Bioactive glass in cavitary bone defects: a comparative experimental study in rabbits

PubMed Central

Camargo, André Ferrari de França; Baptista, André Mathias; Natalino, Renato; de Camargo, Olavo Pires

2015-01-01

OBJECTIVES: To compare bioactive glass and autograft regarding their histomorphometric characteristics. METHODS: The authors conducted a prospective case-control experimental study on animals in order to compare the histomorphometric characteristics of bioactive glass versus autograft. Eight rabbits underwent surgery in which a cavitary defect was created in both proximal femurs. One side was filled with bioactive glass granules and the other, with autograft grafted from the contralateral side. The sides were randomized. Fourteen days after surgery, the animals were euthanized. RESULTS: Histologic analysis revealed that bone neoformation was equivalent among the two groups and the osteoblasts cell-count was higher in the femurs treated with bioactive glass. The osteocytes cell-count, however, was lower. The similarity in bone formation between both groups was consistent to literature findings. CONCLUSION: Bioactive glass is similar to autograft regarding bone neoformation in this animal model of cavitary bone defects. Level of Evidence III, Case-Control Study. PMID:26327802

Comparative Pathology of Hepatitis A Virus and Hepatitis E Virus Infection.

PubMed

Cullen, John M; Lemon, Stanley M

2018-04-30

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute, self-limiting hepatic infections that are usually spread by the fecal-oral route in humans. Naturally occurring and experimental infections are possible in a variety of nonhuman primates and, in the case of HEV, a number of other species. Many advances in understanding the pathogenesis of these viruses have come from studies in experimental animals. In general, animals infected with these viruses recapitulate the histologic lesions seen in infected humans, but typically with less severe clinical and histopathological manifestations. This review describes the histopathologic changes associated with HAV and HEV infection in humans and experimental animals. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

PubMed

Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E -16 ). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Experimental palaeobiomechanics: What can engineering tell us about evolution in deep time?

NASA Astrophysics Data System (ADS)

Anderson, Philip

2016-04-01

What did Tyrannosaurus rex eat? This is the sort of question that immediately bombards any palaeontologist when interacting with the general public. Even among scientists, how extinct animals moved or fed is a major objective of the palaeobiological research agenda. The last decade has seen a sharp increase in the technology and experimental methods available for collecting biomechanical data, which has greatly improved out ability to examine the function of both live and extinct animals. With new technologies and methods come new pitfalls and opportunities. In this review, I address three aspects of experimental biomechanics that exemplify the challenges and opportunities it provides for addressing deep-time problems in palaeontology. 1) Interpretation: It has never been easier to acquire large amounts of high-quality biomechanical data on extinct animals. However, the lack of behavioural information means that interpreting this data can be problematic. We will never know precisely what a dinosaur ate, but we can explore what constraints there might have been on the mechanical function of its jaws. Palaeobiomechanics defines potential function and becomes especially effective when dealing with multiple examples. 2) Comparison: Understanding the potential function of one extinct animal is interesting; however, examining mechanical features across multiple taxa allows for a greater understanding of biomechanical variation. Comparative studies help identify common trends and underlying mechanical principles which can have long reaching influences on morphological evolution. 3) Evolution: The physical principles established through comparative biomechanical studies can be utilized in phylogenetic comparative methods in order to explore evolutionary morphology across clades. Comparative evolutionary biomechanics offers potential for exploring the evolution of functional systems in deep time utilizing experimental biomechanical data.

Performance, nitrogen balance and microbial efficiency of beef cattle under concentrate supplementation strategies in intensive management of a tropical pasture.

PubMed

Rocha, Tiago Cunha; Fontes, Carlos Augusto de Alencar; da Silva, Renata Tavares Soares; Processi, Elizabeth Fonsêca; do Valle, Felipe Roberto Amaral Ferreira; Lombardi, Cláudio Teixeira; Oliveira, Ronaldo Lopes; Bezerra, Leilson Rocha

2016-03-01

The objective of this study was to evaluate the effect of concentrate supplementation strategies on the nutritional characteristics of beef cattle in intensive management of tropical pasture. Twenty-four Nellore steer at 250 kg body weight (BW) were used, divided into two plots, with 12 animals in each plot. The experimental area consisted of 32 paddocks with 0.25 ha of Panicum maximum cv. Mombaça. The experiment consisted of 96-day experimental periods, with three periods of 32 days. The strategies studied were P = exclusively on pasture and without concentrate supplementation (control), ES = pasture and supplemented with a concentrate low in protein, PS = pasture and supplemented with high protein content, and PES = pasture and supplementation with balanced protein-energy. There was reduced intake of DM in animals of the treatment P in relation to supplemented pasture, regardless of supplementation. Animals fed on ES showed an intake of more nutrients than the animals on PS. The CP and TDN were also lower in P than in pastures where animals received the additional types of concentrate, and the PS animals showed greater digestibility of CP and TDN than the ES animals. However, the animals exhibited similar weight gains. Animals on P ingested smaller amounts of N and had lower fecal excretion compared to the supplemented animals, but there was no difference between treatments in nitrogen balance. Urea nitrogen and urea from the blood were higher in the supplemented animals than in animals fed on pasture; these levels were also higher in PS animals compared to animals receiving ES. Both the purines absorbed and microbial protein production were similar between treatments. However, the animals fed with concentrate supplementation, independent of the strategy involved, showed higher microbial efficiency compared to animals fed exclusively on pasture.

Can Animations Effectively Substitute for Traditional Teaching Methods? Part II: Potential for Differentiated Learning

ERIC Educational Resources Information Center

Gregorius, Roberto Ma.; Santos, Rhodora; Dano, Judith B.; Gutierrez, Jose J.

2010-01-01

Animations were prepared using Adobe Flash MX and tested on elementary (3rd-5th grade) and secondary chemistry students. A pre- and post-test study was used to compare the learning gains of students who received the animations with those who received textbook reading time and discussion in class. The control and experimental groups were further…

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.

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

PubMed

Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

2013-07-15

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

Prevention of renal scarring from pyelonephritis in nonhuman primates by vaccination with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate.

PubMed Central

Roberts, J A; Kaack, M B; Baskin, G; Svenson, S B

1993-01-01

Rhesus monkeys were vaccinated with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate. Using our experimental pyelonephritis monkey model, we tested whether such immunization was protective against the renal damage from inflammation following experimental infection with a P-fimbriated O-antigenically homologous E. coli strain. The vaccination did not significantly alter the duration of bacteriuria or interfere with the infection. However, the vaccine was efficient in renal protection, as vaccinated animals showed significantly less intratubular infiltration of neutrophils (P < 0.02) and the degree of renal scarring was also significantly less in these animals (P > 0.005) than in the control animals. Total kidney involvement in the vaccinated animals was 16.9%, compared with 32.5% in the control animals (P = 0.07). PMID:8225595

Report on first certificate course on applied physiology of pain, analgesia, anesthesia, and euthanasia for laboratory animals held in Sri Lanka.

PubMed

Gunatilake, Mangala

2018-06-01

Similar to human beings, pain is an unpleasant sensation experienced by animals as well. There is no exception when the animals are subjected to experimental procedures. Our duty as researchers/scientists is to prevent or minimize the pain in animals so as to lessen their suffering and distress during experimental procedures. The basics of the physiology of pain and pain perception, analgesia, anesthesia, and euthanasia of laboratory animals were included to complete the program, before the practical part was attempted and before advanced topics, such as comparison of anesthetic combinations, were discussed. Therefore, this course was organized in Sri Lanka for the first time in collaboration with the Comparative Biology Centre of Newcastle University, UK. During this course, we were able to demonstrate how an anesthesia machine could be used in laboratory animal anesthesia for the first time in the country. None of the animal houses in the country were equipped with an anesthesia machine at the time of conducting the course.

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

PubMed Central

Ng, Chun-Yi; Jaarin, Kamsiah

2015-01-01

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

Experimental dermatophytosis in nude guinea pigs compared with infections in Pirbright White animals.

PubMed

Hänel, H; Braun, B; Löschhorn, K

1990-04-01

With this investigation we wanted to compare the suitability of two different strains of guinea pigs to evaluate topical antifungals after experimental Trichophyton mentagrophytes infection. The "hairless"-strain was compared with the hairy Pirbright White strain. The infection areas were treated with a skin retention test (application before infection) and two sets of therapy tests (application after infection). In the retention test the different antimycotic compounds led to better gradations. Also, in the two sets of therapy tests the gradations among the compounds were more clearly and more comparable to published results of clinical trials. In the histological investigations the infections in the "hairless" animals developed in a way which is known from dermatophytoses in human skin. In the Pirbright White strain, however, due to the adjacent hair roots, a marked inflammatory reaction of the tissue persisted for 3 weeks which is not observed on human skin of the trunk and extremities. We, therefore, consider the "hairless" strain of guinea pigs to be more suitable than hairy animals for the comparison of topical antimycotics.

Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis.

PubMed Central

Rouse, M S; Steckelberg, J M; Brandt, C M; Patel, R; Miro, J M; Wilson, W R

1997-01-01

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model. PMID:9257739

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2013 CFR

2013-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2014 CFR

2014-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2012 CFR

2012-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2011 CFR

2011-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2010 CFR

2010-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

PubMed

Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

2015-06-01

The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model.

PubMed

Herington, Jennifer L; Glore, Dana R; Lucas, John A; Osteen, Kevin G; Bruner-Tran, Kaylon L

2013-02-01

To examine whether dietary fish oil supplementation reduces development of spontaneous endometriosis-associated adhesions using an established model. Laboratory-based study. Medical center research laboratory. PATIENT(S)/ANIMAL(S): Disease-free women of reproductive age and nude mice. Women were not provided any intervention. Mice were randomized to receive fish oil supplementation or control diet. Experimental endometriosis was established in mice via injection of human endometrial tissue within 16 hours of ovariectomy. Mice were provided standard or menhaden fish oil-supplemented diets for ≥ 2 weeks before initiation of experimental endometriosis and until killing them 1 week later. At necropsy, mice were examined for the presence and extent of adhesions and endometriotic-like lesions. Tissues were excised and morphologically characterized. Adhesions/lesions were reduced in mice provided with dietary fish oil compared with control animals. Leukocytes were more numerous within the adhesions/lesions of the mice maintained on the standard diet compared with animals provided with fish oil. As indicated by staining intensity, collagen deposition was greater at adhesion sites within control mice compared with fish oil-supplemented animals. Wound-healing associated with surgery created an inflammatory peritoneal microenvironment that promoted the development of both experimental endometriosis and adhesions in a murine model. Targeting excessive inflammation with fish oil may be an effective adjuvant therapy to reduce the development of postsurgical adhesions related to endometriosis. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Increased Vulnerability to Soman Exposure in Aged Compared to Adult F344 Rats

DTIC Science & Technology

2016-10-01

or the U.S. Government. The experimental protocol was approved by the Animal Care and Use Committee at the United States Army Medical Research...Laboratory Animals and the Animal Welfare Act of 1966 (P.L. 89-544), as amended. The use of trade names does not constitute an official endorsement or...medical countermeasures to CWNAs has been conducted on young adult male animal models of CWNA exposure, focusing on the potential for drug therapies to

[Carcinogenic efficacy of the transuranium elements americium-241 and curium-244].

PubMed

Rudnitskaia, E I

1984-01-01

Albino female rats were used in the experiments. After a single intraperitoneal administration of 241Am and 244Cm chloride is doses ranging from 0.37 to 185 kBq/kg (14 doses were used) it was established that the doses applied had different effect on the average life of animals. The largest doses shortened and the lowest increased the life span of experimental animals as compared to the controls. The carcinogenic effect of the studied radionuclides and the development of malignant tumors were detected at sufficiently low doses absorbed. Malignant tumors developed in the experimental and control animals were different not only in their incidence but also their localization and spectrum.

Using robots to understand animal cognition.

PubMed

Frohnwieser, Anna; Murray, John C; Pike, Thomas W; Wilkinson, Anna

2016-01-01

In recent years, robotic animals and humans have been used to answer a variety of questions related to behavior. In the case of animal behavior, these efforts have largely been in the field of behavioral ecology. They have proved to be a useful tool for this enterprise as they allow the presentation of naturalistic social stimuli whilst providing the experimenter with full control of the stimulus. In interactive experiments, the behavior of robots can be controlled in a manner that is impossible with real animals, making them ideal instruments for the study of social stimuli in animals. This paper provides an overview of the current state of the field and considers the impact that the use of robots could have on fundamental questions related to comparative psychology: namely, perception, spatial cognition, social cognition, and early cognitive development. We make the case that the use of robots to investigate these key areas could have an important impact on the field of animal cognition. © 2016 Society for the Experimental Analysis of Behavior.

The search for cognitive terminology: an analysis of comparative psychology journal titles.

PubMed

Whissell, Cynthia; Abramson, Charles I; Barber, Kelsey R

2013-03-01

This research examines the employment of cognitive or mentalist words in the titles of articles from three comparative psychology journals (Journal of Comparative Psychology, International Journal of Comparative Psychology, Journal of Experimental Psychology: Animal Behavior Processes; 8,572 titles, >100,000 words). The Dictionary of Affect in Language, coupled with a word search of titles, was employed to demonstrate cognitive creep. The use of cognitive terminology increased over time (1940-2010) and the increase was especially notable in comparison to the use of behavioral words, highlighting a progressively cognitivist approach to comparative research. Problems associated with the use of cognitive terminology in this domain include a lack of operationalization and a lack of portability. There were stylistic differences among journals including an increased use of words rated as pleasant and concrete across years for Journal of Comparative Psychology, and a greater use of emotionally unpleasant and concrete words in Journal of Experimental Psychology: Animal Behavior Processes.

SYRCLE’s risk of bias tool for animal studies

PubMed Central

2014-01-01

Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies. PMID:24667063

Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice.

PubMed

Monzote, L; Pastor, J; Scull, R; Gille, L

2014-01-01

Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide). Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. EO prevented lesion development compared (p<0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p<0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment. Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis. Copyright © 2014 Elsevier GmbH. All rights reserved.

9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... research sponsor to control disposition of all animals administered experimental biological products or... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL...

Development of a Competitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against the 3B Protein of Foot-and-Mouth Disease Virus

PubMed Central

Yang, Ming; Parida, Satya; Salo, Tim; Hole, Kate; Velazquez-Salinas, Lauro

2015-01-01

Foot-and-mouth disease (FMD) is one of the most highly contagious and economically devastating diseases, and it severely constrains the international trade of animals. Vaccination against FMD is a key element in the control of FMD. However, vaccination of susceptible animals raises critical issues, such as the differentiation of infected animals from vaccinated animals. The current study developed a reliable and rapid test to detect antibodies against the conserved, nonstructural proteins (NSPs) of the FMD virus (FMDV) to distinguish infected animals from vaccinated animals. A monoclonal antibody (MAb) against the FMDV NSP 3B was produced. A competitive enzyme-linked immunosorbent assay (cELISA) for FMDV/NSP antibody detection was developed using a recombinant 3ABC protein as the antigen and the 3B-specific MAb. Sera collected from naive, FMDV experimentally infected, vaccinated carrier, and noncarrier animals were tested using the 3B cELISA. The diagnostic specificity was 99.4% for naive animals (cattle, pigs, and sheep) and 99.7% for vaccinated noncarrier animals. The diagnostic sensitivity was 100% for experimentally inoculated animals and 64% for vaccinated carrier animals. The performance of this 3B cELISA was compared to that of four commercial ELISA kits using a panel of serum samples established by the World Reference Laboratory for FMD at The Pirbright Institute, Pirbright, United Kingdom. The diagnostic sensitivity of the 3B cELISA for the panel of FMDV/NSP-positive bovine serum samples was 94%, which was comparable to or better than that of the commercially available NSP antibody detection kits. This 3B cELISA is a simple, reliable test to detect antibodies against FMDV nonstructural proteins. PMID:25651918

Students' Understanding of Salt Dissolution: Visualizing Animation in the Chemistry Classroom

NASA Astrophysics Data System (ADS)

Malkoc, Ummuhan

The present study explored the effect of animation implementation in learning a chemistry topic. 135 high school students taking chemistry class were selected for this study (quasi-experimental groups = 67 and control groups = 68). Independent samples t-tests were run to compare animation and control groups between and within the schools. The over-arching finding of this research indicated that when science teachers used animations while teaching salt dissolution phenomena, students will benefit the application of animations. In addition, the findings informed the TPACK framework on the idea that visual tools are important in students' understanding of salt dissolution concepts.

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

PubMed

Mähler Convenor, M; Berard, M; Feinstein, R; Gallagher, A; Illgen-Wilcke, B; Pritchett-Corning, K; Raspa, M

2014-07-01

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... research sponsor to control disposition of all animals administered experimental biological products or... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... research sponsor to control disposition of all animals administered experimental biological products or... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... research sponsor to control disposition of all animals administered experimental biological products or... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

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.

Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed

PubMed Central

Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

2010-01-01

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of ‘high-quality’ SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments. PMID:20551243

Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed.

PubMed

Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

2010-07-01

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of 'high-quality' SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments.

A Comparative Histopathology, Serology and Molecular Study, on Experimental Ocular Toxocariasis by Toxocara cati in Mongolian Gerbils and Wistar Rats

PubMed Central

Zibaei, Mohammad; Sadjjadi, Seyed Mahmoud; Karamian, Mehdi; Uga, Shoji; Oryan, Ahmad; Jahadi-Hosseini, Seyed Hamidreza

2013-01-01

The aim of this study was to compare the performance of three in-house diagnostic tests, that is, histopathology, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR), for the diagnosis after experimental infection with Toxocara cati. Twenty Mongolian gerbils and Wistar rats were divided into ten groups (n = 2/group). Toxocara cati infections were established in Mongolian gerbils and Wistar rats by administering doses of 240 and 2500 embryonated Toxocara cati eggs by gavage, respectively. Tissue sections were stained with Haematoxylin and Eosin and observed under the light microscope. Sera and vitreous fluid collected from separate infected groups were tested against Toxocara cati antigens, for 92 days postinfection. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) blocks, and aqueous fluids belong to the animals. The histopathology test gave negative results among the groups of animals examined between 5 and 92 days postinfection. The ELISA results showed that anti-Toxocara antibodies have risen between 7 and 61 days postinfection in sera and vitreous fluid in the animals infected, respectively. Analysis of PCR products revealed positive band (660 bp) in the orbital tissue infected Mongolian gerbils at 5 days postinfection. Of the three evaluated methods, the PCR could be recommended for scientific and laboratory diagnoses of toxocariasis in experimentally infected animals. PMID:24069585

A comparative histopathology, serology and molecular study, on experimental ocular toxocariasis by Toxocara cati in Mongolian gerbils and Wistar rats.

PubMed

Zibaei, Mohammad; Sadjjadi, Seyed Mahmoud; Karamian, Mehdi; Uga, Shoji; Oryan, Ahmad; Jahadi-Hosseini, Seyed Hamidreza

2013-01-01

The aim of this study was to compare the performance of three in-house diagnostic tests, that is, histopathology, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR), for the diagnosis after experimental infection with Toxocara cati. Twenty Mongolian gerbils and Wistar rats were divided into ten groups (n = 2/group). Toxocara cati infections were established in Mongolian gerbils and Wistar rats by administering doses of 240 and 2500 embryonated Toxocara cati eggs by gavage, respectively. Tissue sections were stained with Haematoxylin and Eosin and observed under the light microscope. Sera and vitreous fluid collected from separate infected groups were tested against Toxocara cati antigens, for 92 days postinfection. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) blocks, and aqueous fluids belong to the animals. The histopathology test gave negative results among the groups of animals examined between 5 and 92 days postinfection. The ELISA results showed that anti-Toxocara antibodies have risen between 7 and 61 days postinfection in sera and vitreous fluid in the animals infected, respectively. Analysis of PCR products revealed positive band (660 bp) in the orbital tissue infected Mongolian gerbils at 5 days postinfection. Of the three evaluated methods, the PCR could be recommended for scientific and laboratory diagnoses of toxocariasis in experimentally infected animals.

Animal experimentation in Japan: regulatory processes and application for microbiological studies.

PubMed

Takahashi-Omoe, H; Omoe, K

2007-07-01

We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

Animal rights and animal experimentation. Implications for physicians.

PubMed Central

Gelpi, A. P.

1991-01-01

Practicing physicians are just becoming aware of the animal rights movement, which during the 1980s spawned numerous acts of violence against research facilities throughout the United States. The animal rightists are challenging physicians to show moral justification for the human exploitation of nature and the world of subhuman species. They have aroused public interest in animal welfare, sparked protective legislation for experimental animals, and indirectly encouraged the creation of committees to oversee the conduct of animal experimentation and the conditions of animal confinement. This controversy has necessitated a closer look at the questions of animal experimentation and animal rights against the backdrop of human experimentation and human rights. Physicians and specialists in animal care seek to alleviate suffering and anxiety, and, as moderates, they may be able to bring both sides of the animal rights controversy together in a spirit of mutual tolerance and in the common cause of promoting both human and animal welfare. PMID:1949772

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

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

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

1962-01-01

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

When neuroscience met clinical pathology: partitioning experimental variation to aid data interpretation in neuroscience.

PubMed

Jeffery, Nick D; Bate, Simon T; Safayi, Sina; Howard, Matthew A; Moon, Lawrence; Jeffery, Unity

2018-03-01

In animal experiments, neuroscientists typically assess the effectiveness of interventions by comparing the average response of groups of treated and untreated animals. While providing useful insights, focusing only on group effects risks overemphasis of small, statistically significant but physiologically unimportant, differences. Such differences can be created by analytical variability or physiological within-individual variation, especially if the number of animals in each group is small enough that one or two outlier values can have considerable impact on the summary measures for the group. Physicians face a similar dilemma when comparing two results from the same patient. To determine whether the change between two values reflects disease progression or known analytical and physiological variation, the magnitude of the difference between two results is compared to the reference change value. These values are generated by quantifying analytical and within-individual variation, and differences between two results from the same patient are considered clinically meaningful only if they exceed the combined effect of these two sources of 'noise'. In this article, we describe how the reference change interval can be applied within neuroscience. This form of analysis provides a measure of outcome at an individual level that complements traditional group-level comparisons, and therefore, introduction of this technique into neuroscience can enrich interpretation of experimental data. It can also safeguard against some of the possible misinterpretations that may occur during analysis of the small experimental groups that are common in neuroscience and, by illuminating analytical error, may aid in design of more efficient experimental methods. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Comparative systems biology between human and animal models based on next-generation sequencing methods.

PubMed

Zhao, Yu-Qi; Li, Gong-Hua; Huang, Jing-Fei

2013-04-01

Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

The flaws and human harms of animal experimentation.

PubMed

Akhtar, Aysha

2015-10-01

Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

Effects of Static Visuals and Computer-Generated Animations in Facilitating Immediate and Delayed Achievement in the EFL Classroom

ERIC Educational Resources Information Center

Lin, Huifen; Chen, Tsuiping; Dwyer, Francis M.

2006-01-01

The purpose of this experimental study was to compare the effects of using static visuals versus computer-generated animation to enhance learners' comprehension and retention of a content-based lesson in a computer-based learning environment for learning English as a foreign language (EFL). Fifty-eight students from two EFL reading sections were…

‘Wanted—standard guinea pigs’: standardisation and the experimental animal market in Britain ca. 1919–1947

PubMed Central

Kirk, Robert G.W.

2012-01-01

In 1942 a coalition of twenty scientific societies formed the Conference on the Supply of Experimental Animals (CSEA) in an attempt to pressure the Medical Research Council to accept responsibility for the provision of standardised experimental animals in Britain. The practice of animal experimentation was subject to State regulation under the Cruelty to Animals Act of 1876, but no provision existed for the provision of animals for experimental use. Consequently, day-to-day laboratory work was reliant on a commercial small animal market which had emerged to sustain the hobby of animal fancying. This paper explores how difficulties encountered in experimental practice within the laboratory led to the problematisation of biomedical science’s reliance upon a commercial market for animals during the inter-war period. This is shown to have produced a crisis within animal reliant experimental science in the early 1940s which enabled the left-wing Association of Scientific Workers to cast science’s reliance on a free market as economically inefficient and a threat to the reliability of British research. It is argued that the development of standard experimental animals in Britain was, therefore, embedded within the wider cultural, societal, political and economic national context of the time. PMID:18761280

Causal cognition in human and nonhuman animals: a comparative, critical review.

PubMed

Penn, Derek C; Povinelli, Daniel J

2007-01-01

In this article, we review some of the most provocative experimental results to have emerged from comparative labs in the past few years, starting with research focusing on contingency learning and finishing with experiments exploring nonhuman animals' understanding of causal-logical relations. Although the theoretical explanation for these results is often inchoate, a clear pattern nevertheless emerges. The comparative evidence does not fit comfortably into either the traditional associationist or inferential alternatives that have dominated comparative debate for many decades now. Indeed, the similarities and differences between human and nonhuman causal cognition seem to be much more multifarious than these dichotomous alternatives allow.

E-ADA activity in erythrocytes of lambs experimentally infected with Haemonchus contortus and its possible functional correlations with anemia.

PubMed

Da Silva, Aleksandro S; Schafer, Andressa S; Aires, Adelina R; Tonin, Alexandre A; Pimentel, Victor C; Oliveira, Camila B; Zanini, Daniela; Schetinger, Maria R C; Lopes, Sonia T A; Leal, Marta L R

2013-12-01

The aim of this study was to evaluate the ecto-adenosine deaminase (E-ADA) activity in erythrocytes of lambs experimentally infected with Haemonchus contortus, correlating it with the degrees of anemia of the experimental animals. A total of 14 healthy lambs, with negative fecal exam for parasites, were to carry out the present study. They were divided into two groups, composed by seven animals: Group A represented the healthy animals (uninfected), while in Group B the animals were infected with 15,000 larvae of H. contortus. Blood was drawn on the days 15, 45 and 75 post-infection (PI) in order to perform the hematological analysis, as well as the mensuration of E-ADA activity in erythrocytes. Parasitological stool exam were performed on the same days mentioned above to follow up the evolution of the infection, as well to determine the number of eggs per gram of feces (EPG). On day 15PI, the animals presented negative EPG and there was not significant (P>0.05) difference between groups in relation to E-ADA activity and hematologic parameters. Animals in Group B had positive EPG for helminths on days 45 and 75 PI, accompanied by varying degrees of anemia, when compared to Group A. At the same periods E-ADA activity was significantly (P<0.05) increased in the erythrocytes of animals of Group B when compared with the not-infected ones. Statistically, there was a negative correlation (P<0.01) between activity E-ADA in erythrocytes and hematocrit on days 45 (r = -0.76) and 75 (r = -0.85)PI. Based on these results and in the scientific literature, it is possible to conclude that the E-ADA may participate on mechanisms related with the pathogenesis and host response against anemia caused by H. contortus. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthetic torpor: A method for safely and practically transporting experimental animals aboard spaceflight missions to deep space.

PubMed

Griko, Yuri; Regan, Matthew D

2018-02-01

Animal research aboard the Space Shuttle and International Space Station has provided vital information on the physiological, cellular, and molecular effects of spaceflight. The relevance of this information to human spaceflight is enhanced when it is coupled with information gleaned from human-based research. As NASA and other space agencies initiate plans for human exploration missions beyond low Earth orbit (LEO), incorporating animal research into these missions is vitally important to understanding the biological impacts of deep space. However, new technologies will be required to integrate experimental animals into spacecraft design and transport them beyond LEO in a safe and practical way. In this communication, we propose the use of metabolic control technologies to reversibly depress the metabolic rates of experimental animals while in transit aboard the spacecraft. Compared to holding experimental animals in active metabolic states, the advantages of artificially inducing regulated, depressed metabolic states (called synthetic torpor) include significantly reduced mass, volume, and power requirements within the spacecraft owing to reduced life support requirements, and mitigated radiation- and microgravity-induced negative health effects on the animals owing to intrinsic physiological properties of torpor. In addition to directly benefitting animal research, synthetic torpor-inducing systems will also serve as test beds for systems that may eventually hold human crewmembers in similar metabolic states on long-duration missions. The technologies for inducing synthetic torpor, which we discuss, are at relatively early stages of development, but there is ample evidence to show that this is a viable idea and one with very real benefits to spaceflight programs. The increasingly ambitious goals of world's many spaceflight programs will be most quickly and safely achieved with the help of animal research systems transported beyond LEO; synthetic torpor may enable this to be done as practically and inexpensively as possible. Published by Elsevier Ltd.

Synthetic torpor: A method for safely and practically transporting experimental animals aboard spaceflight missions to deep space

NASA Astrophysics Data System (ADS)

Griko, Yuri; Regan, Matthew D.

2018-02-01

Animal research aboard the Space Shuttle and International Space Station has provided vital information on the physiological, cellular, and molecular effects of spaceflight. The relevance of this information to human spaceflight is enhanced when it is coupled with information gleaned from human-based research. As NASA and other space agencies initiate plans for human exploration missions beyond low Earth orbit (LEO), incorporating animal research into these missions is vitally important to understanding the biological impacts of deep space. However, new technologies will be required to integrate experimental animals into spacecraft design and transport them beyond LEO in a safe and practical way. In this communication, we propose the use of metabolic control technologies to reversibly depress the metabolic rates of experimental animals while in transit aboard the spacecraft. Compared to holding experimental animals in active metabolic states, the advantages of artificially inducing regulated, depressed metabolic states (called synthetic torpor) include significantly reduced mass, volume, and power requirements within the spacecraft owing to reduced life support requirements, and mitigated radiation- and microgravity-induced negative health effects on the animals owing to intrinsic physiological properties of torpor. In addition to directly benefitting animal research, synthetic torpor-inducing systems will also serve as test beds for systems that may eventually hold human crewmembers in similar metabolic states on long-duration missions. The technologies for inducing synthetic torpor, which we discuss, are at relatively early stages of development, but there is ample evidence to show that this is a viable idea and one with very real benefits to spaceflight programs. The increasingly ambitious goals of world's many spaceflight programs will be most quickly and safely achieved with the help of animal research systems transported beyond LEO; synthetic torpor may enable this to be done as practically and inexpensively as possible.

WOUND HEALING ACTIVITY OF EXTRACT FROM THYMUS DAENENSIS IN BURN WOUND MODEL: AN EXPERIMENTAL ANIMAL STUDY.

PubMed

Babaeizadeh, Simin; Heydarnejhad, Saeed; Pirbalouti, Abdollah Ghasemi; Khamesipoor, Faham; Moghtadaei-Khorasgani, Elham; Heydari-Soureshjani, Parisa

2016-11-01

Bum wound is one of the most common complications and remains a major public health issue affecting all ages groups in both developed and developing countries. This study was aimed to evaluate the extract from Thymus daenensis and silver sulfadiazine on healing bum wounds in mice. In this experimental study, the ethanol extract from the aerial parts of T. daenensis (Lamiaceae) was used. Second-degree bum wounds were induced in three groups of eight Balb/C mice each. Group-I: the animals were treated with simple cream (control), Group-II: the animals were treated with simple cream containing the herb extract, and Group-III: the animals received the standard drug (silver sulfadiazine). The experimental groups were evaluated based on wound area, epithelialization time and histopathological characteristics. There were significant differences in surface area and the period of bum wound healing between the groups, particularly among Group-II when the animals received the extract of T. daenensis in comparison with control. At the 18" day, there was no significant improvement in healing percentage of the herb treated (94.6%) in comparison to the animals receiving the standard drug (95.8%). The best results of histopathological investigation were obtained with the extract of T. daenensis, when compared to the other group as well as to the control and standard drug. The herbal cream experimentally and histopathologically revealed a bum wound healing activity probably due to the antioxidant and anti-inflammatory activity of its phytochemical contents, especially phenolic compounds. Therefore, T. daenensis accelerated wound healing in mice and thus supports its traditional use.

Animal Metacognition: A Tale of Two Comparative Psychologies

PubMed Central

Smith, J. David; Couchman, Justin J.; Beran, Michael J.

