to zero-g during the last term of pregnancy, i. e., at the stage of active organogenesis, can grow and develop in the normal way. A large body of biological material has been obtained for biochemical and histological examinations that will help evaluate the condition of dams, fetuses, and newborns.

Energy restriction and the prevention of breast cancer.

PubMed

Harvie, Michelle; Howell, Anthony

2012-05-01

Energy restriction (ER) to control weight is a potential strategy for breast cancer prevention. The protective effects of habitual continuous energy restriction (CER) and weight loss on breast tumour formation have been conclusively demonstrated in animal studies over the past 100 years, and more recently in women using data from observational studies and bariatric surgery. Intermittent energy restriction (IER) and intermittent fasting (IF) are possible alternative preventative approaches which may be easier for individuals to undertake and possibly more effective than standard CER. Here, we summarise the available data on CER, IER and IF with special emphasis on their potential for breast cancer prevention. In animals, IER is superior or equivalent to CER with the exception of carcinogen-induced tumour models when initiated soon after carcinogen exposure. There are no human data on IER and breast cancer risk, but three studies demonstrated IER and CER to be equivalent for weight loss. IF regimens also reduce mammary tumour formation in animal models and also led to weight loss in human subjects, but have not been directly compared with CER. Animal and some human data suggest that both IER and IF may differ mechanistically compared with CER and may bring about greater reduction in hepatic and visceral fat stores, insulin-like growth factor 1 (IGF-1) levels and cell proliferation, and increased insulin sensitivity and adiponectin levels. Although IER and IF were first studied 65 years ago, we conclude that further studies are required to assess their values compared with CER.

Viral Infection-Homograft Interactions in a Murine Model

PubMed Central

Hamilton, John D.; Fitzwilliam, James F.; Cheung, K. S.; Shelburne, John; Lang, David J.; Amos, D. B.

1978-01-01

The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL4, a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities. Limited studies demonstrated no effect of EL4 inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL4 was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL4 was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL4. PMID:219027

Traumatic Neuroma in Continuity Injury Model in Rodents

PubMed Central

Kemp, Stephen William Peter; Khu, Kathleen Joy Ong Lopez; Kumar, Ranjan; Webb, Aubrey A.; Midha, Rajiv

2012-01-01

Abstract Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. Optimal experimental injuries that consistently resulted in NIC combined both intense focal compression and traction forces. Nerves were harvested at 0, 5, 13, 21, and 65 days for histological examination. Skilled locomotion and ground reaction force (GRF) analysis were performed up to 9 weeks on the experimental (n=6) and crush-control injuries (n=5). Focal widening, disruption of endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated in 14 of 14 nerves with refined experimental injuries. At 8 weeks, experimental animals displayed a significantly greater slip ratio in both skilled locomotor assessments, compared to nerve crush animals (p<0.01). GRFs of the crush- injured animals showed earlier improvement compared to the experimental animals, whose overall GRF patterns failed to recover as well as the crush group. We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes. PMID:22011082

Action Enhances Acoustic Cues for 3-D Target Localization by Echolocating Bats

PubMed Central

Wohlgemuth, Melville J.

2016-01-01

Under natural conditions, animals encounter a barrage of sensory information from which they must select and interpret biologically relevant signals. Active sensing can facilitate this process by engaging motor systems in the sampling of sensory information. The echolocating bat serves as an excellent model to investigate the coupling between action and sensing because it adaptively controls both the acoustic signals used to probe the environment and movements to receive echoes at the auditory periphery. We report here that the echolocating bat controls the features of its sonar vocalizations in tandem with the positioning of the outer ears to maximize acoustic cues for target detection and localization. The bat’s adaptive control of sonar vocalizations and ear positioning occurs on a millisecond timescale to capture spatial information from arriving echoes, as well as on a longer timescale to track target movement. Our results demonstrate that purposeful control over sonar sound production and reception can serve to improve acoustic cues for localization tasks. This finding also highlights the general importance of movement to sensory processing across animal species. Finally, our discoveries point to important parallels between spatial perception by echolocation and vision. PMID:27608186

Compendium of animal rabies prevention and control, 2011.

PubMed

2011-11-04

Rabies has one of the highest case-fatality ratios of any infectious disease. This report provides recommendations for public health officials, veterinarians, animal control officials, and other parties engaged in rabies prevention and control activities and should serve as the basis for standardizing procedures among jurisdictions. The recommendations regarding domestic animal vaccination, management of animals exposed to rabies, and management of animals that bite humans are the core elements of animal rabies control and human rabies prevention. These updated 2011 guidelines include the national case definition for animal rabies and clarify the role of the CDC rabies laboratory in providing confirmatory testing of suspect animals. The table of rabies vaccines licensed and marketed in the United States has been updated, and additional references have been included to provide scientific support for information in this report.

40 CFR 799.9539 - TSCA mammalian erythrocyte micronucleus test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... randomly assigned to the control and treatment groups. The animals are identified uniquely. The animals are... substance, animals in the control groups should be handled in an identical manner to animals of the treatment groups. (2) Positive controls shall produce micronuclei in vivo at exposure levels expected to...

40 CFR 799.9539 - TSCA mammalian erythrocyte micronucleus test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... randomly assigned to the control and treatment groups. The animals are identified uniquely. The animals are... substance, animals in the control groups should be handled in an identical manner to animals of the treatment groups. (2) Positive controls shall produce micronuclei in vivo at exposure levels expected to...

40 CFR 799.9539 - TSCA mammalian erythrocyte micronucleus test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... randomly assigned to the control and treatment groups. The animals are identified uniquely. The animals are... substance, animals in the control groups should be handled in an identical manner to animals of the treatment groups. (2) Positive controls shall produce micronuclei in vivo at exposure levels expected to...

Criteria to distinguish between natural situations and illegal use of boldenone, boldenone esters and boldione in cattle 1. Metabolite profiles of boldenone, boldenone esters and boldione in cattle urine.

PubMed

Le Bizec, Bruno; Courant, Frédérique; Gaudin, Isabelle; Bichon, Emanuelle; Destrez, Blandine; Schilt, Robert; Draisci, Rosa; Monteau, Fabrice; André, François

2006-12-01

Boldenone is an androgenic steroid that improves the growth and food conversion in food producing animals. In most countries worldwide, this anabolic steroid is forbidden for meat production. Until recently, the control of its illegal use was based either on 17beta-boldenone or 17alpha-boldenone (its main metabolite in cattle) identification in edible tissues, hair, faeces or urine. Recent observations and data tend to demonstrate the natural occurrence (but not ubiquitous) in cattle of these steroids, making the analytical strategy of the control more complicated. We investigated the metabolism of boldenone in cattle after intramuscular and oral treatment of boldenone, boldenone esters and boldione. The central objective was to elucidate the structures of the main metabolites (phase I and phase II) in urine, with main objective to be further in position to compare boldenone urinary profiles of treated and non-treated animals. Nine metabolites have been identified, only four were present whatever the treatment and the administered boldenone source. Nevertheless, all of them have been detected at least once in non-treated animals which did not permit us to use them as biomarkers of an illegal treatment. At last, but not at least, all metabolites were found mainly glucuro-conjugated, and rarely sulfo-conjugated, with the only exception of 17beta-boldenone. Current investigations are showing the absence of 17beta-boldenone sulfoconjugate in non-treated animals; that would permit to distinguish non-treated from treated animals with boldione, boldenone and boldenone esters.

Neuroprotective effects of Quercetin on radiation-induced brain injury in rats.

PubMed

Kale, Aydemir; Piskin, Özcan; Bas, Yilmaz; Aydin, Bengü Gülhan; Can, Murat; Elmas, Özlem; Büyükuysal, Çagatay

2018-04-24

Extensive research has been focused on radiation-induced brain injury. Animal and human studies have shown that flavonoids have remarkable toxicological profiles. This study aims to investigate the neuroprotective effects of quercetin in an experimental radiation-induced brain injury. A total of 32 adult male Wistar-Albino rats were randomly divided into four groups (control, quercetin, radiation, and radiation+quercetin groups, with eight rats in each group). Doses (50 mg/kg) of quercetin were administered to the animals in the quercetin and radiation+quercetin groups; radiation and radiation+quercetin groups were exposed to a dose of 20 Gy to the cranium region. Tissue samples, and biochemical levels of tissue injury markers in the four groups were compared. In all measured parameters of oxidative stress, administration of quercetin significantly demonstrated favorable effects. Both plasma and tissue levels of malondialdehyde and total antioxidant status significantly changed in favor of antioxidant activity. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after quercetin administration. Quercetin demonstrated significant neuroprotection after radiation-induced brain injury. Further studies of neurological outcomes under different experimental settings are required in order to achieve conclusive results.

Chronic ovine evaluation of a totally implantable electrical left ventricular assist system.

PubMed

Ramasamy, N; Chen, H; Miller, P J; Jassawalla, J S; Greene, B A; Ocampo, A; Siegel, L C; Oyer, P E; Portner, P M

1989-01-01

The totally implantable Novacor left ventricular assist system (LVAS) comprises a pump/drive unit (VAD), electronic control and power subsystem (ECP), variable volume compensator (VVC), and belt skin transformer (BST). The system is now undergoing chronic in vivo evaluation. Cumulative animal testing of VAD, VVC, and BST subsystems are 12.1, 4.9, and 43 years, respectively. The longest implants were 279 days for the VAD, 767 days for the VVC, and 1,148 days for the BST. A chronic implant of the total system was electively terminated at 260 days. The LVAS was powered via the BST. Continuously monitored hemodynamic and pump parameters have demonstrated normal hemodynamics and LVAS operation. Periodic VVC determinations suggest a 0.8 ml/day diffusive gas loss. Tether-free operation has been demonstrated with an Ag-Zn battery backpack. The animal was healthy and free of infection as indicated by routine hematologic, biochemical and serum enzyme determinations. Hemolysis is minimal (plasma free hemoglobin less than 5 mg%). Pump output ranged from 7 to 8 L/min. Severe valve calcification was the reason for elective termination at 260 days. This preclinical in vivo experience, and in vitro reliability studies, demonstrate efficacy of the total system.

Assessment of the safety of aquatic animal commodities for international trade: the OIE Aquatic Animal Health code.

PubMed

Oidtmann, B; Johnston, C; Klotins, K; Mylrea, G; Van, P T; Cabot, S; Martin, P Rosado; Ababouch, L; Berthe, F

2013-02-01

Trading of aquatic animals and aquatic animal products has become increasingly globalized during the last couple of decades. This commodity trade has increased the risk for the spread of aquatic animal pathogens. The World Organisation for Animal Health (OIE) is recognized as the international standard-setting organization for measures relating to international trade in animals and animal products. In this role, OIE has developed the Aquatic Animal Health Code, which provides health measures to be used by competent authorities of importing and exporting countries to avoid the transfer of agents pathogenic for animals or humans, whilst avoiding unjustified sanitary barriers. An OIE ad hoc group developed criteria for assessing the safety of aquatic animals or aquatic animal products for any purpose from a country, zone or compartment not declared free from a given disease 'X'. The criteria were based on the absence of the pathogenic agent in the traded commodity or inactivation of the pathogenic agent by the commercial processing used to produce the commodity. The group also developed criteria to assess the safety of aquatic animals or aquatic animal products for retail trade for human consumption from potentially infected areas. Such commodities were assessed considering the form and presentation of the product, the expected volume of waste tissues generated by the consumer and the likely presence of viable pathogenic agent in the waste. The ad hoc group applied the criteria to commodities listed in the individual disease chapters of the Aquatic Animal Health Code (2008 edition). Revised lists of commodities for which no additional measures should be required by the importing countries regardless of the status for disease X of the exporting country were developed and adopted by the OIE World Assembly of Delegates in May 2011. The rationale of the criteria and their application will be explained and demonstrated using examples. © 2012 Crown Copyright. Reproduced with the permission of the Controller of Her Majesty’s Stationery Office and Cefas, Aquatic Animal Disease Group.

3D animation of facial plastic surgery based on computer graphics

NASA Astrophysics Data System (ADS)

Zhang, Zonghua; Zhao, Yan

2013-12-01

More and more people, especial women, are getting desired to be more beautiful than ever. To some extent, it becomes true because the plastic surgery of face was capable in the early 20th and even earlier as doctors just dealing with war injures of face. However, the effect of post-operation is not always satisfying since no animation could be seen by the patients beforehand. In this paper, by combining plastic surgery of face and computer graphics, a novel method of simulated appearance of post-operation will be given to demonstrate the modified face from different viewpoints. The 3D human face data are obtained by using 3D fringe pattern imaging systems and CT imaging systems and then converted into STL (STereo Lithography) file format. STL file is made up of small 3D triangular primitives. The triangular mesh can be reconstructed by using hash function. Top triangular meshes in depth out of numbers of triangles must be picked up by ray-casting technique. Mesh deformation is based on the front triangular mesh in the process of simulation, which deforms interest area instead of control points. Experiments on face model show that the proposed 3D animation facial plastic surgery can effectively demonstrate the simulated appearance of post-operation.

Efficacy of Four Solanum spp. Extracts in an Animal Model of Cutaneous Leishmaniasis.