2014-01-01

A growing literature considers whether animals have capacities that are akin to human metacognition (i. e., humans’ capacity to monitor their states of uncertainty and knowing). Comparative psychologists have approached this question by testing a dolphin, pigeons, rats, monkeys and apes using perception, memory and food-concealment paradigms. As part of this consideration, some associative modelers have attempted to describe animals’ “metacognitive” performances in low-level, associative terms—an important goal if achievable. The authors summarize the empirical and theoretical situation regarding these associative descriptions. The associative descriptions in the animal-metacognition literature fail to encompass important phenomena. The sharp focus on abstract, mathematical associative models creates serious interpretative problems. The authors compare these failed associative descriptions to an alternative theoretical approach within contemporary comparative psychology. The alternative approach has the potential to strengthen comparative psychology as an empirical science and integrate it more fully within the mainstream of experimental psychology and cognitive science. PMID:23957740

Is animal experimentation fundamental?

PubMed

d'Acampora, Armando José; Rossi, Lucas Félix; Ely, Jorge Bins; de Vasconcellos, Zulmar Acciolli

2009-01-01

The understanding about the utilization of experimental animals in scientific research and in teaching is many times a complex issue. Special attention needs to be paid to attain the understanding by the general public of the importance of animal experimentation in experimental research and in undergraduate medical teaching. Experimental teaching and research based on the availability of animals for experimentation is important and necessary for the personal and scientific development of the physician-to-be. The technological arsenal which intends to mimic experimentation animals and thus fully replace their use many times does not prove to be compatible with the reality of the living animal. The purpose of this paper is to discuss aspects concerning this topic, bringing up an issue which is complex and likely to arouse in-depth reflections.

[REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

PubMed

Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

2016-02-01

A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

Consider a non-spherical elephant: computational fluid dynamics simulations of heat transfer coefficients and drag verified using wind tunnel experiments.

PubMed

Dudley, Peter N; Bonazza, Riccardo; Porter, Warren P

2013-07-01

Animal momentum and heat transfer analysis has historically used direct animal measurements or approximations to calculate drag and heat transfer coefficients. Research can now use modern 3D rendering and computational fluid dynamics software to simulate animal-fluid interactions. Key questions are the level of agreement between simulations and experiments and how superior they are to classical approximations. In this paper we compared experimental and simulated heat transfer and drag calculations on a scale model solid aluminum African elephant casting. We found good agreement between experimental and simulated data and large differences from classical approximations. We used the simulation results to calculate coefficients for heat transfer and drag of the elephant geometry. Copyright © 2013 Wiley Periodicals, Inc.

9 CFR 103.1 - Preparation of experimental biological products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL...

Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies

PubMed Central

Cascella, Marco; Palma, Giuseppe; Barbieri, Antonio; Bimonte, Sabrina; Amruthraj, Nagoth Joseph; Muzio, Maria Rosaria; del Vecchio, Vitale; Rea, Domenica; Falco, Michela; Luciano, Antonio; Arra, Claudio; Cuomo, Arturo

2017-01-01

Background: Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that Nigella sativa (NS), or its isolated compound Thymoquinone (TQ), has a potential role in combating chemotherapy-induced nephrotoxicity. AIM: To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications. Design: Standard systematic review and narrative synthesis. Data Sources: MEDLINE, EMBASE databases were searched for relevant articles published up to March 2017. Additionally, a manual search was performed. Criteria for a study’s inclusion were: conducted in animals, systematic reviews and meta-analysis, containing data on nephroprotective effects of NS/TQ compared to a placebo or other substance. All strains and genders were included. Results: The database search yielded 71 studies, of which 12 (cisplatin-induced nephrotoxicity 8; methotrexate-induced nephrotoxicity 1; doxorubicin-induced nephrotoxicity 2; ifosfamide-induced nephrotoxicity 1) were included in this review. Conclusions: Experimental animal studies showed the protective effect of NS, or TQ, on chemotherapy-induced nephrotoxicity. These effects are caused by decreasing lipid peroxidation and increasing activity of antioxidant enzymes in renal tissue of chemotherapy-treated animals. PMID:28629150

Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice.

PubMed

Niemiec, T; Sikorska, J; Harrison, A; Szmidt, M; Sawosz, E; Wirth-Dzieciolowska, E; Wilczak, J; Pierzynowski, S

2011-02-01

The objective of this study was to evaluate the effect of α-ketoglutarate on redox state parameters and arterial elasticity in elderly mice. Mice in the control group were fed with standard diet, while the experimental animals received the diet supplemented either with calcium (Ca-AKG) or sodium salt of α-ketoglutarate (Na-AKG). The experimental animals were divided into 4 groups with 10 individuals in each: control I (12 months old), control II (2 months old), experimental group I fed with Ca-AKG (12 months old) and experimental group II fed with Na-AKG (12 months old). Mice treated with Ca-AKG as well as the control II animals demonstrated significantly higher level of total antioxidant status (TAS), comparing to the control I animals and those treated with Ca-AKG. Thiobarbituric acid reactive substances (TBARS) level in blood plasma was found significantly lower in young and Ca-AKG treated mice. TBARS liver concentration was significantly different in each examined group. The study also demonstrates the decrease in TBARS level in Ca-AKG treated animals. Treatment with Na-AKG significantly increased glutathione peroxidase activity and decreased the activity of superoxide dismutase. The presented results suggest that Ca-AKG protects the organism against the free radicals related elderly processes. The study presents also the effect of Ca-AKG treatment on arterial elastic characteristics in elderly mice. The beneficial effect of Ca-AKG on ageing organisms was confirmed via redox state stabilization and blood vessel elasticity improvement.

Secrets and lies: "selective openness" in the apparatus of animal experimentation.

PubMed

Holmberg, Tora; Ideland, Malin

2012-04-01

Researchers and other (human) actors within the apparatus of animal experimentation find themselves in a tight corner. They rely on public acceptance to promote their legitimacy and to receive funding. At the same time, those working with animal experimentation take risks by going public, fearing that the public will misunderstand their work and animal rights activists may threaten them. The dilemma that emerges between openness and secrecy is fairly prevalent in scientific culture as a whole, but the apparatus of animal experimentation presents specific patterns of technologies of secrets. The aim of the paper is to describe and analyse the meanings of secrets and openness in contemporary animal experimentation. We suggest that these secrets--or "selective openness"--can be viewed as grease in the apparatus of animal experimentation, as a unifying ingredient that permits maintenance of status quo in human/animal relations and preserves existing institutional public/ science relations.

Effects of consuming fructose- or glucose-sweetened beverages for 10 weeks on lipids, insulin sensitivity and adiposity

USDA-ARS?s Scientific Manuscript database

Animal studies have documented that, compared with glucose, dietary fructose promotes dyslipidemia and insulin resistance. Experimental evidence that fructose consumption in humans promotes dyslipidemia and insulin resistance compared with glucose consumption has been equivocal. We tested the hypoth...

Healing characteristics of a new silver-coated, gelatine impregnated vascular prosthesis in the porcine model.

PubMed

Ueberrueck, T; Meyer, L; Zippel, R; Nestler, G; Wahlers, T; Gastinger, I

2005-02-01

To investigate the intraluminal and extraluminal healing behaviour of a new metallic silver coated, gelatine impregnated vascular graft. Comparative animal experimental investigation with randomisation of the animals to control and experimental groups. 24 pigs were assigned to two control and two experimental groups. The prostheses were interposed in the pigs' infrarenal aorta. For the evaluation, macroscopic, histological and immunohistochemical criteria were applied. The macroscopic evaluation after explantation of the prosthesis revealed similar healing characteristics in the control and experimental groups. The microscopic determination of neo-intimal thickness showed no significant differences between the groups; nor did the immunohistochemical investigations show any significant difference between the control group and the silver-coated prosthesis group. No disadvantage of the silver coating in terms of healing and graft patency was found. A possible advantage in terms of the antibacterial effect of the silver coating must be investigated in the clinical setting.

Femur-bending properties as influenced by gravity. I - Ultimate load and moment for 3-G rats

NASA Technical Reports Server (NTRS)

Wunder, C. C.; Welch, R. C.; Glade, R.; Fleming, B. P.; Cook, K. M.

1977-01-01

Fresh experimental bones can withstand greater bending forces and moments after 1.0 to 2.5 weeks of 3-G exposure. This appears more attributable to a 50% greater strength of bone material than to effects upon size or shape, and is most measurable for animals of 5 to 8 weeks of age. Experimental bone material seems to grow to its mature level at a younger age rather then there being so marked an effect upon the mature level itself. We simulated 3.1 G by chronic centrifugation of 66 albino rats and compared them to 63 1-G controls. Extrapolation of the simplest mathematical description of the present results to weaker, zero-G bones could be tested by a total of 60 space-based control and experimental animals. A flight of only 15 animals would be necessary for comparison to ground-based control animals. This is consistent with reports of bone demineralization during space-flight. In light of the differences in bone histology, however, extrapolation of these results to humans would be premature and, if at all applicable, are most likely to be so for children rather than adults.

Vulnerable subjects? The case of nonhuman animals in experimentation.

PubMed

Johnson, Jane

2013-12-01

The concept of vulnerability is deployed in bioethics to, amongst other things, identify and remedy harms to participants in research, yet although nonhuman animals in experimentation seem intuitively to be vulnerable, this concept and its attendant protections are rarely applied to research animals. I want to argue, however, that this concept is applicable to nonhuman animals and that a new taxonomy of vulnerability developed in the context of human bioethics can be applied to research animals. This taxonomy does useful explanatory work, helping to pinpoint the limitations of the 3Rs/welfare approach currently adopted in the context of animal experimentation. On this account, the 3Rs/welfare approach fails to deliver for nonhuman animals in experimentation because it effectively addresses only one element of their vulnerability (inherent) and paradoxically through the institution of Animal Ethics Committees intended to protect experimental animals in fact generates new vulnerabilities that exacerbate their already precarious situation.

Comparing the Hematopoetic Syndrome Time Course in the NHP Animal Model to Radiation Accident Cases From the Database Search.

PubMed

Graessle, Dieter H; Dörr, Harald; Bennett, Alexander; Shapiro, Alla; Farese, Ann M; MacVittie, Thomas J; Meineke, Viktor

2015-11-01

Since controlled clinical studies on drug administration for the acute radiation syndrome are lacking, clinical data of human radiation accident victims as well as experimental animal models are the main sources of information. This leads to the question of how to compare and link clinical observations collected after human radiation accidents with experimental observations in non-human primate (NHP) models. Using the example of granulocyte counts in the peripheral blood following radiation exposure, approaches for adaptation between NHP and patient databases on data comparison and transformation are introduced. As a substitute for studying the effects of administration of granulocyte-colony stimulating factor (G-CSF) in human clinical trials, the method of mathematical modeling is suggested using the example of G-CSF administration to NHP after total body irradiation.

[Resection anastomosis of the small intestine by celioscopy in swine. Comparative experimental study between manual and mechanical anastomosis].

PubMed

Noël, P; Fagot, H; Fabre, J M; Mann, C; Quenet, F; Guillon, F; Baumel, H; Domergue, J

1994-01-01

Laparoscopic intestinal anastomosis is not very reliable and needs to be evaluate in an experimental model in animals before being performed in man. The purpose of this study was to evaluate the feasibility, efficacy and safety of manual anastomosis comparatively to the standard stapling suture. Twenty female pigs weighing 20 +/- 5 kg. were used for this study. A 5 cm ileal segment resection was performed under laparoscopy. The animals were assigned to 2 groups. Group I: 10 animals underwent end-to-end hand-swen anastomosis with Polyglactin 910, dec 1.5. Group II: 10 animals underwent side-to-side anastomosis using the Endo stapler. Operating time and anastomosis time were compared using the Mann-Whitney test for statistical analysis. On the 15th postoperative day, the animals were sacrificed and the anastomoses were evaluated. There was no operating death in the 2 groups. The operative time was significantly longer in group I than in group II (p < 0.01), with 180 +/- 40 min vs 49 +/- 25 min respectively. This difference was due to the anastomosis time of 130 +/- 40 min vs 16 +/- 6 min respectively (p < 0.01). There was 1 postoperative death related to fistula and peritonitis in group I and none in group II. The post-operative follow-ing showed 5 anastomotic leakages (4 in group I and 1 in group II) and 2 relative stenoses in group I. This study shows the simplicity and rapidity of performing stapling intestinal anastomosis under laparoscopy. Hand-sewn anastomosis is technically more difficult to perform under laparoscopy and requires a greater experience.

A new statistical method for transfer coefficient calculations in the framework of the general multiple-compartment model of transport for radionuclides in biological systems.

PubMed

Garcia, F; Arruda-Neto, J D; Manso, M V; Helene, O M; Vanin, V R; Rodriguez, O; Mesa, J; Likhachev, V P; Filho, J W; Deppman, A; Perez, G; Guzman, F; de Camargo, S P

1999-10-01

A new and simple statistical procedure (STATFLUX) for the calculation of transfer coefficients of radionuclide transport to animals and plants is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. By using experimentally available curves of radionuclide concentrations versus time, for each animal compartment (organs), flow parameters were estimated by employing a least-squares procedure, whose consistency is tested. Some numerical results are presented in order to compare the STATFLUX transfer coefficients with those from other works and experimental data.

Neurochemical and behavioural correlates in cassava-induced neurotoxicity in rats.

PubMed

Mathangi, D C; Namasivayam, A

2000-01-01

Chronic cyanide intoxication from cassava has been implicated as the cause for a degenerative neuropathy known widely as tropical ataxic neuropathy. An attempt has been made in this study to identify the specific cause for neuropathy caused by cassava using Wistar strain albino rats as the experimental animal model. The results of cassava fed animals were compared with control animals, animals given cyanide, malnourished animals and malnourished animals fed cyanide, to identify the causative factors. This study revealed that though the behavioural pattern in motor coordination of the cassava fed animals was similar to the other groups studied, the neurochemical basis for the observed behavioural pattern was unique for cassava. Hence the neurotoxicity of cassava could be attributed to unmetabolized linamarin, more than its nutritional status and/or cyanide toxicity.

[Thoughts on the complex relationship between medicine and animals: a death prayer for a loyal cat].

PubMed

Cabello C, Felipe

2013-11-01

From its basis in the writings of the philosopher Peter Singer and the bioethical shortcomings of animal experimentation and animal husbandry, the animal rights movement has evolved into an important societal movement critical of animal experimentation in biomedical research. A lack of dialogue and transparency, an absence of understanding and an unreasonable radicalization of different positions regarding animal experimentation has frequently resulted in an adversarial relationship between some members of the scientific community and societal groups aggressively protecting animal rights. In response to this problem, both the bioethical regulations pertaining to biomedical experimentation with animals and the powers of animal care committees (IACUCs) have been strengthened. Careful analysis of the relevance of animal models to human conditions, replacement of these models with non-animal models when possible, adequate re-examination of existing knowledge before undertaking new experimental projects involving animals, and the improvement of methods to avoid animal stress and pain have further strengthened the bioethical basis of animal experimentation. To improve the ethical integrity of research conducted with animals, it is also necessary to increase the editorial scrutiny of the bioethical standards of potentially publishable research utilizing animals. Of note is also the recent use of animals in alternative animal associated therapies (AAT) to ameliorate several medical conditions. Education of the biomedical community, including students and professionals, and of societal groups concerned about this issue as well as directness and continuous dialogue among all the stakeholders are essential to insure the wellbeing of animals and the ethical integrity of biomedical research.

Laboratory animal science: a resource to improve the quality of science.

PubMed

Forni, M

2007-08-01

The contribution of animal experimentation to biomedical research is of undoubted value, nevertheless the real usefulness of animal models is still being hotly debated. Laboratory Animal Science is a multidisciplinary approach to humane animal experimentation that allows the choice of the correct animal model and the collection of unbiased data. Refinement, Reduction and Replacement, the "3Rs rule", are now widely accepted and have a major influence on animal experimentation procedures. Refinement, namely any decrease in the incidence or severity of inhumane procedures applied to animals, has been today extended to the entire lives of the experimental animals. Reduction of the number of animals used to obtain statistically significant data may be achieved by improving experimental design and statistical analysis of data. Replacement refers to the development of validated alternative methods. A Laboratory Animal Science training program in biomedical degrees can promote the 3Rs and improve the welfare of laboratory animals as well as the quality of science with ethical, scientific and economic advantages complying with the European requirement that "persons who carry out, take part in, or supervise procedures on animals, or take care of animals used in procedures, shall have had appropriate education and training".

The '3Is' of animal experimentation.

PubMed

2012-05-29

Animal experimentation in scientific research is a good thing: important, increasing and often irreplaceable. Careful experimental design and reporting are at least as important as attention to welfare in ensuring that the knowledge we gain justifies using live animals as experimental tools.

Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation.

PubMed

Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

2017-08-01

Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo-Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, "our" fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles - Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell-culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human-derived three-dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

E-ADA activity in serum of lambs experimentally infected with Haemonchus contortus.

PubMed

Da Silva, Aleksandro S; Fausto, Guilherme C; Grando, Thirssa H; Cadore, Carlos A; Pimentel, Victor C; Jaques, Jeandre A; Schetinger, Maria R C; Monteiro, Silvia G; Leal, Marta L R

2013-08-01

The aim of this study was to evaluate adenosine deaminase (E-ADA) activity in sera of lambs experimentally infected with Haemonchus contortus. We used 12 lambs divided into 2 groups; Group A had 5 healthy, non-infected animals (control) and Group B had 7 healthy animals infected with H. contortus . Lambs were infected orally with 500 larvae (L3) per animal every 2 days, for a period of 20 days, and later the infection was confirmed by examination of feces (eggs per gram [EPG] via fecal egg count). Blood collection was performed at days 0, 20, 40, 60, and 80 post-infection (PI) for analysis of E-ADA activity. Animals in Group A showed negative EPG throughout the experiment unlike those from Group B that had elevated EPG counts. E-ADA activity was reduced in the serum of animals infected with H. contortus when compared to non-infected controls at days 20, 40, 60, and 80 PI. Therefore, it is concluded that infection with H. contortus influences the E-ADA activity in lambs.

[Comparative studies on fibrogenic properties of diatomites and other silica dusts].

PubMed

Woźniak, H

1983-01-01

The experiment carried out on animals was aimed at testing fibrogenic properties of two samples of the Carpathian diatomites and silica earth from Piotrowice. Experimental pneumoconiosis was induced by intratracheal administration of 50 mg of dust suspended in 0,6 ml of NaCl physiological solution to experimental animals (rats). The animals were killed after 3,6 and 9 months since dust administration and the examinations consisted in determination of wet lungs weight, hydroxyproline content in lungs, mediastinum nodes weight and lipids content. Comparison of the achieved results indicated that diatomites fibrogenic properties are many times lower than fibrogenic properties of silica earth. This fact, at similar physico-chemical properties of these raw materials, creates a possibility of elimination of workers exposure to highly aggressive silica earth dust by replacing it by diatomite.

Structural differences in the brain between wild and laboratory rats (Rattus norvegicus): potential contribution to wariness.

PubMed

Koizumi, Ryoko; Kiyokawa, Yasushi; Mikami, Kaori; Ishii, Akiko; Tanaka, Kazuyuki D; Tanikawa, Tsutomu; Takeuchi, Yukari

2018-05-11

Wild animals typically exhibit defensive behaviors in response to a wider range and/or a weaker intensity of stimuli compared with domestic animals. However, little is known about the neural mechanisms underlying "wariness" in wild animals. Wild rats are one of the most accessible wild animals for experimental research. Laboratory rats are a domesticated form of wild rat, belonging to the same species, and are therefore considered suitable control animals for wild rats. Based on these factors, we analyzed structural differences in the brain between wild and laboratory rats to elucidate the neural mechanisms underlying wariness. We examined wild rats trapped in Tokyo, and weight-matched laboratory rats. We then prepared brain sections and compared the basolateral complex of the amygdala (BLA), the bed nucleus of the stria terminalis (BNST), the main olfactory bulb, and the accessory olfactory bulb. The results revealed that wild rats exhibited larger BLA, BNST and caudal part of the accessory olfactory bulb compared with laboratory rats. These results suggest that the BLA, BNST, and vomeronasal system potentially contribute to wariness in wild rats.

"Watch out for the gerbils, my child!" the role of maternal information on children's fear in an experimental setting using real animals.

PubMed

Remmerswaal, Danielle; Muris, Peter; Huijding, Jorg

2013-06-01

Using an experimental approach, we examined the effects of verbal information as provided by the mothers on children's fear of real novel animals. Mothers of children aged 8 to 12 years (N=47) were shown a cage containing a pair of exotic rodents (i.e., Mongolian gerbils) and then received either positive or negative information about these animals. Mothers were told that their child would have to approach the animals and had the opportunity to prepare their children for this confrontation. Results showed that mothers spontaneously passed over the information they had received to their children. Most importantly, this information to some extent determined children's fear reactions towards the animals. That is, whereas no clear effects of information were found on subjective fear ratings, the data did indicate that children of mothers in the negative information condition were more reluctant to approach the animals as compared to children of mothers who had received positive information. The findings provide further support for the idea that verbal information as provided by parents may induce fear in their offspring. Copyright © 2013. Published by Elsevier Ltd.

Evaluation of a new immunocapture test for the diagnosis of ovine brucellosis caused by Brucella melitensis.

PubMed

Durán-Ferrer, M; Mendoza, J; Osuna, A; Caporale, V; Lucas, A; León, L; Garrido, F

2002-11-23

A new immunocapture technique has been applied to the diagnosis of ovine brucellosis under experimental conditions. The tests were made on a serum bank derived from both young and adult ewes vaccinated conjunctivally with the Rev 1 strain at a dose of 10(8) to 10(9) colony-forming units. Adult ewes were infected experimentally two-and-a-half years after they had been vaccinated and the results were compared with an unvaccinated control group. The condition of each animal in terms of infection with Brucella melitensis was determined by clinical and bacteriological investigations. The development of the immune response was compared by the rose bengal test, the complement fixation test, the Coombs' test and the immunocapture technique for 180 days after the vaccination and for 410 days after the experimental infection, that is, the two following gestations. The results suggest that the new technique is more specific in animals vaccinated conjunctivally, regardless of their age when they were vaccinated. After the experimental infection, significantly (P < 0.05) fewer of the vaccinated sheep which were free of clinical signs and were not excreting B melitensis reacted positively to the test.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position.

PubMed

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position

PubMed Central

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

Objective To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Methods Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Results Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. Conclusion High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation. PMID:29236845

Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes.

PubMed

Belcastro, A N; Maybank, P; Rossiter, M; Secord, D

1985-09-01

Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming.

Aeromonas caviae alters the cytosolic and mitochondrial creatine kinase activities in experimentally infected silver catfish: Impairment on renal bioenergetics.

PubMed

Baldissera, Matheus D; Souza, Carine F; Júnior, Guerino B; Verdi, Camila Marina; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Santos, Roberto C V; Vizzotto, Bruno S; Baldisserotto, Bernardo

2017-09-01

Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na + , K + -ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na + , K + -ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Involvement of cholinergic and adenosinergic systems on the branchial immune response of experimentally infected silver catfish with Streptococcus agalactiae.

PubMed

Baldissera, M D; Souza, C F; Doleski, P H; Moreira, K L S; da Veiga, M L; da Rocha, M I U M; Santos, R C V; Baldisserotto, B

2018-01-01

It has been recognized that the cholinergic and adenosinergic systems have an essential role in immune and inflammatory responses during bacterial fish pathogens, such as the enzymes acetylcholinesterase (AChE) and adenosine deaminase (ADA), which are responsible for catalysis of the anti-inflammatory molecules acetylcholine (ACh) and adenosine (Ado) respectively. Thus, the aim of this study was to investigate the involvement of the cholinergic and adenosinergic systems on the immune response and inflammatory process in gills of experimentally infected Rhamdia quelen with Streptococcus agalactiae. Acetylcholinesterase activity decreased, while ACh levels increased in gills of infected animals compared to uninfected animals. On the other hand, a significant increase in ADA activity with a concomitant decrease in Ado levels was observed in infected animals compared to uninfected animals. Based on this evidence, we concluded that infection by S. agalactiae in silver catfish alters the cholinergic and adenosinergic systems, suggesting the involvement of AChE and ADA activities on immune and inflammatory responses, regulating the ACh and Ado levels. In summary, the downregulation of AChE activity exerts an anti-inflammatory profile in an attempt to reduce or prevent the tissue damage, while the upregulation of ADA activity exerts a pro-inflammatory profile, contributing to disease pathophysiology. © 2017 John Wiley & Sons Ltd.

A novel combined method of osteosynthesis in treatment of tibial fractures: a comparative study on sheep with application of rod-through-plate fixator and bone plating.

PubMed

Tralman, G; Andrianov, V; Arend, A; Männik, P; Kibur, R T; Nõupuu, K; Uksov, D; Aunapuu, M

2013-04-01

The study compares the efficiency of a new bone fixator combining periostal and intramedullary osteosynthesis to bone plating in treatment of tibial fractures in sheep. Experimental osteotomies were performed in the middle third of the left tibia. Animals were divided into two groups: in one group (four animals) combined osteosynthesis (rod-through-plate fixator, RTP fixator) was applied, and in the other group (three animals) bone plating was used. The experiments lasted for 10 weeks during which fracture union was followed by radiography, and the healing process was studied by blood serum markers reflecting bone turnover and by histological and immunohistochemical investigations. In the RTP fixator group, animals started to load body weight on the operated limbs the next day after the surgery, while in the bone plating group, this happened only on the seventh day. In the RTP fixator group, consolidation of fractures was also faster, as demonstrated by radiographical, histological, and immunohistochemical investigations and in part by blood serum markers for bone formation. It can be concluded that application of RTP fixation is more efficient than plate fixation in the treatment of experimental osteotomies of long bones in sheep. © 2012 Blackwell Verlag GmbH.

[Origin of animal experimentation legislation in the 19th century].

PubMed

Pocard, M

1999-01-01

The first legislation in the world, designed to protect animals used in research, was passed in England in 1876, and is still in force today. It is one of the strictest in Europe. At the same period, France had no such law, and was the country conducting the greatest amount of animal experimentation. Comparing, these two countries, in the middle of the 19th century, can account for this difference. The most important difference seems to be related to the theological question: are animals endowed with a soul? Saint Augustine, claimed, in the 4th century, perhaps because of an experiment with the centipede, that animals do not have a soul. In the 17th century, René Descartes, using a different philosophical system, reached a similar conclusion, in France. On the other hand, under the influence of Charles Darwin, England rejected the Roman Catholic conclusion, about the soul of animals. The industrial revolution, occurring earlier in England than in France, also changed the society, developing urban areas, where people were cut off from rural life and changing human relationships with animals. The industrial revolution enabled the development of the press, giving impetus to public opinion. These facts, combined with a caution of science, which was more developed in England than in France, brought about the first important "anti-doctor" campaign.

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.

[Application of animal models in gingival retraction experimental curriculum].

PubMed

Cai, He; Yang, Shu-ying; Zeng, Yong-xiang; Qin, Han; Hu, Shan-shan; Wang, Jian

2016-02-01

To introduce a teaching method for gingival retraction, and evaluate its efficacy for implementation into experimental curricula. First, two kinds of animal models using pigs and cows (below 6 months of age) were established. Twenty-two experienced prosthodontists were then asked to apply gingival retraction on each animal model and evaluate the biofidelity of the 2 models' dento-gingival environment. The data was analyzed with SPSS19.0 software package for paired t test.Then, eighty pre-internship students were randomly divided into 2 groups. Besides the traditional teaching (lecture-based teaching), the experimental group (group A) also had access to skill training (using animal models to practice gingival retraction), while the control group (group B) only used the traditional teaching modality. All students' performance in gingival retraction and impression taking were evaluated in their internship. The data was analyzed with SPSS19.0 software package for Chi-square test. Both pig and cow's dento-gingival environment were similar to that of human being, and there was no significant difference between the two models'biofidelities (P>0.05). In addition, both the effect of gingival retraction and the quality of impression in group A were significantly better than those in group B (P<0.05). Compared with the traditional strategy,practising gingival retraction on animal models can offer greater opportunities for skill development,and be implemented for a wider range of applications.

[RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

PubMed

Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

2015-12-01

To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

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.

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

PubMed Central

Garcia-de-la-Maria, C.; Xiong, Y. Q.; Pericas, J. M.; Armero, Y.; Moreno, A.; Mishra, N. N.; Rybak, M. J.; Tran, T. T.; Arias, C. A.; Sullam, P. M.; Bayer, A. S.

2017-01-01

ABSTRACT Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be β-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAPs) S. mitis/S. oralis strain and its daptomycin-resistant (DAPr) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAPr variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAPs strain following treatment with daptomycin. The parental strain and the DAPr variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 106- and 107-CFU/ml challenge inocula, the parental strain outcompeted the DAPr variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAPs strain was completely eliminated, while the DAPr variant persisted in all target tissues. These data underscore that the acquisition of DAPr in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen. PMID:28264848

A comparative cellular and molecular biology of longevity database.

PubMed

Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

2013-10-01

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

Effect of music therapy on pain behaviors in rats with bone cancer pain.

PubMed

Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

2016-01-01

To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (p<0.05). After 1-2 weeks of treatment, spontaneous foot withdrawal reflection caused by pain in the experimental group was significantly lower than that in the control group, heat pain threshold and free walking pain scoring in the experimental group were also significantly higher as compared with the control group (p<0.05). The expression of p38á and p38β in animals' spinal cord and dorsal root ganglion was significantly lower in the experimental group than in the control group (p< 0.05). Music therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

INTEGRATING EPIDEMIOLOGY AND TOXICOLOGY IN NEUROTOXICITY RISK ASSESSMENT.

EPA Science Inventory

Neurotoxicity risk assessments depend on the best available scientific information, including data from animal toxicity, human experimental studies and human epidemiology studies. There are several factors to consider when evaluating the comparability of data from studies. Reg...

[Comparative efficacy of two topical formulations containing 10% fipronil on the control of Ctenocephalides felis felis on cats].

PubMed

Tancredi, Michelle Godan de Freitas; Correia, Thaís Ribeiro; Ribeiro, Francisco de Assis; Botelho, Maria Clara da Silva Negreiros; Tavares, Pedro Vianna; Scott, Fabio Barbour; Verocai, Guilherme Gomes; Coumendouros, Katherina

2009-01-01

The goal of the present study was to evaluate the comparative efficacy of two topical formulations containing 10% fipronil on the control of Ctenocephalides felis felis on cats. The trial was performed at the Laboratory of Experimental Chemotherapy in Veterinary Parasitology from the Department of Animal Parasitology of the Institute of Veterinary of the Universidade Federal Rural do Rio de Janeiro. Eighteen mixed-breed cats were divided in three groups of six animals each. One group remained without treatment (control). The other groups received as treatment the two topical formulations, a commercial reference and the novel one, both containing 10% fipronil. Treated animals received 0.5 mL of product along their cervical region. Cats were infested on days - 2, +5, +12, +19, +26 and +33. Evaluations were made using the "comb test". The first one was undertaken 4 days after the initial infestation (day +2), and others 48 hours after following infestations (days +7, +14, +21, +28 and + 35). Both tested formulations had satisfactory efficacy until day + 35. No differences were observed comparing the efficacy levels between both formulations throughout the experimental period. The novel topical 10% fipronil formulation presented desirable efficacy on the control of C. f. felis on cats.

Helicobacter pylori induces an antimicrobial response in rhesus macaques in a cag pathogenicity island-dependent manner.