PubMed

Cos, Paul; Janssens, Jo; Piñón, Abel; Cuesta-Rubio, Osmany; Yglesias-Rivera, Arianna; Díaz-García, Alexis; Vilegas, Wagner; Monzote, Lianet

2018-06-05

Background: Leishmaniasis is a complex protozoa disease caused by Leishmania genus (Trypanosomatidae family). Currently, there have been renewed interests worldwide in plants as pharmaceutical agents. In this study, the in vivo efficacy of Solanum spp. is assessed in an L. amazonensis BALB/c mice model for experimental cutaneous leishmaniasis. Methods: Animals were infected with 5 × 10⁶ metacyclic promastigotes and 30-day post-infection, a treatment with 30 mg/kg of Solanum extracts or Glucantime ® (GTM) was applied intralesionally every four days to complete 5 doses. Results: Neither death nor loss of weight higher than 10% was observed. All the tested extracts were able to control the infection, compared with the infected and untreated group. Solanum havanense Jacq. extract showed the highest efficacy and was superior ( p < 0.05) to GTM. Solanum myriacanthum Dunal., S. nudum Dunal. and S. seaforthianum Andr. extracts demonstrated a similar effect ( p > 0.05) to GTM. An increase of IFN-γ ( p < 0.05) was displayed only by animals treated with S. nudum compared to the group treated with a vehicle, while no differences ( p > 0.05) were observed for IL-12. Conclusions: In vivo effects of Solanum extracts were demonstrated, suggesting that this genus could be further explored as a new antileishmanial alternative.

Effects of ethanol consumption and alcohol detoxification on the biomechanics and morphology the bone in rat femurs.

PubMed

Garcia, J A D; Souza, A L T; Cruz, L H C; Marques, P P; Camilli, J A; Nakagaki, W R; Esteves, A; Rossi-Junior, W C; Fernandes, G J M; Guerra, F D; Soares, E A

2015-11-01

The objective of this study was to verify the effects of ethanol consumption and alcohol detoxification on the biomechanics, area and thickness of cortical and trabecular bone in rat femur. This was an experimental study in which 18 male Wistar rats were used, with 40 days of age, weighing 179 ± 2.5 g. The rats were divided into three groups (n=06): CT (control), AC (chronic alcoholic), DT (detoxification). After experimental procedures, the animals were euthanized by an overdose of the anesthetic and their femurs were collected for mechanical testing and histological processing. All animals did not present malnutrition or dehydration during experimentation period. Morphometric analysis of cortical and trabecular bones in rat femurs demonstrated that AC animals showed inferior dimensions and alcohol detoxification (DT) allowed an enhancement in area and thickness of cortical and trabecular bone. Material and structural properties data of AC group highlighted the harmful effects of ethanol on bone mechanical properties. The results of this study demonstrated that chronic alcoholic rats (AC) presented major bone damage in all analyzed variables. Those findings suggested that alcohol detoxification is highly suggested in pre-operative planning and this corroborates to the success of bone surgery and bone tissue repair. Thanks to the financial support offered by PROBIC - UNIFENAS.

Structural and functional maturation of rat gastrointestinal barrier with thyroxine

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

Israel, E.J.; Pang, K.Y.; Harmatz, P.R.

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed in rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activitymore » of treated animals (T) was 1.5-2 times less than that of controls (C), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased, while the K/sub a/ remained the same, demonstrating the functional maturation of the MVM. In conclusion, thryoid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.« less

Lipid nanocapsules loaded with rhenium-188 reduce tumor progression in a rat hepatocellular carcinoma model.

PubMed

Vanpouille-Box, Claire; Lacoeuille, Franck; Roux, Jérôme; Aubé, Christophe; Garcion, Emmanuel; Lepareur, Nicolas; Oberti, Frédéric; Bouchet, Francis; Noiret, Nicolas; Garin, Etienne; Benoît, Jean-Pierre; Couturier, Olivier; Hindré, François

2011-03-07

Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.

Electrical Stimulation as a Means for Improving Vision.

PubMed

Sehic, Amer; Guo, Shuai; Cho, Kin-Sang; Corraya, Rima M; Chen, Dong F; Utheim, Tor P

2016-11-01

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum, the Agent of Syphilis

PubMed Central

Silver, Adam C.; Dunne, Dana W.; Zeiss, Caroline J.; Bockenstedt, Linda K.; Radolf, Justin D.; Salazar, Juan C.; Fikrig, Erol

2013-01-01

Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR)-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT) mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes. PMID:23940747

Steady-state balance model to calculate the indoor climate of livestock buildings, demonstrated for finishing pigs

NASA Astrophysics Data System (ADS)

Schauberger, G.; Piringer, M.; Petz, E.

The indoor climate of livestock buildings is of importance for the well-being and health of animals and their production performance (daily weight gain, milk yield etc). By using a steady-state model for the sensible and latent heat fluxes and the CO2 and odour mass flows, the indoor climate of mechanically ventilated livestock buildings can be calculated. These equations depend on the livestock (number of animals and how they are kept), the insulation of the building and the characteristics of the ventilation system (ventilation rate). Since the model can only be applied to animal houses where the ventilation systems are mechanically controlled (this is the case for a majority of finishing pig units), the calculations were done for an example of a finishing pig unit with 1000 animal places. The model presented used 30 min values of the outdoor parameters temperature and humidity, collected over a 2-year period, as input. The projected environment inside the livestock building was compared with recommended values. The duration of condensation on the inside surfaces was also calculated.

E2F function in muscle growth is necessary and sufficient for viability in Drosophila

PubMed Central

Zappia, Maria Paula; Frolov, Maxim V.

2016-01-01

The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

Determination of the hormonal growth promoter 17alpha-methyltestosterone in food-producing animals: bovine hair analysis by HPLC-MS/MS.

PubMed

Regal, P; Nebot, C; Vázquez, B I; Cepeda, A; Fente, C A

2010-01-01

This paper describes the development, validation and application of a confirmatory method to detect 17alpha-methyltestosterone (MT) in bovine hair, to aid in controlling the administration of this growth promoter in meat-producing animals. After cryogenic grinding, MT was removed from the hair matrix using a single step extraction procedure with acetonitrile. Hydroxylamine derivatisation was used to enhance analyte determination with an electrospray ionisation (ESI) source. Determination was carried out using a triple quadrupole liquid chromatography tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode (MRM). The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC and using deuterated testosterone (T-d(3)) as the internal standard. The decision limit (CCalpha) was 0.07 ng g(-1) and the detection capability (CCbeta) was 0.12 ng g(-1). Repeatability was CV% (7%), within-laboratory reproducibility was CV% (11.0%), and trueness was (87%). Applicability of the method was demonstrated in an animal study. Samples obtained from animal experiments were analyzed and the presence of MT was confirmed.

9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 79.7 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Waiver of requirements for scrapie control pilot projects. 79.7 Section 79.7 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

9 CFR 54.9 - Waiver of requirements for scrapie control pilot projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... contains testing or other procedures that indicate that an animal, despite meeting the definition of high... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Waiver of requirements for scrapie control pilot projects. 54.9 Section 54.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

Is Wildlife Fertility Control Always Humane?

PubMed Central

Hampton, Jordan O.; Hyndman, Timothy H.; Barnes, Anne; Collins, Teresa

2015-01-01

Simple Summary There are various fertility control methods (modalities) currently available that aim to reduce the abundance of problematic free-ranging mammalian wildlife. Here, we propose that dissimilarities in the mechanism of action indicate these methods produce great variation in animal welfare outcomes. We present a framework to assist managers in minimising animal welfare risks. Abstract Investigation of fertility control techniques to reduce reproductive rates in wildlife populations has been the source of much research. Techniques targeting wildlife fertility have been diverse. Most research into fertility control methods has focused upon efficacy, with few studies rigorously assessing animal welfare beyond opportunistic anecdote. However, fertility control techniques represent several very different mechanisms of action (modalities), each with their own different animal welfare risks. We provide a review of the mechanisms of action for fertility control methods, and consider the role of manipulation of reproductive hormones (“endocrine suppression”) for the long-term ability of animals to behave normally. We consider the potential welfare costs of animal manipulation techniques that are required to administer fertility treatments, including capture, restraint, surgery and drug delivery, and the requirement for repeated administration within the lifetime of an animal. We challenge the assumption that fertility control modalities generate similar and desirable animal welfare outcomes, and we argue that knowledge of reproductive physiology and behaviour should be more adeptly applied to wild animal management decisions. We encourage wildlife managers to carefully assess long-term behavioural risks, associated animal handling techniques, and the importance of positive welfare states when selecting fertility control methods as a means of population control. PMID:26506395

Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic radiation of resonant radiofrequencies.

PubMed

Avdikos, Antonios; Karkabounas, Spyridon; Metsios, Apostolos; Kostoula, Olga; Havelas, Konstantinos; Binolis, Jayne; Verginadis, Ioannis; Hatziaivazis, George; Simos, Ioannis; Evangelou, Angelos

2007-01-01

In the present study, the effects of a resonant low intensity static electromagnetic field (EMF), causing no thermal effects, on Wistar rats have been investigated. Sarcoma cell lines were isolated from leiomyosarcoma tumors induced in Wistar rats by the subcutaneous (s.c) injection of 3,4-benzopyrene. Furthermore, smooth muscle cells (SMC) were isolated from the aorta of Wistar rats and cultivated. Either leiomyosarcoma cells (LSC) or SMC were used to record a number of characteristic resonant radiofrequencies, in order to determine the specific electromagnetic fingerprint spectrum for each cell line. These spectra were used to compose an appropriate algorithm, which transforms the recorded radiofrequencies to emitted ones. The isolated LSC were cultured and then exposed to a resonant low intensity radiofrequency EMF (RF-EMF), at frequencies between 10 kHz to 120 kHz of the radiowave spectrum. The exposure lasted 45 consecutive minutes daily, for two consecutive days. Three months old female Wistar rats were inoculated with exposed and non-exposed to EMF LSC (4 x 10(6) LCS for animal). Inoculated with non-exposed to EMF cells animals were then randomly separated into three Groups. The first Group was sham exposed to the resonant EMF (control Group-CG), the second Group after the inoculation of LSC and appearance of a palpable tumor mass, was exposed to a non-resonant EMF radiation pattern, for 5 h per day till death of all animals (experimental control Group-ECG). The third Group of animals after inoculation of LSC and the appearance of a palpable tumor mass, was exposed to the resonant EMF radiation for 5 h per day, for a maximum of 60 days (experimental Group-I, EG-I). A fourth Group of animals was inoculated with LSC exposed to EMF irradiation and were not further exposed to irradiation (experimental Group-II, EG-II). Tumor induction was 100% in all Groups studied and all tumors were histologically identified as leiomyosarcomas. In the case of the EG-I, a number of tumors were completely regretted (final tumor induction: 66%). Both Groups of animals inoculated with exposed or non-exposed to the EMF LSC, (EG-I and EG-II, respectively) demonstrated a significant prolongation of the survival time and a lower tumor growth rate, in comparison to the control Group (CG) and the experimental control Group (ECG). However, the survival time of EG-I animals was found to be significantly longer and tumor growth rate significantly lower compared to EG-II animals. In conclusion, our results indicate a specific anticancer effect of resonant EMF irradiation. These results may possibly be attributed to (a) the duration of exposure of LSC and (b) the exposure of the entire animal to this irradiation.

Distributed recurrent neural forward models with synaptic adaptation and CPG-based control for complex behaviors of walking robots

PubMed Central

Dasgupta, Sakyasingha; Goldschmidt, Dennis; Wörgötter, Florentin; Manoonpong, Poramate

2015-01-01

Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain a variety of movements, the neural mechanisms generate movements while making appropriate predictions crucial for achieving adaptation. Such predictions or planning ahead can be achieved by way of internal models that are grounded in the overall behavior of the animal. Inspired by these findings, we present here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures) with the underlying neural mechanisms. The neural mechanisms consist of (1) central pattern generator based control for generating basic rhythmic patterns and coordinated movements, (2) distributed (at each leg) recurrent neural network based adaptive forward models with efference copies as internal models for sensory predictions and instantaneous state estimations, and (3) searching and elevation control for adapting the movement of an individual leg to deal with different environmental conditions. Using simulations we show that this bio-inspired approach with adaptive internal models allows the walking robot to perform complex locomotive behaviors as observed in insects, including walking on undulated terrains, crossing large gaps, leg damage adaptations, as well as climbing over high obstacles. Furthermore, we demonstrate that the newly developed recurrent network based approach to online forward models outperforms the adaptive neuron forward models, which have hitherto been the state of the art, to model a subset of similar walking behaviors in walking robots. PMID:26441629

Stars Can't Spin Out of Control (Artist's Animation)

NASA Technical Reports Server (NTRS)

2006-01-01

[figure removed for brevity, see original site] Click on the image for QuickTime Movie of Stars Can't Spin Out of Control

This artist's animation demonstrates how a dusty planet-forming disk can slow down a whirling young star, essentially saving the star from spinning itself to death. Evidence for this phenomenon comes from NASA's Spitzer Space Telescope.

The movie begins by showing a developing star (red ball). The star is basically a giant ball of gas that is collapsing onto itself. As it shrinks, it spins faster and faster, like a skater folding in his or her arms. The green lines represent magnetic fields.

As gravity continues to pull matter inward, the star spins so fast, it starts to flatten out. The same principle applies to the planet Saturn, whose spin has caused it to be slightly squashed or oblate.