PubMed

Hornsby, Michael J; Huff, Jennifer L; Kays, Robert J; Canfield, Don R; Bevins, Charles L; Solnick, Jay V

2008-04-01

We used the rhesus macaque model to study the effects of the cag pathogenicity island (cag PAI) on the H pylori host-pathogen interaction. H pylori-specific pathogen-free (SPF) monkeys were experimentally challenged with wild-type (WT) H pylori strain J166 (J166WT, n = 4) or its cag PAI isogenic knockout (J166Deltacag PAI, n = 4). Animals underwent endoscopy before and 1, 4, 8, and 13 weeks after challenge. Gastric biopsies were collected for quantitative culture, histopathology, and host gene expression analysis. Quantitative cultures showed that all experimentally challenged animals were infected with J166WT or its isogenic J166Deltacag PAI. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166Deltacag PAI compared with J166WT. Microarray analysis showed that of the 119 up-regulated genes in the J166WT-infected animals, several encode innate antimicrobial effector proteins, including elafin, siderocalin, DMBT1, DUOX2, and several novel paralogues of human-beta defensin-2. Quantitative RT-PCR confirmed that high-level induction of each of these genes depended on the presence of the cag PAI. Immunohistochemistry confirmed increased human-beta defensin-2 epithelial cell staining in animals challenged with J166WT compared with either J166Deltacag PAI-challenged or uninfected control animals. We propose that one function of the cag PAI is to induce an antimicrobial host response that may serve to increase the competitive advantage of H pylori in the gastric niche and could even provide a protective benefit to the host.

Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

PubMed Central

Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

2016-01-01

Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

[Animal testing ethics and human testing. Thoughts on our conduct with and our relationship to animals].

PubMed

Locker, Alfred

2004-01-01

After many years of experimental work with animals of diverse species, the author felt confronted with the question whether the great expenditure of sacrificed animal life would pay off when compared with the results gained. By self-critically considering his work, he gradually experienced a conversion from an unconcerned experimenter to a man feeling a deep sympathy with his fellow creatures. This motivated him to ponder the true nature of animals. Instead of applying ethics--though justified in its own realm--the author preferred to look at the problem using the General Systems Theory (GST), which can describe "the other side" of any system, the side into which any system may occasionally or necessarily transform. It occurred to him to assume that--provided we see a living organism as a system (as Ludwig von Bertalanffy, the founder of GST, did)--the "other side" of the animal would correspond to an innocent "genius" who suffers for man (thereby assuming a Christ-like position), whereas in its transitory life the true essence of the animal is hidden. Thus, by fancifully viewing the role of animals destined to suffer, a connection between GST and theology or religion arises. The consequence for us would be to pay honour to the test animal, irrespective of whether or not painful experiments could be avoided. The differentiation between a sacrifice (spiritually surrendering for a greater good) and a victim (involuntarily subjected to suffering) reveals that the experimental animal primarily belongs to the latter. But it can be elevated to the former when the full meaning of its suffering becomes obvious. The same holds true for "human testing", if, in contrast to the formidable atrocities, e.g. of concentration camps, the momentum of voluntariness is guaranteed, as pioneers of medical research frequently demonstrated by carrying out experiments on themselves.

A Novel Interactive Exoskeletal Robot for Overground Locomotion Studies in Rats.

PubMed

Song, Yun Seong; Hogan, Neville

2015-07-01

This paper introduces a newly developed apparatus, Iron Rat, for locomotion research in rodents. Its main purpose is to allow maximal freedom of voluntary overground movement of the animal while providing forceful interaction to the hindlimbs. Advantages and challenges of the proposed exoskeletal apparatus over other existing designs are discussed. Design and implementation challenges are presented and discussed, emphasizing their implications for free, voluntary movement of the animal. A live-animal experiment was conducted to assess the design. Unconstrained natural movement of the animal was compared with its movement with the exoskeletal module attached. The compact design and back-drivable implementation of this apparatus will allow novel experimental manipulations that may include forceful yet compliant dynamic interaction with the animal's overground locomotion.

Morphologic variations in the pineal gland of the albino rat after a chronic alcoholisation process.

PubMed

Martínez-Salvador, J; Ruiz-Torner, A; Blasco-Serra, A; Martínez-Soriano, F; Valverde-Navarro, A A

2018-04-01

We studied the effect of alcohol on the pineal gland of 48 male Wistar rats. Animals were divided into control and experimental groups. The experimental group underwent a previous progressive alcoholisation period with ethanol diluted in water at a concentration of 40%. Animals were sacrificed at 3, 6, 9 and 12 months, and the ultrastructure, karyometric indices, and number of synaptic bodies in the pineal gland were analysed. The results showed progressive morphologic alterations in the ethanol-treated animals, which culminated in fatty degeneration of the pineal parenchyma after 6 months. The karyometric indices decreased in both the central and peripheral areas compared with the control group. Moreover, the seasonal rhythmicity observed in the controls disappeared in the experimental groups, whose number of different populations of synaptic bodies (synaptic ribbons and synaptic spherules) considerably lowered with inversion of their normal seasonal rhythm. These results support that chronic alcoholisation leads to fatty degeneration of the pineal parenchyma, and a considerable alteration in nuclear functional rhythms and synaptic bodies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oleanolic acid improves pulmonary morphofunctional parameters in experimental sepsis by modulating oxidative and apoptotic processes.

PubMed

Santos, Raquel Souza; Silva, Pedro Leme; de Oliveira, Gisele Pena; Santos, Cintia Lourenço; Cruz, Fernanda Ferreira; de Assis, Edson Fernandes; de Castro-Faria-Neto, Hugo Caire; Capelozzi, Vera Luiza; Morales, Marcelo Marcos; Pelosi, Paolo; Gattass, Cerli Rocha; Rocco, Patricia Rieken Macedo

2013-12-01

We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups. Sepsis was induced by cecal ligation and puncture, while the control group underwent sham surgery. 1h after surgery, all animals were further randomized to receive saline (SAL), OA and dexamethasone (DEXA) intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which were associated with fewer lung neutrophils and less cell apoptosis in lung, liver, and kidney than SAL. However, only animals in the DEXA group had lower levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar lavage fluid than SAL animals. Conversely, OA was associated with lower inducible nitric oxide synthase expression and higher superoxide dismutase than DEXA. In the experimental sepsis model employed herein, OA and DEXA reduced lung damage and distal organ apoptosis through distinct anti-inflammatory mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

Animal-Assisted Therapies for Youth with or at risk for Mental Health Problems: A Systematic Review.

PubMed

Hoagwood, Kimberly Eaton; Acri, Mary; Morrissey, Meghan; Peth-Pierce, Robin

2017-01-01

To systematically review experimental evidence about animal-assisted therapies (AAT) for children or adolescents with or at risk for mental health conditions, we reviewed all experimental AAT studies published between 2000-2015, and compared studies by animal type, intervention, and outcomes. Studies were included if used therapeutically for children and adolescents (≤21 years) with or at risk for a mental health problem; used random assignment or a waitlist comparison/control group; and included child-specific outcome data. Of 1,535 studies, 24 met inclusion criteria. Of 24 studies identified, almost half were randomized controlled trials, with 9 of 11 published in the past two years. The largest group addresses equine therapies for autism. Findings are generally promising for positive effects associated with equine therapies for autism and canine therapies for childhood trauma. The AAT research base is slim; a more focused research agenda is outlined.

Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats.

PubMed

Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Maślak, Edyta; Topolska, Kinga

2015-03-01

The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

[Laboratory animals and official Mexican norms (NOM-062-ZOO-1999)].

PubMed

de Aluja, Aline S

2002-01-01

This article concerns animal experimentation and official Mexican norm Nom 0062-Zoo-1999 entitled Technical specifications for the production, care and use of laboratory animals. The history of animal experimentation is briefly resumed. During the nineteenth century, doubts arose as to the right to expose animals to experimental procedures that frequently cause pain and suffering. The first law which protected animals against cruelty was passed in Great Britain in 1876; subsequently, other nations approved similar legislation. During the second part of the twentieth century, opposition to animal experimentation grew. Other groups, mainly scientists and pharmaceutical concerns, defended the right to use animals in research. New knowledge concerning the neurophysiology, cognitive capacity, and the animal faculty to experience pain is briefly mentioned. Guidelines on care and use of animals used in research published in several countries are listed. Finally, the recently published Mexican legislation (Norm) referring to production, care and use of laboratory animals is discussed and its benefits are stressed.

Comparison of Combat Gauze with Fibrin Sealant Patch in Hemorrhage Control after Vascular or Hepatic Trauma

DTIC Science & Technology

2017-05-15

experimentation are needed to determine the role of fibrin patches in acute traumatic hemorrhage control . 2.0 BACKGROUND Hemorrhage remains the most...Compare performance of CG to EVARREST in a porcine model of vascular trauma. Animals were separated into three groups : 1. Control : Arterial and...trauma. Animals were separated into three groups : 1. Control : Arterial and venous cannulation followed by laparotomy with liver injury and

Comparison of Combat Gauze with Fibrin Sealant Patch in Hemorrhage Control after Vascular or Hepatic Trauma

DTIC Science & Technology

2017-05-01

experimentation are needed to determine the role of fibrin patches in acute traumatic hemorrhage control . 2.0 BACKGROUND Hemorrhage remains the most...Compare performance of CG to EVARREST in a porcine model of vascular trauma. Animals were separated into three groups : 1. Control : Arterial and...trauma. Animals were separated into three groups : 1. Control : Arterial and venous cannulation followed by laparotomy with liver injury and

Anatomy of large animal spines and its comparison to the human spine: a systematic review.

PubMed

Sheng, Sun-Ren; Wang, Xiang-Yang; Xu, Hua-Zi; Zhu, Guo-Qing; Zhou, Yi-Fei

2010-01-01

Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980-2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and differences found in the animal studies must be kept in mind.

The perception of animal experimentation ethics among Indian teenage school pupils.

PubMed

Kim, Justin Namuk; Choi, Eun Hee; Kim, Soo-Ki

2017-03-01

To promote awareness of animal experimentation ethics among teenagers, we created an educational pamphlet and an accompanying questionnaire. One hundred Indian teenage school pupils were given the pamphlet and subsequently surveyed with the questionnaire, to evaluate: a) their perception of animal experimentation ethics; and b) their opinion on the effectiveness of the pamphlet, according to gender and school grade/age. There was a significant correlation between grade/age and support for animal experimentation, i.e. senior students were more inclined to show support for animal experimentation. There was also a significant correlation between gender and perception of the need to learn about animal experimentation ethics, with girls more likely to feel the need to learn about ethics than boys. In addition, the four questions relating to the usefulness of the pamphlet, and student satisfaction with its content, received positive responses from the majority of the students. Even though the pamphlet was concise, it was apparent that three quarters of the students were satisfied with its content. Gender and age did not influence this level of satisfaction. Overall, our study shows that there is a significant correlation between a pupil`s school grade/age and their support for animal experimentation, and that there is also a significant correlation between gender and the perceived need to learn about animal experimentation ethics. This pilot scheme involving an educational pamphlet and questionnaire could be beneficial in helping to formulate basic strategies for educating teenage school pupils about animal ethics. 2017 FRAME.

Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats.

PubMed

Starcevic, Ana; Petricevic, Sasa; Radojicic, Zoran; Djulejic, Vuk; Ilankovic, Andrej; Starcevic, Branislav; Filipovic, Branislav

2016-05-01

This study was conducted to explore the effects of specific psychosocial paradigm on predator animal posttraumatic stress model and to test the hypothesis that psychosocially stressed rats would exibit abnormal levels of cortisol and a larger suppression of cortisol levels after the application of dexamethasone. Animals were divided in two groups: experimental and control groups. The experimental group was exposed to two types of stressors: acute immobilization stress, and combined predator stress and daily social stress with application of dexamethasone. Blood sampling was performed at three different times. We found statistically significant results after analyzing the differences between cortisol levels in different times of blood sampling in the group of animals exposed to stress with dexamethasone application. Statistical significance was found when we compared the experimental group with the control group in terms of elevated cortisol levels during blood sampling after stress paradigm exposition. Many significant disruptions in the functioning of the hypothalamic-pituitary-adrenal axis were observed, such as decrease in basal cortisol levels and enhanced dexamethasone-induced inhibition of cortisol levels. These findings are important because their impact can translate to human individuals with posttraumatic stress disorder, which is the most important role of every animal model in research. Copyright © 2016. Published by Elsevier Taiwan.

Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT using GATE

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

Bretin, Florian; Bahri, Mohamed Ali; Luxen, André

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies involving microCT, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low-level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non-invasively using Monte Carlo simulationsmore » in GATE and to compare results to previously obtained experimental values. Methods: Tungsten X-ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half-value layers were simulated for spectra validation against experimentally measured values of the physical X-ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat. Results: Simulated half-value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%. Conclusions: Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup.« less

Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

PubMed

Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

2017-09-01

Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

Animal Experimentation: Bringing Ethical Issues into Biology Teaching.

ERIC Educational Resources Information Center

Van Rooy, Wilhelmina

2000-01-01

There are many possibilities for the use of controversial issues such as animal experimentation in biology classrooms. Outlines a series of three lessons that asked senior biology students to consider the issue of animal experimentation from three perspectives. (Author/LM)

Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

PubMed

Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

2012-08-01

Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

[Ethical issue in animal experimentation].

PubMed

Parodi, André-Laurent

2009-11-01

In the 1970s, under pressure from certain sections of society and thanks to initiatives by several scientific research teams, committees charged with improving the conditions of laboratory animals started to be created, first in the United States and subsequently in Europe. This led to the development of an ethical approach to animal experimentation, taking into account new scientific advances. In addition to the legislation designed to provide a legal framework for animal experimentation and to avoid abuses, this ethical approach, based on the concept that animals are sentient beings, encourages greater respect of laboratory animals and the implementation of measures designed to reduce their suffering. Now, all animal experiments must first receive ethical approval--from in-house committees in the private sector and from regional committees for public institutions. Very recently, under the impetus of the French ministries of research and agriculture, the National committee for ethical animal experimentation published a national ethical charter on animal experimentation, setting the basis for responsible use of animals for scientific research and providing guidelines for the composition and functioning of ethics committees. Inspired by the scientific community itself this ethical standardization should help to assuage--but not eliminate--the reticence and hostility expressed by several sections of society.

[Alternatives to animal experimentation v.s. animal rights terrorism].

PubMed

Kurosawa, Tsutomu Miki

2008-05-01

Systematic modern animal experimentation was established by Bernard Claude who wrote "An Introduction to the Study of Experimental Medicine" in 1865. At this point, the public was already asking that the pain and distress of experimental animals be reduced. For this, scientists, William Russell and Rex Burch in 1959 proposed the principles of alternatives to animal experimentation, the "3Rs". Since that time, animal welfare advocates have promoted the 3Rs concept in biomedical research communities. However, cruel animal experiments have continued and there are reports of radical extremists showing their opposition by invasion, arson, theft and even bombing of institutions involved, resulting in killing of the animals. SHAC, one extremist group believed to be animal welfare activitists was recognized as a terrorist group after the 9.11 tragedy in USA and the government viewed their activities very seriously. In 2001, British animal extremists invaded Japanese universities and stole laboratory resources; one individual was arrested and sentenced to prison for three years; Japanese who assisted in the incident were arrested and one was sentenced for one year. In 2006, SHAC USA members were prosecuted and sentenced for up to 6 years for their terrorism activities including arson. We need to consider the background of these activities which are financially supported by animal welfare advocates. The way we, as scientists who conduct such experiments can respond is by promoting alternatives to this experimentation. In Japan, the animal welfare law was revised in 2005 stressing the importance of 3Rs in scientific activities with animals. The promotion of 3Rs should be strengthened in the pharmaceutical community.

Effects of euthanasia on brain physiological activities monitored in real-time.

PubMed

Mayevsky, Avraham; Barbiro-Michaely, Efrat; Ligeti, Laszlo; MacLaughlin, Alan C

2002-10-01

Animal experimentation is terminated by the euthanasia procedure in order to avoid pain and minimize suffering. Very little is known about the real time physiological changes taking place in the brain of animals during the euthanasia. Since there is no way to evaluate the suffering of animals under euthanasia, it is assumed that objective physiological changes taking place could serve as a good way to compare various types of euthanasia procedures. In the present study we compared the effect of euthanasia induced by i. v. injection of concentrated KCL to that of Taxan T-61 (a standard mixture used by veterinarians). The responses of the cat brain were evaluated by monitoring the hemodynamic (CBF), metabolic (NADH redox state), electrical (EcoG) and extracellular ion levels, as an indicator to the ionic homeostasis.

Automated Computational Processing of 3-D MR Images of Mouse Brain for Phenotyping of Living Animals.

PubMed

Medina, Christopher S; Manifold-Wheeler, Brett; Gonzales, Aaron; Bearer, Elaine L

2017-07-05

Magnetic resonance (MR) imaging provides a method to obtain anatomical information from the brain in vivo that is not typically available by optical imaging because of this organ's opacity. MR is nondestructive and obtains deep tissue contrast with 100-µm 3 voxel resolution or better. Manganese-enhanced MRI (MEMRI) may be used to observe axonal transport and localized neural activity in the living rodent and avian brain. Such enhancement enables researchers to investigate differences in functional circuitry or neuronal activity in images of brains of different animals. Moreover, once MR images of a number of animals are aligned into a single matrix, statistical analysis can be done comparing MR intensities between different multi-animal cohorts comprising individuals from different mouse strains or different transgenic animals, or at different time points after an experimental manipulation. Although preprocessing steps for such comparisons (including skull stripping and alignment) are automated for human imaging, no such automated processing has previously been readily available for mouse or other widely used experimental animals, and most investigators use in-house custom processing. This protocol describes a stepwise method to perform such preprocessing for mouse. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

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.

Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea.

PubMed

Hrnčić, Dragan; Grubač, Željko; Rašić-Marković, Aleksandra; Šutulović, Nikola; Šušić, Veselinka; Bjekić-Macut, Jelica; Stanojlović, Olivera

2016-03-01

Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6h: 1) sleep disruption (sleep interrupted, SI; 30s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI+L, AC+L and TC+L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI+L group) compared with the animals from TC+L. Seizure latency was also significantly decreased in SI+L compared to AC+L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI+L comparing to AC+L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of short-term weightlessness on inner ear carbonic anhydrase reactivity in fish - a parabolic aircraft flight study

NASA Astrophysics Data System (ADS)

Anken, Ralf; Hilbig, Reinhard; Weigele, Jochen; Anken, Ralf

We have shown earlier that some fish of a given batch reveal motion sickness (a kinetosis) at the transition from increased gravity (hypergravity, hg; centrifuge) to 1g earth gravity. Total macular carbonic anhydrase (CA)-reactivity as well as the difference in reactivities between left and right maculae (asymmetry) were significantly lower in normally swimming hg-animals as compared to the kinetotically behaving hg-fish. This result clearly indicated the existence of a regulatory mechanism, which adjusts otolithic calcium carbonate incorporation via CA- reactivity towards the gravity vector. Thus, we were prompted to investigate, whether fish swimming kinetotically under weightlessness also would reveal an asymmetric CA-reactivity. Therefore, larval cichlid fish (Oreochromis mossambicus) were subjected to parabolic aircraft flights. During the flights, the animals were videorecorded. Subsequently, fish were separated according to their respective swimming behaviour into normally and abnormally (kinetotic) moving individuals (the latter performed spinning movements, i.e., turns around their longitudinal axis). Finally, CA was localized histochemically and densitometrically determined in inner ear maculae. It was found that the total macular CA-reactivity did not differ between ground controls and kinetotically or normally swimming experimental fish. Asymmetry of CA- reactivity, however, was considerably higher in experimental animals as compared to the ground controls. No difference in asymmetry of CA-reactivity was obtained when comparing kinetotic with normally behaving individuals. These results indicate that parabolic flights do not affect CA-reactivity in general, possibly due to the relatively quickly alternating G-levels (g-profile of single parabola: 1g/1.8g/0.04g/1.8g/1g, performed in 70 seconds) in up to 30 parabolas per flight day. The high asymmetry of CA-reactivity in the experimental animals - irrespective of their behaviour - probably indicates an adaptation process, which has presumably been successful in the normally swimming samples. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 0527).

Effect of protein supplementation on ruminal parameters and microbial community fingerprint of Nellore steers fed tropical forages.

PubMed

Bento, C B P; Azevedo, A C; Gomes, D I; Batista, E D; Rufino, L M A; Detmann, E; Mantovani, H C

2016-01-01

In tropical regions, protein supplementation is a common practice in dairy and beef farming. However, the effect of highly degradable protein in ruminal fermentation and microbial community composition has not yet been investigated in a systematic manner. In this work, we aimed to investigate the impact of casein supplementation on volatile fatty acids (VFA) production, specific activity of deamination (SAD), ammonia concentration and bacterial and archaeal community composition. The experimental design was a 4×4 Latin square balanced for residual effects, with four animals (average initial weight of 280±10 kg) and four experimental periods, each with duration of 29 days. The diet comprised Tifton 85 (Cynodon sp.) hay with an average CP content of 9.8%, on a dry matter basis. Animals received basal forage (control) or infusions of pure casein (230 g) administered direct into the rumen, abomasum or divided (50 : 50 ratio) in the rumen/abomasum. There was no differences (P>0.05) in ruminal pH and microbial protein concentration between supplemented v. non-supplemented animals. However, in steers receiving ruminal infusion of casein the SAD and ruminal ammonia concentration increased 33% and 76%, respectively, compared with the control. The total concentration of VFA increased (P0.05) in species richness and diversity of γ-proteobacteria, firmicutes and archaea between non-supplemented Nellore steers and steers receiving casein supplementation in the rumen. However, species richness and the Shannon-Wiener index were lower (P<0.05) for the phylum bacteroidetes in steers supplemented with casein in the rumen compared with non-supplemented animals. Venn diagrams indicated that the number of unique bands varied considerably among individual animals and was usually higher in number for non-supplemented steers compared with supplemented animals. These results add new knowledge about the effects of ruminal and postruminal protein supplementation on metabolic activities of rumen microbes and the composition of bacterial and archaeal communities in the rumen of steers.

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke

PubMed Central

Souza, Celice C.; da Silva, Michelle Castro; Lopes, Rosana Telma; Cardoso, Marcelo M.; Santos, Adriano Guimarães; dos Santos, Ijair Rogério

2017-01-01

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells (p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control (p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation. PMID:28713482

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke.

PubMed

Souza, Celice C; da Silva, Michelle Castro; Lopes, Rosana Telma; Cardoso, Marcelo M; de Souza, Lucas Lacerda; Santos, Adriano Guimarães; Dos Santos, Ijair Rogério; Franco, Edna C S; Gomes-Leal, Walace

2017-01-01

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated ( N = 5), minocycline-treated ( N = 5), and BMMC-transplanted ( N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells ( p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control ( p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation.

Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis

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

Seidman, E.G.; Hanson, D.G.; Walker, W.A.

1986-01-01

Little information is available regarding colonic permeability to macromolecules in health or disease states. In vivo permeability of rabbit colon to (/sup 14/C)polyethylene glycol 4000 (/sup 14/C-PEG) was examined in the presence of immune complex-mediated experimental colitis and compared with that of partially treated (control) and normal rabbits. Permeability was assessed by urinary /sup 14/C-PEG excretion after intrarectal administration of 0.1 mM solution of /sup 14/C-PEG (1 ml/kg, 7.5 X 10(6) cpm/ml). Experimental colitis greatly increased colonic permeability (p less than 0.001 in two-way analysis of variance) compared with control and normal groups (2.06% +/- 0.19%, 0.14% +/- 0.04%, andmore » 0.01% +/- 0.004%, respectively, of rectally administered counts). Gel diffusion chromatography showed that absorbed /sup 14/C-PEG was excreted into urine unchanged, demonstrating its applicability as an inert, nonmetabolizable macromolecular probe. Urinary clearance after mesenteric vein administration of /sup 14/C-PEG was similar in normal animals and animals with colitis, implicating colonic absorption as the source of the group differences. Postmortem histology confirmed the acute colitis lesions in the experimental group. These findings support the hypothesis that nonspecific colonic inflammation is associated with significant alterations of mucosal permeability.« less

Small animal radiotherapy research platforms

NASA Astrophysics Data System (ADS)

Verhaegen, Frank; Granton, Patrick; Tryggestad, Erik

2011-06-01

Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research.

Suppression of male reproduction in rats after exposure to sodium fluoride during early stages of development

NASA Astrophysics Data System (ADS)

Reddy, P. Sreedhar; Pushpalatha, T.; Reddy, P. Sreenivasula

2007-07-01

Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3β hydroxysteroid dehydrogenase and 17β hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.

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

PubMed

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

1991-01-01

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

Metabolomic phenotyping of a cloned pig model

PubMed Central

2011-01-01

Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals. PMID:21859467

Liquid chromatography tandem-mass spectrometry (LC-MS/MS) and dried blood spot sampling applied to pharmacokinetics studies in animals: Correlation of classic and block design.

PubMed

Baldo, Matías N; Angeli, Emmanuel; Gareis, Natalia C; Hunzicker, Gabriel A; Murguía, Marcelo C; Ortega, Hugo H; Hein, Gustavo J

2018-04-01

A relative bioavailability study (RBA) of two phenytoin (PHT) formulations was conducted in rabbits, in order to compare the results obtained from different matrices (plasma and blood from dried blood spot (DBS) sampling) and different experimental designs (classic and block). The method was developed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) in plasma and blood samples. The different sample preparation techniques, plasma protein precipitation and DBS, were validated according to international requirements. The analytical method was validated with ranges 0.20-50.80 and 0.12-20.32 µg ml -1 , r > 0.999 for plasma and blood, respectively. Accuracy and precision were within acceptance criteria for bioanalytical assay validation (< 15 for bias and CV% and < 20 for limit of quantification (LOQ)). PHT showed long-term stability, both for plasma and blood, and under refrigerated and room temperature conditions. Haematocrit values were measured during the validation process and RBA study. Finally, the pharmacokinetic parameters (C max , T max and AUC 0-t ) obtained from the RBA study were tested. Results were highly comparable for matrices and experimental designs. A matrix correlation higher than 0.975 and a ratio of (PHT blood) = 1.158 (PHT plasma) were obtained. The results obtained herein show that the use of classic experimental design and DBS sampling for animal pharmacokinetic studies should be encouraged as they could help to prevent the use of a large number of animals and also animal euthanasia. Finally, the combination of DBS sampling with LC-MS/MS technology showed to be an excellent tool not only for therapeutic drug monitoring but also for RBA studies.

9 CFR 103.1 - Preparation of experimental biological products.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of...

Ethical issues associated with the use of animal experimentation in behavioral neuroscience research.

PubMed

Ohl, Frauke; Meijboom, Franck

2015-01-01

This chapter briefly explores whether there are distinct characteristics in the field of Behavioral Neuroscience that demand specific ethical reflection. We argue that although the ethical issues in animal-based Behavioral Neuroscience are not necessarily distinct from those in other research disciplines using animal experimentation, this field of endeavor makes a number of specific, ethically relevant, questions more explicit and, as a result, may expose to discussion a series of ethical issues that have relevance beyond this field of science. We suggest that innovative research, by its very definition, demands out-of-the-box thinking. At the same time, standardization of animal models and test procedures for the sake of comparability across experiments inhibits the potential and willingness to leave well-established tracks of thinking, and leaves us wondering how open minded research is and whether it is the researcher's established perspective that drives the research rather than the research that drives the researcher's perspective. The chapter finishes by introducing subsequent chapters of this book volume on Ethical Issues in Behavioral Neuroscience.

Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy: a case report

PubMed Central

Sadoun, A.; Strelnikov, K.; Bonté, E.; Fonta, C.; Girard, P.

2015-01-01

The number of studies that use the common marmoset (Callithrix jacchus) in various fields of neurosciences is increasing dramatically. In general, animals enter the study when their health status is considered satisfactory on the basis of classical clinical investigations. In behavioral studies, variations of score between individuals are frequently observed, some of them being considered as poor performers or outliers. Experimenters rarely consider the fact that it could be related to some brain anomaly. This raises the important issue of the reliability of such classical behavioral approaches without using complementary imaging, especially in animals lacking striking external clinical signs. Here we report the case of a young marmoset which presented a set of cognitive impairments in two different tasks compared to other age-matched animals. Brain imaging revealed a patent right lateral ventricular enlargement with a mild hippocampal atrophy. This abnormality could explain the cognitive impairments of this animal. Such a case points to the importance of complementing behavioral studies by imaging explorations to avoid experimental bias. PMID:26527211

Establishment of a New Zealand rabbit model of spinal tuberculosis.

PubMed

Geng, Guangqi; Wang, Qian; Shi, Jiandang; Yan, Junfa; Niu, Ningkui; Wang, Zili

2015-04-01

This was an experimental study. To investigate and evaluate the experimental method of establishing a New Zealand rabbit model of spinal tuberculosis. Establishing animal models of tuberculosis is critical to the experimental and clinical study of tuberculosis, especially spinal tuberculosis. However, the rapid spread of Mycobacterium tuberculosis and subsequent high mortality thwarted their effort. Since then, no animal models have been established of spinal tuberculosis. Forty-two New Zealand rabbits were randomly divided into experimental (n=20), control (n=20), and blank groups (n=2). Experimental animals were sensitized by complete Freund's adjuvant. A hole drilled under the upper endplate of the L4 vertebral body was filled with a gelfoam sponge infused with 0.1 mL H37Rv standard M. tuberculosis suspension (in controls, culture medium, and saline). Blank animals received no treatment. Survival 8 weeks after surgery was 89.5%, 94.7%, and 100% in experimental, control, and blank groups, respectively. The model was successfully established in all surviving experimental rabbits. In experimental animals, vertebral body destruction at 4 weeks was 50% by x-ray; 83.3% by computed tomography reconstruction and magnetic resonance imaging; at 8 weeks, 58.8% by x-ray and 100% by computed tomograph reconstruction and magnetic resonance imaging. At 8 weeks, experimental animals developed vertebral destruction, granulation, and necrosis and 17.6% had psoas abscess. Histopathology revealed numerous lymphocytes and epithelioid cells, trabecular bone fracture, and coagulative necrosis in the vertebrae of experimental animals; bacterium culture was 52.9% positive. Control and blank animals showed no such changes. A New Zealand rabbit of spinal tuberculosis model can be successfully established by drilling a hole in the upper endplate of the vertebral body, filling with gelfoam sponge infused with H37Rv standard M. tuberculosis suspension after sensitization by complete Freund's adjuvant.

The effectiveness of health animations in audiences with different health literacy levels: an experimental study.

PubMed

Meppelink, Corine S; van Weert, Julia C M; Haven, Carola J; Smit, Edith G

2015-01-13

Processing Web-based health information can be difficult, especially for people with low health literacy. Presenting health information in an audiovisual format, such as animation, is expected to improve understanding among low health literate audiences. The aim of this paper is to investigate what features of spoken health animations improve information recall and attitudes and whether there are differences between health literacy groups. We conducted an online experiment among 231 participants aged 55 years or older with either low or high health literacy. A 2 (spoken vs written text) x 2 (illustration vs animation) design was used. Participants were randomly exposed to one of the four experimental messages, all providing the same information on colorectal cancer screening. The results showed that, among people with low health literacy, spoken messages about colorectal cancer screening improved recall (P=.03) and attitudes (P=.02) compared to written messages. Animations alone did not improve recall, but when combined with spoken text, they significantly improved recall in this group (P=.02). When exposed to spoken animations, people with low health literacy recalled the same amount of information as their high health literate counterparts (P=.12), whereas in all other conditions people with high health literacy recalled more information compared to low health literate individuals. For people with low health literacy, positive attitudes mediated the relationship between spoken text and the intention to have a colorectal cancer screening (b=.12; 95% CI 0.02-0.25). We conclude that spoken animation is the best way to communicate complex health information to people with low health literacy. This format can even bridge the information processing gap between audiences with low and high health literacy as the recall differences between the two groups are eliminated. As animations do not negatively influence high health literate audiences, it is concluded that information adapted to audiences with low health literacy suits people with high health literacy as well.

The Effectiveness of Health Animations in Audiences With Different Health Literacy Levels: An Experimental Study

PubMed Central

van Weert, Julia CM; Haven, Carola J; Smit, Edith G

2015-01-01

Background Processing Web-based health information can be difficult, especially for people with low health literacy. Presenting health information in an audiovisual format, such as animation, is expected to improve understanding among low health literate audiences. Objective The aim of this paper is to investigate what features of spoken health animations improve information recall and attitudes and whether there are differences between health literacy groups. Methods We conducted an online experiment among 231 participants aged 55 years or older with either low or high health literacy. A 2 (spoken vs written text) x 2 (illustration vs animation) design was used. Participants were randomly exposed to one of the four experimental messages, all providing the same information on colorectal cancer screening. Results The results showed that, among people with low health literacy, spoken messages about colorectal cancer screening improved recall (P=.03) and attitudes (P=.02) compared to written messages. Animations alone did not improve recall, but when combined with spoken text, they significantly improved recall in this group (P=.02). When exposed to spoken animations, people with low health literacy recalled the same amount of information as their high health literate counterparts (P=.12), whereas in all other conditions people with high health literacy recalled more information compared to low health literate individuals. For people with low health literacy, positive attitudes mediated the relationship between spoken text and the intention to have a colorectal cancer screening (b=.12; 95% CI 0.02-0.25). Conclusions We conclude that spoken animation is the best way to communicate complex health information to people with low health literacy. This format can even bridge the information processing gap between audiences with low and high health literacy as the recall differences between the two groups are eliminated. As animations do not negatively influence high health literate audiences, it is concluded that information adapted to audiences with low health literacy suits people with high health literacy as well. PMID:25586711

Effects of the short-chain triglyceride triacetin on intestinal mucosa and metabolic substrates in rats.

PubMed

Lynch, J W; Miles, J M; Bailey, J W

1994-01-01

Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCTs) were fed to rats to determine the effects on intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed one of three diets, a control diet containing 5% of energy as LCTs or one of two experimental diets that contained 30% of energy as lipid. The lipid component of the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma lactate, glucose, and total ketone body concentrations were not significantly different among dietary treatment groups. Compared with animals fed LCTs and control diet, plasma pyruvate and free fatty acid concentrations were decreased in animals fed triacetin. In contrast, plasma triglyceride concentrations were elevated in animals fed triacetin compared with other groups. Intestinal biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio. Histologic indices measured were villus height in the jejunum and crypt depth in the colon. No significant difference in mucosal protein concentration was observed in the jejunum and colon. Jejunal RNA was significantly decreased in animals fed triacetin compared with other diets. Triacetin feeding significantly increased the DNA content in the jejunum and colon (thereby lowering the protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus height and colonic crypt depth were not significantly different among dietary treatment groups. Provision of a balanced diet containing 28.5% of the total calories as triacetin had no adverse effects on metabolic substrates and resulted in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental evaluation of clinical colon anastomotic leakage.

PubMed

Pommergaard, Hans-Christian

2014-03-01

Colorectal anastomotic leakage remains a frequent and serious complication in gastrointestinal surgery. Patient and procedure related risk factors for anastomotic leakage have been identified. However, the responsible pathophysiological mechanisms are still unknown. Among these, ischemia and insufficient surgical technique have been suggested to play a central role. Animal models are valuable means to evaluate pathophysiological mechanisms and may be used to test preventive measures aiming at reducing the risk of anastomotic leakage, such as external anastomotic coating. The aim of this thesis was to: Clarify the best suited animal to model clinical anastomotic leakage in humans; Create animal models mimicking anastomotic leakage in humans induced by insufficient surgical technique and tissue ischemia; Determine the best suited coating materials to prevent anastomotic leakage. This study is a systematic review using the databases MEDLINE and Rex. MEDLINE was searched up to October 2010 to identify studies on experimental animal models of clinical colon anastomotic leakage. From the Rex database, textbooks on surgical aspects as well as gastrointestinal physiology and anatomy of experimental animals were identified. The results indicated that the mouse and the pig are the best suited animals to evaluate clinical anastomotic leakage. However, the pig model is less validated and more costly to use compared with the mouse. Most frequently, rats are used as models. However, extreme interventions are needed to create clinical leakage in these animals. The knowledge from this study formed the basis for selecting the animal species most suited for the models in the next studies. STUDY 2: In this experimental study, technically insufficient colonic anastomoses were performed in 110 C57BL/6 mice. The number of sutures in the intervention group was reduced to produce a suitable leakage rate. Moreover, the analgesia and suture material were changed in order to optimize the model. In the final experiment, the four-suture anastomoses resulted in a 40% leakage rate in the intervention groups, whereas the eight-suture control anastomoses had a 0% leakage rate. Furthermore, the use of absorbable suture together with voluntarily ingested Temgesic in chocolate spread as analgesic regimen were feasible. This model may be used to test the leakage reducing potential of coating materials. STUDY 3: This experimental study used 53 C57BL/6 mice, in which sufficient eight-suture anastomoses were created. By using bipolar electro-cautery, blood supply was reduced in a stepwise manner to create anastomotic leakage as a result of ischemia. The study showed that reduced blood supply led to large bowel obstruction instead of clinical leakage. However, anastomotic breaking strength was reduced in the ischemic anastomoses. STUDY 4: In this systematic review MEDLINE, Embase and Cinahl were searched up to September 2011 to identify studies evaluating external coating of colonic anastomoses. Most studies were experimental, in which designs were not comparable and many results were contradictory. In a clinical study, a non-significant benefit of fibrin sealant was found. Based on the available clinical and experimental data it was concluded that the fibrin-based sealants, such as Tisseel and Tachosil, and polyethylene glycols may be beneficial. However, further experimental and clinical studies are needed before routine clinical use can be recommended. The studies in this thesis may be valuable for the experimental research field of clinical anastomotic leakage. The model of technical insufficiency has been improved and is now thoroughly validated. If used by researchers worldwide, comparison of results is possible. Pure ischemia/anoxia may be too simple an approach to create a clinical leakage model. Thus, future models could focus on multiple risk factors. Conclusively, large-scale clinical multicenter studies are needed to definitively evaluate whether coating of colorectal anastomoses may reduce the leakage rate.

Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis.

PubMed

Tambella, Adolfo Maria; Attili, Anna Rita; Dupré, Gilles; Cantalamessa, Andrea; Martin, Stefano; Cuteri, Vincenzo; Marcazzan, Sabrina; Del Fabbro, Massimo

2018-01-01

The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges' g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007-2016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced full-thickness skin wounds in animals. PRP can therefore be considered an effective adjunctive therapy in stimulating second intention healing of acute wounds in healthy animals.

Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis

PubMed Central

Attili, Anna Rita; Dupré, Gilles; Cantalamessa, Andrea; Martin, Stefano; Cuteri, Vincenzo; Marcazzan, Sabrina; Del Fabbro, Massimo

2018-01-01

The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges’ g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007–2016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced full-thickness skin wounds in animals. PRP can therefore be considered an effective adjunctive therapy in stimulating second intention healing of acute wounds in healthy animals. PMID:29324848

Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

PubMed Central

2013-01-01

Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

PubMed

Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

2010-02-01

The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

An automated psychoacoustic testing apparatus for use in cats.

PubMed

Benovitski, Yuri B; Blamey, Peter J; Rathbone, Graeme D; Fallon, James B

2014-03-01

Animal behavioral studies make a significant contribution to hearing research and provide vital information which is not available from human subjects. Animal psychoacoustics is usually extremely time consuming and labor intensive; in addition, animals may become stressed, especially if restraints or negative reinforcers such as electric shocks are used. We present a novel behavioral experimental system that was developed to allow efficient animal training in response to acoustic stimuli. Cats were required to perform a relatively simple task of moving toward and away from the device depending on whether the members of a tone pair were different or the same in frequency (go/no-go task). The experimental setup proved to be effective, with all animals (N = 7) performing at above 90% correct on an easy task. Animals were trained within 2-4 weeks and then generated a total of 150-200 trials per day, distributed within approximately 8 self initiated sessions. Data collected using this system were stable over 1 week and repeatable over long test periods (14 weeks). Measured frequency discrimination thresholds from 3 animals at 3 different reference frequencies were comparable with previously published results. The main advantages of the system are: relatively simple setup; large amounts of data can be generated without the need of researcher supervision; multiple animals can be tested simultaneously without removal from home pens; and no electric shocks or restraints are required. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma.

PubMed

Morrison, J C; Nylander, K B; Lauer, A K; Cepurna, W O; Johnson, E

1998-03-01

To determine whether chronic topical glaucoma therapy can control intraocular pressure (IOP) and protect nerve fibers in a rat model of pressure-induced optic nerve damage. Sixteen adult Brown Norway rats were-administered unilateral episcleral vein injections of hypertonic saline to produce scarring of the aqueous humor outflow pathways. Twice daily applications of either artificial tears (n = 6), 0.5% betaxolol (n = 5), or 0.5% apraclonidine (n = 5) were delivered to both eyes, and awake pressures were monitored with a TonoPen XL tonometer for 17 days before the rats were killed. For animals administered artificial tears, the mean IOP of the experimental eyes was 39 +/- 2 mm Hg compared with 29 +/- 1 mm Hg for the control eyes. This difference was statistically significant (P < 0.001). Mean IOPs in the experimental eyes of animals administered betaxolol and apraclonidine were 29 +/- 7 and 29 +/- 4 mm Hg, respectively, whereas the mean IOP in the control eyes was 28 +/- 1 mm Hg for both groups. There was no statistically significant difference among these values. The mean IOP for the experimental eyes in the betaxolol and apraclonidine groups was lower than that in animals administered artificial tears (P = 0.003). Quantitative histologic analysis of optic nerve damage in experimental eyes showed that four of the six animals administered artificial tears had damage involving 100% of the neural area. This degree of damage appeared in only 3 of 10 animals administered glaucoma therapy. Optic nerve protection was closely correlated with IOP history because damage was limited to less than 10% of the cross-sectional area in all animals in which the maximal IOP was less than or equal to 39 mm Hg, more than 2 SD below the mean value for eyes administered artificial tears. Topical glaucoma therapy in this model can prevent IOP elevation and protect optic nerve fibers.

The Impact of Environmental Light Intensity on Experimental Tumor Growth.

PubMed

Suckow, Mark A; Wolter, William R; Duffield, Giles E

2017-09-01

Cancer research requires for consistent models that minimize environmental variables. Within the typical laboratory animal housing facility, animals may be exposed to varying intensities of light as a result of cage type, cage position, light source, and other factors; however, studies evaluating the differential effect of light intensity during the light phase on tumor growth are lacking. The effect of cage face light intensity, as determined by cage rack position was evaluated with two tumor models using the C57Bl/6NHsd mouse and transplantable B16F10 melanoma cells or Lewis lung carcinoma (LLC) cells. Animals were housed in individually-ventilated cages placed at the top, middle, or bottom of the rack in a diagonal pattern so that the top cage was closest to the ceiling light source, and cage face light intensity was measured. Following a two-week acclimation period at the assigned cage position, animals were subcutaneously administered either 1.3×10 6 B16F10 melanoma cells or 2.5×10 5 Lewis lung carcinoma cells. Weights of excised tumors were measured following euthanasia 18 days (melanoma) or 21 days (LCC) after tumor cell administration. Cage face light intensity was significantly different depending on the location of the cage, with cages closest to the light source have the greatest intensity. Mean tumor weights were significantly less (p<0.001 for melanoma; p≤0.01 for LCC) in middle light intensity mice compared to high and low light intensity mice. The environmental light intensity to which experimental animals are exposed may vary markedly with cage location and can significantly influence experimental tumor growth, thus supporting the idea that light intensity should be controlled as an experimental variable for animals used in cancer research. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Animal experimentation--a personal view.

PubMed

Gershoff, Stanley N

2009-02-01

Disagreement about the use of animals in biomedical research has resulted in absurd positions by both sides. Increasingly, some zealots against animal experimentation have resorted to violence or other illegal acts to support their points of view. The value of animal research in providing better health for man and animals is incontrovertible. This is illustrated by references to animal research in the field of nutrition.

The rights of man and animal experimentation.

PubMed Central

Martin, J

1990-01-01

Since emotions give contradictory signals about animal experimentation in medical science, man's relationship to animals must be based upon reason. Thomas Aquinas argues that man is essentially different from animals because man's intellectual processes show evidence of an abstract mechanism not possessed by animals. Man's rights arise in association with this essential difference. The consequence is that only man possesses true rights by Aquinas's definition; animals have them only by analogy. However, cruelty to animals is illicit and they should be protected, principally not because they have rights, but because he who is cruel to animals is more likely to be cruel to his fellowman. If there is a need for animal experimentation in science for the good of man, this approach gives philosophical justification for experimentation, since man's well-being must come before that of animals because of his unique possession of rights. However, those experiments should be carried out in the kindest way possible, to promote kindness towards man. To see man as solely part of a biological continuum in competition for rights with those beings close to him biologically, detracts from man's dignity. PMID:2135948

Resveratrol regulates hyperglycemia-induced modulations in experimental diabetic animal model.

PubMed

Rehman, Kanwal; Saeed, Kiran; Munawar, Syeda Mehak; Akash, Muhammad Sajid Hamid

2018-06-01

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium. The results of present study indicate the RSV (P < 0.001) alone and/or in combination with Vit-E (P < 0.001) exhibited a highly significant therapeutic potentials by ameliorating the glycemia-induced modulations. Moreover, we also found that RSV in combination with Vit-E also exhibited a better therapeutic effects when compared with that of MF (P < 0.001) and Vit-E (P < 0.05), respectively. Hence, we conclude that RSV alone and/or in combination with Vit-E exhibit its significant therapeutic potentials against hyperglycemia-induced modulations in experimental diabetic animal model and may be one of the most exciting prospect for future treatment of T2DM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

PubMed Central

Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

2011-01-01

Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

Animal experimentation in snake venom research and in vitro alternatives.

PubMed

Sells, Paula G

2003-08-01

Current experimental techniques used in snake venom research (with and without the use of animals) are reviewed. The emphasis is on the reduction of the use of animals in the development of antivenoms for the clinical treatment of snakebite. Diagnostic and research techniques for the major pathologies of envenoming are described and those using animals are contrasted with non-sentient methods where possible. In particular, LD50 and ED50 assays using animals (in vivo) and fertilised eggs (in vivo, non-sentient) are compared as well as in vitro procedures (ELISA and haemolytic test) for ED50 estimations. The social context of antivenom production, supply and demand is outlined together with the consequent tension between the benefits derived and the increase in opposition to experiments on animals. Stringent regulations governing the use of animals, limited research funds and public pressure all focus the need for progress towards non-animal, or non-sentient, research methods. Some achievements are noted but success is hampered by lack of detailed knowledge of the many constituents of venom which have to be assessed as a whole rather than individually. The only way to evaluate the net pathological effect of venom is to use a living system, usually a rodent, and similarly, the efficacy of antivenoms is also measured in vivo. The pre-clinical testing of antivenoms in animals is therefore a legal requirement in many countries and is strictly monitored by government authorities. New technologies applied to the characterisation of individual venom proteins should enable novel in vitro assays to be designed thus reducing the number of animals required. In the meantime, the principles of Reduce, Refine and Replace relating to animals in research are increasingly endorsed by those working in the field and the many agencies regulating ethical and research policy.

Extraluminal biodegradable splint to treat upper airway anterior malacia: A preclinical proof of principle.

PubMed

Gorostidi, François; Courbon, Cécile; Burki, Marco; Reinhard, Antoine; Sandu, Kishore

2018-02-01

Upper airway malacia highly complicates the treatment of benign laryngotracheal stenosis, and no ideal option is available to date. We here explore the use of extraluminal biodegradable splints in an animal model of long-segment anterior tracheomalacia (TM). We show the efficacy, as well as the tissue tolerance, of a custom-made biodegradable extraluminal device surgically inserted around the trachea. Preclinical animal study. Anterior TM was induced in rabbits through an anterior neck approach by removing eight consecutive anterior tracheal rings without damaging the underlying mucosa. Malacia was corrected during the same surgery by pexy sutures, suspending the tracheal mucosa to an experimental biodegradable device. Symptoms, survival, and tissue reaction were compared to healthy and sham surgery controls. The model induced death by respiratory failure within minutes. Ten animals received the experimental treatment, and those who survived the perioperative period remained asymptomatic with a maximum follow-up of 221 days. Histological studies at programmed euthanasia showed complete degradation of the prosthesis, with significant remnant fibrosis around the trachea. However, the tracheal stiffness of test segments was comparatively less than that of control segments. Extraluminal biodegradable splints rescued animals with a condition otherwise incompatible with life. It was well tolerated, leaving peritracheal fibrosis that was not as stiff as normal trachea. The external tracheal stiffening was sufficient for the test animals to live through the phase of severe acute hypercollapsibility. This represents a valid option to help pediatric patients with laryngotracheal stenosis and associated cartilaginous airway malacia. NA. Laryngoscope, 128:E53-E58, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

They See a Rat, We Seek a Cure for Diseases: The Current Status of Animal Experimentation in Medical Practice

PubMed Central

Kehinde, Elijah O.

2013-01-01

The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. PMID:24217224

They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice.

PubMed

Kehinde, Elijah O

2013-01-01

The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. © 2013 S. Karger AG, Basel.

Evaluation of cross-protection by immunization with an experimental trivalent companion animal periodontitis vaccine in the mouse periodontitis model.

PubMed

Hardham, John; Sfintescu, Cornelia; Evans, Richard T

2008-03-01

Companion animal periodontal disease is one of the most prevalent diseases seen by veterinarians. The goal of this study was to evaluate the vaccine performance of a trivalent canine periodontitis vaccine in the mouse oral challenge model of periodontitis. Mice vaccinated subcutaneously with an inactivated, whole-cell vaccine preparation of Porphyromonas denticanis, Porphyromonas gulae, and Porphyromonas salivosa displayed significantly reduced alveolar bone loss in response to heterologous and cross-species challenges as compared to sham vaccinated animals. Based on the results of these studies, a periodontitis vaccine may be a useful tool in preventing the initiation and progression of periodontitis caused by the most commonly isolated pigmenting anaerobic bacteria in animals.

Direct agglutination test for serologic diagnosis of Neospora caninum infection.

PubMed

Romand, S; Thulliez, P; Dubey, J P

1998-01-01

A direct agglutination test was evaluated for the detection and quantitation of IgG antibodies to Neospora caninum in both experimental and natural infections in various animal species. As compared with results obtained by the indirect fluorescent antibody test, the direct agglutination test appeared reliable for the serologic diagnosis of neosporosis in a variety of animal species. The direct agglutination test should provide easily available and inexpensive tools for serologic testing for antibodies to N. caninum in many host species.

[Animal experiment comparison of the therapeutic efficacy of tumor excision with a scalpel or with a CO2 laser in subcutaneously implanted Lewis lung cancer].

PubMed

Mahn, H R; Nowak, C; Audring, H; Liebetruth, J; Lindenau, K F

1982-02-01

An animal experimental study was carried out in order to compare the therapeutical value of two different surgical methods for excising the subcutaneous implanted Lewis lung carcinoma - tumor excision with scalpel or with carbon dioxide laser. The radicalism of operation methods, the survival time, and the tumor local recurrences were performed. The therapeutic effectivity of tumor excision with the carbon dioxide laser is more favourable than the scalpel method.

A comparison of blood loss during the Halal slaughter of lambs following Traditional Religious Slaughter without stunning, Electric Head-Only Stunning and Post-Cut Electric Head-Only Stunning.

PubMed

Khalid, Rizvan; Knowles, Toby G; Wotton, Steve B

2015-12-01

Blood lost at exsanguination during the Halal slaughter of lambs was compared between the slaughter methods of Traditional Religious Slaughter without stunning (TRS), Electric Head-Only Stunning (EHOS) and Post-Cut Electric Head-Only Stunning (PCEHOS). Two protocols were examined, Experimental (80 lambs) and Commercial (360 lambs), assessing varying periods of animal orientation during the 4 min bleeding process (upright orientation before vertical hanging). Live-weight, blood weight (Experimental only), carcass weights and by-product weights were recorded. The Experimental protocol highlighted an increase in blood loss at 60s in EHOS and PCEHOS compared to TRS (P<0.001) but by 90 s there was no significant difference. A post-slaughter change in animal orientation from an upright to a vertical hanging position aided the amount of blood loss. The bleeding of lambs is largely completed by 2 min. There were no significant differences (P>0.05) in final blood loss between treatments. This research was undertaken to inform discussion on the merits of different slaughter methods compatible with Halal requirements. Copyright © 2015. Published by Elsevier Ltd.

[EFFECTIVENESS OF FULLERENE-(TRIS-AMINOCAPRONIC ACID) HYDRATE IN THE MODEL OF EXPERIMENTAL VIRAL-BACTERIAL PNEUMONIA OF MICE].

PubMed

Falynskova, I N; Leonova, E I; Fedyakina, I T; Makhmudova, N R; Lepekha, L N; Mikhailova, N A; Rasnetsov, L D; Zverev, V V; Leneva, I A

2015-01-01

Study the effectiveness of the substance and various drug formulations of fullerene-(tris-aminocapronic acid) hydrate (FTAAH onwards) in the model of experimental viral-bacterial pneumonia of mice. BALB/c mice were infected with influenza virus A/California/04/2009 and subsequently infected with Staphylococcus aureus. The animals were treated after viral infection with the substance and various drug forms of FTAAH, as well as comparative preparations--oseltamivir and arbidol. Therapy effectiveness was evaluated by clinical indicators (survival, lifespan, animal mass decrease reduction), virological (virus titer), microbiological (density of bacteria in lungs) parameters, confirmed by pathomorphological characteristics of lungs. FTAAH therapy in injectable form was effective in the model of a combined viral-bacterial pneumonia of mice by all the studied criteria: treatment increased mice survival, reduced the decrease of their body weight, resulted in a reduction of virus titers and density of bacteria in lungs, that correlated with the data from morphological study and signs of bronchopneumonia resolution in mice. FTAAH therapy in rectal form depended on animal infection schemes, as well as preparation dose, increasing with its increase. FTAAH substance is effective in the model of experimental viral-bacterial pneumonia of mice.

Aeromonas caviae inhibits hepatic enzymes of the phosphotransfer network in experimentally infected silver catfish: Impairment on bioenergetics.

PubMed

Baldissera, M D; Souza, C F; Verdi, C M; Dos Santos, K L M; Da Veiga, M L; da Rocha, M I U M; Santos, R C V; Vizzotto, B S; Baldisserotto, B

2018-03-01

Several studies have been demonstrated that phosphotransfer network, through the adenylate kinase (AK) and pyruvate kinase (PK) activities, allows for new perspectives leading to understanding of disease conditions associated with disturbances in energy metabolism, metabolic monitoring and signalling. In this sense, the aim of this study was to evaluate whether experimental infection by Aeromonas caviae alters hepatic AK and PK activities of silver catfish Rhamdia quelen. Hepatic AK and PK activities decreased in infected animals compared to uninfected animals, as well as the hepatic adenosine triphosphate (ATP) levels. Also, a severe hepatic damage was observed in the infected animals due to the presence of dilation and congestion of vessels, degeneration of hepatocytes and loss of liver parenchyma architecture and sinusoidal structure. Therefore, we have demonstrated, for the first time, that experimental infection by A. caviae inhibits key enzymes linked to the communication between sites of ATP generation and ATP utilization. Moreover, the absence of a reciprocal compensatory mechanism between these enzymes contributes directly to hepatic damage and for a severe energetic imbalance, which may contribute to disease pathophysiology. © 2017 John Wiley & Sons Ltd.

Pre-existing periodontitis exacerbates experimental arthritis in a mouse model.

PubMed

Cantley, Melissa D; Haynes, David R; Marino, Victor; Bartold, P Mark

2011-06-01

Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid arthritis (RA) and that patients with periodontitis are at a greater risk of developing RA. The aim of this study was to develop an animal model to assess the relationship between pre-existing periodontitis and experimental arthritis (EA). Periodontitis was first induced in mice by oral gavage with Porphyromonas gingivalis followed by EA using the collagen antibody-induced arthritis model. These animals were compared with animals with periodontitis alone, EA alone and no disease (controls). Visual changes in paw swelling were assessed to determine clinical development of EA. Alveolar bone and joint changes were assessed using micro-CT, histological analyses and immunohistochemistry. Serum levels of C-reactive protein were used to monitor systemic inflammation. Mice with pre-existing periodontitis developed more severe arthritis, which developed at a faster rate. Mice with periodontitis only also showed evidence of loss of bone within the radiocarpal joint. There was also evidence of alveolar bone loss in mice with EA alone. The results of this study indicate that pre-existing periodontitis exacerbated experimental arthritis in a mouse model. © 2011 John Wiley & Sons A/S.

Children's Attitudes To the Use of Animals in Education and Research: What Are Their Justifications and Reservations?

ERIC Educational Resources Information Center

Foster, Craig; And Others

1994-01-01

Describes the results of a survey using an open-form questionnaire to determine student attitudes toward animal experimentation. Results indicate that children's views about animal experimentation for research depend on the purpose of the research. More than half felt experimentation for pure research is inappropriate. (DDR)

Amitriptyline reverses hyperalgesia and improves associated mood-like disorders in a model of experimental monoarthritis.

PubMed

Amorim, D; David-Pereira, A; Pertovaara, A; Almeida, A; Pinto-Ribeiro, F

2014-05-15

Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-01-01

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

Feeding type affects microplastic ingestion in a coastal invertebrate community.

PubMed

Setälä, Outi; Norkko, Joanna; Lehtiniemi, Maiju

2016-01-15

Marine litter is one of the problems marine ecosystems face at present, coastal habitats and food webs being the most vulnerable as they are closest to the sources of litter. A range of animals (bivalves, free swimming crustaceans and benthic, deposit-feeding animals), of a coastal community of the northern Baltic Sea were exposed to relatively low concentrations of 10 μm microbeads. The experiment was carried out as a small scale mesocosm study to mimic natural habitat. The beads were ingested by all animals in all experimental concentrations (5, 50 and 250 beads mL(-1)). Bivalves (Mytilus trossulus, Macoma balthica) contained significantly higher amounts of beads compared with the other groups. Free-swimming crustaceans ingested more beads compared with the benthic animals that were feeding only on the sediment surface. Ingestion of the beads was concluded to be the result of particle concentration, feeding mode and the encounter rate in a patchy environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluating rodent motor functions: Which tests to choose?

PubMed

Schönfeld, Lisa-Maria; Dooley, Dearbhaile; Jahanshahi, Ali; Temel, Yasin; Hendrix, Sven

2017-12-01

Damage to the motor cortex induced by stroke or traumatic brain injury (TBI) can result in chronic motor deficits. For the development and improvement of therapies, animal models which possess symptoms comparable to the clinical population are used. However, the use of experimental animals raises valid ethical and methodological concerns. To decrease discomfort by experimental procedures and to increase the quality of results, non-invasive and sensitive rodent motor tests are needed. A broad variety of rodent motor tests are available to determine deficits after stroke or TBI. The current review describes and evaluates motor tests that fall into three categories: Tests to evaluate fine motor skills and grip strength, tests for gait and inter-limb coordination and neurological deficit scores. In this review, we share our thoughts on standardized data presentation to increase data comparability between studies. We also critically evaluate current methods and provide recommendations for choosing the best behavioral test for a new research line. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trends in animal experimentation.

PubMed

Monteiro, Rosangela; Brandau, Ricardo; Gomes, Walter J; Braile, Domingo M

2009-01-01

The search of the understanding of etiological factors, mechanisms and treatment of the diseases has been taking to the development of several animal models in the last decades. To discuss aspects related to animal models of experimentation, animal choice and current trends in this field in our country. In addition, this study evaluated the frequency of experimental articles in medical journals. Five Brazilian journals indexed by LILACS, SciELO, MEDLINE, and recently incorporate for Institute for Scientific Information Journal of Citation Reports were analyzed. All the papers published in those journals, between 2007 and 2008, that used animal models, were selected based on the abstracts. Of the total of 832 articles published in the period, 92 (11.1%) experimentation papers were selected. The number of experimental articles ranged from 5.2% to 17.9% of the global content of the journal. In the instructions to the authors, four (80%) journals presented explicit reference to the ethical principles in the conduction of studies with animals. The induced animal models represented 100% of the articles analyzed in this study. The rat was the most employed animal in the analyzed articles (78.3%). The present study can contribute, supplying subsidies for adoption of future editorials policies regarding the publication of animal research papers in Brazilian Journal of Cardiovascular Surgery.

Diet-Induced Obesity Enhances TRPV1-Mediated Neurovascular Reactions in the Dura Mater.

PubMed

Marics, Balázs; Peitl, Barna; Pázmándi, Kitti; Bácsi, Attila; Németh, József; Oszlács, Orsolya; Jancsó, Gábor; Dux, Mária

2017-03-01

Exploring the pathophysiological changes in transient receptor potential vanilloid 1 (TRPV1) receptor of the trigeminovascular system in high-fat, high-sucrose (HFHS) diet-induced obesity of experimental animals. Clinical and experimental observations suggest a link between obesity and migraine. Accumulating evidence indicates that metabolic and immunological alterations associated with obesity may potentially modulate trigeminovascular functions. A possible target for obesity-induced pathophysiological changes is the TRPV1/capsaicin receptor which is implicated in the pathomechanism of headaches in a complex way. Male Sprague-Dawley rats were fed a regular (n = 25) or HFHS diet (n = 26) for 20 weeks. At the end of the dietary period, body weight of the animals was normally distributed in both groups and it was significantly higher in animals on HFHS diet. Therefore, experimental groups were regarded as control and HFHS diet-induced obese groups. Capsaicin-induced changes in meningeal blood flow and release of calcitonin gene-related peptide (CGRP) from dural trigeminal afferents were measured in control and obese rats. The distribution of TRPV1- and CGRP-immunoreactive meningeal sensory nerves was also compared in whole mount preparations of the dura mater. Metabolic parameters of the animals were assessed by examining glucose and insulin homeostasis as well as plasma cytokine concentrations. HFHS diet was accompanied by reduced food consumption and greater fluid and energy intakes in addition to increased body weight of the animals. HFHS diet increased fasting blood glucose and insulin concentrations as well as levels of circulating proinflammatory cytokines interleukin-1β and interleukin-6. In obese animals, dural application of the archetypal TRPV1 agonist capsaicin resulted in significantly augmented vasodilatory and vasoconstrictor responses as compared to controls. Diet-induced obesity was also associated with enhanced basal and capsaicin-induced CGRP release from meningeal afferents ex vivo. Except for minor morphological changes, the distribution of dural TRPV1- and CGRP-immunoreactive afferents was similar in control and obese animals. Our results suggest that obesity induced by long-term HFHS diet results in sensitization of the trigeminovascular system. Changes in TRPV1-mediated vascular reactions and CGRP release are pathophysiological alterations that may be of relevance to the enhanced headache susceptibility of obese individuals. © 2017 American Headache Society.

Acute and chronic anxiogenic-like response to fluoxetine in rats in the elevated plus-maze: modulation by stressful handling.

PubMed

Robert, Gabriel; Drapier, Dominique; Bentué-Ferrer, Danièle; Renault, Alain; Reymann, Jean-Michel

2011-07-07

While antidepressants are widely prescribed to humans for the treatment of anxiety, the results achieved with animal anxiety models are conflicting. The experimental procedure and the prior test history of the animals are critical parameters that are largely susceptible to influence the results and their interpretation. We compared the effect of 5mg fluoxetine administered to six groups of rats subjected to the psychopharmacological test of the elevated plus-maze, under experimental conditions designed to demonstrate the effect of handling and one daily injection on the response to fluoxetine. The results show that for animals with the same recent experience, fluoxetine, when administered once or over a period of 15 days, induces anxiogenic-like behaviour. On the other hand, our results also show that stressful handling has an anxiolytic-like effect modulating the anxiogenic-like effect of fluoxetine, without eliminating it altogether. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

PubMed Central

Rajkumar, D. S. R.; Faitelson, A. V.; Gudyrev, O. S.; Dubrovin, G. M.; Pokrovski, M. V.; Ivanov, A. V.