A forming star can theoretically whip around fast enough to overcome gravity and flatten itself into a state where it can no longer become a full-fledged star. But stars don't spin out of control, possibly because swirling disks of dust slow them down. Such disks can be found orbiting young stars, and are filled with dust that might ultimately stick together to form planets.

The second half of the animation demonstrates how a disk is thought to keep its star's speed in check. A developing star is shown twirling inside its disk. As it turns, its magnetic fields pass through the disk and get bogged down like a spoon in molasses. This locks the star's rotation to the slower-turning disk, so the star, while continuing to shrink, does not spin faster.

Spitzer found evidence for star-slowing disks in a survey of nearly 500 forming stars in the Orion nebula. It observed that slowly spinning stars are five times more likely to host disks than rapidly spinning stars.

36 CFR 331.23 - Control of animals.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Control of animals. 331.23..., KENTUCKY AND INDIANA § 331.23 Control of animals. (a) No person shall bring or allow horses, cattle, or.... Unclaimed or unattended animals are subject to immediate impoundment and removal in accordance with State...

36 CFR § 331.23 - Control of animals.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Control of animals. § 331.23... CONSERVATION AREA, KENTUCKY AND INDIANA § 331.23 Control of animals. (a) No person shall bring or allow horses... times. Unclaimed or unattended animals are subject to immediate impoundment and removal in accordance...

36 CFR 331.23 - Control of animals.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Control of animals. 331.23..., KENTUCKY AND INDIANA § 331.23 Control of animals. (a) No person shall bring or allow horses, cattle, or.... Unclaimed or unattended animals are subject to immediate impoundment and removal in accordance with State...

36 CFR 331.23 - Control of animals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Control of animals. 331.23..., KENTUCKY AND INDIANA § 331.23 Control of animals. (a) No person shall bring or allow horses, cattle, or.... Unclaimed or unattended animals are subject to immediate impoundment and removal in accordance with State...

36 CFR 331.23 - Control of animals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Control of animals. 331.23..., KENTUCKY AND INDIANA § 331.23 Control of animals. (a) No person shall bring or allow horses, cattle, or.... Unclaimed or unattended animals are subject to immediate impoundment and removal in accordance with State...

9 CFR 355.16 - Control of flies, rats, mice, etc.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded from...

9 CFR 355.16 - Control of flies, rats, mice, etc.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded from...

9 CFR 355.16 - Control of flies, rats, mice, etc.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded from...

9 CFR 355.16 - Control of flies, rats, mice, etc.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded from...

9 CFR 355.16 - Control of flies, rats, mice, etc.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded from...

9 CFR 355.9 - Numbers granted same ownership or control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Numbers granted same ownership or control. 355.9 Section 355.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....9 Numbers granted same ownership or control. Two or more official plants under the same ownership or...

Reprint of: From the 90׳s to now: A brief historical perspective on more than two decades of estrogen neuroprotection.

PubMed

Engler-Chiurazzi, E B; Singh, M; Simpkins, J W

2016-08-15

Historical perspective abstract:From the 90׳s to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90׳s, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer׳s Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen׳s neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be among these. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats: We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-βE2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions. ChAT activity was decreased in the hippocampus but not the frontal cortex of 5-week OVX animals. E2 replacement resulted in a reversal of this effect. At the 28-week time period, an unexpected decrease in ChAT activity was observed across all treatment groups. Interestingly, E2-pellet animals demonstrated the least severe decline in ChAT. This phenomenon was most evident in the frontal cortex where ChAT decreased by 61 and 56% in INTACT and OVX animals, respectively, whereas the decline in E2-pellet animals was only 16% over the same time period, suggesting a previously unreported cytoprotective effect of E2. Taken together, these findings demonstrate important effects of estrogens on cholinergic neurons and support the potential use of estrogen therapy in treatment of dementias in postmenopausal women. © 1994. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

From the 90's to now: A brief historical perspective on more than two decades of estrogen neuroprotection.

PubMed

Engler-Chiurazzi, E B; Singh, M; Simpkins, J W

2016-02-15

Historical perspective abstract:From the 90's to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90's, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer's Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen's neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be among these. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats: We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-βE2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions. ChAT activity was decreased in the hippocampus but not the frontal cortex of 5-week OVX animals. E2 replacement resulted in a reversal of this effect. At the 28-week time period, an unexpected decrease in ChAT activity was observed across all treatment groups. Interestingly, E2-pellet animals demonstrated the least severe decline in ChAT. This phenomenon was most evident in the frontal cortex where ChAT decreased by 61 and 56% in INTACT and OVX animals, respectively, whereas the decline in E2-pellet animals was only 16% over the same time period, suggesting a previously unreported cytoprotective effect of E2. Taken together, these findings demonstrate important effects of estrogens on cholinergic neurons and support the potential use of estrogen therapy in treatment of dementias in postmenopausal women. © 1994. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of Pictorial Display on Operator Learning and Performance. M.S. Thesis

NASA Technical Reports Server (NTRS)

Miller, R. A.; Messing, L. J.; Jagacinski, R. J.

1984-01-01

The effects of pictorially displayed information on human learning and performance of a simple control task were investigated. The controlled system was a harmonic oscillator and the system response was displayed to subjects as either an animated pendulum or a horizontally moving dot. Results indicated that the pendulum display did not effect performance scores but did significantly effect the learning processes of individual operators. The subjects with the pendulum display demonstrated more vertical internal models early in the experiment and the manner in which their internal models were tuned with practice showed increased variability between subjects.

Effect of Chicken Egg Yolk Antibodies (IgY) against Diarrhea in Domesticated Animals: A Systematic Review and Meta-Analysis

PubMed Central

Diraviyam, Thirumalai; Zhao, Bin; Wang, Yuan; Schade, Ruediger; Michael, Antonysamy; Zhang, Xiaoying

2014-01-01

Background IgY antibodies are serum immunoglobulin in birds, reptiles and amphibians, and are transferred from serum to egg yolk to confer passive immunity to their embryos and offspring. Currently, the oral passive immunization using chicken IgY has been focused as an alternative to antibiotics for the treatment and control of diarrhea in animals and humans. This systematic review was focused to determine the effect of IgY in controlling and preventing diarrhea in domesticated animals including Piglets, Mice, Poultry and Calves. Methods and Results Previous research reports focused on treatment effect of Chicken IgY against diarrhea were retrieved from different electronic data bases (MEDLINE, EMBASE, SPRINGER-LINK, WILEY, AGRICOLA, MEDWELL Journals, Scientific Publish, Chinese articles from Core periodicals in 2012). A total of 61 studies in 4 different animal classes met the inclusion criteria. Data on study characteristics and outcome measures were extracted. The pooled relative risk (RR) of 49 studies of different animals [Piglets – 22; Mice – 14; Poultry – 7 and Calves – 6] in meta-analyses revealed that, IgY significantly reduced the risk of diarrhea in treatment group when compare to the placebo. However, the 95% confidence intervals of the majority of studies in animal class piglets and calves embrace RR of one. The same results were obtained in sub group analyses (treatment regiment – prophylactic or therapeutic; pathogen type – bacterial or viral). Perhaps, this inconsistency in the effect of IgY at the individual study level and overall effect measures could be influenced by the methodological heterogeneity. Conclusion The present systematic review (SR) and meta-analysis demonstrated the beneficial effect of IgY. This supports the opinion that IgY is useful for prophylaxis and treatment. However, more intensive studies using the gold standard animal experiments with the focus to use IgY alone or in combination with other alternative strategies are indispensable. PMID:24846286

DEMONSTRATION IN VITRO OF ANAPHYLACTOID RESPONSE OF THE UTERUS AND ILEUM OF GUINEA PIGS INJECTED WITH TESTIS OR SPERM

PubMed Central

Katsh, Seymour

1958-01-01

Female guinea pigs were injected with the following materials: homogenates of guinea pig testis in saline or in adjuvant; suspensions of washed guinea pig sperm in saline or in adjuvant; homogenates of rabbit testis in adjuvant; guinea pig sperm and rabbit sperm in adjuvant. Control animals were not injected or were injected with adjuvant alone. At various times between 15 and 39 days after injection, the animals were sacrificed. Their ilea and uterine horns were removed and tested in vitro for reaction to washed epididymal sperm of the guinea pig, rabbit, or bull. It was found that the animals which were injected with homologous testis or sperm in adjuvant possessed organs which responded strongly to the challenge with homologous sperm. The response was a contracture which began 10 to 30 seconds after the sperm were injected into the bath and lasted for 5 minutes to 4 hours, the longest period of observation. Responses which lasted for periods of 5 minutes to 30 minutes were obtained with the uteri of the animals injected with guinea pig testis in saline or with guinea pig sperm in saline. Animals which were injected with rabbit testis and adjuvant responded to rabbit sperm, and animals injected with guinea pig sperm and rabbit sperm in adjuvant reacted to both gametes. A large proportion of the control animals possessed organs which reacted weakly to the challenge with homologous sperm. Retesting the organ which had contracted following exposure to sperm indicated that desensitization had occurred. Testing with heterologous sperm indicated a species selectivity. The evidence is interpreted to mean that injections of sperm or testis induce a hypersensitivity which is similar in some respects but differs from true anaphylaxis. The findings are discussed from the point of view of the nature of the response and the implications regarding natural immunity to sperm. PMID:13481258

NASA Rat Acoustic Tolerance Test 1994-1995: 8 kHz, 16 kHz, 32 kHz Experiments

NASA Technical Reports Server (NTRS)

Mele, Gary D.; Holley, Daniel C.; Naidu, Sujata

1996-01-01

Adult male Sprague-Dawley rats were exposed to chronic applied sound (74 to 79 dB, SPL) with octave band center frequencies of either 8, 16 or 32 kHz for up to 60 days. Control cages had ambient sound levels of about 62 dB (SPL). Groups of rats (test vs. control; N=9 per group) were euthanized after 0. 5. 14, 30, and 60 days. On each euthanasia day, objective evaluation of their physiology and behavior was performed using a Stress Assessment Battery (SAB) of measures. In addition, rat hearing was assessed using the brain stem auditory evoked potential (BAER) method after 60 days of exposure. No statistically significant differences in mean daily food use could be attributed to the presence of the applied test sound. Test rats used 5% more water than control rats. In the 8 kHz and 32 kHz tests this amount was statistically significant(P less than .05). This is a minor difference of questionable physiological significance. However, it may be an indication of a small reaction to the constant applied sound. Across all test frequencies, day 5 test rats had 6% larger spleens than control rats. No other body or organ weight differences were found to be statistically significant with respect to the application of sound. This spleen effect may be a transient adaptive process related to adaptation to the constant applied noise. No significant test effect on differential white blood cell counts could be demonstrated. One group demonstrated a low eosinophil count (16 kHz experiment, day 14 test group). However this was highly suspect. Across all test frequencies studied, day 5 test rats had 17% fewer total leukocytes than day 5 control rats. Sound exposed test rats exhibited 44% lower plasma corticosterone concentrations than did control rats. Note that the plasma corticosterone concentration was lower in the sound exposed test animals than the control animals in every instance (frequency exposure and number of days exposed).

Impaired specific immunoreactivity in cows with hepatic lipidosis.

PubMed

Wentink, G H; Rutten, V P; van den Ingh, T S; Hoek, A; Müller, K E; Wensing, T

1997-05-01

In this study, hepatic lipidosis in cows was experimentally induced by offering an energy surplus during the dry period. Liver triacylglycerol (TAG) was 16% in the experimental group. In the control group fed the same diet in restricted quantities, liver TAG was about 7%. The animals of both groups were vaccinated with tetanus vaccine at Day 3 after parturition. It was demonstrated that the cows with high liver TAG percentages had lower humoral and cellular (P < 0.05) immunological responses compared with the animals with low liver TAG levels at Day 14 after vaccination. The results obtained in the high TAG group support the notion that the frequent occurrence of aspecific infections in cows with hepatic lipidosis may be due to impaired immunoreactivity.

Flight of Sharovipteryx mirabilis: the world's first delta-winged glider.

PubMed

Dyke, G J; Nudds, R L; Rayner, J M V

2006-07-01

The 225 million-year-old reptile Sharovipteryx mirabilis was the world's first delta-winged glider; this remarkable animal had a flight surface composed entirely of a hind-limb membrane. We use standard delta-wing aerodynamics to reconstruct the flight of S. mirabilis demonstrating that wing shape could have been controlled simply by protraction of the femora at the knees, and by variation in incidence of a small forelimb canard. Our method has allowed us to address the question of how identifying realistic glide performance can be used to set limits on aerodynamic design in this small animal. Our novel interpretation of the bizarre flight mode of S. mirabilis is the first based directly on interpretation of the fossil itself and the first grounded in aerodynamics.

Use of rhodamine B as a biomarker for oral plague vaccination of prairie dogs.

PubMed

Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E

2011-07-01

Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of <60 days in black-tailed prairie dogs (C. ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

Code of Federal Regulations, 2011 CFR

2011-07-01

... five female and five male animals per experimental and control group shall be used. Thus, 10 animals...) Assignment to groups. Animals shall be randomized and assigned to treatment and control groups. (4) Control groups—(i) Concurrent controls. Concurrent positive and negative (vehicle) controls shall be included in...