2013-01-01

In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing. PMID:23401845

Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

PubMed Central

Chandran, Preethi K.; Kuttan, Ramadasan

2008-01-01

Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

9 CFR 303.2 - Experimentation: Intensity of inspection coverage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Experimentation: Intensity of inspection coverage. 303.2 Section 303.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

9 CFR 303.2 - Experimentation: Intensity of inspection coverage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Experimentation: Intensity of inspection coverage. 303.2 Section 303.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

9 CFR 303.2 - Experimentation: Intensity of inspection coverage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Experimentation: Intensity of inspection coverage. 303.2 Section 303.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

Induction of Social Behavior in Zebrafish: Live Versus Computer Animated Fish as Stimuli

PubMed Central

Qin, Meiying; Wong, Albert; Seguin, Diane

2014-01-01

Abstract The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish. PMID:24575942

Induction of social behavior in zebrafish: live versus computer animated fish as stimuli.

PubMed

Qin, Meiying; Wong, Albert; Seguin, Diane; Gerlai, Robert

2014-06-01

The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish.

Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

NASA Astrophysics Data System (ADS)

Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

1995-11-01

The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

Usefulness of real-time elastography strain ratio in the assessment of bile duct ligation-induced liver injury and the hepatoprotective effect of chitosan: an experimental animal study.

PubMed

Dudea, Marina; Clichici, Simona; Olteanu, Diana Elena; Nagy, Andras; Cucoş, Maria; Dudea, Sorin

2015-01-01

The purpose of the study described here was to evaluate the usefulness of the elastographic strain ratio in the assessment of liver changes in an experimental animal setting and the hepatoprotective effects of chitosan. Ultrasonography and Strain Ratio calculation were performed before and after bile duct ligation (BDL) in three groups of Wistar albino rats (n = 10 animals per group): (i) rats subjected to bile duct ligation only; (ii) rats subjected to bile duct ligation and administered chitosan for 14 d; (iii) rats subjected to bile duct ligation and administered chitosan for 7 d. The results were compared with the laboratory data and pathologic findings. Strain ratios revealed an increase in liver stiffness after bile duct ligation (p < 0.05), except in the group with chitosan administered for 7 d, and agreed with laboratory and pathology data. In conclusion, strain ratio can be used as an experimental research instrument in the assessment of liver response to injury. To the best of our knowledge, this is the first study reporting on the usefulness of the sonoelastographic liver-to-kidney strain ratio in assessing the effects of experimentally induced liver lesions. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

[Establishment of animal model for Pneumocystis carinii and study on etiological and molecular biological detection technology].

PubMed

Tian, Li-guang; Ai, Lin; Chu, Yan-hong; Wu, Xiu-ping; Cai, Yu-chun; Chen, Zhuo; Chen, Shao-hong; Chen, Jia-xu

2015-04-01

To establish an animal model for Pneumocystis pneumonia (PCP) and to study the etiological and molecular biological technology for PCP detection. SD and Wistar rats were divided into experimental and control groups randomly. The animals in the experimental group were immunosuppressed by subcutaneous injection with dexamethasone 2 mg per time per rat, twice a week, while those in the control group underwent the same way of injection with physiological saline simultaneously. After the induction for 8 weeks, all the rats were killed and their bronchoalveolar lavage fluid (BALF) and lung tissues were collected for smear making and microscopic detection. Meanwhile, the BALF samples were detected by PCR, and the products were sequenced and compared with rat source PCP in GenBank. A total of 34 samples of lung tissue and BALF were observed. The etiological detection showed that the infection rates of the rats in the experimental and control groups were 29.2% (7/24) and 0, respectively. In the experimental group, the infection rates of SD and Wistar rats were 25.0% (3/12) and 33.3% (4/12), respectively, and the difference between them was not statistically significant (P = 0.31). The positive detection rates of the lung smears and BALF from SD rats in the experimental group were 25.0% (3/12) and 16.7% (2/12), respectively, while those in Wistar rats in the experimental group were 33.3% (4/12) and 16.7% (2/12), respectively, and there were no statistically significant difference between them (P = 0.34, 0.24). A total of 28 samples of BALF were detected by PCR, and the positive detection rates of rats in the experimental group and control group were 91.7% (26/28) and 0, respectively. The sequence analysis of the PCR products showed that it shared 100% homology with the genes of rat source PCP in Gen Bank (JX499145, GU133622 and EF646865). The animal model of PCP can be established by subcutaneous injection with dexamethasone. As animal models, there are no significant difference between SD rats and Wistar rats. PCR method is suitable for PCP detection at the early stage of infection, while etiological detection with high missing rate is not a right option.

A COMPARATIVE REVIEW OF THE GENOTOXICANTS FOUND IN AMBIENT AIR

EPA Science Inventory

Although research efforts have associated the induction of cancer in man and in experimental animals with exposure to airborne substances for a long time, major insights into the specific sources, chemicals, and mechanisms of action have emerged mainly since the 1970s. It is now ...

Are animal models predictive for human postmortem muscle protein degradation?

PubMed

Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

2017-11-01

A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

Micromorphology of neurohypophysis of rats under experimental conditions

NASA Technical Reports Server (NTRS)

Meitner, E. R.; Proksova, E.

1979-01-01

The changes of the quantity of neurosecretory substance in neurohypophysis of rats under various experimental conditions are investigated. Comparing to the norm the quantity of neurosecretion after a long stay in the dark was larger. In animals subjected to immobilization stress the picture of neurohypophysis remained unchanged. It changed only in correlation with the administered water. Results indicate that the immobilization stress, in contradistinction to dolorose stress, has no substantial influence upon the quantity of neurosecretion in neurohypophysis.

Humoral immune response kinetics in Philander opossum and Didelphis marsupialis infected and immunized by Trypanosoma cruzi employing an immunofluorescence antibody test.

PubMed

Legey, A P; Pinho, A P; Chagas Xavier, S C; Leon, L L; Jansen, A M

1999-01-01

Philander opossum and Didelphis marsupialis considered the most ancient mammals and an evolutionary success, maintain parasitism by Trypanosoma cruzi without developing any apparent disease or important tissue lesion. In order to elucidate this well-balanced interaction, we decided to compare the humoral immune response kinetics of the two didelphids naturally and experimentally infected with T. cruzi and immunized by different schedules of parasite antigens, employing an indirect fluorescence antibody test (IFAT). Both didelphids responded with high serological titers to different immunization routes, while the earliest response occurred with the intradermic route. Serological titers of naturally infected P. opossum showed a significant individual variation, while those of D. marsupialis remained stable during the entire follow-up period. The serological titers of the experimentally infected animals varied according to the inoculated strain. Our data suggest that (1) IFAT was sensitive for follow-up of P. opossum in natural and experimental T. cruzi infections; (2) both P. opossum and D. marsupialis are able to mount an efficient humoral immune response as compared to placental mammals; (3) experimentally infected P. opossum and D. marsupialis present distinct patterns of infection, depending on the subpopulation of T. cruzi, (4) the differences observed in the humoral immune responses between P. opossum and D. marsupialis, probably, reflect distinct strategies selected by these animals during their coevolution with T. cruzi.

Animal models in biological and biomedical research - experimental and ethical concerns.

PubMed

Andersen, Monica L; Winter, Lucile M F

2017-09-04

Animal models have been used in experimental research to increase human knowledge and contribute to finding solutions to biological and biomedical questions. However, increased concern for the welfare of the animals used, and a growing awareness of the concept of animal rights, has brought a greater focus on the related ethical issues. In this review, we intend to give examples on how animals are used in the health research related to some major health problems in Brazil, as well as to stimulate discussion about the application of ethics in the use of animals in research and education, highlighting the role of National Council for the Control of Animal Experimentation (Conselho Nacional de Controle de Experimentação Animal - CONCEA) in these areas. In 2008, Brazil emerged into a new era of animal research regulation, with the promulgation of Law 11794, previously known as the Arouca Law, resulting in an increased focus, and rapid learning experience, on questions related to all aspects of animal experimentation. The law reinforces the idea that animal experiments must be based on ethical considerations and integrity-based assumptions, and provides a regulatory framework to achieve this. This review describes the health research involving animals and the current Brazilian framework for regulating laboratory animal science, and hopes to help to improve the awareness of the scientific community of these ethical and legal rules.

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.

The Metabolic Effects of Consumption of Yellow Cassava (Manihot esculenta Crantz) on Some Biochemical Parameters in Experimental Rats.

PubMed

Udeme, Nelson; Okafor, Polycarp; Eleazu, Chinedum

2015-01-01

The metabolism of yellow cassava (variety TMS 01/1368) was investigated in male albino rats fed a diet containing yellow cassava for 7 to 28 days. There were significant increases (P < 0.05) in total and free cyanide and thiocyanate in the sera and urine samples of the experimental rats compared with the control, significant increases (P < 0.05) in serum glucose, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase levels of the experimental rats compared with the control, significant decreases (P < 0.05) in serum albumin of the experimental rats compared with the control, but no significant differences (P > 0.05) in the serum total proteins of the experimental rats compared with the control. The experimental rats treated for 7, 14, 21, or 28 days exhibited body weight decreases of 5.11%, 11.10%, 19.16%, and 24.18%, respectively, whereas the control group showed 9.17% gain in body weight. Total and free cyanide concentrations were detected in the liver, kidney, and heart of most of the rats in both the experimental and control groups, except for free cyanide in the control group that was not detected. Metabolism of the yellow cassava variety in experimental rats was capable of exposing the animals to cyanide, underscoring the need for its proper processing before consumption by humans. © The Author(s) 2015.

Innovativeness as an emergent property: a new alignment of comparative and experimental research on animal innovation

PubMed Central

Griffin, Andrea S.

2016-01-01

Innovation and creativity are key defining features of human societies. As we face the global challenges of the twenty-first century, they are also facets upon which we must become increasingly reliant. But what makes Homo sapiens so innovative and where does our high innovation propensity come from? Comparative research on innovativeness in non-human animals allows us to peer back through evolutionary time and investigate the ecological factors that drove the evolution of innovativeness, whereas experimental research identifies and manipulates underpinning creative processes. In commenting on the present theme issue, I highlight the controversies that have typified this research field and show how a paradigmatic shift in our thinking about innovativeness will contribute to resolving these tensions. In the past decade, innovativeness has been considered by many as a trait, a direct product of cognition, and a direct target of selection. The evidence I review here suggests that innovativeness will be hereon viewed as one component, or even an emergent property of a larger array of traits, which have evolved to deal with environmental variation. I illustrate how research should capitalize on taxonomic diversity to unravel the full range of psychological processes that underpin innovativeness in non-human animals. PMID:26926287

Noncompliance with Public Health Service (PHS) policy on humane care and use of laboratory animals: an exploratory analysis.

PubMed

Gomez, Leah M; Conlee, Kathleen M; Stephens, Martin L

2010-01-01

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS's animal care and use standards must report these incidents to the NIH's OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies the most common issues reported and species involved. The study found that the majority of the incidents resulted in animal pain and distress and that 75% ended in animal death. This study offers preliminary recommendations to address the most common problems identified in this analysis. This study urges OLAW and other stakeholders to analyze larger, more recent samples of reported deviations to compare with these results and ultimately improve adherence to animal welfare standards.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

PubMed Central

Messina, J. A.; St. Paul, Alison; Hargis, Sarah; Thompson, Wengora E.; McClellan, Andrew D.

2017-01-01

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations. PMID:29225569

[The ethics of animal experimentation].

PubMed

Goffi, Jean-Yves

2013-01-01

The paper starts with a short definition of animal experimentation, then three main approaches to the practice are considered: unconditional approval (as advocated by Claude Bernard), conditional and restricted approval (as advocated by Peter Singer) and strict prohibition (as advocated by Tom Regan and Gary Francione). It is argued that what is actually approved or condemned in animal experimentation is the value of the scientific enterprise.

Animal experimentation.

PubMed

Kolar, Roman

2006-01-01

Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

[Animal welfare and corporate welfare in pharmaceutical R&D - the future of third-party assessment].

PubMed

Suzuki, Makoto

For research and development (R&D) of new drugs, animal experimentation is indispensable, and research institutes, pharmaceutical companies, or contract research organizations routinely conduct preclinical studies of efficacy, safety, or metabolism using laboratory animals. However, animal experimentation entails some organizational risks. One is the suspension of R&D of a new drug, because in the course of clinical studies it becomes apparent that the drug has limited efficacy, unexpected side effects, and/or unexpected metabolites. Another risk is damage to the company image by development of an unfavorable reputation. Society has accepted animal experimentation as a necessary evil, but if such experimentation is not conducted with adequate concern for animal welfare, social sanctions will against that institute, company or organization will result. Once this happens, it is difficult to recover a good public image. Therefore, pharmaceutical companies must conduct animal experiments so as to obtain highly useful data without sacrificing public favor. One way to maintain a good reputation is through third-party accreditation, which verifies that the institute, company or organization and its researchers value animal welfare appropriately.

9 CFR 103.1 - Preparation of experimental biological products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

9 CFR 103.1 - Preparation of experimental biological products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

9 CFR 103.1 - Preparation of experimental biological products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

Administration of Intravenous Inf liximab for Prevention of Peritoneal Adhesions Formation in Rats.

PubMed

Nikeghbalian, Saman; Vafaei, Homeira; Moradian, Farid; Kazemi, Kourosh; Tanideh, Nader; Shayan, Leila; Nikeghbalian, Zahra

2015-07-01

To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. This was an experimental study being performed in animal laboratory of Shiraz University of Medical Sciences during 2012. Sixty albino rats were randomly assigned in to three groups by Random Design Method. The first group received single infliximab injection (n=20), the second one received double infliximab injection (n=20) and the third received nothing (n=20), after receiving intra-peritoneal injection of talc for induction of peritoneal adhesions. All the animals were sacrificed after 6 weeks and the peritoneal adhesions were evaluated according to Nair classification. We observed that the mean adhesion grade was lower in those who received double dose of infliximib when compared to single dose and controls. However the difference did not reach a significant value (p=0.178). The grade of peritoneal adhesion was also comparable between the three study groups (p=0.103). The mean number of 1st WBC count was also comparable between three study groups (p=0.382). We observed that 2nd WBC count was also comparable between two study groups (p=0.317). Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat.

Environmental impact of the production of mealworms as a protein source for humans - a life cycle assessment.

PubMed

Oonincx, Dennis G A B; de Boer, Imke J M

2012-01-01

The demand for animal protein is expected to rise by 70-80% between 2012 and 2050, while the current animal production sector already causes major environmental degradation. Edible insects are suggested as a more sustainable source of animal protein. However, few experimental data regarding environmental impact of insect production are available. Therefore, a lifecycle assessment for mealworm production was conducted, in which greenhouse gas production, energy use and land use were quantified and compared to conventional sources of animal protein. Production of one kg of edible protein from milk, chicken, pork or beef result in higher greenhouse gas emissions, require similar amounts of energy and require much more land. This study demonstrates that mealworms should be considered a more sustainable source of edible protein.

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

PubMed

Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

2015-11-01

Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction.

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review

PubMed Central

Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

2015-01-01

Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

Cariogenicity of soluble starch in oral in vitro biofilm and experimental rat caries studies: a comparison.

PubMed

Thurnheer, T; Giertsen, E; Gmür, R; Guggenheim, B

2008-09-01

Common belief suggests that starch is less cariogenic than sugar; however, the related literature is quite controversial. We aimed to compare cariogenic and microbiological effects of soluble starch in both a standard animal model and an oral biofilm system, and to assess the possible substitution of the animal model. Six-species biofilms were grown anaerobically on enamel discs in saliva and medium with glucose/sucrose, starch (average molecular weight of 5000, average polymerization grade of 31), or mixtures thereof. After 64.5 h of biofilm formation, the microbiota were quantitated by cultivation and demineralization was measured by quantitative light-induced fluorescence. To assess caries incidence in rats, the same microbiota as in the biofilm experiments were applied. The animals were fed diets containing either glucose, glucose/sucrose, glucose/sucrose/starch or starch alone. Results with both models show that demineralization was significantly smaller with starch than sucrose. The data demonstrate that soluble starch is substantially less cariogenic than glucose/sucrose. By leading to the same scientific evidence as its in vivo counterpart, the described in vitro biofilm system provides an interesting and valuable tool in the quest to reduce experimentation with animals.

Experimental infection of cattle with Listeria monocytogenes: Participation of purinergic metabolism in disease pathogenesis.

PubMed

Jaguezeski, Antonise M; Perin, Gessica; Rhoden, Leandro A; da Silva, Teane M A; Mendes, Ricardo E; Bottari, Nathieli B; Faccin, Thalisson; Baldissera, Matheus D; Morsch, Vera M; Schetinger, Maria Rosa C; Giongo, Janice L; da Silva, Aleksandro S

2018-05-30

The objective of this study was to evaluate whether experimental infection with Listeria monocytogenes alters the activity of triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA) in cattle. Ten male Holstein breed cattle were divided in two groups of five animals each: a control group, and a group infected with a pathogenic strain of L. monocytogenes. We drew blood for platelets on days 0, 7 and 14 of the experiment. On the 14th day post infection (PI), the animals were euthanized. Brain, spleen and liver were processed for histopathological examination and measurement of enzyme activities. The five (n = 5/5) bovines experimentally infected by L. monocytogene were positive-PCR in hepatic tissue. In the brain, only four (n = 4/5) of these animals were positive-PCR for listeriosis. There were no differences in platelet counts between groups (P > 0.05). In platelets, NTPDase activity (with ATP and ADP as substrates) were higher on the 7th PI day in the infected group, whereas the activities of 5'-nucleotidase and ADA were higher on the 7th and 14th PI. In serum and liver, ADA activity was higher in infected animals, but was lower on day 14 PI in spleen. NTPDase activity (with ATP as substrate) was higher in the cerebellum of infected animals, but was lower in the cerebral cortex and medulla oblongata. NTPDase activity (with ADP as substrate) was lower in the cerebellum and cerebral cortex of infected animals, whereas 5'-nucleotidase was higher. ADA activity was lower in the cerebellum, cerebral cortex and medulla oblongata in infected animals compared with controls. In conclusion, there appears to be a protective immunomodulatory response in spleen and brain structures of cattle infected with L. monocytogenes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals

PubMed Central

Osier, Nicole D.; Carlson, Shaun W.; DeSana, Anthony

2015-01-01

Abstract The purpose of this review is to survey the use of experimental animal models for studying the chronic histopathological and behavioral consequences of traumatic brain injury (TBI). The strategies employed to study the long-term consequences of TBI are described, along with a summary of the evidence available to date from common experimental TBI models: fluid percussion injury; controlled cortical impact; blast TBI; and closed-head injury. For each model, evidence is organized according to outcome. Histopathological outcomes included are gross changes in morphology/histology, ventricular enlargement, gray/white matter shrinkage, axonal injury, cerebrovascular histopathology, inflammation, and neurogenesis. Behavioral outcomes included are overall neurological function, motor function, cognitive function, frontal lobe function, and stress-related outcomes. A brief discussion is provided comparing the most common experimental models of TBI and highlighting the utility of each model in understanding specific aspects of TBI pathology. The majority of experimental TBI studies collect data in the acute postinjury period, but few continue into the chronic period. Available evidence from long-term studies suggests that many of the experimental TBI models can lead to progressive changes in histopathology and behavior. The studies described in this review contribute to our understanding of chronic TBI pathology. PMID:25490251

Immunomodulatory properties and anti-apoptotic effects of zinc and melatonin in an experimental model of chronic Chagas disease.

PubMed

Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Azevedo, Angela Palamin; Toldo, Míriam Paula Alonso; de Morais, Fabiana Rossetto; do Prado, José Clóvis

2015-05-01

The immunomodulatory effects of melatonin and zinc during chronic experimental Chagas' disease were studied. Early and late apoptosis by Annexin V-propidium iodide staining were evaluated. The expression of CD28, CD80, CD86, CD45RA and CD4(+)T and CD8(+)T cells were also evaluated by flow cytometry analysis. The combination of zinc and melatonin notably reduced the apoptotic ratios of splenic cells in the infected and treated animals when compared to untreated rats, during early and late stages of apoptosis. The percentages of CD8(+)T cells in Zn, Mel or Zn and Mel treated rats were reduced when compared to infected and untreated animals. Higher percentages of CD28 expression in CD4(+) and CD8(+) T cell populations were observed in control and infected Zn-treated group as compared to untreated ones. Zn, Mel or the combination of both did not induce any statistically significant differences for B cells when comparing to treated control and infected groups. Zinc or Mel-treated animals presented a lower expression of CD86 when compared to untreated counterparts. According to our data, this work strongly suggest that the modulation of the immune system operated by zinc and melatonin administration affected the balance among T cell immune response, apoptosis and expression of co-stimulatory molecules during chronic Trypanosoma cruzi infection, inducing important changes in the host's immune response against the parasite. Future experiments in this field should be focused in improving our understanding of the key mechanisms underlying the involvement of melatonin and zinc in the immune response during chronic Chagas' disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

[The 1, 2, 3 of laboratory animal experimentation].

PubMed

Romero-Fernandez, Wilber; Batista-Castro, Zenia; De Lucca, Marisel; Ruano, Ana; García-Barceló, María; Rivera-Cervantes, Marta; García-Rodríguez, Julio; Sánchez-Mateos, Soledad

2016-06-01

The slow scientific development in Latin America in recent decades has delayed the incorporation of laboratory animal experimentation; however, this situation has started to change. Today, extraordinary scientific progress is evident, which has promoted the introduction and increased use of laboratory animals as an important tool for the advancement of biomedical sciences. In the aftermath of this boom, the need to provide the scientific community with training and guidance in all aspects related to animal experimentation has arisen. It is the responsibility of each country to regulate this practice, for both bioethical and legal reasons, to ensure consideration of the animals' rights and welfare. The following manuscript is the result of papers presented at the International Workshop on Laboratory Animal Testing held at the Technical University of Ambato, Ecuador; it contains information regarding the current state of affairs in laboratory animal testing and emphasizes critical aspects such as main species used, ethical and legal principles, and experimental and alternative designs for animal use. These works aim to ensure good practices that should define scientific work. This document will be relevant to both researchers who aim to newly incorporate animal testing into their research and those who seek to update their knowledge.

Side-Effects of Irinotecan (CPT-11), the Clinically Used Drug for Colon Cancer Therapy, Are Eliminated in Experimental Animals Treated with Latex Proteins from Calotropis procera (Apocynaceae).

PubMed

de Alencar, Nylane Maria Nunes; da Silveira Bitencourt, Flávio; de Figueiredo, Ingrid Samantha Tavares; Luz, Patrícia Bastos; Lima-Júnior, Roberto César P; Aragão, Karoline Sabóia; Magalhães, Pedro Jorge Caldas; de Castro Brito, Gerly Anne; Ribeiro, Ronaldo Albuquerque; de Freitas, Ana Paula Fragoso; Ramos, Marcio Viana

2017-02-01

Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1β, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Influence of proximal end diverting colostomy on the healing of left-sided colonic anastomosis: an experimental study in rats.

PubMed

Bielecki, K; Grotowski, M; Kalczak, M

1995-01-01

The purpose of this study was to evaluate the healing of an experimental left-sided colonic anastomosis in rats protected by an end diverting proimal colostomy. The anastomoses were studied by radiological and biochemical examination and breaking strength was estimated. The results were compared with a non-operated group and with a group of rats having a non-defunctional anastomosis constructed in the same manner. In animals with an end diverting colostomy, anastomotic protein levels and enzymic activity were lower than in those with a colostomy, and the development of anastomotic strength was delayed compared with those not defunctioned.

Treatment of experimental myasthenia gravis with total lymphoid irradiation

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

de Silva, S.; Blum, J.E.; McIntosh, K.R.

1988-07-01

Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented themore » primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.« less

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

Influence of apical enlargement on the repair of apical periodontitis in rats.

PubMed

Jara, C M; Hartmann, R C; Böttcher, D E; Souza, T S; Gomes, M S; Figueiredo, J A P

2018-05-08

To evaluate the influence of different apical enlargement protocols on the radiographic and histological healing of apical periodontitis in rats. Apical periodontitis was induced bilaterally in the mandibular right and left first molars of 24 Wistar rats by pulp exposure to the oral cavity for 3 weeks. A standard serial root canal preparation technique was performed in the molar of one side, whilst the opposite side was the control group. Rats were randomly divided into three experimental groups (n = 8), according to the diameter of apical enlargement during root canal preparation: K-files size 20 (EG1), size 25 (EG2) and size 30 (EG3). Each animal was its own positive control, because the opposite arch remained untreated. Root canals were filled with a standard technique. After 3 weeks, the animals were euthanized. The main outcome of apical periodontitis healing was evaluated radiographically (mm 2 ) and histologically (ordinal scores of inflammation) using a HE staining technique. The measurement of effect was obtained between the three experimental groups by carrying out generalized estimating equations, with Poisson regression with robust variance, pairing each experimental group with its respective control group within animals, adjusted for the mean within animal differences, with α = 5%. The mean and standard deviations of radiographic apical periodontitis size (mm 2 ) and intensity of histological inflammatory scores were, respectively: EG1 (0.44 ± 0.27; 2.25 ± 0.46), EG2 (0.33 ± 0.10; 2.50 ± 0.53) and EG3 (0.22 ± 0.08; 2.63 ± 0.74). After 3 weeks, a significantly more favourable radiographic repair was observed when larger apical enlargement was performed (EG3), compared to EG1 and EG2 (P = 0.001). All experimental groups were associated with a significant difference on the radiographic and histological healing of apical periodontitis compared with its respective control group. Under the experimental conditions of this study, a larger apical enlargement protocol favoured a more rapid radiographic repair of apical periodontitis in rats after a 3-week follow-up. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

[Animal experimentation, computer simulation and surgical research].

PubMed

Carpentier, Alain

2009-11-01

We live in a digital world In medicine, computers are providing new tools for data collection, imaging, and treatment. During research and development of complex technologies and devices such as artificial hearts, computer simulation can provide more reliable information than experimentation on large animals. In these specific settings, animal experimentation should serve more to validate computer models of complex devices than to demonstrate their reliability.

Comparisons of Auricular Cartilage Tissues from Different Species.

PubMed

Chiu, Loraine L Y; Giardini-Rosa, Renata; Weber, Joanna F; Cushing, Sharon L; Waldman, Stephen D

2017-12-01

Tissue engineering of auricular cartilage has great potential in providing readily available materials for reconstructive surgeries. As the field of tissue engineering moves forward to developing human tissues, there needs to be an interspecies comparison of the native auricular cartilage in order to determine a suitable animal model to assess the performance of engineered auricular cartilage in vivo. Here, we performed interspecies comparisons of auricular cartilage by comparing tissue microstructure, protein localization, biochemical composition, and mechanical properties of auricular cartilage tissues from rat, rabbit, pig, cow, and human. Human, pig, and cow auricular cartilage have smaller lacunae compared to rat and rabbit cartilage ( P < .05). Despite differences in tissue microstructure, human auricular cartilage has similar biochemical composition to both rat and rabbit. Auricular cartilage from pig and cow, alternatively, display significantly higher glycosaminoglycan and collagen contents compared to human, rat, and rabbit ( P < .05). The mechanical properties of human auricular cartilage were comparable to that of all 4 animal species. This is the first study that compares the microstructural, biochemical, and mechanical properties of auricular cartilage from different species. This study showed that different experimental animal models of human auricular cartilage may be suitable in different cases.

Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

PubMed Central

Steiner, Malte; Volkheimer, David; Meyers, Nicholaus; Wehner, Tim; Wilke, Hans-Joachim; Claes, Lutz; Ignatius, Anita

2015-01-01

For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens’ axis of gravity and the torsional axis of rotation. PMID:25781027

Diffusion model to describe osteogenesis within a porous titanium scaffold.

PubMed

Schmitt, M; Allena, R; Schouman, T; Frasca, S; Collombet, J M; Holy, X; Rouch, P

2016-01-01

In this study, we develop a two-dimensional finite element model, which is derived from an animal experiment and allows simulating osteogenesis within a porous titanium scaffold implanted in ewe's hemi-mandible during 12 weeks. The cell activity is described through diffusion equations and regulated by the stress state of the structure. We compare our model to (i) histological observations and (ii) experimental data obtained from a mechanical test done on sacrificed animal. We show that our mechano-biological approach provides consistent numerical results and constitutes a useful tool to predict osteogenesis pattern.

[Animal experimentation, animal welfare and scientific research].

PubMed

Tal, H

2013-10-01

Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals.

Ventilation of Animal Shelters in Wildland Fire Scenarios

NASA Astrophysics Data System (ADS)

Bova, A. S.; Bohrer, G.; Dickinson, M. B.

2009-12-01

The effects of wildland fires on cavity-nesting birds and bats, as well as fossorial mammals and burrow-using reptiles, are of considerable interest to the fire management community. However, relatively little is known about the degree of protection afforded by various animal shelters in wildland fire events. We present results from our ongoing investigation, utilizing NIST’s Fire Dynamics Simulator (FDS) and experimental data, of the effectiveness of common shelter configurations in protecting animals from combustion products. We compare two sets of simulations with observed experimental results. In the first set, wind tunnel experiments on single-entry room ventilation by Larsen and Heiselberg (2008) were simulated in a large domain resolved into 10 cm cubic cells. The set of 24 simulations comprised all combinations of incident wind speeds of 1,3 and 5 m/s; angles of attack of 0, 45, 90 and 180 degrees from the horizontal normal to the entrance; and temperature differences of 0 and 10 degrees C between the building interior and exterior. Simulation results were in good agreement with experimental data, thus providing a validation of FDS code for further ventilation experiments. In the second set, a cubic simulation domain of ~1m on edge and resolved into 1 cm cubic cells, was set up to represent the experiments by Ar et al. (2004) of wind-induced ventilation of woodpecker cavities. As in the experiments, we simulated wind parallel and perpendicular to the cavity entrance with different mean forcing velocities, and monitored the rates of evacuation of a neutral-buoyancy tracer from the cavity. Simulated ventilation rates in many, though not all, cases fell within the range of experimental data. Reasons for these differences, which include vagueness in the experimental setup, will be discussed. Our simulations provide a tool to estimate the viability of an animal in a shelter as a function of the shelter geometry and the fire intensity. In addition to the above, we explore the role of turbulence and its effect on ventilation rates, especially in single-entrance shelters. The goal of this work is to provide engineering formulas to estimate the probable levels of harmful or irritating combustion products in animal shelters during wildland fires.

Towards ethically improved animal experimentation in the study of animal reproduction.

PubMed

Blache, D; Martin, G B; Maloney, S K

2008-07-01

The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

Experimental task-based optimization of a four-camera variable-pinhole small-animal SPECT system

NASA Astrophysics Data System (ADS)

Hesterman, Jacob Y.; Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.

2005-04-01

We have previously utilized lumpy object models and simulated imaging systems in conjunction with the ideal observer to compute figures of merit for hardware optimization. In this paper, we describe the development of methods and phantoms necessary to validate or experimentally carry out these optimizations. Our study was conducted on a four-camera small-animal SPECT system that employs interchangeable pinhole plates to operate under a variety of pinhole configurations and magnifications (representing optimizable system parameters). We developed a small-animal phantom capable of producing random backgrounds for each image sequence. The task chosen for the study was the detection of a 2mm diameter sphere within the phantom-generated random background. A total of 138 projection images were used, half of which included the signal. As our observer, we employed the channelized Hotelling observer (CHO) with Laguerre-Gauss channels. The signal-to-noise (SNR) of this observer was used to compare different system configurations. Results indicate agreement between experimental and simulated data with higher detectability rates found for multiple-camera, multiple-pinhole, and high-magnification systems, although it was found that mixtures of magnifications often outperform systems employing a single magnification. This work will serve as a basis for future studies pertaining to system hardware optimization.

Physiology, propaganda, and pound animals: medical research and animal welfare in mid-twentieth century America.

PubMed

Parascandola, John

2007-07-01

In 1952, the University of Michigan physiologist Robert Gesell shocked his colleagues at the business meeting of the American Physiological Society by reading a prepared statement in which he claimed that some of the animal experimentation being carried out by scientists was inhumane. He especially attacked the National Society for Medical Research (NSMR), an organization that had been founded to defend animal experimentation. This incident was part of a broader struggle taking place at the time between scientists and animal welfare advocates with respect to what restrictions, if any, should be placed on animal research. A particularly controversial issue was whether or not pound animals should be made available to laboratories for research. Two of the prominent players in this controversy were the NSMR and the Animal Welfare Institute, founded and run by Gesell's daughter, Christine Stevens. This article focuses on the interaction between these two organizations within the broader context of the debate over animal experimentation in the mid-twentieth century.

SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs.

PubMed

Blyth, Karen; Carter, Phil; Morrissey, Bethny; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

2016-04-01

Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating to the original projects. Despite being developed at considerable cost, this material is an invisible and hence an underutilised resource, which often ends up being discarded. Within the breast cancer research community there is both a need and desire to make this valuable material available for researchers. Lack of a coordinated system for visualisation and localisation of this has prevented progress. To fulfil this unmet need, we have developed a novel initiative called Sharing Experimental Animal Resources: Coordinating Holdings-Breast (SEARCHBreast) which facilitates sharing of archival tissue between researchers on a collaborative basis and, de facto will reduce overall usage of animal models in breast cancer research. A secure searchable database has been developed where researchers can find, share, or upload materials related to animal models of breast cancer, including genetic and transplant models. SEARCHBreast is a virtual compendium where the physical material remains with the original laboratory. A bioanalysis pipeline is being developed for the analysis of transcriptomics data associated with mouse models, allowing comparative study with human and cell line data. Additionally, SEARCHBreast is committed to promoting the use of humanised breast tissue models as replacement alternatives to animals. Access to this unique resource is freely available to all academic researchers following registration at https://searchbreast.org.

Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration.

PubMed

Varnalidis, Ioannis; Ioannidis, Orestis; Karamanavi, Elisavet; Ampas, Zafeiris; Poutahidis, Theofilos; Taitzoglou, Ioannis; Paraskevas, George; Botsios, Dimitrios

2011-10-01

omega 3 polyunsaturated fatty acids have anti-inflammatory properties and can be beneficial in the treatment of inflammatory diseases, such as ulcerative colitis. Dextran sodium sulphate (DSS) colitis in rats appears to mimic nearly all of the morphological characteristics and lesion distributions of ulcerative colitis. The purpose of the current study was to investigate the efficacy of omega 3 fatty acids in the treatment of experimental ulcerative colitis. thirty-six Wistar rats were randomly assigned to group A or group B receiving 5% dextran sulfate sodium (DSS) in their drinking water for eight days. For the next eight days post-DSS, group A animals received tap-water, and group B animals were fed a nutritional solution containing high levels of omega 3 polyunsaturated fatty acids (ProSure®, Abbott Laboratories, Zwolle, Netherlands) once per day, administrated with a orogastric feeding tube. animals fed an omega 3 rich diet exhibited a statistically significant increase in hematocrit and hemoglobin levels, compared to animals drinking tap water, and a trend towards histopathological and clinical improvement, with the administration of omega 3 fatty acids ameliorating epithelial erosion by day 8 post-DSS, but no statistically significant difference was observed between group A and group B animals at 4 or 8 days post-DSS. Also, a statistically significant increase in neutrophil infiltration was observed, as depicted by myelohyperoxidase activity. our findings support a positive role of omega 3 polyunsaturated fatty acids supplementation in an experimental model of ulcerative colitis despite the increased colonic neutrophil infiltration. Further studies are needed in order to investigate the role of increased neutrophils in colonic mucosa.

Quantitative analysis of macrophages in wound healing of rat skin subjected to loud noise stress.

PubMed

Rafi, Aisha; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2014-01-01

Factors affecting skin wound healing have always been a central consideration in medical practice. Loud noise is biological stressor affecting the body systems at various levels. The present study was taken to study the effect of loud noise stress on the macrophages during wound healing process in male rat skin. One hundred and eighty male Sprague Dawley rats were randomly divided into control group-A and experimental group-B. Each group comprised 90 animals. Control and experimental groups were further subdivided into three subgroups of 30 animals each, corresponding to the day of sacrifice of animals, i.e., day 3, 5 and 7 after surgery. After induction of local anaesthesia a linear full thickness incision paravertebral to thoracic spine was made on the dorsum of rat. The experimental group B was exposed to loud noise stimulus (recorded noise of aero planes and gun fire) set at 97dBA to 102 dBA with a sound level meter. The animals were decapitated on day 3, 5 and 7 after surgery. Tissue was processed for paraffin embedding and stained by Hematoxylin and Eosin and Mallory's trichrome stain. Data was collected for the incisional space of the wound. Quantitative data of number of macrophages was analysed by Student's' test for the detection of any significant differences between the mean number in the experimental and control groups. All the quantitative data was expressed as means ± SE. A p-value of ≤ 0.05 was considered statistically significant. In this study macrophages were decreased statistically significantly at day 3 after surgery and thereafter increased significantly on day 5 and 7 after surgery in the experimental subgroups as compared to their match control subgroups. These results show that loud noise stress affects the cells (macrophages) involved in the healing of the wound therefore it is expected to have impact on the stages of wound healing.

Studying Biological Responses to Global Change in Atmospheric Oxygen

PubMed Central

Powell, Frank L.

2010-01-01

A popular book recently hypothesized that change in atmospheric oxygen over geological time is the most important physical factor in the evolution of many fundamental characteristics of modern terrestrial animals. This hypothesis is generated primarily using fossil data but the present paper considers how modern experimental biology can be used to test it. Comparative physiology and experimental evolution clearly show that changes in atmospheric O2 over the ages had the potential to drive evolution, assuming the physiological O2-sensitivity of animals today is similar to the past. Established methods, such as phylogenetically independent contrasts, as well new approaches, such as adding environmental history to phylogenetic analyses or modeling interactions between environmental stresses and biological responses with different rate constants, may be useful for testing (disproving) hypotheses about biological adaptations to changes in atmospheric O2. PMID:20385257

Effects of single and simultaneous lesions of serotonergic and noradrenergic pathways on open-space and bright-space anxiety-like behavior in two animal models.

PubMed

Sziray, Nóra; Kuki, Zsófia; Nagy, Katalin M; Markó, Bernadett; Kompagne, Hajnalka; Lévay, György

2010-05-01

The objective of the present study is to investigate the effects of single and simultaneous lesions of the noradrenergic and serotonergic pathways (NA-X, 5-HT-X and XX, respectively) by intracerebroventricular administration of selective neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-HCl (DSP-4) and 5,7-dihydroxytryptamine (5,7-DHT) on anxiety-like behavior in rats. To evaluate the effects of the various lesions, animals were tested in elevated plus-maze (EPM) and light-dark (LD) paradigms. In EPM, single lesions produced strong, statistically significant increase (p<0.001) of both time spent in the open arms (OT) and number of entries into the open arms (OE) compared to sham-lesioned animals. Simultaneous lesion further strengthened this anxiolytic effect causing an approximate 500% elevation of OT compared to sham-lesioned animals. In LD, 5-HT lesion caused a significant (p<0.05) increase in both light movement time and light horizontal activity parameters compared to intact, sham, and NA-lesioned groups. Neither of the lesions caused any change in the spontaneous locomotor activity of the animals up to 15min as measured in activity meter. These findings suggest that single and simultaneous lesions of 5-HT- and NA-pathways modify anxiety-related state of experimental animals to different extents and these modifications alter the behavior of animals differently in the two models used: NA-X and 5-HT-X reduce open space anxiety-like behavior and XX further strengthens this effect in the EPM, while only 5-HT-X is resulting in reduced bright-space anxiety-like behavior leaving the performance of NA-X and XX animals unchanged.

Testing for cognitive function in animals in a regulatory context.

PubMed

Bushnell, Philip J

2015-01-01

Superior cognitive functions have allowed the human species to proliferate in a world of incredible biological diversity. Threats to these essential capacities cannot be ignored, and a strategy is needed to evaluate the hazard posed by exposure to chemical and other agents. Because people exposed to chemicals often complain about confusion and forgetfulness, it is commonly thought that cognitive functions should be sensitive indicators of adverse consequences of chemical exposure. For these reasons, complex tests of cognitive function have been developed and deployed in experimental animal laboratories for decades. However, the results of these tests are rarely used as points of departure for chemical risk assessments. Due to their high cost in time, animals, and equipment, the efficacy and utility of these tests need to be evaluated in relation to cheaper and faster whole-animal screening methods. This review examines evidence for the assertions that cognitive functions represent uniquely sensitive indicators of chemical exposure, and that animal models of these functions are necessary to detect and quantify the neurotoxicity of chemicals. Studies conducted since the early 1980s to compare these approaches to assess the neurotoxicity of chemicals are reviewed for both adult and perinatal exposures in experimental rodents. Forty-one studies of 35 chemicals were found that directly compared acute effects using complex tests (i.e., tests that require training animals) with acute effects using screening tests (i.e., tests that do not require training animals) in adult rodents. Complex tests detected effects of three substances (bitertanol, iso-amyl nitrite, and Pfiesteria toxin) that had no effect on screening tests; for an additional five chemicals (carbaryl, deltamethrin, methyl mercury, tetraethyl tin, and Isopar-C), complex tests identified effects at lower doses than did screening tests. Fewer comparable cases were found for developmental exposures: screening and complex tests were found to be equivalent for trimethyltin, n-propylthiouracil (PTU), and elemental mercury. Analysis of two studies yielded an inconclusive case for lead. Evidence for the insufficiency of screening tests was found for PCBs and inhaled ethanol, though it is not clear that the measured effects of these chemicals reflected cognitive deficits per se. Whether these benefits are worth the additional time and expense of conducting complex tests is a matter for discussion in the research and risk management communities. Published by Elsevier Inc.

Mutant mice: experimental organisms as materialised models in biomedicine.

PubMed

Huber, Lara; Keuck, Lara K

2013-09-01

Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

PubMed Central

Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel

2014-01-01

Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in the use of animals and an increase in empirical evidence of biomedical research. PMID:24964011

Uneasiness among laboratory technicians.

PubMed

Arluke, A

1999-01-01

Four aspects of animal experimentation cause uneasiness among many animal laboratory technicians. First, if technicians form strong attachments to lab animals, they feel conflict between their nurturing and the experimental manipulations they perform. Most technicians learn to curtail these attachments. Second, the "sacrifice" of lab animals becomes routinized and stripped of special meaning for many technicians, making killing uncomfortably rote. Third, technicians sometimes encounter outsiders who are critical of animal experimentation and ridicule the technicians for doing this work. Most technicians avoid telling outsiders about their work or take an educational approach to deal with these awkward encounters. Finally, most technicians report some ethical uneasiness about certain types of experiments and their clinical value, as well as about the use of certain animals, and they feel they cannot turn to investigators or fellow technicians to pursue such issues.

The Microminipig as an Animal Model for Influenza A Virus Infection

PubMed Central

Nakajima, Noriko; Shibata, Masatoshi; Takahashi, Kenta; Sato, Yuko; Kiso, Maki; Yamayoshi, Seiya; Ito, Mutsumi; Enya, Satoko; Otake, Masayoshi; Kangawa, Akihisa; da Silva Lopes, Tiago Jose; Ito, Hirotaka; Hasegawa, Hideki

2016-01-01

ABSTRACT Pigs are considered a mixing vessel for the generation of novel pandemic influenza A viruses through reassortment because of their susceptibility to both avian and human influenza viruses. However, experiments to understand reassortment in pigs in detail have been limited because experiments with regular-sized pigs are difficult to perform. Miniature pigs have been used as an experimental animal model, but they are still large and require relatively large cages for housing. The microminipig is one of the smallest miniature pigs used for experiments. Introduced in 2010, microminipigs weigh around 10 kg at an early stage of maturity (6 to 7 months old) and are easy to handle. To evaluate the microminipig as an animal model for influenza A virus infection, we compared the receptor distribution of 10-week-old male pigs (Yorkshire Large White) and microminipigs. We found that both animals have SAα2,3Gal and SAα2,6Gal in their respiratory tracts, with similar distributions of both receptor types. We further found that the sensitivity of microminipigs to influenza A viruses was the same as that of larger miniature pigs. Our findings indicate that the microminipig could serve as a novel model animal for influenza A virus infection. IMPORTANCE The microminipig is one of the smallest miniature pigs in the world and is used as an experimental animal model for life science research. In this study, we evaluated the microminipig as a novel animal model for influenza A virus infection. The distribution of influenza virus receptors in the respiratory tract of the microminipig was similar to that of the pig, and the sensitivity of microminipigs to influenza A viruses was the same as that of miniature pigs. Our findings suggest that microminipigs represent a novel animal model for influenza A virus infection. PMID:27807225

Basic mechanisms of MCD in animal models.

PubMed

Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

2009-09-01

Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

Environmental Impact of the Production of Mealworms as a Protein Source for Humans – A Life Cycle Assessment

PubMed Central

Oonincx, Dennis G. A. B.; de Boer, Imke J. M.

2012-01-01

The demand for animal protein is expected to rise by 70–80% between 2012 and 2050, while the current animal production sector already causes major environmental degradation. Edible insects are suggested as a more sustainable source of animal protein. However, few experimental data regarding environmental impact of insect production are available. Therefore, a lifecycle assessment for mealworm production was conducted, in which greenhouse gas production, energy use and land use were quantified and compared to conventional sources of animal protein. Production of one kg of edible protein from milk, chicken, pork or beef result in higher greenhouse gas emissions, require similar amounts of energy and require much more land. This study demonstrates that mealworms should be considered a more sustainable source of edible protein. PMID:23284661

Intrinsic Fluctuations and Driven Response of Insect Swarms

NASA Astrophysics Data System (ADS)

Ni, Rui; Puckett, James G.; Dufresne, Eric R.; Ouellette, Nicholas T.

2015-09-01

Animals of all sizes form groups, as acting together can convey advantages over acting alone; thus, collective animal behavior has been identified as a promising template for designing engineered systems. However, models and observations have focused predominantly on characterizing the overall group morphology, and often focus on highly ordered groups such as bird flocks. We instead study a disorganized aggregation (an insect mating swarm), and compare its natural fluctuations with the group-level response to an external stimulus. We quantify the swarm's frequency-dependent linear response and its spectrum of intrinsic fluctuations, and show that the ratio of these two quantities has a simple scaling with frequency. Our results provide a new way of comparing models of collective behavior with experimental data.

[Animal experimentation in Israel].

PubMed

Epstein, Yoram; Leshem, Micah

2002-04-01

In 1994 the Israeli parliament (Knesset) amended the Cruelty to Animals Act to regulate the use of experimental animals. Accordingly, animal experiments can only be carried out for the purposes of promoting health and medical science, reducing suffering, advancing scientific research, testing or production of materials and products (excluding cosmetics and cleaning products) and education. Animal experiments are only permitted if alternative methods are not possible. The National Board for Animal Experimentation was established to implement the law. Its members are drawn from government ministries, representatives of doctors, veterinarians, and industry organizations, animal rights groups, and academia. In order to carry out an animal experiment, the institution, researchers involved, and the specific experiment, all require approval by the Board. To date the Board has approved some 35 institutions, about half are public institutions (universities, hospitals and colleges) and the rest industrial firms in biotechnology and pharmaceutics. In 2000, 250,000 animals were used in research, 85% were rodents, 11% fowls, 1,000 other farm animals, 350 dogs and cats, and 39 monkeys. Academic institutions used 74% of the animals and industry the remainder. We also present summarized data on the use of animals in research in other countries.

Critical Emergency Medicine Procedural Skills: A Comparative Study of Methods for Teaching and Assessment.

ERIC Educational Resources Information Center

Chapman, Dane M.; And Others

Three critical procedural skills in emergency medicine were evaluated using three assessment modalities--written, computer, and animal model. The effects of computer practice and previous procedure experience on skill competence were also examined in an experimental sequential assessment design. Subjects were six medical students, six residents,…

Reading Authentic EFL Text Using Visualization and Advance Organizers in a Multimedia Learning Environment

ERIC Educational Resources Information Center

Lin, Huifen; Chen, Tsuiping

2007-01-01

The purpose of this experimental study was to compare the effects of different types of computer-generated visuals (static versus animated) and advance organizers (descriptive versus question) in enhancing comprehension and retention of a content-based lesson for learning English as a Foreign Language (EFL). Additionally, the study investigated…

Increased Skin Inflammation and Blood Vessel Density in Human and Experimental Diabetes

PubMed Central

Tellechea, Ana; Kafanas, Antonios; Leal, Ermelindo C; Tecilazich, Francesco; Kuchibhotla, Sarada; Auster, Michael E; Kontoes, Iraklis; Paolino, Jacqueline; Carvalho, Eugenia; Nabzdyk, Leena Pradhan; Veves, Aristidis

2013-01-01

Systemic inflammation is associated with impaired wound healing in diabetic patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all diabetic animal models compared to their non-diabetic controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around pre-existing skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes. PMID:23446362

Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice.

PubMed

Chatterjee, Manavi; Verma, Pinki; Palit, Gautam

2010-03-01

The present study was undertaken to compare medicinal plants against mixed anxiety-depressive disorder (MAD) to evaluate their potency in combating MAD disorders. Previous studies from our lab have shown that Bacopa monniera (BM), and Panax quniquefolium (PQ) have significant adaptogenic properties. Hence, we have further confirmed their activity in stress related disorders like anxiety and depression in animal model, rodents and assessed their efficacy. In our experimental protocol, gross behaviour was observed through Digiscan animal activity monitor. Anxiety was studied through light dark test, elevated plus maze test and holeboard test. Depression experiments were conducted following tail suspension test and forced swim test. Further, rotarod test was also used to study any defects in motor in-coordination in mice. It was observed that BM at the dose of 80 mg/kg (po) and PQ at 100 mg/kg (po) were effective as an anti-anxiety as well anti-depressant activity and had no motor in-coordination in mice. Hence, these extracts can be used as a potent therapeutic agent in treating mixed anxiety-depressive disorder (MAD).

Critical evaluation of challenges and future use of animals in experimentation for biomedical research.

PubMed

Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree

2016-12-01

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. © The Author(s) 2016.

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

PubMed Central

Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree

2016-01-01

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. PMID:27694614

Survey of basic medical researchers on the awareness of animal experimental designs and reporting standards in China.

PubMed

Ma, Bin; Xu, Jia-Ke; Wu, Wen-Jing; Liu, Hong-Yan; Kou, Cheng-Kun; Liu, Na; Zhao, Lulu

2017-01-01

To investigate the awareness and use of the Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) risk-of-bias tool, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) reporting guidelines, and Gold Standard Publication Checklist (GSPC) in China in basic medical researchers of animal experimental studies. A national questionnaire-based survey targeting basic medical researchers was carried in China to investigate the basic information and awareness of SYRCLE's risk of bias tool, ARRIVE guidelines, GSPC, and animal experimental bias risk control factors. The EpiData3.1 software was used for data entry, and Microsoft Excel 2013 was used for statistical analysis in this study. The number of cases (n) and percentage (%) of classified information were statistically described, and the comparison between groups (i.e., current students vs. research staff) was performed using chi-square test. A total of 298 questionnaires were distributed, and 272 responses were received, which included 266 valid questionnaires (from 118 current students and 148 research staff). Among the 266 survey participants, only 15.8% was aware of the SYRCLE's risk of bias tool, with significant difference between the two groups (P = 0.003), and the awareness rates of ARRIVE guidelines and GSPC were only 9.4% and 9.0%, respectively; 58.6% survey participants believed that the reports of animal experimental studies in Chinese literature were inadequate, with significant difference between the two groups (P = 0.004). In addition, only approximately 1/3 of the survey participants had read systematic reviews and meta-analysis reports of animal experimental studies; only 16/266 (6.0%) had carried out/participated in and 11/266 (4.1%) had published systematic reviews/meta-analysis of animal experimental studies. The awareness and use rates of SYRCLE's risk-of-bias tool, the ARRIVE guidelines, and the GSPC were low among Chinese basic medical researchers. Therefore, specific measures are necessary to promote and popularize these standards and specifications and to introduce these standards into guidelines of Chinese domestic journals as soon as possible to raise awareness and increase use rates of researchers and journal editors, thereby improving the quality of animal experimental methods and reports.

Comparative psychology and the grand challenge of drug discovery in psychiatry and neurodegeneration.

PubMed

Brunner, Dani; Balcı, Fuat; Ludvig, Elliot A

2012-02-01

Drug discovery for brain disorders is undergoing a period of upheaval. Faced with an empty drug pipeline and numerous failures of potential new drugs in clinical trials, many large pharmaceutical companies have been shrinking or even closing down their research divisions that focus on central nervous system (CNS) disorders. In this paper, we argue that many of the difficulties facing CNS drug discovery stem from a lack of robustness in pre-clinical (i.e., non-human animal) testing. There are two main sources for this lack of robustness. First, there is the lack of replicability of many results from the pre-clinical stage, which we argue is driven by a combination of publication bias and inappropriate selection of statistical and experimental designs. Second, there is the frequent failure to translate results in non-human animals to parallel results in humans in the clinic. This limitation can only be overcome by developing new behavioral tests for non-human animals that have predictive, construct, and etiological validity. Here, we present these translational difficulties as a "grand challenge" to researchers from comparative cognition, who are well positioned to provide new methods for testing behavior and cognition in non-human animals. These new experimental protocols will need to be both statistically robust and target behavioral and cognitive processes that allow for better connection with human CNS disorders. Our hope is that this downturn in industrial research may represent an opportunity to develop new protocols that will re-kindle the search for more effective and safer drugs for CNS disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

In search of consolidation of short-term memory in nonhuman animals.

PubMed

Calder, Amanda; White, K Geoffrey

2014-03-01

Wixted (Annual Review of Psychology, 55, 235 – 269, 2004) has argued that forgetting is due to consolidation failure. Previous research with humans and nonhuman animals has reported evidence for consolidation in intermediate or long-term memory (LTM). The present study examines whether consolidation occurs in short-term memory in pigeons. Delayed matching-to-sample accuracy was reduced when retroactive interference (an extraneous task in Experiment 1 or houselight illumination in Experiment 2) was interpolated in the retention interval. Accuracy was not greater, however, when interference occurred at the end of the retention interval, as compared with when it occurred at the beginning. That is, there was no evidence for consolidation in short-term memory for pigeons. We did find, however, the beginning–end effect originally reported by Roberts and Grant (Journal of Experimental Psychology: Animal Behavior Processes, 4, 219–236, 1978) and the recovery from forgetting reported by White and Brown (Journal of the Experimental Analysis of Behavior, 96, 177–189, 2011). The results are discussed in relation to temporal distinctiveness theory as an alternative to consolidation.

Experimental Evaluation of Depth-of-Interaction Correction in a Small-Animal Positron Emission Tomography Scanner

PubMed Central

Green, Michael V.; Ostrow, Harold G.; Seidel, Jurgen; Pomper, Martin G.

2013-01-01

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This “depth-of-interaction” (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling. PMID:21084028

Experimental evaluation of depth-of-interaction correction in a small-animal positron emission tomography scanner.

PubMed

Green, Michael V; Ostrow, Harold G; Seidel, Jurgen; Pomper, Martin G

2010-12-01

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling.

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.

Maternal hypothyroidism: An overview of current experimental models.

PubMed

Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-10-15

Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

The potential benefits of repeated measure experiments for fish disease-challenge host-pathogen investigations.

PubMed

Hall, L Malcolm; Collins, Catherine; Collet, Bertrand

2018-02-02

The utility of molecular response data arising from in-vivo single and repeated measure fish disease-challenge experiments is compared. An in-silico 'experiment' involving the generation of two imaginary immune-molecule quantity response profiles over time for individual animals was carried out. Daily 'observed' molecule quantities were drawn from the 'known' individual response profiles to mimic the results of single and repeated measurement. The results indicate that repeated measure experiments are required to infer individual level response profiles, and that these experiments also provide more accurate summary statistics and data more suited to inferring the dependent ordering of the molecular response. Additionally repeated measure experiments utilise fewer animals than single measure experiments. These results are described alongside a discussion of experimental methodological issues pertinent to the adoption of aquatic animal repeated measure experimental designs. We conclude that investigators need to take particular care when making inferences from single measure experiments and that serious consideration should be given to using repeated measure experiments for in-vivo fish disease-challenge investigations. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Experimental Animal Models for Studies on the Mechanisms of Blast-Induced Neurotrauma

PubMed Central

Risling, Mårten; Davidsson, Johan

2012-01-01

A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments and studies of human cases. However, in order for mathematical simulations to be completely useful, the predictions will most likely have to be validated by detailed data from animal experiments. Some aspects of BINT can conceivably be studied in vitro. However, factors such as systemic response, brain edema, inflammation, vasospasm, or changes in synaptic transmission and behavior must be evaluated in experimental animals. Against this background, it is necessary that such animal experiments are carefully developed imitations of actual components in the blast injury. This paper describes and discusses examples of different designs of experimental models relevant to BINT. PMID:22485104

Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study.

PubMed

El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas

2018-02-01

Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

Monte Carlo simulations versus experimental measurements in a small animal PET system. A comparison in the NEMA NU 4-2008 framework

NASA Astrophysics Data System (ADS)

Popota, F. D.; Aguiar, P.; España, S.; Lois, C.; Udias, J. M.; Ros, D.; Pavia, J.; Gispert, J. D.

2015-01-01

In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system’s sensitivity and scatter fraction for an energy window of 350-650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system’s dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems.

Monte Carlo simulations versus experimental measurements in a small animal PET system. A comparison in the NEMA NU 4-2008 framework.

PubMed

Popota, F D; Aguiar, P; España, S; Lois, C; Udias, J M; Ros, D; Pavia, J; Gispert, J D

2015-01-07

In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system's sensitivity and scatter fraction for an energy window of 350-650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system's dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems.

Animal Experimentation: Issues for the 1980s.

ERIC Educational Resources Information Center

Zola, Judith C.; And Others

1984-01-01

Examines the extent to which issues related to animal experimentation are in conflict and proposes choices that might least comprise them. These issues include animal well-being, human well-being, self-interest of science, scientific validity and responsibility, progress in biomedical and behavioral science, and the future quality of medical care.…

[Experimental study of the collagen matrix for increase the gums using a 3D-modeling].

PubMed

Baulin, I M; Badalyan, V A; Ryakhovsky, A N

2015-01-01

In an experimental study on mini-pigs demonstrated that the use of collagen matrix Mucograft open method leads to the formation of mature connective tissue around the implants, more pronounced after 70 days, and the width of attached mucosa already 45th day (from 4.4 ± 0.3 to 7.7 ± 0.5 mm) is comparable to that of free gingival graft. Three-dimensional computer modeling of jaws experimental animals showed the soft tissue augmentation by 0.8 ± 0.1 cm3 after use of collagen matrix Mucograft and 1.1 ± 0.12 cm3 after free gingival graft.

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

PubMed

Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

2015-12-01

Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P < .05). The tumor necrosis factor alpha and interleukin-8 levels in the BALF reached baseline levels when the humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P < .05). Moreover, humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

Histopathological changes induced in an animal model by potentially pathogenic Enterococcus faecalis strains recovered from ready-to-eat food outlets in Osun State, Nigeria.

PubMed

Olawale, Adetunji Kola; David, Oluwole Moses; Oluyege, Adekemi Olubukunola; Osuntoyinbo, Richard Temitope; Laleye, Solomon Anjuwon; Famurewa, Oladiran

2015-01-01

Enterococci have been implicated as an emerging important cause of several diseases and multiple antibiotic resistance. However, there is little information about the prevalence of pathogenic and/or antibiotic-resistant Enterococcus faecalis in ready-to-eat foods in Nigeria. Here we report the pathogenic potential of three selected antibiotic-resistant E. faecalis strains isolated from food canteens and food outlets with different virulence determinant genes, including EFC 12 (with gel (+), esp (+), cylA (+), and asa1 (+)), EFT 148 (with gel (+), ace (+), and asa1 (+)), and EFS 18 (with esp (+) and cylA (+)) in an animal model. Enterococcemia, hematological parameters, and histopathological changes in organ tissues were examined in experimental animals. The results showed differences in enterococcemia and hematological parameters between the control group and experimental animal group. Enterococcemia was observed for 7 days, and the animal group infected with EFC 12 showed the highest growth rate, followed by EFT 148, with the lowest growth rate seen in the EFS 18-infected group. White blood cell count, packed cell volume, and platelets were significantly reduced (P<0.05) in the experimental animals compared with the controls. White blood cells decreased drastically during the study period in rats challenged with EFC 12 (from 7,800 to 6,120 per mm(3)) but levels remained higher in the control group (from 9,228 to 9,306 per mm(3)). Histopathological changes included areas of pronounced hemorrhage, necrosis, and distortion in liver tissues, which were more marked in rats infected with EFC 12, followed by EFT 148, then EFS 18. The results of this study suggest the presence of potentially pathogenic E. faecalis strains in food canteens and food outlets; hence, there is a need for strict adherence to good hygiene practices in the study area owing to the epidemiological significance of foods.

Histological and serological evidence of experimental paracoccidioidomycosis in Calomys callosus (Rodentia: Cricetidae)

PubMed Central

Berbert, Alceu LCV; Faria, Gabriele G; Gennari-Cardoso, Margareth L; Silva, Maria MMD; Mineo, José R; Loyola, Adriano M

2007-01-01

The responses of animal experimental models related to the infectivity, virulence and pathogenicity of Paracoccidioides brasiliensis is constantly used to develop new perspectives of investigation. The rodent Calomys callosus, Rengger 1830 (Rodentia: Cricetidae) is an indigenous inhabitant of the savannah environment found in the central regions of Brazil. The aim of the present work was to evaluate the histopathological and serological features of C. callosus after inoculation with the Pb18 strain of P. brasiliensis. Furthermore, A/Sn and B10.A mice strains were also tested to compare the results obtained in C. callosus to these well-established experimental models of resistance and susceptibility respectively. In every instance, survival analysis was performed, and histopathological study of the lungs, liver and spleen was employed to investigate tissue involvement, degree of inflammation and fungal presence. Levels of antibodies to P. brasiliensis were measured by using an enzyme-linked immunosorbent assay after 4 weeks and at the advanced stage of infection. The mortality rate was proportional to inoculation dose in all groups, but overall it was much superior in C. callosus than in the B10.A-susceptible mice. Macroscopical and microscopical pathological alterations were also more extensive and remarkable for C. callosus, once again proportional to inoculation dose, but more noticeable differences among the studied groups were found with 0.6 × 105 inoculum. In addition, the serological profile of C. callosus was similar to that found for B10.A-susceptible mice. Infection of C. callosus with 0.6 × 108 Pb18 inoculum resulted in more serious illness, and it decreased in severity in proportion to the inoculum dose. This difference was more pronounced in C. callosus, and the clinical, serological and pathological findings in this animal were more intense and precocious compared with the B10.A-susceptible mice. The present results suggest that C. callosus is a potentially alternative experimental animal model for paracoccidioidomycosis infection. PMID:17244339

Pulmonary fat embolism after reamed and unreamed nailing of femoral fractures.