40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

Code of Federal Regulations, 2012 CFR

2012-07-01

... five female and five male animals per experimental and control group shall be used. Thus, 10 animals...) Assignment to groups. Animals shall be randomized and assigned to treatment and control groups. (4) Control groups—(i) Concurrent controls. Concurrent positive and negative (vehicle) controls shall be included in...

40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

Code of Federal Regulations, 2014 CFR

2014-07-01

... five female and five male animals per experimental and control group shall be used. Thus, 10 animals...) Assignment to groups. Animals shall be randomized and assigned to treatment and control groups. (4) Control groups—(i) Concurrent controls. Concurrent positive and negative (vehicle) controls shall be included in...

40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

Code of Federal Regulations, 2010 CFR

2010-07-01

... five female and five male animals per experimental and control group shall be used. Thus, 10 animals...) Assignment to groups. Animals shall be randomized and assigned to treatment and control groups. (4) Control groups—(i) Concurrent controls. Concurrent positive and negative (vehicle) controls shall be included in...

40 CFR 798.5395 - In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay.

Code of Federal Regulations, 2013 CFR

2013-07-01

... five female and five male animals per experimental and control group shall be used. Thus, 10 animals...) Assignment to groups. Animals shall be randomized and assigned to treatment and control groups. (4) Control groups—(i) Concurrent controls. Concurrent positive and negative (vehicle) controls shall be included in...

9 CFR 2.8 - Notification of change of name, address, control, or ownership of business.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Notification of change of name, address, control, or ownership of business. 2.8 Section 2.8 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.8...

9 CFR 2.8 - Notification of change of name, address, control, or ownership of business.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Notification of change of name, address, control, or ownership of business. 2.8 Section 2.8 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.8...

9 CFR 2.8 - Notification of change of name, address, control, or ownership of business.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Notification of change of name, address, control, or ownership of business. 2.8 Section 2.8 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.8...

9 CFR 2.8 - Notification of change of name, address, control, or ownership of business.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Notification of change of name, address, control, or ownership of business. 2.8 Section 2.8 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.8...

Role of 3D animation in periodontal patient education: a randomized controlled trial.

PubMed

Cleeren, Gertjan; Quirynen, Marc; Ozcelik, Onur; Teughels, Wim

2014-01-01

This randomized controlled parallel trial investigates the effect of 3D animation on the increase and recall of knowledge on periodontitis by patients with periodontitis. The effects of a 3D animation (3D animation group) were compared with narration and drawing (control group) for periodontal patient education. A total of 68 periodontitis patients were stratified according to educational level and then randomly allocated to control or 3D animation groups. All patients received: (1) a pre-test (baseline knowledge), (2) a patient education video (3D animation or control video), (3) a post-test (knowledge immediately after looking at the video), and (4) a follow-up test (knowledge recall after 2 weeks). Each test contained 10 multiple-choice questions. There was no significant difference in baseline knowledge. Patients receiving the 3D animations had significantly higher scores for both the post-test and the follow-up test, when compared with patients receiving sketch animations. 3D animations are more effective than real-time drawings for periodontal patient education in terms of knowledge recall. 3D animations may be a powerful tool for assisting in the information process. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Models for Trypanosoma evansi (surra), its control and economic impact on small-hold livestock owners in the Philippines.

PubMed

Dobson, R J; Dargantes, A P; Mercado, R T; Reid, S A

2009-08-01

Simple demographic and infectious disease models of buffaloes and other domestic hosts for animal trypanosomosis (surra) caused by Trypanosoma evansi were developed. The animal models contained deterministic and stochastic elements and were linked to simulate the benefit of control regimes for surra in village domestic animal populations in Mindanao, Philippines. The impact of the disease on host fertility and mortality were key factors in determining the economic losses and net-benefit from the control regimes. If using a high (99%) efficacy drug in surra-moderate to high risk areas, then treating all animals twice each year yielded low prevalence in 2 years; targeted treatment of clinically sick animals, constantly monitored (monthly), required 75% fewer treatments but took longer to reach a low prevalence than treating all animals twice each year. At high drug efficacy both of these treatment strategies increased the benefit over untreated animals by 81%. If drug efficacy declined then the benefit obtained from twice yearly treatment of all animals declined rapidly compared with regular monitoring and targeting treatment to clinically sick animals. The current control regimen applied in the Philippines of annual sero-testing for surra and only treating sero-positive animals provided the lowest net-benefit of all the control options simulated and would not be regarded as effective control. The total net-benefit from effective surra control for a typical village in a moderate/high risk area was 7.9 million pesos per annum (US $158,000). The value added to buffaloes, cattle, horses, goats/sheep and pigs as a result of this control was US $88, $84, $151, $7, $114 per animal/year, respectively.

The social and emotional context of childhood and adolescent animal cruelty: is there a link to adult interpersonal crimes?

PubMed

Tallichet, Suzanne E; Hensley, Christopher

2009-10-01

The link between early animal abuse and later violence toward humans may depend on how acts of animal cruelty are experienced by those whose behavior demonstrates this graduation. Unfortunately, the research investigating the social and emotional context for the youthful commission of animal cruelty as it escalates to adult interpersonal violence is relatively nonexistent. Using 112 cases from a larger sample of 261 inmates surveyed at both medium and maximum security prisons in a southern state, the present study examined the effects of age of onset and frequency of animal cruelty, the covertness of animal cruelty, the commission of animal cruelty within a group or in isolation, and empathy for the abused animals. Inmates who had covered up their childhood and adolescent animal cruelty were more likely to have been convicted of repeated acts of interpersonal violence, demonstrating that the role of empathy and individuals present during acts of animal cruelty were less important than concealing those acts.

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

PubMed Central

Hsu, Mayla; Aravantinou, Meropi; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, Jose A.; Zydowsky, Thomas M.

2014-01-01

Abstract Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides. PMID:24117013

A combination microbicide gel protects macaques against vaginal simian human immunodeficiency virus-reverse transcriptase infection, but only partially reduces herpes simplex virus-2 infection after a single high-dose cochallenge.

PubMed

Hsu, Mayla; Aravantinou, Meropi; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa

2014-02-01

Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides.

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma.

PubMed

Fonseca, Begoña; Martínez-Águila, Alejandro; de Lara, María J Pérez; Pintor, Jesús

2017-06-01

Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap 4 A to reduce IOP. The topical application of Ap 4 A when IOP is maximal (9-12 months) reduced IOP 30.6 ± 6.6% in the DBA/2J and 17.9 ± 4.0% in the C57BL/6J mice. Concentration response curves in both animal strains produced similar pD2 values; these being 4.9 ± 0.5 and 5.1 ± 0.4 for the normotensive C57BL/6J and the glaucomatous DBA/2J respectively. Antagonist studies showed differences between the control and the glaucomatous animals. In particular, the main receptor reducing IOP in the control animal was the P2Y 1 receptor and in the glaucomatous model the P2Y 6 , although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap 4 A applied three times a week for 3 months showed a clear stop in the elevation of IOP in the glaucomatous model, thus indicating the possibility of using Ap 4 A as an effective compound for the treatment of glaucoma.

Protective effect of caspase inhibition on compression-induced muscle damage

PubMed Central

Teng, Bee T; Tam, Eric W; Benzie, Iris F; Siu, Parco M

2011-01-01

Abstract There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague–Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mmHg compression was applied to an area of 1.5 cm2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n = 8) or 6 mg kg−1 of caspase inhibitor (z-VAD-fmk; n = 8) prior to the 6 h compression on the two consecutive days. Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure. Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression. PMID:21540338

Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

PubMed

Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

2012-12-01

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

Pilot study of the antifibrotic effects of the multikinase inhibitor pacritinib in a mouse model of liver fibrosis

PubMed Central

Al-Fayoumi, Suliman; Hashiguchi, Taishi; Shirakata, Yuka; Mascarenhas, John; Singer, Jack W

2018-01-01

Background Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK–STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients. In two Phase III clinical trials, pacritinib, however, demonstrated improvements in platelet counts and hemoglobin and reductions in transfusion burden in some patients with baseline cytopenias, suggesting it may improve bone-marrow function. Unlike ruxolitinib, pacritinib suppresses signaling through IRAK1, a key control point for inflammatory and fibrotic signaling. Purpose To investigate potential antifibrotic effects of pacritinib in an animal model of liver fibrosis relevant to the observed course of human disease. Methods Pacritinib, negative control (vehicle), and positive control (the angiotensin 2-receptor antagonist and PPARγ partial agonist telmisartan) were assessed in the murine Stelic animal model, which mimics the clinically observed progression from hepatic steatosis to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Histopathological analysis used hematoxylin and eosin staining. Body and liver weight changes, nonalcoholic fatty-liver disease activity scores, and plasma cytokeratin 18 fragment levels (a biomarker of hepatic necrosis) were measured. Results Pacritinib-treated mice had significantly (P<0.01) reduced fibrotic areas in liver compared to vehicle control and significantly (P<0.05) lower levels of CK18. The antifibrotic effect of pacritinib was comparable to that of telmisartan, but without significant effects on fat accumulation. Conclusion These results, the first to demonstrate hepatic antifibrotic effects for pacritinib in an animal model of liver disease, provide preliminary support for potential clinical applications of pacritinib in fibrotic diseases other than myelofibrosis. PMID:29785143

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

Running has differential effects on NPY, opiates, and cell proliferation in an animal model of depression and controls.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2006-02-01

Physical activity has documented beneficial effect in treatment of depression. Recently, we found an antidepressant-like effect of running in an animal model of depression, the Flinders Sensitive Line (FSL) and demonstrated that it was associated with increased hippocampal cell proliferation. In this study, we analyzed levels of mRNAs encoding the neuropeptide Y (NPY) and the opioid peptides dynorphin and enkephalin in hippocampus and correlated these to cell proliferation in the FSL and in the 'nondepressed' Flinders Resistant Line (FRL) strain, with/without access to running wheels. Running increased NPY mRNA in dentate gyrus and the CA4 region in FSL, but not in FRL rats. NPY mRNA increase was correlated to increased cell proliferation in the subgranular zone of dentate gyrus. Baseline dynorphin and enkephalin mRNA levels in the dentate gyrus were lower in the FSL compared to the FRL strain. Running had no effect on dynorphin and enkephalin mRNAs in the FSL strain but it decreased dynorphin mRNA, and there was a trend to increased enkephalin mRNA in the FRL rats. Thus, it would appear that the CNS effects of running are different in 'depressed' and control animals; modification of NPY, a peptide associated with depression and anxiety, in depressed animals, vs effects on opioids, associated with the reward systems, in healthy controls. Our data support the hypothesis that NPY neurotransmission in hippocampus is malfunctioning in depression and that antidepressive treatment, in this case wheel running, will normalize it. In addition, we also show that the increased NPY after running is correlated to increased cell proliferation, which is associated with an antidepressive-like effect.

Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading

PubMed Central

Siu, Parco M.; Pistilli, Emidio E.; Alway, Stephen E.

2008-01-01

Oxidative stress increases during unloading in muscle from young adult rats. The present study examined the markers of oxidative stress and antioxidant enzyme gene and protein expressions in medial gastrocnemius muscles of aged and young adult (30 and 6 mo of age) Fischer 344 × Brown Norway rats after 14 days of hindlimb suspension. Medial gastrocnemius muscle weight was decreased by ∼30% in young adult and aged rats following suspension. When muscle weight was normalized to animal body weight, it was reduced by 12% and 22% in young adult and aged rats, respectively, after suspension. Comparisons between young adult and aged control animals demonstrated a 25% and 51% decline in muscle mass when expressed as absolute muscle weight and muscle weight normalized to the animal body weight, respectively. H2O2 content was elevated by 43% while Mn superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended muscles compared with control muscles exclusively in the aged animals. Suspended muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE) (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine (76% and 65% increase in young adult and aged rats, respectively), and catalase activity (69% and 43% increase in young adult and aged rats, respectively) relative to control muscles. Changes in oxidative stress markers MDA/4-HAE, H2O2, and MnSOD protein contents in response to hindlimb unloading occurred in an age-dependent manner. These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia-associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading. PMID:18801960

9 CFR 54.21 - Participation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Participation. 54.21 Section 54.21 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES CONTROL OF SCRAPIE Scrapie Flock Certification Program § 54.21 Participation. Any...

9 CFR 56.9 - Claims not allowed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Claims not allowed. 56.9 Section 56.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES CONTROL OF H5/H7 LOW PATHOGENIC AVIAN...

9 CFR 56.9 - Claims not allowed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Claims not allowed. 56.9 Section 56.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES CONTROL OF H5/H7 LOW PATHOGENIC AVIAN...

Body side-specific control of motor activity during turning in a walking animal

PubMed Central

Gruhn, Matthias; Rosenbaum, Philipp; Bockemühl, Till; Büschges, Ansgar

2016-01-01

Animals and humans need to move deftly and flexibly to adapt to environmental demands. Despite a large body of work on the neural control of walking in invertebrates and vertebrates alike, the mechanisms underlying the motor flexibility that is needed to adjust the motor behavior remain largely unknown. Here, we investigated optomotor-induced turning and the neuronal mechanisms underlying the differences between the leg movements of the two body sides in the stick insect Carausius morosus. We present data to show that the generation of turning kinematics in an insect are the combined result of descending unilateral commands that change the leg motor output via task-specific modifications in the processing of local sensory feedback as well as modification of the activity of local central pattern generating networks in a body-side-specific way. To our knowledge, this is the first study to demonstrate the specificity of such modifications in a defined motor task. DOI: http://dx.doi.org/10.7554/eLife.13799.001 PMID:27130731

Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

PubMed

Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

2015-01-01

In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

Bovine leptospirosis in urban and peri-urban dairy farming in low-income countries: a "One Health" issue?

PubMed

Rajala, Elisabeth Lindahl; Sattorov, Nosirjon; Boqvist, Sofia; Magnusson, Ulf

2017-12-12

Global trends in urbanization are increasing the spread of neglected zoonotic infections such as leptospirosis, and reducing the number of human cases of leptospirosis is best accomplished by controlling the infection in the animal reservoir. The aim of this study was to determine the seroprevalence of Leptospira borgpetersenii serovar Hardjo and L. interrogans serovar Hardjo (L. Hardjo) exposure and to assess the associated risk factors for infection in small-scale dairy farming in the urban and peri-urban area of Dushanbe, Tajikistan. The true individual seroprevalence among the dairy cows was 13%, and the level of seroprevalence was positively associated with older cows and with communal grazing practices. The study shows that dairy cows are commonly exposed to L. Hardjo in the study region, and this constitutes a public health risk and demonstrates the importance of including urban and peri-urban areas, where large numbers of humans and animals coexist, when investigating zoonotic infections and when planning and implementing control measures for cattle-associated leptospirosis.

Use of Phage Display technology in development of canine visceral leishmaniasis vaccine using synthetic peptide trapped in sphingomyelin/cholesterol liposomes.

PubMed

Toledo-Machado, Christina Monerat; Bueno, Lilian Lacerda; Menezes-Souza, Daniel; Machado-de-Avila, Ricardo Andrez; Nguyen, Christophe; Granier, Claude; Bartholomeu, Daniella Castanheira; Chávez-Olórtegui, Carlos; Fujiwara, Ricardo Toshio

2015-02-28

Leishmania parasites can cause visceral or cutaneous disease and are found in subtropical and tropical regions of the Old and New World. The pathology of the infection is determined by both host immune factors and species/strain differences of the parasite. Dogs represent the major reservoir of Leishmania infantum (syn. L. chagasi) and vaccines are considered the most cost-effective control tools for canine disease. Selection of immunodominant peptides was performed by Phage Display to identify sequences recognized by L. infantum naturally infected animals. Sera from Leishmania infected animals were used in the biopanning to selection of specific peptides. Serum samples from T. cruzi infected and healthy animals were used as control. After selection, synthetic peptides were produced in membrane (spot-synthesis) in soluble form and blotting and ELISA were performed for validation of serum reactivity. Selected peptide was formulated with aluminum hydroxide and liposomes and immunization was performed in BALB/c mice. Protection was determined by qPCR after challenge infection with virulent L. infantum. We reported the selection of Peptide 5 through Phage Display technique and demonstrate its ability to promote a state of immunity against L. infantum infection in murine model after immunization using liposomes as vaccine carrier. Our results demonstrate that immunization with Peptide 5 when formulated with aluminum hydroxide and liposomes is immunogenic and elicited significant protection associated with the induction of mixed Th1/Th2 immune response against L. infantum infection. Peptide 5 is a promising vaccine candidate and the findings obtained in the present study encourage canine trials to confirm the effectiveness of a vaccine against CVL.

Immunoreactivity of the AAA+ chaperone ClpB from Leptospira interrogans with sera from Leptospira-infected animals.

PubMed

Krajewska, Joanna; Arent, Zbigniew; Więckowski, Daniel; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2016-07-16

Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that L. interrogans ClpB (ClpBLi) is essential for bacterial survival under stressful conditions and also during infection. The aim of this study was to provide further insight into the role of ClpB in L. interrogans and answer the question whether ClpBLi as a potential virulence factor may be a target of the humoral immune response during leptospiral infections in mammals. ClpBLi consists of 860 amino acid residues with a predicted molecular mass of 96.3 kDa and shows multi-domain organization similar to that of the well-characterized ClpB from Escherichia coli. The amino acid sequence identity between ClpBLi and E. coli ClpB is 52 %. The coding sequence of the clpB Li gene was cloned and expressed in E. coli BL21(DE3) strain. Immunoreactivity of the recombinant ClpBLi protein was assessed with the sera collected from Leptospira-infected animals and uninfected healthy controls. Western blotting and ELISA analysis demonstrated that ClpBLi activates the host immune system, as evidenced by an increased level of antibodies against ClpBLi in the sera from infected animals, as compared to the control group. Additionally, ClpBLi was found in kidney tissues of Leptospira-infected hamsters. ClpBLi is both synthesized and immunogenic during the infectious process, further supporting its involvement in the pathogenicity of Leptospira. In addition, the immunological properties of ClpBLi point to its potential value as a diagnostic antigen for the detection of leptospirosis.

Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71.

PubMed

Zhang, Fei; Zhao, Qin; Quan, Keji; Zhu, Zhuang; Yang, Yusheng; Wen, Xintian; Chang, Yung-Fu; Huang, Xiaobo; Wu, Rui; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping; Han, Xinfeng; Cao, Sanjie

2018-01-01

GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.

The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats

PubMed Central

2013-01-01

Background Otomycosis is defined as an infection of the external ear canal with fungal agents. The treatment of the disease is cleansing and drying of the external ear canal, identification and treatment of any predisposing factors and application of topical antifungal agents. Terbinafine is used as an antifungal agent to treat otomycosis. We proposed to investigate the probable ototoxic effect of terbinafine solution on auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) when applied intratympanically in the middle ear of rats. Methods The experiment was performed on 30 female Wistar albino rats. Thirty animals were divided into three groups of 10 animals each. 1% terbinafine solution was administered to the first group (group T). The second group (group G) was administered 40 mg/ml gentamicin solution (ototoxic control). The third group (group S) was administered saline solution (negative control). Baseline DPOAE measurements and ABR testing from the left ears were obtained from the animals in all groups under general anesthesia. Ear solutions were applied in the middle ear intratympanically with a dental needle. Treatment was initiated after baseline measurements and repeated once every two days for fifteen days. Results Pre and post-treatment DPOAE responses for all tested frequencies of group T and Group S showed no statistically significant difference. However, the group G demonstrated a significant change in ABR thresholds and DPOAE responses. Conclusions Terbinafine solution is a broad spectrum antifungal agent effective in the treatment of otomycosis. The present study demonstrated that its direct administration in the middle ear of rats does not affect inner ear function as measured by ABR and DPOAE responses. PMID:23663536

Morphologic and Histologic Comparison of Hypertrophic Scar in Nude Mice, T-Cell Receptor, and Recombination Activating Gene Knockout Mice.

PubMed

Momtazi, Moein; Ding, Jie; Kwan, Peter; Anderson, Colin C; Honardoust, Dariush; Goekjian, Serge; Tredget, Edward E

2015-12-01

Proliferative scars in nude mice have demonstrated morphologic and histologic similarities to human hypertrophic scar. Gene knockout technology provides the opportunity to study the effect of deleting immune cells in various disease processes. The authors' objective was to test whether grafting human skin onto T-cell receptor (TCR) αβ-/-γδ-/-, recombination activating gene (RAG)-1-/-, and RAG-2γ-/-c-/- mice results in proliferative scars consistent with human hypertrophic scar and to characterize the morphologic, histologic, and cellular changes that occur after removing immune cells. Nude TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice (n = 20 per strain) were grafted with human skin and euthanized at 30, 60, 120, and 180 days. Controls (n = 5 per strain) were autografted with mouse skin. Scars and normal skin were harvested at each time point. Sections were stained with hematoxylin and eosin, Masson's trichrome, and immunohistochemistry for anti-human leukocyte antigen-ABC, α-smooth muscle actin, decorin, and biglycan. TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice grafted with human skin developed firm, elevated scars with histologic and immunohistochemical similarities to human hypertrophic scar. Autografted controls showed no evidence of pathologic scarring. Knockout animals demonstrated a capacity for scar remodeling not observed in nude mice where reductions in α-smooth muscle actin staining pattern and scar thickness occurred over time. Human skin transplanted onto TCRαβ-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice results in proliferative scars with morphologic and histologic features of human hypertrophic scar. Remodeling of proliferative scars generated in knockout animals is analogous to changes in human hypertrophic scar. These animal models may better represent the natural history of human hypertrophic scar.

Endoscopic closure of duodenal perforations by using an over-the-scope clip: a randomized, controlled porcine study.

PubMed

von Renteln, Daniel; Rudolph, Hans-Ulrich; Schmidt, Arthur; Vassiliou, Melina C; Caca, Karel

2010-01-01

Duodenal perforations during diagnostic upper endoscopy are rare; however, when therapeutic techniques are performed, the reported incidence is as great as 2.8%. Surgical repair is usually mandated, but it is associated with significant morbidity and mortality. To compare closure of duodenal perforations by using an over-the-scope clip (OTSC) with a surgical closure. Randomized, controlled animal study. Animal facility laboratory. Domestic pigs (24 females). Large (10-mm) duodenal perforations were created by using an endoscopic needle-knife. The animals were randomly assigned to either open surgical repair (n=12) or endoscopic closure by using the OTSC system (n=12). Pressurized leak tests were performed during necropsy. One major bleed occurred because of a liver injury during creation of the duodenotomy. Mean time for endoscopic closure was 5 minutes (range, 3-8 min; SD +/- 2). No complications occurred during any of the closure procedures. At necropsy, all OTSC and surgical closures demonstrated complete sealing of duodenotomy sites. Pressurized leak tests demonstrated a mean burst pressure of 166 mm Hg (range, 80-260; SD +/- 65) for OTSC closures and 143 mm Hg (range, 30-300, SD +/- 83) for surgical sutures. Ex vivo intact duodenal specimens exhibited a mean burst pressure of 247 mm Hg (range, 200-300; SD +/- 35), which was significantly higher compared with in vivo OTSC and surgical closures (P < .01). There were no significant differences between burst pressures of OTSC and surgical closures (P = .461). Nonsurvival setting. Endoscopic closure of duodenal perforations by using the OTSC system is comparable with surgical closure in a nonsurvival porcine model. This technique is easy to perform and seems suitable for repairing duodenal perforations. 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

PubMed

Zhang, S; Chu, W C; Lai, R C; Lim, S K; Hui, J H P; Toh, W S

2016-12-01

Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 μg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Acute toxicity and bioaccumulation of tributyltin in tissues of Urolophus jamaicensis (yellow stingray).

PubMed

Dwivedi, J; Trombetta, L D

2006-07-01

Tributyltin oxide (TBTO) is the main constituent of tin-based antifouling marine paint used on the hulls of ships to prevent the growth of fouling organisms. TBTO was shown to be hazardous to nontarget organisms. The stingray, Urolophus jamaicensis, may represent the ideal study organism for the adverse effects of TBTO to elasmobranches. This study investigated the toxicity and accumulation of tin in the gill tissue of the stingray U. jamaicensis after acute exposure to TBTO. This work demonstrates the alterations in the morphological architecture of the gill using electron and light microscopy, the induction of stress proteins, and peroxidative damage in response to tributyltin (TBT) exposure. A captured population of U. jamaicencis was housed in isolated, static tank systems. After a minimum 30-d acclimation period, the animals were exposed to one of 5 experimental doses of TBTO (4 microg/L, 2 microg/L, 1 microg/L, 0.5 microg/L, or 0.05 microg/L). A sixth group served as a control population. At 3h following treatment, animals were sacrificed and gill tissue was extracted, processed, and stored for analysis. Results indicate that U. jamaicensis is hypersensitive to TBT exposure. The elasmobranch gill showed a distorted, swollen epithelium with exfoliation following acute exposure to as little as 0.05 microg/L TBTO for 3 h. Graphite furnace atomic absorption spectroscopy (GFAAS) results indicate that tissues of treated animals contained a significantly increased tin concentration as compared to controls. Western blot analysis demonstrated the induction of the stress proteins Hsp 70 and HO1. 4-Hydroxynonenol (4HNE) adduct formation determined by Western blot analysis provides further evidence that observed membrane degradation is a result of lipid peroxidation.

Evaluating the Role of Subacromial Impingement in Rotator Cuff tendinopathy: Development and Analysis of a Novel Murine Model.