PubMed

Högel, F; Gerlach, U V; Südkamp, N P; Müller, C A

2010-12-01

To determine whether reamed or unreamed intramedullary nailing of femoral fractures results in higher incidence of pulmonary fat embolism, three different methods of intramedullary nailing were compared in sheep. To analyze the presence of bone marrow fat embolism in pulmonary arteries, histological evaluation was undertaken using a quantitative computer-assisted measurement system. In this experimental model of 27 female Swiss alpine sheep, an osteotomy of the proximal femur was conducted in each animal. Then, the animals were divided into three groups according to the method of treatment: two different reamed intramedullary nailing techniques and an unreamed nailing technique were used. In the first group "ER" (experimental reamer; n=9), the nail was inserted after reaming with an experimental reamer; in the second group "CR" (conventional reamer; n=7), the intramedullary nail was inserted after reaming with the conventional AO-reamer. In the third group "UN" (unreamed; n=8) unreamed nailing was performed. During the operation procedure intramedullary pressure was measured in the distal fragment. After sacrificing the animals, quantitative histological analyses of bone marrow fat embolism in pulmonary arteries were done using osmium tetroxide fixation and staining of the fat. The measurement of intramedullary pressure showed significantly lower values for reamed nailing than for the unreamed technique. The quantitative histological evaluation of lung vessels concerning bone marrow fat embolism revealed a statistically significant difference between reamed and unreamed insertion of the nail: 7.77%±6.93 (ER) and 6.66%±5.61 (CR) vs. 16.25%±10.05 (UN) (p<0.05) of the assessed lung vessels were filled with fat emboli. However, no difference was found between the traditional and experimental reamer. Intramedullary nailing after reaming is a safe procedure with low systemic embolisation when compared to the unreamed insertion of the nail. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bariatric embolization for suppression of the hunger hormone ghrelin in a porcine model.

PubMed

Paxton, Ben E; Kim, Charles Y; Alley, Christopher L; Crow, Jennifer H; Balmadrid, Bryan; Keith, Christopher G; Kankotia, Ravi J; Stinnett, Sandra; Arepally, Aravind

2013-02-01

To prospectively test in a porcine model the hypothesis that bariatric embolization with commercially available calibrated microspheres can result in substantial suppression of systemic ghrelin levels and affect weight gain over an 8-week period. The institutional animal care and use committee approved this study. Twelve healthy growing swine (mean weight, 38.4 kg; weight range, 30.3-47.0 kg) were evaluated. Bariatric embolization was performed by infusion of 40-μm calibrated microspheres selectively into the gastric arteries that supply the fundus. Six swine underwent bariatric embolization, while six control animals underwent a sham procedure with saline. Weight and fasting plasma ghrelin and glucose levels were obtained in animals at baseline and at weeks 1-8. Statistical testing for differences in serum ghrelin levels and weight at each time point was performed with the Wilcoxon signed rank test for intragroup differences and the Wilcoxon rank sum test for intergroup differences. The pattern of change in ghrelin levels over time was significantly different between control and experimental animals. Weekly ghrelin levels were measured in control and experimental animals as a change from baseline ghrelin values. Average postprocedure ghrelin values increased by 328.9 pg/dL ± 129.0 (standard deviation) in control animals and decreased by 537.9 pg/dL ± 209.6 in experimental animals (P = .004). The pattern of change in weight over time was significantly different between control and experimental animals. The average postprocedure weight gain in experimental animals was significantly lower than that in control animals (3.6 kg ± 3.8 vs 9.4 kg ± 2.8, respectively; P = .025). Bariatric embolization can significantly suppress ghrelin and significantly affect weight gain. Further study is warranted before this technique can be used routinely in humans.

In vivo analysis of intestinal permeability following hemorrhagic shock

PubMed Central

Alsaigh, Tom; Chang, Marisol; Richter, Michael; Mazor, Rafi; Kistler, Erik B

2015-01-01

AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation. RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units (× 105, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure. PMID:26557479

Radiation carcinogenesis and acute radiation mortality in the rat as produced by 2.2 GeV protons

NASA Technical Reports Server (NTRS)

Shellabarger, C. J.; Straub, R. F.; Jesseph, J. E.; Montour, J. L.

1972-01-01

Biological studies, proton carcinogenesis, the interaction of protons and gamma-rays on carcinogenesis, proton-induced acute mortality, and chemical protection against proton-induced acute mortality were studied in the rat and these proton-produced responses were compared to similar responses produced by gamma-rays or X-rays. Litter-mate mice were assigned to each experimental and control group so that approximately equal numbers of litter mates were placed in each group. Animals to be studied for mammary neoplasia were handled for 365 days post-exposure when all animals alive were killed. All animals were examined frequently for mammary tumors and as these were found, they were removed, sectioned and given a pathologic classification.

Acute and chronic animal models for the evaluation of anti-diabetic agents

PubMed Central

2012-01-01

Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential. PMID:22257465

Efficacy of celecoxib in the treatment of CNS lymphomas: an in vivo model.

PubMed

Wang, Weijun; Kardosh, Adel; Su, Yuzhuang S; Schonthal, Axel H; Chen, Thomas C

2006-11-15

The incidence of primary central nervous system lymphomas (PCNSLs) has increased over the past several decades. Unfortunately, even with the most effective therapeutic regimen (that is, methotrexate with wholebrain radiation therapy), PCNSL recurs within a few years in more than half of the treated patients and is eventually fatal. Because PCNSL usually occurs in older patients and in those with acquired immunodeficiency syndrome, combination treatments in which both chemo- and radiation therapy are used is often poorly tolerated and results in a significant reduction in the quality of life. Recently, it has been demonstrated that the selective cyclooxygenase- 2 inhibitor celecoxib (Celebrex), can block the growth of lymphoma cells in vitro. To create an experimental animal model in vivo for the PCNSL study, the authors intracranially injected a human B-cell lymphoma cell line into nude mice. Their data demonstrate that this experimental model is an excellent one for human PCNSL with brain and leptomeningeal involvement. They also evaluated the feasibility of using celecoxib as a therapeutic agent in the treatment of PCNSL. Nude mice with intracranial lymphomas were treated with celecoxib contained in the animal chow. The treated animals demonstrated significantly prolonged survival times compared with the untreated animals. Based on the authors' data, celecoxib may be a promising therapeutic agent for the treatment of PCNSL.

The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response.

PubMed

Wellman, Laurie L; Fitzpatrick, Mairen E; Hallum, Olga Y; Sutton, Amy M; Williams, Brook L; Sanford, Larry D

2017-01-01

Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABA A agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5μl) into BLA of either Mus (1.0μM; n=13) or vehicle (Veh; n=15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

The Basolateral Amygdala Can Mediate the Effects of Fear Memory on Sleep Independently of Fear Behavior and the Peripheral Stress Response

PubMed Central

Wellman, Laurie L.; Fitzpatrick, Mairen E.; Hallum, Olga Y.; Sutton, Amy M.; Williams, Brook L.; Sanford, Larry D.

2016-01-01

Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABAA agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5ul) into BLA of either Mus (1.0uM; n = 13) or vehicle (Veh; n = 15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4 h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep. PMID:27818268

Historical view of development of comparative endocrinology in Japan.

PubMed

Kikuyama, Sakae; Tsutsui, Kazuyoshi

2011-04-01

This article describing a brief history of development of comparative endocrinology in Japan is contributed to the journal General and Comparative Endocrinology, in commemoration of the 50th anniversary of its publication. It covers significant works in the field of comparative endocrinology that have been done by Japanese endocrinologists, focusing those achieved during the past 70 years. The contents were arranged according to the taxonomical order of the experimental animals with which individual researchers or research groups have contributed to the acquisition of important knowledge in comparative endocrinology. Copyright © 2011 Elsevier Inc. All rights reserved.

Wet and dry extraction of coconut oil: impact on lipid metabolic and antioxidant status in cholesterol coadministered rats.

PubMed

Nevin, K Govindan; Rajamohan, Thankappan

2009-08-01

Because coconut oil extracted by wet process (virgin coconut oil, VCO) is gaining popularity among consumers, this study was conducted to evaluate VCO compared with coconut oil extracted by dry process (copra oil, CO) for their influence on lipid parameters, lipid peroxidation, and antioxidant status in rats coadministered with cholesterol. VCO, CO, and cholesterol were fed in a semi-synthetic diet to 24 male Sprague-Dawley rats for 45 days. After the experimental period, lipid and lipid peroxide levels and antioxidant enzyme activities were observed. Chemical composition and antioxidant properties of the polyphenolic fraction from VCO and CO were also analyzed. The results showed that lipid and lipid peroxide levels were lower in VCO-fed animals than in animals fed either CO or cholesterol alone. Antioxidant enzyme activities in VCO-fed animals were comparable with those in control animals. Although the fatty acid profiles of both oils were similar, a significantly higher level of unsaponifiable components was observed in VCO. Polyphenols from VCO also showed significant radical-scavenging activity compared with those from CO. This study clearly indicates the potential benefits of VCO over CO in maintaining lipid metabolism and antioxidant status. These effects may be attributed in part to the presence of biologically active minor unsaponifiable components.

Comparing Plant and Animal Glutamate Receptors: Common Traits but Different Fates?

PubMed

Wudick, Michael M; Michard, Erwan; Oliveira Nunes, Custódio; Feijó, José A

2018-04-19

Animal ionotropic glutamate receptors (iGluRs) are ligand-gated channels whose evolution is intimately linked to the one of the nervous system, where the agonist glutamate and co-agonists glycine/D-serine act as neuro-transmitters or -modulators. While iGluRs are specialized in neuronal communication, plant glutamate receptor-like (GLR) homologues have evolved many plant-specific physiological functions, such as sperm signaling in moss, pollen tube growth, root meristem proliferation, innate immune and wound responses. GLRs have been associated with Ca2+ signaling by directly channeling its extracellular influx into the cytosol. Nevertheless, very limited information on functional properties of GLRs is available, and we mostly rely on structure/function data obtained for animal iGluRs to interpret experimental results obtained for plant GLRs. Yet, a deeper characterization and better understanding of plant GLRs is progressively unveiling original and different mode of functions when compared to their mammalian counterparts. Here, we review the function of plant GLRs comparing their predicted structure and physiological roles to the well-documented ones of iGluRs. We conclude that interpreting GLR function based on comparison to their animal counterparts calls for caution, especially when presuming physiological roles and mode of action for plant GLRs from comparison to iGluRs in peripheral, non-neuronal tissues.

Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals.

PubMed

Amiot, Catherine E; Bastian, Brock

2017-01-01

Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals.

Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals

PubMed Central

Amiot, Catherine E.; Bastian, Brock

2017-01-01

Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals. PMID:28045909

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

PubMed Central

Morck, D W; Merrill, J K; Gard, M S; Olson, M E; Nation, P N

1997-01-01

Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that were non-infected and tilmicosin-treated were also included for determining tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h (n = 3-per time). In the infected calves, response to therapy was monitored clinically. Serum samples were collected for determination of tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded significantly better to therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight. Images Figure 2A. Figure 2B. PMID:9242998

The European politics of animal experimentation: From Victorian Britain to 'Stop Vivisection'.

PubMed

Germain, Pierre-Luc; Chiapperino, Luca; Testa, Giuseppe

2017-08-01

This paper identifies a common political struggle behind debates on the validity and permissibility of animal experimentation, through an analysis of two recent European case studies: the Italian implementation of the European Directive 2010/63/EC regulating the use of animals in science, and the recent European Citizens' Initiative (ECI) 'Stop Vivisection'. Drawing from a historical parallel with Victorian antivivisectionism, we highlight important threads in our case studies that mark the often neglected specificities of debates on animal experimentation. From the representation of the sadistic scientist in the XIX century, to his/her claimed capture by vested interests and evasion of public scrutiny in the contemporary cases, we show that animals are not simply the focus of the debate, but also a privileged locus at which much broader issues are being raised about science, its authority, accountability and potential misalignment with public interest. By highlighting this common socio-political conflict underlying public controversies around animal experimentation, our work prompts the exploration of modes of authority and argumentation that, in establishing the usefulness of animals in science, avoid reenacting the traditional divide between epistemic and political fora. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel phenotype in beagle dogs characterized by skin response to compound 48/80 focusing on skin mast cell degranulation

PubMed Central

Uchida, Mitsuhiro; Ito, Fumi; Tsuchiya, Toshiyuki; Shoji, Yoko; Kurosawa, Toru

2015-01-01

Beagle dogs have long been employed in toxicology studies and as skin disease models. Compared with other experimental animal species, they are known to be susceptible to skin responses, such as rashes, from exposure to various chemical compounds. Here, a unique dog phenotype was identified that showed no skin response to compound 48/80, a mast cell degranulating agent. Although the skin responses to intradermal injection of polyoxyethylene castor oil derivative (HCO-60, a nonionic detergent), histamine dihydrochloride, concanavalin A (IgE receptor-mediated stimuli), or calcium ionophore A23187 were comparable in wild-type (WT) dogs and these nonresponder (NR) dogs, only the response to compound 48/80 was entirely absent from NR dogs. The skin mast cell density and histamine content per mast cell were histologically comparable between WT and NR dogs. By checking for skin responses to compound 48/80, NR dogs were found to exist at the proportion of 17–20% among four animal breeders. From retrospective analysis of in-house breeding histories, the NR phenotype appears to conform to the Mendelian pattern of recessive inheritance. The standard skin response in WT dogs developed at 2–4 months of age. In conclusion, this unique phenotype, typified by insensitivity in the compound 48/80-induced degranulation pathway in mast cells, has been widely retained by recessive inheritance in beagle dogs among general experimental animal breeders. The knowledge concerning this phenotype could lead to better utilization of dogs in studies and aid in model development. PMID:26062768

T Cells

MedlinePlus

... cells — have proven successful in treating animals with experimental allergic encephalomyelitis (EAE), an animal model of MS. Pilot clinical trials are in progress. Future experimental therapies may involve antibodies directed against the cytokines ...

Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

PubMed

Henderson, William R; Barnbrook, Julian; Dominelli, Paolo B; Griesdale, Donald Eg; Arndt, Tara; Molgat-Seon, Yannick; Foster, Glen; Ackland, Gareth L; Xu, James; Ayas, Najib T; Sheel, Andrew W

2014-12-01

The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation.

Electrogastrography in experimental pigs: the influence of gastrointestinal injury induced by dextran sodium sulphate on porcine gastric erythromycin-stimulated myoelectric activity.

PubMed

Tachecí, Ilja; Kvetina, Jaroslav; Kunes, Martin; Edakkanambeth Varayil, Jithinraj; Ali, Shahzad Marghoob; Pavlik, Michal; Kopacova, Marcela; Rejchrt, Stanislav; Bures, Jan; Pleskot, Miloslav

2011-01-01

Electrogastrography (EGG) is a non-invasive investigation of gastric myoelectrical activity. The aim of study was to evaluate the impact of erythromycin on EGG in gastrointestinal toxic injury induced by dextran sodium sulphate (DSS) in experimental pigs. The experiments were carried out on 12 adult pigs (weighing 30-35 kg). EGG was recorded using Digitrapper equipment (Synectics Medical AB, Stockholm). Running spectrum activity was used for EGG evaluation. There were two groups of animals: Group I: 6 controls with erythromycin administration (1,600 mg intragastrically); Group II: 6 animals treated with DSS (for 5 days, 0.25 g/kg per day in a dietary bolus) followed by erythromycin administration. Baseline and subsequent six separate 30-minute EGG-recordings (from time 0 to 360 min) were accomplished in each animal. A total of 84 records were analysed. Baseline dominant frequency of slow waves was fully comparable in both groups. In Group I, there was a significant increase in dominant frequency after erythromycin administration (maximum between 240-360 min). There was a flat non-significant and delayed increase in dominant frequency after erythromycin administration in Group II. The difference between Group I and II at particular time intervals was not significant but a diverse trend was evident. EGG recording enables us to register a gastric myoelectrical effect of prokinetic drugs. Erythromycin induced a significant increase in the dominant frequency of slow waves. DSS caused toxic injury to the porcine gastrointestinal tract responsible for the delayed and weaker myoelectrical effect of erythromycin in experimental animals.

Improved exercise capacity and reduced systemic inflammation after adenoviral-mediated SERCA-2a gene transfer.

PubMed

Gupta, Dipin; Palma, Jon; Molina, Ezequiel; Gaughan, John P; Long, Walter; Houser, Steven; Macha, Mahender

2008-04-01

We hypothesized that sarcoplasmic reticulum Ca2+ ATPase pump (SERCA-2a) gene delivery would have beneficial effects upon exercise capacity and markers of inflammation in the setting of heart failure. A pressure-overload model of experimental heart failure was used in rats. Following a decrease in fractional shortening of >or=25%, animals underwent intracoronary adenoviral-mediated gene transfection using SERCA-2a. Heart failure animals were randomized to receive the SERCA-2a gene, the beta galactosidase (control) gene, or followed without any further intervention. Exercise and hemodynamic testing were performed, and myocardial and systemic markers of inflammation were assayed after 7 and 21 d. Animals receiving Ad.SERCA-2a showed an increase in exercise tolerance (499.0 +/- 14.9 versus 312.8 +/- 10.5 s, P < 0.0001) relative to Ad.Gal group. Groups treated with Ad.SERCA-2a had significantly decreased serum levels of the inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor-alpha compared with Ad.Gal-treated animals. Serum levels of atrial natriuretic peptide were decreased in animals receiving Ad.SERCA-2a compared with animals receiving Ad.Gal at day 7 (0.35 +/- 0.03 versus 0.52 +/- 0.11 pg/mL, P = 0.001). Myocardial levels of the proapoptotic protein bax were reduced in Ad.SERCA-2a -treated animals compared with those receiving Ad.Gal at day 7 (protein level/actin: 0.24 +/- 0.05 versus 0.33 +/- 0.04, P = 0.04) and day 21 (protein level/actin: 0.61 +/- 0.04 versus 0.69 +/- 0.01, P = 0.001). Genetic modulation of heart failure using the SERCA-2a gene was associated with improvement in cardiac function and exercise capacity as well as improvements in heart-failure associated inflammatory markers.

Improved nonhuman animal welfare is related more to income equality than it is to income.

PubMed

Morris, Michael C

2013-01-01

The link between nonhuman animal welfare, income, and income inequality (Gini coefficient) was tested using consumption of animal products, laws protecting animals on the farm from the worst abuses, and animals used in experimentation as indicators. Experimentation on all animals and on rodents significantly increased in high-income European countries, although there was some evidence that the increase in experimentation on cats and dogs started to flatten out for the highest income countries. Consumption of all flesh products in high-income countries declined in more equal societies. More equal high-income countries also had stricter regulations protecting animals, although the same correlation was not seen between U.S. states. In New Zealand, there was some evidence that testing on cats and dogs declined during years when equality was improving. The results provide little evidence for a Kuznets effect of income on animal welfare, with the possible exception of companion animal treatment. They do, however, suggest that greater equality can be a predictor for better treatment of animals. Previous research has strongly suggested that social conditions for humans improve with greater equality. The same may be true for nonhuman animals. Alternatively, conditions conducive to improving human income equality may also lead to better animal welfare outcomes.

Efficacy of tigecycline alone and in combination with gentamicin in the treatment of experimental endocarditis due to linezolid-resistant Enterococcus faecium.

PubMed

Pontikis, Konstantinos; Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

2013-07-01

We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups.

Efficacy of Tigecycline Alone and in Combination with Gentamicin in the Treatment of Experimental Endocarditis Due to Linezolid-Resistant Enterococcus faecium

PubMed Central

Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

2013-01-01

We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups. PMID:23587961

THE ACTION OF SOME PREPARATIONS FROM THE ARALIA FAMILY IN EXPERIMENTAL RADIATION SICKNESS (in Russian)

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

Brekhman, I.I.; Oskotskii, L.I.; Khakham, A.I.

1960-02-01

In ginseng therapy of irradiated mice (400 r), the survival was 2 1/2 times higher, and in eleutherococcus treatment the survival was almost 5 times higher as compared with the control group. In the combined action of x-ray irradiation and overloading (rotation of mice for 15 seconds in a centrifuge at 400 to 500 rounds per minute), the therapeutic effect of ginseng and eleutherococcus was more pronounced than in an isolated affection of experimental animals with x rays. (auth)

Comparative acute toxicity of gallium(III), antimony(III), indium(III), cadmium(II), and copper(II) on freshwater swamp shrimp (Macrobrachium nipponense).

PubMed

Yang, Jen-Lee

2014-04-01

Acute toxicity testing were carried out the freshwater swamp shrimp, Macrobrachium nipponense, as the model animal for the semiconductor applied metals (gallium, antimony, indium, cadmium, and copper) to evaluate if the species is an suitable experimental animal of pollution in aquatic ecosystem. The static renewal test method of acute lethal concentrations determination was used, and water temperature was maintained at 24.0 ± 0.5°C. Data of individual metal obtained from acute toxicity tests were determined using probit analysis method. The median lethal concentration (96-h LC50) of gallium, antimony, indium, cadmium, and copper for M. nipponense were estimated as 2.7742, 1.9626, 6.8938, 0.0539, and 0.0313 mg/L, respectively. Comparing the toxicity tolerance of M. nipponense with other species which exposed to these metals, it is obviously that the M. nipponense is more sensitive than that of various other aquatic animals.

Osseointegration of alumina bioceramic granules: A comparative experimental study

NASA Astrophysics Data System (ADS)

Rerikh, V. V.; Avetisyan, A. R.; Zaydman, A. M.; Anikin, K. A.; Bataev, V. A.; Nikulina, A. A.; Sadovoy, M. A.; Aronov, A. M.; Semantsova, E. S.

2016-08-01

To perform a comparative analysis of osseointegration of bioceramic alumina-based granules, hydroxyapatite-based granules, and deproteinized bone granules. The experiment was conducted on 52 adult male Kyoto-Wistar rats weighing 350 to 520 g. The animals were divided into five matched groups that differed only in the type of an implanted material. The granules were implanted in the lumbar vertebral bodies and in the distal right femur of each laboratory animal. Two months after surgery, the animals were euthanized, followed by tissue sampling for morphological studies. An examination of specimens from the groups with implanted alumina granules revealed the newly formed trabecular bone with remodeling signs. The bone tissue filled the intragranular space, tightly adhering to the granule surface. There was no connective tissue capsule on the border between bone tissue and alumina granules. Cylindrical bioceramic alumina-based granules with an open internal channel have a higher strength surpassing than that of analogs and the osseointegration ability close to that of hydroxyapatite and deproteinized bone granules.

Leaf litter bags as an index to populations of northern two-lined salamanders (Eurycea bislineata)

USGS Publications Warehouse

Chalmers, R.J.; Droege, S.

2002-01-01

Concern about recent amphibian declines has led to research on amphibian populations, but few statistically tested, standardized methods of counting amphibians exist. We tested whether counts of northern two-lined salamander larvae (Eurycea bislineata) sheltered in leaf litter bags--a relatively new, easily replicable survey technique--had a linear correlation to total number of larvae. Using experimental enclosures placed in streams, we compared number of salamanders found in artificial habitat (leaf litter bags) with total number of salamanders in each enclosure. Low numbers of the animals were found in leaf litter bags, and the relative amount of variation in the index (number of animals in leaf litter bags compared to total number of animals in stream enclosures) was high. The index of salamanders in leaf litter bags was not significantly related to total number of salamanders in enclosures for two-thirds of the replicates or with pooled replicates (P= 0.066). Consequently, we cannot recommend using leaf litter bags to index populations of northern two-lined salamanders.

The effect of hypergravity on the lens, cornea and tail regeneration in Urodela

NASA Astrophysics Data System (ADS)

Grigoryan, E. N.; Dvorochkin, N.; Poplinskaya, V. A.; Yousuf, R.; Radugina, E. A.; Almeida, E. A.

2017-09-01

In previous experiments onboard Russian Bion/Foton satellites it was found that exposure to microgravity causes changes in eye lens regeneration of Urodela. The changes included higher rate of regeneration, increased cell proliferation in lens anlage, and synchronization of lens restoration. Similar changes were observed regarding tail regeneration. Recently, investigations were performed to find out whether exposure to hypergravity could also alter lens, cornea and tail regeneration in the newt P. waltl. Nine days prior to exposure the left lens was surgically removed through corneal incision and distal 1/3 of the tail was amputated, thus initiating regeneration. The experimental animals were allowed to recover for 9 days at 1 g and then exposed to 2 g for 12 days in an 8 ft diameter centrifuge at NASA Ames Research Center. The experimental animals were divided into 1 g controls, 2 g centrifugation animals, basal controls, and aquarium controls. Lens and corneal regeneration appeared to be inhibited in 2 g group compared to 1 g animals. In all 1 g controls, lens regeneration reached stages VII-IX in a synchronous fashion and corneal regeneration was nearly complete. In the 2 g newts, neural retinal detachment from the pigmented epithelium was seen in most operated eyes. It was also observed in the non-operated (right) eyes of the animals exposed to 2 g. The level of retinal detachment varied and could have been caused by hypergravity-induced high intraocular pressure. Regeneration (when it could be assessed) proceeded asynchronously, reaching stages from II to IX. Corneal restoration was also noticeably delayed and corneal morphology changed. Cell proliferation was measured using BrdU; the results were not comparable to the 1 g data because of retinal detachment. Previous investigations demonstrated that lens regeneration was controlled by the neural retina; therefore, lower regeneration rate at 2 g was, at least in part, associated with retinal detachment. FGF2 release by the neural retina and FGFR2 expression in the iris and other tissues could accelerate lens proliferation whereas its delay could be caused by retinal detachment, which may explain compromised regeneration at 2 g. Hypergravity (both 1 g and 2 g) increased tissue growth compared to aquarium control (as measured by regenerate volume) and altered the shape of tail regenerates - they became curved downwards. The experimental results emphasize the important and versatile role gravity plays in tissue regeneration. They also suggest that, when considering hypergravity as a countermeasure that can be used in future space missions, its potential impact on the eye should not be ignored.

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.

Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya.

PubMed

Oduola, Taofeeq; Bello, Ibrahim; Idowu, Thomas; Avwioro, Godwin; Adeosun, Ganiyu; Olatubosun, Luqman

2010-05-01

Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

Skull Base Cerebrospinal Fluid Leakage Control with a Fibrin-Based Composite Tissue Adhesive

PubMed Central

Rock, Jack P.; Sierra, David H.; Castro-Moure, Frederico; Jiang, Feng

1996-01-01

Cerebrospinal fluid (CSF) leaks can be responsible for significant patient morbidity and mortality. While the majority of leaks induced after head trauma will seal without intervention, spontaneous or surgically-induced leaks often require operative repair. Many modifications on standard surgical technique are available for repair of CSF fistulae, but none assures adequate closure. We have studied the efficacy of a novel fibrin-based composite tissue adhesive (CTA) for closure of experimentally-induced CSF leaks in rats. Fistulae were created in two groups of animals. Two weeks after creation of the leaks, the animals were sacrificed and analyzed for persistence of leak. A 58% leakage rate was noted in the control group (n = 12), and no leaks were noted in the experimental group closed after application of CTA to the surgical defect followed by skin closure (n = 11). Comparing the control group to the experimental group, results were statistically significant (p = 0.015). These data suggest that CTA may be effective as an adjunct for the closure of CSF fistulae. ImagesFigure 2Figure 3 PMID:17170969

Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors.

PubMed

Ale, Angelique; Schulz, Ralf B; Sarantopoulos, Athanasios; Ntziachristos, Vasilis

2010-05-01

The performance is studied of two newly introduced and previously suggested methods that incorporate priors into inversion schemes associated with data from a recently developed hybrid x-ray computed tomography and fluorescence molecular tomography system, the latter based on CCD camera photon detection. The unique data set studied attains accurately registered data of high spatially sampled photon fields propagating through tissue along 360 degrees projections. Approaches that incorporate structural prior information were included in the inverse problem by adding a penalty term to the minimization function utilized for image reconstructions. Results were compared as to their performance with simulated and experimental data from a lung inflammation animal model and against the inversions achieved when not using priors. The importance of using priors over stand-alone inversions is also showcased with high spatial sampling simulated and experimental data. The approach of optimal performance in resolving fluorescent biodistribution in small animals is also discussed. Inclusion of prior information from x-ray CT data in the reconstruction of the fluorescence biodistribution leads to improved agreement between the reconstruction and validation images for both simulated and experimental data.

Meat product based on porcine hearts and aortas ameliorates serum lipid profile and inflammation in hyperlipidemic rats

NASA Astrophysics Data System (ADS)

Chernukha, I. M.; Kotenkova, E. A.; Fedulova, L. V.

2017-09-01

The biological effect of porcine hearts and aortas in a hyperlipidemic rat model was confirmed. Porcine heart and aorta mixture in a 3:1 ratio was blended, canned and sterilized at 115°C and 0.23 Mpa for 40 min. Administration of experimental meat product to the animal model decreased total cholesterol, triglycerides and cholesterol low density lipoproteins by 31.8% (P<0.05), 28.2%, and 21.6% (P<0.05), respectively, compared to those of hyperlipidemic control rats, as well significantly reducing the serum atherogenic index by 41.3% (P<0.05) in rats fed the experimental meat product compared with hyperlipidemic control rats. Normalization of white blood cell populations was also detected. Monocyte and granulocyte counts in blood of rats fed the meat product decreased by 71.1% (P<0.05) and 57.6% (P<0.05) compared to those of the hyperlipidemic control animals. The granulocyte/leucocyte ratio was also reduced by an average of 38.6% (P<0.05) in rats fed the meat product compared with hyperlipidemic control rats. The data confirmed the hypolipidemic action of the sterilized meat product. Normalization of white blood cell populations led us to hypothesize an anti-inflammatory action of the new meat product, which, therefore, could be recommended as a part of maintenance therapy for people with lipid disorders or atherosclerosis.

The interstitial stem cells in Hydractinia and their role in regeneration.

PubMed

Gahan, James M; Bradshaw, Brian; Flici, Hakima; Frank, Uri

2016-10-01

Hydractinia species have been animal models in developmental biology and comparative immunology for over a century, but are having a renaissance due to the establishment of modern genetic and genomic tools by the growing community of researchers utilizing them. Hydractinia has a predictable and accessible life cycle and its stem cell system, known as interstitial- or i-cells has been a paradigm for animal stem cells since the late 1800s. In adult Hydractinia, i-cells continuously provide progenitors to sustain clonal growth, tissue homeostasis, sexual reproduction and regeneration. We review recent developments in stem cell and regeneration research centered on this animal. Hydractinia joins an established team of cnidarian genetic models in times of rapid progress in these disciplines. While each animal is particularly suited to specific experimental settings, jointly they can provide an integrative insight into the diversity of animal stem cell systems, how they drive regeneration, and how they evolved. Copyright © 2016 Elsevier Ltd. All rights reserved.

The dynamic genome of Hydra.

PubMed

Chapman, Jarrod A; Kirkness, Ewen F; Simakov, Oleg; Hampson, Steven E; Mitros, Therese; Weinmaier, Thomas; Rattei, Thomas; Balasubramanian, Prakash G; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E; Putnam, Nicholas H; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E; Gee, Lydia; Kibler, Dennis F; Law, Lee; Lindgens, Dirk; Martinez, Daniel E; Peng, Jisong; Wigge, Philip A; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R H; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M; Wheeler, Benjamin M; Peterson, Kevin J; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C G; Holstein, Thomas W; Fujisawa, Toshitaka; Bode, Hans R; David, Charles N; Rokhsar, Daniel S; Steele, Robert E

2010-03-25

The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.

Learning in Plants: Lessons from Mimosa pudica

PubMed Central

Abramson, Charles I.; Chicas-Mosier, Ana M.

2016-01-01

This article provides an overview of the early Mimosa pudica literature; much of which is in journals not easily accessible to the reader. In contrast to the contemporary plant learning literature which is conducted primarily by plant biologists, this early literature was conducted by comparative psychologists whose goal was to search for the generality of learning phenomena such as habituation, and classical conditioning using experimental designs based on animal conditioning studies. In addition to reviewing the early literature, we hope to encourage collaborations between plant biologists and comparative psychologists by familiarizing the reader with issues in the study of learning faced by those working with animals. These issues include no consistent definition of learning phenomena and an overreliance on the use of cognition. We suggested that greater collaborative efforts be made between plant biologists and comparative psychologists if the study of plant learning is to be fully intergraded into the mainstream behavior theory. PMID:27065905

Intrascrotal CGRP 8-37 causes a delay in testicular descent in mice.