PubMed

Cong, Guang-Ting; Lebaschi, Amir H; Camp, Christopher L; Carballo, Camila B; Nakagawa, Yusuke; Wada, Susumu; Deng, Xiang-Hua; Rodeo, Scott A

2018-04-23

Subacromial impingement of the rotator cuff is understood as a contributing factor in the development of rotator cuff tendinopathy. However, changes that occur in the impinged tendon are poorly understood and warrant further study. To enable further study of rotator cuff tendinopathy, we performed a controlled laboratory study to determine feasibility and baseline characteristics of a new murine model for subacromial impingement. This model involves surgically inserting a microvascular clip into the subacromial space in adult C57Bl/6 mice. Along with a sham surgery arm, 90 study animals were distributed among time point groups for sacrifice up to 6 weeks. All animals underwent bilateral surgery (total N = 180). Biomechanical, histologic, and molecular analyses were performed to identify and quantify the progression of changes in the supraspinatus tendon. Decreases in failure force and stiffness were found in impinged tendon specimens compared to sham and no-surgery controls at all study time points. Semi-quantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 6 weeks. Quantitative real-time polymerase chain reaction analysis of impinged tendon specimens demonstrated persistently increased expression of genes related to matrix remodeling, inflammation, and tendon development. Overall, this novel murine subacromial impingement model creates changes consistent with acute tendonitis, which may mimic the early stages of rotator cuff tendinopathy. This article is protected by copyright. All rights reserved Clinical Significance: A robust, simple, and reproducible animal model of rotator cuff tendinopathy is a valuable research tool to allow further studies of cellular and molecular mechanisms and evaluation of therapeutic interventions in rotator cuff tendinopathy. This article is protected by copyright. All rights reserved.

Conservatism predicts lapses from vegetarian/vegan diets to meat consumption (through lower social justice concerns and social support).

PubMed

Hodson, Gordon; Earle, Megan

2018-01-01

Lapses from vegetarian and vegan (i.e., veg*n) food choices to meat consumption are very common, suggesting that sustaining veg*nism is challenging. But little is known about why people return to eating animals after initially deciding to avoid meat consumption. Several potential explanatory factors include personal inconvenience, meat cravings, awkwardness in social settings, or health/nutrition concerns. Here we test the degree to which political ideology predicts lapsing to meat consumption. Past research demonstrates that political ideology predicts present levels of meat consumption, whereby those higher in right-wing ideologies eat more animals, even after controlling for their hedonistic liking of meat (e.g., Dhont & Hodson, 2014). To what extent might political ideology predict whether one has lapsed from veg*n foods back to meat consumption? In a largely representative US community sample (N = 1313) of current and former veg*ns, those higher (vs. lower) in conservatism exhibited significantly greater odds of being a former than current veg*n, even after controlling for age, education, and gender. This ideology-lapsing relation was mediated (i.e., explained) by those higher (vs. lower) in conservatism: (a) adopting a veg*n diet for reasons less centered in justice concerns (animal rights, environment, feeding the poor); and (b) feeling socially unsupported in their endeavor. In contrast, factors such as differential meat craving or lifestyle inconvenience played little mediational role. These findings demonstrate that ideology and justice concerns are particularly relevant to understanding resilience in maintaining veg*n food choices. Implications for understanding why people eat meat, and how to develop intervention strategies, are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gingerol Fraction from Zingiber officinale Protects against Gentamicin-Induced Nephrotoxicity

PubMed Central

Rodrigues, Francisco A. P.; Prata, Mara M. G.; Oliveira, Iris C. M.; Alves, Natacha T. Q.; Freitas, Rosa E. M.; Monteiro, Helena S. A.; Silva, Jame's A.; Vieira, Paulo C.; Viana, Daniel A.; Libório, Alexandre B.

2014-01-01

Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidative stress and nitric oxide production. Also, there were increases of the mRNA levels for proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], IL-2, and gamma interferon [IFN-γ]). Histopathological findings of tubular degeneration and inflammatory cell infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated by previous oral treatment with GF. Animals from the GM+GF groups showed amelioration in renal function parameters and reduced lipid peroxidation and nitrosative stress, in addition to an increment in the levels of glutathione (GSH) and superoxide dismutase (SOD) activity. Gingerols also promoted significant reductions in mRNA transcription for TNF-α, IL-2, and IFN-γ. These effects were dose dependent. These results demonstrate that GF promotes a nephroprotective effect on GM-mediated nephropathy by oxidative stress, inflammatory processes, and renal dysfunction. PMID:24395230

Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).

PubMed

Olson, Brian M; Bradley, Eric S; Sawicki, Thomas; Zhong, Weixiong; Ranheim, Erik A; Bloom, Jordan E; Colluru, Viswa T; Johnson, Laura E; Rekoske, Brian T; Eickhoff, Jens C; McNeel, Douglas G

2017-05-01

The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Temperature controlled CO(2) laser welding of soft tissues: urinary bladder welding in different animal models (rats, rabbits, and cats).

PubMed

Lobel, B; Eyal, O; Kariv, N; Katzir, A

2000-01-01

Laser welding of tissues is a method of closure of surgical incisions that, in principle, may have advantages over conventional closure methods. It is a noncontact technique that introduces no foreign body, the closure is continuous and watertight, and the procedure is faster and requires less skill to master. However, in practice, there have been difficulties in obtaining strong and reliable welding. We assumed that the quality of the weld depends on the ability to monitor and control the surface temperature of the welded zone during the procedure. Our objective was to develop a "smart" fiberoptic laser system for controlled temperature welding. We have developed a welding system based on a CO(2) laser and on infrared transmitting AgClBr fibers. This fiberoptic system plays a double role: transmitting laser power for tissue heating and noncontact (radiometric) temperature monitoring and control. The "true" temperature of the heated tissue was determined by using an improved calibration method. We carried out long-studies of CO(2) laser welding of urinary bladders in various animal models. Cystotomies were performed on the animals, and complete closure of the bladder was obtained with a surface temperature of 55 +/- 5 degrees C at the welding site. In early experiments on 31 rats, the success rate was 73%. In later experiments with 10 rabbits and 3 cats, there was an 80% and a 100% success rate, respectively. The success rate in these preliminary experiments and the quality of the weld, as determined histologically, demonstrate that temperature controlled CO(2) laser welding can produce effective welding of tissues. The fiberoptic system can be adapted for endoscopic laser welding. Copyright 2000 Wiley-Liss, Inc.

Otoliths developed in microgravity

NASA Technical Reports Server (NTRS)

Wiederhold, M. L.; Harrison, J. L.; Parker, K.; Nomura, H.

2000-01-01

Little is known about mechanisms that regulate the development of the otoliths in the gravity-sensing organs. Several reported experiments suggest that the growth of the otoliths is adjusted to produce a test mass of the appropriate weight. If this is the case, larger than normal otoliths would be expected in animals reared in reduced gravity and a reduced mass, relative to 1-g controls, would be expected in animals reared at elevated g. In gastropod mollusks, the gravity-sensing organ is the statocyst, a spherical organ whose wall is made largely of sensory receptor cells with motile cilia facing the lumen. Dense statoconia in the cyst lumen interact with cilia of receptor cells at the bottom of the cyst and action potentials in their axons carry information on direction and magnitude of gravity and linear acceleration. In the marine mollusk, Aplysia californica, larvae reared at 2 to 5-g, the volume of statoconia was reduced in a graded manner, compared to 1-g control animals. In the statocyst of the fresh-water pond snail, Biomphalaria glabrata, reared in space in the Closed Equilibrated Biological Aquatic System (CEBAS), the number and total volume of statoconia was increased approximately 50%, relative to ground-reared controls. Lychakov found the utricular otolith to be 30% larger in space-reared Xenopus, whereas we found the saccular otolith to be significantly larger in newt larvae reared in space. In cichlid fish reared on a centrifuge, the saccular otolith was smaller than in 1-g controls. Here, we demonstrate that the otoliths of late-stage embryos of the swordtail fish, Xiphophorus helleri, reared in space on STS-89 and STS-90 (Neurolab) were significantly larger than those of ground-controls reared in functionally identical hardware.

Controlling infectious disease through the targeted manipulation of contact network structure

PubMed Central

Gates, M. Carolyn; Woolhouse, Mark E.J.

2015-01-01

Individuals in human and animal populations are linked through dynamic contact networks with characteristic structural features that drive the epidemiology of directly transmissible infectious diseases. Using animal movement data from the British cattle industry as an example, this analysis explores whether disease dynamics can be altered by placing targeted restrictions on contact formation to reconfigure network topology. This was accomplished using a simple network generation algorithm that combined configuration wiring with stochastic block modelling techniques to preserve the weighted in- and out-degree of individual nodes (farms) as well as key demographic characteristics of the individual network connections (movement date, livestock market, and animal production type). We then tested a control strategy based on introducing additional constraints into the network generation algorithm to prevent farms with a high in-degree from selling cattle to farms with a high out-degree as these particular network connections are predicted to have a disproportionately strong role in spreading disease. Results from simple dynamic disease simulation models predicted significantly lower endemic disease prevalences on the trade restricted networks compared to the baseline generated networks. As expected, the relative magnitude of the predicted changes in endemic prevalence was greater for diseases with short infectious periods and low transmission probabilities. Overall, our study findings demonstrate that there is significant potential for controlling multiple infectious diseases simultaneously by manipulating networks to have more epidemiologically favourable topological configurations. Further research is needed to determine whether the economic and social benefits of controlling disease can justify the costs of restricting contact formation. PMID:26342238

Controlling infectious disease through the targeted manipulation of contact network structure.

PubMed

Gates, M Carolyn; Woolhouse, Mark E J

2015-09-01

Individuals in human and animal populations are linked through dynamic contact networks with characteristic structural features that drive the epidemiology of directly transmissible infectious diseases. Using animal movement data from the British cattle industry as an example, this analysis explores whether disease dynamics can be altered by placing targeted restrictions on contact formation to reconfigure network topology. This was accomplished using a simple network generation algorithm that combined configuration wiring with stochastic block modelling techniques to preserve the weighted in- and out-degree of individual nodes (farms) as well as key demographic characteristics of the individual network connections (movement date, livestock market, and animal production type). We then tested a control strategy based on introducing additional constraints into the network generation algorithm to prevent farms with a high in-degree from selling cattle to farms with a high out-degree as these particular network connections are predicted to have a disproportionately strong role in spreading disease. Results from simple dynamic disease simulation models predicted significantly lower endemic disease prevalences on the trade restricted networks compared to the baseline generated networks. As expected, the relative magnitude of the predicted changes in endemic prevalence was greater for diseases with short infectious periods and low transmission probabilities. Overall, our study findings demonstrate that there is significant potential for controlling multiple infectious diseases simultaneously by manipulating networks to have more epidemiologically favourable topological configurations. Further research is needed to determine whether the economic and social benefits of controlling disease can justify the costs of restricting contact formation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

Gaylor, David W; Lutz, Werner K; Conolly, Rory B

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Incorporating risk communication into highly pathogenic avian influenza preparedness and response efforts.

PubMed

Voss, Shauna J; Malladi, Sasidhar; Sampedro, Fernando; Snider, Tim; Goldsmith, Timothy; Hueston, William D; Lauer, Dale C; Halvorson, David A

2012-12-01

A highly pathogenic avian influenza (HPAI) outbreak in the United States will initiate a federal emergency response effort that will consist of disease control and eradication efforts, including quarantine and movement control measures. These movement control measures will not only apply to live animals but also to animal products. However, with current egg industry "just-in-time" production practices, limited storage is available to hold eggs. As a result, stop movement orders can have significant unintended negative consequences, including severe disruptions to the food supply chain. Because stakeholders' perceptions of risk vary, waiting to initiate communication efforts until an HPAI event occurs can hinder disease control efforts, including the willingness of producers to comply with the response, and also can affect consumers' demand for the product. A public-private-academic partnership was formed to assess actual risks involved in the movement of egg industry products during an HPAI event through product specific, proactive risk assessments. The risk analysis process engaged a broad representation of stakeholders and promoted effective risk management and communication strategies before an HPAI outbreak event. This multidisciplinary team used the risk assessments in the development of the United States Department of Agriculture, Highly Pathogenic Avian Influenza Secure Egg Supply Plan, a comprehensive response plan that strives to maintain continuity of business. The collaborative approach that was used demonstrates how a proactive risk communication strategy that involves many different stakeholders can be valuable in the development of a foreign animal disease response plan and build working relationships, trust, and understanding.

Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

PubMed

Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

2010-06-01

A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

Can stress in farm animals increase food safety risk?

PubMed

Rostagno, Marcos H

2009-09-01

All farm animals will experience some level of stress during their lives. Stress reduces the fitness of an animal, which can be expressed through failure to achieve production performance standards, or through disease and death. Stress in farm animals can also have detrimental effects on the quality of food products. However, although a common assumption of a potential effect of stress on food safety exists, little is actually known about how this interaction may occur. The aim of this review was to examine the current knowledge of the potential impact of stress in farm animals on food safety risk. Colonization of farm animals by enteric pathogens such as Escherichia coli O157:H7, Salmonella, and Campylobacter, and their subsequent dissemination into the human food chain are a major public health and economic concern for the food industries. This review shows that there is increasing evidence to demonstrate that stress can have a significant deleterious effect on food safety through a variety of potential mechanisms. However, as the impact of stress is difficult to precisely determine, it is imperative that the issue receives more research attention in the interests of optimizing animal welfare and minimizing losses in product yield and quality, as well as to food safety risks to consumers. While there is some evidence linking stress with pathogen carriage and shedding in farm animals, the mechanisms underlying this effect have not been fully elucidated. Understanding when pathogen loads on the farm are the highest or when animals are most susceptible to infection will help identifying times when intervention strategies for pathogen control may be most effective, and consequently, increase the safety of food of animal origin.

Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.

PubMed

Richmond, Jenny; Colombo, Michael

2002-02-22

Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.

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.

Attitudes of veterinarians, animal control directors, and county prosecutors in Michigan regarding enforcement of state animal cruelty legislation.

PubMed

Stolt, L B; Johnson-Ifearulundu, Y J; Kaneene, J B

1997-12-15

To determine attitudes of veterinarians, animal control directors, and country prosecutors in Michigan toward enforcement of state animal cruelty legislation and to identify factors associated with whether veterinarians would report suspected cases of animal cruelty. Survey. Questionnaires were sent to 1,146 Michigan Veterinary Medical Association member veterinarians, 139 animal control directors, and 83 county prosecutors in Michigan. 740 (65%) veterinarians, 70 (50%) animal control directors, and 43 (52%) prosecutors responded. Six hundred forty six of 735 (88%) veterinarians reported having treated an animal that they believed had been a victim of animal cruelty, but only 192 of 719 (27%) had ever reported a case of animal cruelty, and only 217 of 734 (30%) had ever testified in an animal cruelty case. Logistic regression analysis of responses revealed that the only factor associated with whether veterinarians would report cases of suspected animal cruelty was the potential reactions of the involved clients to the accusation of animal cruelty. Veterinarians who rated reaction of the involved client as important, very important, or essential to their decision whether to report a case of animal cruelty were less likely to report such cases than were veterinarians who rated potential client reaction as somewhat important or unimportant. Concern about potential client reaction was the most important factor in whether veterinarians would report cases of suspected animal cruelty.

The curse of planning: dissecting multiple reinforcement-learning systems by taxing the central executive.

PubMed

Otto, A Ross; Gershman, Samuel J; Markman, Arthur B; Daw, Nathaniel D

2013-05-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. In these accounts, a flexible but computationally expensive model-based reinforcement-learning system has been contrasted with a less flexible but more efficient model-free reinforcement-learning system. The factors governing which system controls behavior-and under what circumstances-are still unclear. Following the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrated that having human decision makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement-learning strategy. Further, we showed that, across trials, people negotiate the trade-off between the two systems dynamically as a function of concurrent executive-function demands, and people's choice latencies reflect the computational expenses of the strategy they employ. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources.

The Curse of Planning: Dissecting multiple reinforcement learning systems by taxing the central executive

PubMed Central

Otto, A. Ross; Gershman, Samuel J.; Markman, Arthur B.; Daw, Nathaniel D.

2013-01-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. Along these lines, a flexible but computationally expensive model-based reinforcement learning system has been contrasted with a less flexible but more efficient model-free reinforcement learning system. The factors governing which system controls behavior—and under what circumstances—are still unclear. Based on the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrate that having human decision-makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement learning strategy. Further, we show that across trials, people negotiate this tradeoff dynamically as a function of concurrent executive function demands and their choice latencies reflect the computational expenses of the strategy employed. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources. PMID:23558545

Effects of topical oxiconazole and boric acid in alcohol solutions to rat inner ears.

PubMed

Özdemir, Süleyman; Tuncer, Ülkü; Tarkan, Özgür; Akar, Funda; Sürmelioğlu, Özgür

2013-06-01

The aim of this study is to evaluate the ototoxicity of topical oxiconazole and boric acid in alcohol solutions. Prospective controlled animal study. Research laboratory. Fifty adult Wistar albino rats were divided into 5 groups consisting of 10 animals each. The right tympanic membranes were perforated, and baseline and posttreatment distortion product otoacoustic emission (DPOAE) measurements were performed. The solutions were applied through the external ear canal to the middle ear twice a day for 14 days. The rats in group I and group II received 0.1 mL of oxiconazole-containing solution drops and 4% boric acid in alcohol solution drops, respectively. Group III received gentamicin solution (40 mg/mL) (ototoxic control), group IV received saline solution, and group V was followed without any medication. The baseline DPOAE results of the right ears of all animals tested were normal. Animals in groups I, II, IV, and V showed no statistically significant change in the DPOAE amplitudes. The rats in the gentamicin group showed a significant decrease. This study demonstrates that topically used oxiconazole and boric acid in alcohol solutions to the middle ear appear to be safe on the inner ear of rats. The safety of these drugs has not yet been confirmed in humans. Caution should be taken when prescribing these drugs, especially to patients who had tympanic membrane perforation. Ear drops should be chosen more carefully in an external ear infection for patients with tympanic membrane perforation to avoid ototoxicity.

Safety of Microbubbles and Transcranial Ultrasound in Rabbits

NASA Astrophysics Data System (ADS)

Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

2007-05-01

The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens.

PubMed

Zimmermann, Jana; Saalbach, Isolde; Jahn, Doreen; Giersberg, Martin; Haehnel, Sigrun; Wedel, Julia; Macek, Jeanette; Zoufal, Karen; Glünder, Gerhard; Falkenburg, Dieter; Kipriyanov, Sergey M

2009-09-11

Coccidiosis caused by protozoans of genus Eimeria is a chicken parasitic disease of great economical importance. Conventional disease control strategies depend on vaccination and prophylactic use of anticoccidial drugs. Alternative solution to prevent and treat coccidiosis could be provided by passive immunization using orally delivered neutralizing antibodies. We investigated the possibility to mitigate the parasitic infection by feeding poultry with antibody expressing transgenic crop seeds. Using the phage display antibody library, we generated a panel of anti-Eimeria scFv antibody fragments with high sporozoite-neutralizing activity. These antibodies were expressed either transiently in agrobacteria-infiltrated tobacco leaves or stably in seeds of transgenic pea plants. Comparison of the scFv antibodies purified either from tobacco leaves or from the pea seeds demonstrated no difference in their antigen-binding activity and molecular form compositions. Force-feeding experiments demonstrated that oral delivery of flour prepared from the transgenic pea seeds had higher parasite neutralizing activity in vivo than the purified antibody fragments isolated from tobacco. The pea seed content was found to protect antibodies against degradation by gastrointestinal proteases (>100-fold gain in stability). Ad libitum feeding of chickens demonstrated that the transgenic seeds were well consumed and not shunned. Furthermore, feeding poultry with shred prepared from the antibody expressing pea seeds led to significant mitigation of infection caused both by high and low challenge doses of Eimeria oocysts. The results suggest that our strategy offers a general approach to control parasitic infections in production animals using cost-effective antibody expression in crop seeds affordable for the animal health market.

Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Potential application in liver transplantation

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

Woodle, E.S.; Vera, D.R.; Ward, R.E.

1984-01-01

Tc-NGA is a hepatocyte receptor-specific imaging agent whose uptake by the liver has been shown to be dependent upon blood flow and receptor concentration. The combination of anatomic and physiologic information obtained with Tc-NGA may provide a new tool for studying hepatic function in liver transplant recipients. To evaluate the potential role of Tc-NGA in liver transplant recipients, studies were performed in four groups of pigs: controls (n=18); common bile duct (CBD) ligation (n=8); orthotopic liver transplant (n=9); and acute hepatic artery ligation (n=1). Serial studies performed in two animals with CBD ligation demonstrated normal imaging anatomy with minor changesmore » in the hepatic time-activity curves when compared to control studies. Studies in liver-transplanted animals showed significant changes in the hepatic time-activity curves during acute rejection and in preservation-related ischemic injury. Tc-NGA also demonstrated focal areas of hepatic infarction in a hepatic allograft within 24 hours of transplantation. The hepatic artery ligation study showed massive changes in the hepatic time-activity curve within two hours after ligation, with a diffuse decrease in hepatic activity. These results indicate that: (1) extrahepatic biliary tract obstruction causes only minor changes in Tc-NGA uptake; (2) Tc-NGA uptake by the liver is very sensitive to acute hepatic ischemia; (3) Tc-NGA may indicate the presence of preservation damage in the early postoperative period; and (4) Tc-NGA hepatic time-activity curves demonstrate significant changes during acute rejection.« less

Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens

PubMed Central

Zimmermann, Jana; Saalbach, Isolde; Jahn, Doreen; Giersberg, Martin; Haehnel, Sigrun; Wedel, Julia; Macek, Jeanette; Zoufal, Karen; Glünder, Gerhard; Falkenburg, Dieter; Kipriyanov, Sergey M

2009-01-01

Background Coccidiosis caused by protozoans of genus Eimeria is a chicken parasitic disease of great economical importance. Conventional disease control strategies depend on vaccination and prophylactic use of anticoccidial drugs. Alternative solution to prevent and treat coccidiosis could be provided by passive immunization using orally delivered neutralizing antibodies. We investigated the possibility to mitigate the parasitic infection by feeding poultry with antibody expressing transgenic crop seeds. Results Using the phage display antibody library, we generated a panel of anti-Eimeria scFv antibody fragments with high sporozoite-neutralizing activity. These antibodies were expressed either transiently in agrobacteria-infiltrated tobacco leaves or stably in seeds of transgenic pea plants. Comparison of the scFv antibodies purified either from tobacco leaves or from the pea seeds demonstrated no difference in their antigen-binding activity and molecular form compositions. Force-feeding experiments demonstrated that oral delivery of flour prepared from the transgenic pea seeds had higher parasite neutralizing activity in vivo than the purified antibody fragments isolated from tobacco. The pea seed content was found to protect antibodies against degradation by gastrointestinal proteases (>100-fold gain in stability). Ad libitum feeding of chickens demonstrated that the transgenic seeds were well consumed and not shunned. Furthermore, feeding poultry with shred prepared from the antibody expressing pea seeds led to significant mitigation of infection caused both by high and low challenge doses of Eimeria oocysts. Conclusion The results suggest that our strategy offers a general approach to control parasitic infections in production animals using cost-effective antibody expression in crop seeds affordable for the animal health market. PMID:19747368

Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

PubMed Central

Walker, Lauren Elizabeth; Frigerio, Federica; Ravizza, Teresa; Ricci, Emanuele; Tse, Karen; Jenkins, Rosalind E.; Sills, Graeme John; Jorgensen, Andrea; Porcu, Luca; Alapirtti, Tiina; Peltola, Jukka; Brodie, Martin J.; Park, Brian Kevin; Marson, Anthony Guy; Antoine, Daniel James

2017-01-01

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 isoforms. Moreover, treatment of animals with antiinflammatory drugs during epileptogenesis prevented both disease progression and blood increase in HMGB1 isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation in larger-scale prospective studies. PMID:28504645

Species-specific identification of collagen components in Colla corii asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach.

PubMed

Li, Xue; Shi, Feng; Gong, Liping; Hang, Baojian; Li, Daoyuan; Chi, Lianli

2017-01-01

Colla corii asini (CCA) is a protein-based traditional Chinese medicine made from donkey skins. Because it has the ability to nourish blood, its demand is increasing rapidly. The shortage of donkey skins increases the risk of the adulteration of CCA products with other animal skins. To ensure the drug efficacy and safety of CCA products, a proteomics technique was applied to reveal proteins in the skins of donkey, horse, cattle, and pig. Species-specific peptides for each animal species were predicted using bioinformatics, and their presence in the skins and gelatin samples was examined by nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS). One unique marker peptide for each animal species was selected to develop an LC-MS/MS multiple reaction monitoring method. The capability of this method to identify donkey, horse, cattle, and pig materials was demonstrated by analyzing in-house-made donkey gelatins containing different amounts of other animal skins and commercial CCA products. The adulteration of non-donkey species could be sensitively detected at a low level of 0.5%. Hybrid animals, such as mules and hinnies, were also differentiated from donkeys. We provide a practical tool for the quality control of CCA products. The strategy can also be used to study other important traditional Chinese medicines which contain animal proteins.

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

Revealing glacier flow and surge dynamics from animated satellite image sequences: examples from the Karakoram

NASA Astrophysics Data System (ADS)

Paul, F.

2015-04-01

Although animated images are very popular on the Internet, they have so far found only limited use for glaciological applications. With long time-series of satellite images becoming increasingly available and glaciers being well recognized for their rapid changes and variable flow dynamics, animated sequences of multiple satellite images reveal glacier dynamics in a time-lapse mode, making the otherwise slow changes of glacier movement visible and understandable for a wide public. For this study animated image sequences were created from freely available image quick-looks of orthorectified Landsat scenes for four regions in the central Karakoram mountain range. The animations play automatically in a web-browser and might help to demonstrate glacier flow dynamics for educational purposes. The animations revealed highly complex patterns of glacier flow and surge dynamics over a 15-year time period (1998-2013). In contrast to other regions, surging glaciers in the Karakoram are often small (around 10 km2), steep, debris free, and advance for several years at comparably low annual rates (a few hundred m a-1). The advance periods of individual glaciers are generally out of phase, indicating a limited climatic control on their dynamics. On the other hand, nearly all other glaciers in the region are either stable or slightly advancing, indicating balanced or even positive mass budgets over the past few years to decades.

The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway.

PubMed

Kanika, Nirmala Devi; Tar, Moses; Tong, Yuehong; Kuppam, Dwaraka Srinivasa Rao; Melman, Arnold; Davies, Kelvin Paul

2009-10-01

Intracorporal injection of plasmids encoding opiorphins into retired breeder rats can result in animals developing a priapic-like condition. Microarray analysis demonstrated that following intracorporal gene transfer of plasmids expressing opiorphins the most significantly upregulated gene in corporal tissue was the ornithine decarboxylase gene (ODC). Quantitative RT-PCR confirmed the upregulation of ODC, as well as other genes involved in polyamine synthesis, such as arginase-I and -II, polyamine oxidase, spermidine synthase, spermidine acetyltransferase (SAT), and S-adenosylmethionine decarboxylase. Western blot analysis demonstrated upregulation of arginase-I and -II, ODC, and SAT at the protein level. Levels of the polyamine putrescine were upregulated in animals treated with opiorphin-expressing plasmids compared with controls. A direct role for the upregulation of polyamine synthesis in the development of the priapic-like condition was supported by the observation that the ODC inhibitor 1,3-diaminopropane, when added to the drinking water of animals treated with plasmids expressing opiorphins, prevented experimental priapism. We also demonstrate that in sickle cell mice, another model of priapism, there is increased expression of the mouse opiorphin homologue in corporal tissue compared with the background strain at a life stage prior to evidence of priapism. At a life stage when there is onset of priapism, there is increased expression of the enzymes involved in polyamine synthesis (ODC and arginase-I and -II). Our results suggest that the upregulation of enzymes involved in the polyamine synthetic pathway may play a role in the development of experimental priapism and represent a target for the prevention of priapism.

The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway

PubMed Central

Kanika, Nirmala Devi; Tar, Moses; Tong, Yuehong; Kuppam, Dwaraka Srinivasa Rao; Melman, Arnold

2009-01-01

Intracorporal injection of plasmids encoding opiorphins into retired breeder rats can result in animals developing a priapic-like condition. Microarray analysis demonstrated that following intracorporal gene transfer of plasmids expressing opiorphins the most significantly upregulated gene in corporal tissue was the ornithine decarboxylase gene (ODC). Quantitative RT-PCR confirmed the upregulation of ODC, as well as other genes involved in polyamine synthesis, such as arginase-I and -II, polyamine oxidase, spermidine synthase, spermidine acetyltransferase (SAT), and S-adenosylmethionine decarboxylase. Western blot analysis demonstrated upregulation of arginase-I and -II, ODC, and SAT at the protein level. Levels of the polyamine putrescine were upregulated in animals treated with opiorphin-expressing plasmids compared with controls. A direct role for the upregulation of polyamine synthesis in the development of the priapic-like condition was supported by the observation that the ODC inhibitor 1,3-diaminopropane, when added to the drinking water of animals treated with plasmids expressing opiorphins, prevented experimental priapism. We also demonstrate that in sickle cell mice, another model of priapism, there is increased expression of the mouse opiorphin homologue in corporal tissue compared with the background strain at a life stage prior to evidence of priapism. At a life stage when there is onset of priapism, there is increased expression of the enzymes involved in polyamine synthesis (ODC and arginase-I and -II). Our results suggest that the upregulation of enzymes involved in the polyamine synthetic pathway may play a role in the development of experimental priapism and represent a target for the prevention of priapism. PMID:19657052

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas.

PubMed

Ruban, Angela; Berkutzki, Tamara; Cooper, Itzik; Mohar, Boaz; Teichberg, Vivian I

2012-12-01

L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase(hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma.We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals were drinking oxaloacetate with or without injections of hGOT. In addition, mice were treated with combination treatment, which included drinking oxaloacetate with intracutaneous injections of hGOT and intraperitoneal injection of Temozolomide. Animals drinking oxaloacetate with or without injections of hGOT displayed a smaller tumor volume, reduced invasiveness and prolonged survival than control animals drinking saline. These effects were significantly enhanced by Temozolomide in mice, which increased survival by 237%. This is the first demonstration of blood Glu scavenging in brain cancer, and because of its safety, is likely to be of clinical significance for the future treatment of human gliomas. As we demonstrated, the blood glutamate scavenging treatment in combination with TMZ could be a good candidate or as an alternative treatment to the patients that do not respond to TMZ.

Fever and therapeutic normothermia in severe brain injury: an update.

PubMed

Bohman, Leif-Erik; Levine, Joshua M

2014-04-01

Fever is common in the ICU among patients with severe brain injury. Fever has been consistently shown to exacerbate brain injuries in animal models and has been consistently associated with poor outcome in human studies. However, whether fever control improves outcome and the ideal means of fever control remain unknown. This review will address recent literature on the impact of fever on severe brain injury and on interventions to maintain normothermia. Current guidelines generally recommend maintenance of normothermia after brain injury but have scant recommendations on methods to do this. Observational trials have continued to demonstrate the association between fever and poor outcome after severe brain injury. Recent trials have shown the efficacy of more aggressive approaches to fever reduction, whereas a large randomized trial showed the relative ineffectiveness of acetaminophen alone for fever control. Several studies have also described the impact of fever and of fever control on brain physiology. The value of therapeutic normothermia in the neurocritical care unit (NCCU) is increasingly accepted, yet prospective trials that demonstrate a functional benefit to patients are lacking.

Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

PubMed

Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

2015-07-02

Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

Does the Animal Fun program improve motor performance in children aged 4-6 years?

PubMed

Piek, J P; McLaren, S; Kane, R; Jensen, L; Dender, A; Roberts, C; Rooney, R; Packer, T; Straker, L

2013-10-01

The Animal Fun program was designed to enhance the motor ability of young children by imitating the movements of animals in a fun, inclusive setting. The efficacy of this program was investigated through a randomized controlled trial using a multivariate nested cohort design. Pre-intervention scores were recorded for 511 children aged 4.83 years to 6.17 years (M=5.42 years, SD=3.58 months). Six control and six intervention schools were compared 6 months later following the intervention, and then again at 18 months after the initial testing when the children were in their first school year. Changes in motor performance were examined using the Bruininks-Oseretsky Test of Motor Proficiency short form. Data were analyzed using multi-level-mixed effects linear regression. A significant Condition×Time interaction was found, F(2,1219)=3.35, p=.035, demonstrating that only the intervention group showed an improvement in motor ability. A significant Sex×Time interaction was also found, F(2,1219)=3.84, p=.022, with boys improving over time, but not girls. These findings have important implications for the efficacy of early intervention of motor skills and understanding the differences in motor performance between boys and girls. Copyright © 2012 Elsevier B.V. All rights reserved.

Fipronil-induced genotoxicity and DNA damage in vivo: Protective effect of vitamin E.

PubMed

Badgujar, P C; Selkar, N A; Chandratre, G A; Pawar, N N; Dighe, V D; Bhagat, S T; Telang, A G; Vanage, G R

2017-05-01

Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E.

Collaborative Approach in the Development of High‐Performance Brain–Computer Interfaces for a Neuroprosthetic Arm: Translation from Animal Models to Human Control

PubMed Central

Collinger, Jennifer L.; Kryger, Michael A.; Barbara, Richard; Betler, Timothy; Bowsher, Kristen; Brown, Elke H. P.; Clanton, Samuel T.; Degenhart, Alan D.; Foldes, Stephen T.; Gaunt, Robert A.; Gyulai, Ferenc E.; Harchick, Elizabeth A.; Harrington, Deborah; Helder, John B.; Hemmes, Timothy; Johannes, Matthew S.; Katyal, Kapil D.; Ling, Geoffrey S. F.; McMorland, Angus J. C.; Palko, Karina; Para, Matthew P.; Scheuermann, Janet; Schwartz, Andrew B.; Skidmore, Elizabeth R.; Solzbacher, Florian; Srikameswaran, Anita V.; Swanson, Dennis P.; Swetz, Scott; Tyler‐Kabara, Elizabeth C.; Velliste, Meel; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian

2013-01-01

Abstract Our research group recently demonstrated that a person with tetraplegia could use a brain–computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able‐bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short‐term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real‐world clinical situations. PMID:24528900

Development and Application of Stable Phantoms for the Evaluation of Photoacoustic Imaging Instruments

PubMed Central

Bohndiek, Sarah E.; Bodapati, Sandhya; Van De Sompel, Dominique; Kothapalli, Sri-Rajasekhar; Gambhir, Sanjiv S.

2013-01-01

Photoacoustic imaging combines the high contrast of optical imaging with the spatial resolution and penetration depth of ultrasound. This technique holds tremendous potential for imaging in small animals and importantly, is clinically translatable. At present, there is no accepted standard physical phantom that can be used to provide routine quality control and performance evaluation of photoacoustic imaging instruments. With the growing popularity of the technique and the advent of several commercial small animal imaging systems, it is important to develop a strategy for assessment of such instruments. Here, we developed a protocol for fabrication of physical phantoms for photoacoustic imaging from polyvinyl chloride plastisol (PVCP). Using this material, we designed and constructed a range of phantoms by tuning the optical properties of the background matrix and embedding spherical absorbing targets of the same material at different depths. We created specific designs to enable: routine quality control; the testing of robustness of photoacoustic signals as a function of background; and the evaluation of the maximum imaging depth available. Furthermore, we demonstrated that we could, for the first time, evaluate two small animal photoacoustic imaging systems with distinctly different light delivery, ultrasound imaging geometries and center frequencies, using stable physical phantoms and directly compare the results from both systems. PMID:24086557

Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis.

PubMed

Rocke, Tonie E; Smith, Susan; Marinari, Paul; Kreeger, Julie; Enama, Jeffrey T; Powell, Bradford S

2008-01-01

Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

Mate familiarity and social learning in a monogamous lizard.

PubMed

Munch, Kirke L; Noble, Daniel W A; Wapstra, Erik; While, Geoffrey M

2018-05-08

Social learning is thought to be advantageous as it allows an animal to gather information quickly without engaging in costly trial-and-error learning. However, animals should be selective about when and whom they learn from. Familiarity is predicted to positively influence an animal's reliance on social learning; yet, few studies have empirically tested this theory. We used a lizard (Liopholis whitii) that forms long-term monogamous pair bonds to examine the effects of partner familiarity on social learning in two novel foraging tasks, an association and a reversal task. We allowed female lizards to observe trained conspecifics that were either familiar (social mate) or unfamiliar execute these tasks and compared these two groups with control females that did not receive social information. Lizards preferentially relied on trial-and-error learning in the association task. In the reversal task, lizards that were demonstrated by familiar partners learnt in fewer trials compared to control lizards and made more correct choices. Our results provide some evidence for context-dependent learning with lizards differentiating between when they utilize social learning, and, to a limited degree, whom they learnt from. Understanding the role of the social context in which learning occurs provides important insights into the benefits of social learning and sociality more generally.

Amelioration of cognitive impairment and changes in microtubule-associated protein 2 after transient global cerebral ischemia are influenced by complex environment experience.

PubMed

Briones, Teresita L; Woods, Julie; Wadowska, Magdalena; Rogozinska, Magdalena

2006-04-03

In this study we examined whether expression of microtubule-associated protein 2 (MAP2) after transient global cerebral ischemia can be influenced by behavioral experience and if the changes are associated with functional improvement. Rats received either ischemia or sham surgery then assigned to: complex environment housing (EC) or social housing (SC) as controls for 14 days followed by water maze testing. Upregulation of MAP2 was seen in all ischemic animals with a significant overall increase evident in the EC housed rats. Behaviorally, all animals learned to perform the water maze task over time but the ischemia SC rats had the worst performance overall while all the EC housed animals demonstrated the best performance in general. Regression analysis showed that increase MAP2 expression was able to explain some of the variance in the behavioral parameters in the water maze suggesting that this cytoskeletal protein probably played a role in mediating enhanced functional outcomes.

User-controlled photographic animations, photograph-based questions, and questionnaires: three Internet-based instruments for measuring drivers' risk-taking behavior.

PubMed

Horswill, M S; Coster, M E

2001-02-01

The Internet has been exploited successfully in the past as a medium for behavioral research. This paper presents a series of studies designed to assess Internet-based measures of drivers' risk-taking behavior. First, we compared responses from an Internet sample with a traditional pencil-and-paper sample using established questionnaire measures of risk taking. No significant differences were found. Second, we assessed the validity of new Internet-based instruments, involving photographs and photographic animations, that measured speed, gap acceptance, and passing. Responses were found to reflect known demographic patterns of actual behavior to some degree. Also, a roadside survey of speeds was carried out at the locations depicted in the photographic measure of speeding and, with certain exceptions, differences between the two appeared to be constant. Third, a between-subject experimental manipulation involving the photographic animation measure of gap acceptance was used to demonstrate one application of these techniques.

Intra-nasal infection of macaques with Yellow Fever (YF) vaccine strain 17D: a novel and economical approach for YF vaccination in man.

PubMed

Niedrig, M; Stolte, N; Fuchs, D; Hunsmann, G; Stahl-Hennig, C

1999-03-05

Investigating new and simple application routes for YF vaccine, four groups of 4-6 rhesus monkeys were vaccinated with live attenuated 17D YF-vaccine. In two groups the vaccine was administered either as spray into the oral cavity, or as an encapsulated form directly into the stomach. Only one out of eight animals developed a humoral immune response against 17D. In the third group receiving the vaccine intranasally by spray and in the fourth group serving as control all ten monkeys developed an immune response. From all except one of these seroconverted monkeys virus could be detected either by virus reisolation or RT-PCR. All these animals showed a serological immune response in immunofluorescence and neutralisation test. Parallel to viremia, an increase of neopterin as an unspecified immune activation marker could be demonstrated for these animals. Intra-nasal application of 17D-vaccine seems to be a good alternative to subcutaneous immunisation in mass vaccination campaigns.

Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

NASA Astrophysics Data System (ADS)

Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

2005-03-01

Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.