PubMed

Samarakkody, U K; Hutson, J M

1992-07-01

The genitofemoral nerve is a key factor in the inguinoscrotal descent of the testis. The effect of androgens may be mediated via the central nervous system, which in turn secretes the neurotransmitter calcitonin gene-related peptide (CGRP) at the genitofemoral nerve endings, to cause testicular descent. The effect of endogenous CGRP was examined by weekly injections of a vehicle with or without synthetic antagonist (CGRP 8-37) into the developing scrotum of neonatal mice. The descent of the testis was delayed in the experimental group compared with the control group. At 2 weeks of age 43% of controls had descended testes compared with 0% of experimental animals. At 3 weeks of age 17% of experimentals still had undescended testes, whereas all testes were descended in controls. At 4 weeks 3 testes remained undescended in the experimental group. It is concluded that the CGRP antagonist can retard testicular descent. This result is consistent with the hypothesis that CGRP is an important intermediary in testicular descent.

Diet and liver apoptosis in rats: a particular metabolic pathway.

PubMed

Monteiro, Maria Emilia Lopes; Xavier, Analucia Rampazzo; Azeredo, Vilma Blondet

2017-03-30

Various studies have indicated an association between modifi cation in dietary macronutrient composition and liver apoptosis. To explain how changes in metabolic pathways associated with a high-protein, high-fat, and low-carbohydrate diet causes liver apoptosis. Two groups of rats were compared. An experimental diet group (n = 8) using a high-protein (59.46%), high-fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after eight weeks, the adipose tissue weighed, the liver removed for flow cytometry analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF, triglycerides, malondialdehyde, and β-hydroxybutyrate. Statistical analysis was carried out using the unpaired and parametric Student's t-test and Pearson's correlation coeffi ents. Significance was set at p < 0.05. Animals from the experimental group presented less adipose tissue than dose of the control group. Percentage of nonviable hepatocytes in the experimental group was 2.18 times larger than the control group (p = 0.001). No statistically significant differences were found in capillary glucose, insulin, glucagon, IL-6, or TNF-α between two groups. Plasmatic β-hydroxybutyrate and malondialdehyde of the experimental group expressed higher levels and triglycerides lower levels compared with the control group. The results show a positive and significant correlation between the percentage of nonviable hepatocytes and malondialdehyde levels (p = 0.0217) and a statistically significant negative correlation with triglycerides levels (p = 0.006). Results suggest that plasmatic malondialdehyde and triglyceride levels are probably good predictors of liver damage associated with an experimental low-carbohydrate diet in rats.

Schofield memorial lecture. Bull semen and muscle ATP: some evidence of the dawn of medical science in ancient Egypt.

PubMed Central

Schwabe, C W

1986-01-01

The importance of animal experimentation to human and animal health is not well understood by an increasingly articulate segment of the public. This could have very unfortunate consequences for man and his domestic animals. Even veterinarians and physicians are not as conversant as they need be about the great extent to which advances in human health have depended upon animal observations and experiments. Some believe that resort to "animal models" of biomedical phenomena, including diseases--a comparative or analogical approach to medical studies--is a relatively recent event. Even medical historians often treat these subjects as occasionally recurring aberrations which began with the Greeks, thus largely overlooking the historical meaning and continuing importance of "one medicine" irrespective of species. In fact, comparative medicine has probably been basic to medical progress ever since the dawn of a medical science. Recent research indicates that this approach to biomedical mysteries began to evolve in the minds of Egypt's healer-priests long before Aristotle and the later Alexandrian Greeks made the whole process explicit. Here we examine the origins of what were possibly the first two biomedical theories profounded from inferences based upon dissections, confirmed in at least one instance by experiment, and then applied to medical practice. PMID:3530413

Effect of laser irradiation for healing of the skin-muscle wounds of animals

NASA Astrophysics Data System (ADS)

Lapina, Victoria A.; Veremei, Eduard I.; Pancovets, Evgeniy A.

2000-05-01

The purpose of our investigation was to study the medical effect of low-intensity laser influence on healing of skin- muscle wounds of agricultural animals. We used the laser radiation of low intensity for cub's therapy: to sucking-pigs after herniotomy and castration, to cattle cubs after skin- muscle wounds. The animals were kept under clinical observation up to their recovery. The recuperation dynamic was observed by changing of blood quotients, leukograms, sizes of inflammatory edema, general behavior of animals. The positive dynamic of blood quotients of the experimental animal groups was really higher than that in control. The analysis of wound healing after laser influence shows that wound surface of experimental group was to a great extent smaller in comparison with control group of animals. So, these facts testify about anti-inflammatory action of laser radiation, which hastens regenerative and rehabilitative processes. Analysis of the obtained experimental data has revealed the positive influence of laser irradiation on the dynamics of wound adhesion of agricultural animals.

Comparison of self-efficacy and its improvement after artificial simulator or live animal model emergency procedure training.

PubMed

Hall, Andrew B; Riojas, Ramon; Sharon, Danny

2014-03-01

The objective of this study is to compare post-training self-efficacy between artificial simulators and live animal training for the performance of emergency medical procedures. Volunteer airmen of the 81st Medical Group, without prior medical procedure training, were randomly assigned to two experimental arms consisting of identical lectures and training of diagnostic peritoneal lavage, thoracostomy (chest tube), and cricothyroidotomy on either the TraumaMan (Simulab Corp., Seattle, Washington) artificial simulator or a live pig (Sus scrofa domestica) model. Volunteers were given a postlecture and postskills training assessment of self-efficacy. Twenty-seven volunteers that initially performed artificial simulator training subsequently underwent live animal training and provided assessments comparing both modalities. The results were first, postskills training self-efficacy scores were significantly higher than postlecture scores for either training mode and for all procedures (p < 0.0001). Second, post-training self-efficacy scores were not statistically different between live animal and artificial simulator training for diagnostic peritoneal lavage (p = 0.555), chest tube (p = 0.486), and cricothyroidotomy (p = 0.329). Finally, volunteers undergoing both training modalities indicated preference for live animal training (p < 0.0001). We conclude that artificial simulator and live animal training produce equivalent levels of self-efficacy after initial training, but there is a preference in using a live animal model to achieve those skills. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

[Animal experimentation in the discovery and production of veterinary vaccines].

PubMed

Audonnet, J Ch; Lechenet, J; Verschuere, B

2007-08-01

Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.

Effects of muscle atrophy on motor control

NASA Technical Reports Server (NTRS)

Stuart, D. G.

1985-01-01

As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

Thalidomide prolongs survival after experimental musculoskeletal injury, through an effect on mononuclear apoptosis.

PubMed

Panousis, Konstantinos; Nikolaou, Vassilios S; Tsaganos, Thomas; Lallos, Stergios; Giamarellos-Bourboulis, Evangelos J; Efstathopoulos, Nicolas

2014-05-01

This study was conducted to investigate the effects of intravenous thalidomide administration in an experimental model of musculoskeletal trauma. We hypothesized that because thalidomide inhibits secretion of tumor necrosis factor alpha (TNF-α), survival of animals that received thalidomide would be significantly prolonged. After an open fracture of the right femur, 24 rabbits were randomly assigned to control and thalidomide groups. Intravenous therapy with thalidomide was started 30 min after fracture. Hemodynamic monitoring of all animals was performed for 4 h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-α measurement and for isolation of peripheral blood mononuclear cells (PBMCs). Apoptosis of PBMCs was measured by flow cytometry. Survival was significantly prolonged in the thalidomide group. Apoptosis of PBMCs was increased in the control group compared with the thalidomide group at 24 h. There were no differences in vital signs, blood and tissue cultures, and serum TNF-α concentration between the two groups. Intravenous thalidomide prolonged survival in an experimental model of severe musculoskeletal injury in rabbits. Its mechanism of action did not involve TNF-α suppression but prevention of mononuclear apoptosis. In view of these promising results, further research is needed to clarify the immunomodulatory mechanism of action of thalidomide and its potential use for the management of severe trauma. Copyright © 2014 Elsevier Inc. All rights reserved.

Does age matter? The impact of rodent age on study outcomes.

PubMed

Jackson, Samuel J; Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2017-04-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6-20 week age range regardless of the biology being studied. The age referred to as 'adult' by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans.

Does age matter? The impact of rodent age on study outcomes

PubMed Central

Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2016-01-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans. PMID:27307423

Animal Experimentation in High Schools

ERIC Educational Resources Information Center

Ansevin, Kystyna D.

1970-01-01

Recommends that teacher and student be provided with the broadest possible spectrum of meaningful and feasible experiments in which the comfort of the experimental animal is protected by the design of the experiment. (BR)

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.

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.

Comparing fluid mechanics models with experimental data.

PubMed Central

Spedding, G R

2003-01-01

The art of modelling the physical world lies in the appropriate simplification and abstraction of the complete problem. In fluid mechanics, the Navier-Stokes equations provide a model that is valid under most circumstances germane to animal locomotion, but the complexity of solutions provides strong incentive for the development of further, more simplified practical models. When the flow organizes itself so that all shearing motions are collected into localized patches, then various mathematical vortex models have been very successful in predicting and furthering the physical understanding of many flows, particularly in aerodynamics. Experimental models have the significant added convenience that the fluid mechanics can be generated by a real fluid, not a model, provided the appropriate dimensionless groups have similar values. Then, analogous problems can be encountered in making intelligible but independent descriptions of the experimental results. Finally, model predictions and experimental results may be compared if, and only if, numerical estimates of the likely variations in the tested quantities are provided. Examples from recent experimental measurements of wakes behind a fixed wing and behind a bird in free flight are used to illustrate these principles. PMID:14561348

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

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

PubMed

Witsch, Thilo J; Turowski, Pawel; Sakkas, Elpidoforos; Niess, Gero; Becker, Simone; Herold, Susanne; Mayer, Konstantin; Vadász, István; Roberts, Jesse D; Seeger, Werner; Morty, Rory E

2014-02-01

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD.

Improving basic and translational science by accounting for litter-to-litter variation in animal models

PubMed Central

2013-01-01

Background Animals from the same litter are often more alike compared with animals from different litters. This litter-to-litter variation, or “litter effects”, can influence the results in addition to the experimental factors of interest. Furthermore, sometimes an experimental treatment can only be applied to whole litters rather than to individual offspring. An example is the valproic acid (VPA) model of autism, where VPA is administered to pregnant females thereby inducing the disease phenotype in the offspring. With this type of experiment the sample size is the number of litters and not the total number of offspring. If such experiments are not appropriately designed and analysed, the results can be severely biased as well as extremely underpowered. Results A review of the VPA literature showed that only 9% (3/34) of studies correctly determined that the experimental unit (n) was the litter and therefore made valid statistical inferences. In addition, litter effects accounted for up to 61% (p <0.001) of the variation in behavioural outcomes, which was larger than the treatment effects. In addition, few studies reported using randomisation (12%) or blinding (18%), and none indicated that a sample size calculation or power analysis had been conducted. Conclusions Litter effects are common, large, and ignoring them can make replication of findings difficult and can contribute to the low rate of translating preclinical in vivo studies into successful therapies. Only a minority of studies reported using rigorous experimental methods, which is consistent with much of the preclinical in vivo literature. PMID:23522086

Surgical animal models of neuropathic pain: Pros and Cons.

PubMed

Challa, Siva Reddy

2015-03-01

One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.

kgp, rgpA, and rgpB DNA vaccines induce antibody responses in experimental peri-implantitis.

PubMed

Guo, Meihua; Wang, Zhifeng; Fan, Xin; Bian, Yuanyuan; Wang, Tiantian; Zhu, Lina; Lan, Jing

2014-11-01

Peri-implantitis is the key factor for implant failure. This study aims to evaluate kgp, rgpA, and rgpB DNA vaccines to induce an immune response and prevent peri-implantitis. The kgp, rgpA, and rgpB genes were amplified by polymerase chain reaction (PCR) from Porphyromonas gingivalis (Pg) ATCC 33277 and cloned into the pVAX1 vector. Titanium implants were placed into the mandibular bone of dogs. Three months later, the animals were divided into four groups, immunized with pVAX1-kgp, pVAX1-rgpA, pVAX1-rgpB, or pVAX1. Cotton ligatures infiltrated with Pg were tied around the neck of the implants. Immunoglobulin (Ig)G and IgA antibodies were detected by enzyme-linked immunosorbent assay before and after immunization. The kgp, rgpA, and rgpB genes were successfully cloned into the pVAX1 plasmid. Animals immunized with pVAX1-kgp and pVAX1-rgpA showed higher titers of IgG and IgA antibodies compared to those before immunization (P <0.05) and compared to those that were immunized with pVAX1 and pVAX1-rgpB, whereas there were no significant differences in the animals treated with pVAX1 and pVAX1-rgpB. Furthermore, among these, the kgp DNA vaccine was more effective. The bone losses of the groups with pVAX1-kgp and pVAX1-rgpA were significantly attenuated. pVAX1-kgp and pVAX1-rgpA DNA vaccines enhanced immunity responses and significantly retarded bone loss in experimental peri-implantitis animal models, whereas pVAX1-rgpB was ineffective.

Disruptive effects of light pollution on sleep in free-living birds: Season and/or light intensity-dependent?

PubMed

Raap, Thomas; Sun, Jiachen; Pinxten, Rianne; Eens, Marcel

2017-11-01

Light pollution or artificial light at night (ALAN) is an increasing anthropogenic environmental pollutant posing an important potential threat for wildlife. Evidence of its effects on animal physiology and behaviour is accumulating. However, in order to effectively mitigate light pollution it is important to determine which factors contribute to the severity of effects of ALAN. In this experimental study we explored whether there are seasonal-dependent effects of ALAN on sleep in free-living great tits (Parus major), an important model species. Additionally, we looked at whether light intensity determined the severity of effects of ALAN on sleep. We therefore exposed animals to artificial light inside the nest box (3lx) in December (winter) and February (pre-breeding season). Results from February were compared with the results from a previous study in February, using a lower light intensity (1.6lx). We found little evidence for a season-dependent response. Effects of ALAN hardly differed between high and low light intensity. ALAN disrupted sleep with as main effect a decrease in sleep duration (≈-40min) as animals woke up earlier (≈-24min). However, compared to a natural dark situation sleep onset was delayed by high but not by low light intensity of ALAN. Our study underlines earlier found disruptive effects of ALAN on sleep of free-living animals. While we found no conclusive evidence for seasonal or light intensity-dependent effects of ALAN, additional experimental work using lower light intensities might show such differences. Examining potential management options is crucial in mitigating disruptive effects of light pollution, which will be an important focus for future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.

PubMed

Martin, Keith R G; Levkovitch-Verbin, Hana; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Quigley, Harry A

2002-07-01

High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.

Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia – An Experimental Cardiovascular Magnetic Resonance Study

PubMed Central

Fischer, Kady; Guensch, Dominik P; Shie, Nancy; Lebel, Julie; Friedrich, Matthias G

2016-01-01

Background Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR). Methods and Findings In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point. Conclusion In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This maneuver may allow for detecting severe coronary artery stenosis and have a significant clinical potential as a non-pharmacological method for diagnostic testing in patients with suspected coronary artery disease. PMID:27741282

Anesthesia and Monitoring in Small Laboratory Mammals Used in Anesthesiology, Respiratory and Critical Care Research: A Systematic Review on the Current Reporting in Top-10 Impact Factor Ranked Journals

PubMed Central

Koch, Thea; Gama de Abreu, Marcelo; Spieth, Peter Markus

2015-01-01

Rationale This study aimed to investigate the quality of reporting of anesthesia and euthanasia in experimental studies in small laboratory mammals published in the top ten impact factor journals. Methods A descriptive systematic review was conducted and data was abstracted from the ten highest ranked journals with respect to impact factor in the categories ‘Anesthesiology’, ‘Critical Care Medicine’ and ‘Respiratory System’ as defined by the 2012 Journal Citation Reports. Inclusion criteria according to PICOS criteria were as follows: 1) population: small laboratory mammals; 2) intervention: any form of anesthesia and/or euthanasia; 3) comparison: not specified; 4) primary outcome: type of anesthesia, anesthetic agents and type of euthanasia; secondary outcome: animal characteristics, monitoring, mechanical ventilation, fluid management, postoperative pain therapy, animal care approval, sample size calculation and performed interventions; 5) study: experimental studies. Anesthesia, euthanasia, and monitoring were analyzed per performed intervention in each article. Results The search yielded 845 articles with 1,041 interventions of interest. Throughout the manuscripts we found poor quality and frequency of reporting with respect to completeness of data on animal characteristics as well as euthanasia, while anesthesia (732/1041, 70.3%) and interventions without survival (970/1041, 93.2%) per se were frequently reported. Premedication and neuromuscular blocking agents were reported in 169/732 (23.1%) and 38/732 (5.2%) interventions, respectively. Frequency of reporting of analgesia during (117/610, 19.1%) and after painful procedures (38/364, 10.4%) was low. Euthanasia practice was reported as anesthesia (348/501, 69%), transcardial perfusion (37/501, 8%), carbon dioxide (26/501, 6%), decapitation (22/501, 5%), exsanguination (23/501, 5%), other (25/501, 5%) and not specified (20/501, 4%, respectively. Conclusions The present systematic review revealed insufficient reporting of anesthesia and euthanasia methods throughout experimental studies in small laboratory mammals. Specific guidelines for anesthesia and euthanasia regimens should be considered to achieve comparability, quality of animal experiments and animal welfare. These measures are of special interest when translating experimental findings to future clinical applications. PMID:26305700

A perinatal signature of light on chronobiology? If so, numerous questions arise and experimental animal research must provide more information.

PubMed

Erren, Thomas C; Reiter, Russel J; Meyer-Rochow, V Benno

2012-01-01

That light and melatonin rhythms provide both clock and calendar information in humans and numerous other species is beyond dispute; this holds true for all stages of life, including the very early ones. Experimental evidence elucidates that exposure to light and melatonin titres are keys for the very development of circadian and seasonal rhythms. As evinced by a 2011 publication in Nature Neuroscience such awareness could impact considerably on the design and conduct of experimental studies as well as their subsequent analyses, interpretations and comparisons. Therefore "when and how experimental animals were bred, developed and raised" may be critical when experimenting with animals generally, and not just rodents. As long as the suggested imprinting of circadian system stability via light cues is not falsified, the perinatal season or perinatal experimental light:dark [L:D] conditions that an animal was kept under should be routinely recorded, published and considered in analysing and interpreting study data.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

PubMed

Cheresiz, S V; Semenova, E A; Chepurnov, A A

2016-01-01

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model.

PubMed

Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernandez, Sonsire; Perez, Jose Luis; Acevedo, Reynaldo; Mata Espinoza, Dulce; Payan, Jorge Alberto Barrios; Garcia, Maria de Los A; Kadir, Ramlah; Sarmiento, María E; Hernandez-Pando, Rogelio; Norazmi, Mohd-Nor; Acosta, Armando

2016-12-01

Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of an Advanced Animal Habitat for Spaceflight

NASA Technical Reports Server (NTRS)

Baer, L.; Vasques, M.; Martwick, F.; Hines, M.; Grindeland, R. E.

1994-01-01

It is necessary to fly a group-housed animals for many Life Science spaceflight studies. Currently, group-housed rodents are flown aboard the shuttle in the Animal Enclosure Module (AEM). Although the AEM has been used successfully for a number of flights, it has significant limitations in the number of animals it can accommodate, limited flight duration, passive temperature control and limited in flight data acquisition capability. An Advanced Animal Habitat (AAH) is being developed, which can be flown on the shuttle middeck, both spacelab and spacehab shuttle payload modules, and the space station. The AAH is designed to house 12 rats or 30 mice for up to 30 days. The AAH will have active temperature control, a window mechanism to facilitate video monitoring/recording of the animals, and biotelemetry capabilities. In addition, the design will permit access to the animals for experimental manipulations in space. The AAH can be refitted to experiment-specific requirements as needed. In initial 7-day hardware tests 12 male rats and 10 female mice show no adverse affects with respect to final body and organ weights as compared to vivarium. controls. The Advanced Animal Habitat will provide the science community opportunities to perform a greater variety of studies for longer duration in the microgravity environment than the current Animal Enclosure Module.

Antitumor efficacy of tangeretin by targeting the oxidative stress mediated on 7,12-dimethylbenz(a) anthracene-induced proliferative breast cancer in Sprague-Dawley rats.

PubMed

Periyasamy, Kuppusamy; Baskaran, Kuppusamy; Ilakkia, Aruldass; Vanitha, Kalappan; Selvaraj, Sundaramoorthy; Sakthisekaran, Dhanapal

2015-02-01

The aim of the present study was to assess the chemopreventive and chemotherapeutic efficacy of tangeretin on DMBA-induced oxidative stress in breast cancer-bearing Sprague-Dawley rats. In this study, the experimental animals were divided into five groups of six animals each. Group I was control, Group II was DMBA-induced breast cancer-bearing rats, Group III was tangeretin pre-treated (50 mg/kg body weight for 30 days orally) breast cancer-bearing animals, Group IV was tangeretin post-treated (50 mg/kg body weight for 30 days orally) and Group V was tangeretin (50 mg/kg body weight) alone treated animals. We have observed the general characteristics of cancer, oxidative stress markers, breast cancer marker, antioxidants and histopathological changes in the experimental animals. We have recorded the body weight, tumor weights, tumor volume and antitumor activity of tangeretin in the experimental animals. Oxidative stress markers, like NO and LPO, and breast cancer marker CEA levels were significantly (p < 0.001, p < 0.05) increased as well as the antioxidants like SOD, CAT, GPx, GST, GSH, ascorbic acid and α-tocopherol were found to be significantly (p < 0.05) decreased in cancer-bearing Group II animals. Whereas, the enzymic and non-enzymic antioxidant levels were found to be significantly decreased in cancer-bearing animals. However, in tangeretin pre-treated and post- treated animals, the levels of antioxidants and breast cancer marker were found to be significantly (p < 0.05) reduced with a concomitant increase in the activities of the antioxidants (p < 0.05). In tangeretin alone treated Group V animals, no significant changes were observed in the levels of antioxidants and breast cancer marker. These results were adequately supported by the histopathological studies in the mammary tissues of the experimental animals. From this study, we conclude that the administration of tangeretin was found to be beneficial against DMBA-induced oxidative stress in breast cancer-bearing animals. Hence, we strongly suggest that tangeretin is effective and efficient candidate for the treatment of experimental breast cancer.

Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation

NASA Astrophysics Data System (ADS)

Reilhac, Anthonin; Boisson, Frédéric; Wimberley, Catriona; Parmar, Arvind; Zahra, David; Hamze, Hasar; Davis, Emma; Arthur, Andrew; Bouillot, Caroline; Charil, Arnaud; Grégoire, Marie-Claude

2016-02-01

In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies.

Subclinical cytomegalovirus infection associates with altered host immunity, gut microbiota and vaccine responses.

PubMed

Santos Rocha, Clarissa; Hirao, Lauren A; Weber, Mariana G; Méndez-Lagares, Gema; Chang, W L William; Jiang, Guochun; Deere, Jesse D; Sparger, Ellen E; Roberts, Jeffrey; Barry, Peter A; Hartigan-O'Connor, Dennis J; Dandekar, Satya

2018-04-18

Subclinical viral infections (SVI) including cytomegalovirus (CMV) are highly prevalent in humans, resulting in life-long persistence. However, the impact of SVI on the interplay between the host immunity and gut microbiota in the context of environmental exposures is not well defined. We utilized the preclinical nonhuman primate (NHP) model consisting of SVI-free (SPF) rhesus macaques and compared them to the animals with SVI (non-SPF) acquired through natural exposure and investigated the impact of SVI on immune cell distribution and function as well as on gut microbiota. These changes were examined in animals housed in the outdoor environment as compared to the controlled indoor environment. We report that SVI are associated with altered immune cell subsets and gut microbiota composition in animals housed in the outdoor environment. Non-SPF animals harbored a higher proportion of potential butyrate-producing Firmicutes and higher numbers of lymphocytes, effector T cells and cytokine-producing T cells. Surprisingly, these differences diminished following their transfer to the controlled indoor environment, suggesting that non-SPFs had increased responsiveness to environmental exposures. An experimental infection of indoor SPF animals with CMV resulted in an increased abundance of butyrate-producing bacteria, validating that CMV enhanced colonization of butyrate-producing commensals. Finally, non-SPF animals displayed lower antibody responses to influenza vaccination as compared to SPF animals. Our data show that subclinical CMV infection heightens host immunity and gut microbiota changes in response to environmental exposures. This may contribute to the heterogeneity in host immune response to vaccines and environmental stimuli at the population level. IMPORTANCE Humans harbor several latent viruses that modulate host immunity and commensal microbiota, thus introducing heterogeneity in their responses to pathogens, vaccines and environmental exposures. Most of our understanding of the effect of CMV on the immune system is based on studies of children acquiring CMV or of immune-compromised humans with acute or reactivated CMV infection or in ageing individuals. The experimental mouse models are genetically inbred and are completely adapted to the indoor laboratory environment. In contrast, nonhuman primates are genetically outbred and are raised in the outdoor environment. Our study is the first to report the impact of long-term subclinical CMV infection on host immunity and gut microbiota, which is evident only in the outdoor environment but not in the indoor environment. The significance of this study is in highlighting the impact of SVI on enhancing host immune susceptibility to environmental exposures and immune heterogeneity. Copyright © 2018 American Society for Microbiology.

Histological evaluation of the influence of magnetic field application in autogenous bone grafts in rats.

PubMed

Puricelli, Edela; Dutra, Nardier B; Ponzoni, Deise

2009-01-11

Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field.

Standard of reporting animal-based experimental research in Indian Journal of Pharmacology.

PubMed

Aiman, Umme; Rahman, Syed Ziaur

2015-01-01

The objective of present study was to survey and determine the reporting standards of animal studies published during three years from 2012 to 2014 in the Indian Journal of Pharmacology (IJP). All issues of IJP published in the year 2012, 2013 and 2014 were reviewed to identify animal studies. Each animal study was searched for 15 parameters specifically designed to review standards of animal experimentation and research methodology. All published studies had clearly defined aims and objectives while a statement on ethical clearance about the study protocol was provided in 97% of papers. Information about animal strain and sex was given in 91.8% and 90% of papers respectively. Age of experimental animals was mentioned by 44.4% papers while source of animals was given in 50.8% papers. Randomization was reported by 37.4% while 9.9% studies reported blinding. Only 3.5% studies mentioned any limitations of their work. Present study demonstrates relatively good reporting standards in animal studies published in IJP. The items which need to be improved are randomization, blinding, sample size calculation, stating the limitations of study, sources of support and conflict of interest. The knowledge shared in the present paper could be used for better reporting of animal based experiments.

Activity and milk compositional changes following experimentally induced Streptococcus uberis bovine mastitis.

PubMed

Kester, H J; Sorter, D E; Hogan, J S

2015-02-01

Milk constituents and physical activity of cows experimentally infected with Streptococcus uberis mastitis were compared with those of uninfected cows. Twelve late-lactation Holsteins cows were paired based on milk production and parity. One cow in each pair was experimentally infected in the right front mammary gland with Strep. uberis. The remaining cow in each pair served as an uninfected control. Real-time analyses of milk constituents provided fat, protein, and lactose percentages at each milking. Pedometers were placed on the left front leg of all cows and activity was measured. Intramammary infections with Strep. uberis reduced milk yield in experimental cows by approximately 1.6kg/d in the first week after challenge compared with control cows. Lactose percentage in milk was reduced on d 3, 4, 5, and 6 after challenge in treatment cows compared with controls. Percentages of fat and protein in milk did not differ between infected and uninfected cows the week after infections were induced. Total steps per day were reduced and minutes resting per day were increased the week after experimental challenge in infected cows compared with control cows. The number of resting bouts did not differ between infected and uninfected cows. Changes in percentage of lactose in milk and animal activity caused by experimentally induced Strep. uberis mastitis were detected by the automated milk analyzer and pedometer systems. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Chimeric animal models in human stem cell biology.

PubMed

Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

Conscientious Objection to Animal Experimentation in Italian Universities.

PubMed

Baldelli, Ilaria; Massaro, Alma; Penco, Susanna; Bassi, Anna Maria; Patuzzo, Sara; Ciliberti, Rosagemma

2017-03-13

In Italy, Law 413/1993 states that public and private Italian Institutions, including academic faculties, are obliged to fully inform workers and students about their right to conscientious objection to scientific or educational activities involving animals, hereafter written as "animal CO". However, little monitoring on the faculties' compliance with this law has been performed either by the government or other institutional bodies. Based on this premise, the authors have critically reviewed the existing data and compared them with those emerging from their own investigation to discuss limitations and inconsistencies. The results of this investigation revealed that less than half of Italian academic faculties comply with their duty to inform on animal CO. Non-compliance may substantially affect the right of students to make ethical choices in the field of animal ethics and undermines the fundamental right to express their own freedom of thought. The Italian Ministry of Education, Universities and Research, ethics committees and animal welfare bodies should cooperate to make faculties respect this law. Further research is needed to better understand the reasons for the current trend, as well as to promote the enforcement of Law 413/1993 with particular regard to information on animal CO.

[Ethics and legal aspects of use of animals in experimental studies].

PubMed

Vaculín, S

2000-02-01

Animals have been used in research since ancient times already. Originally they were used for anatomical and physiological demonstrations. Later they started to be used by another fields--microbiology, toxicology and pharmacology, surgery. Animal use is frequently implicated in relation to ethical problems. Actual view is based on biocentric opinion, which part is formed by "three R's" concept--reduction, replacement, refinement in animal use. Laws applied to animal use in Czech Republic are anchored in Law on Animal Protection and Decree of Ministry of Agriculture on Experimental Animal Use and Breeding. Owing to militant behaviour of organisations involved in animal rights movement there is no adequate propagation of experiments, which are ethically and juridically clear and which particularly help mankind in a struggle against diseases.

Role of Dendritic Cells in Immune Dysfunction

NASA Technical Reports Server (NTRS)

Savary, Cherylyn A.

1997-01-01

Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

Experimental evidence for inherent Lévy search behaviour in foraging animals

PubMed Central

Kölzsch, Andrea; Alzate, Adriana; Bartumeus, Frederic; de Jager, Monique; Weerman, Ellen J.; Hengeveld, Geerten M.; Naguib, Marc; Nolet, Bart A.; van de Koppel, Johan

2015-01-01

Recently, Lévy walks have been put forward as a new paradigm for animal search and many cases have been made for its presence in nature. However, it remains debated whether Lévy walks are an inherent behavioural strategy or emerge from the animal reacting to its habitat. Here, we demonstrate signatures of Lévy behaviour in the search movement of mud snails (Hydrobia ulvae) based on a novel, direct assessment of movement properties in an experimental set-up using different food distributions. Our experimental data uncovered clusters of small movement steps alternating with long moves independent of food encounter and landscape complexity. Moreover, size distributions of these clusters followed truncated power laws. These two findings are characteristic signatures of mechanisms underlying inherent Lévy-like movement. Thus, our study provides clear experimental evidence that such multi-scale movement is an inherent behaviour rather than resulting from the animal interacting with its environment. PMID:25904671

Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

PubMed

Cavalcanti, Vinícius; Santos, Cintia Lourenço; Samary, Cynthia Santos; Araújo, Mariana Neves; Heil, Luciana Boavista Barros; Morales, Marcelo Marcos; Silva, Pedro Leme; Pelosi, Paolo; Fernandes, Fatima Carneiro; Villela, Nivaldo; Rocco, Patricia Rieken Macedo

2014-11-01

We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

Considerations for the design and execution of protocols for animal research and treatment to improve reproducibility and standardization: "DEPART well-prepared and ARRIVE safely".

PubMed

Smith, M M; Clarke, E C; Little, C B

2017-03-01

To review the factors in experimental design that contribute to poor translation of pre-clinical research to therapies for patients with osteoarthritis (OA) and how this might be improved. Narrative review of the literature, and evaluation of the different stages of design conduct and analysis of studies using animal models of OA to define specific issues that might reduce quality of evidence and how this can be minimised. Preventing bias and improving experimental rigour and reporting are important modifiable factors to improve translation from pre-clinical animal models to successful clinical trials of therapeutic agents. Despite publication and adoption by many journals of guidelines such as Animals in Research: Reporting In Vivo Experiments (ARRIVE), experimental animal studies published in leading rheumatology journals are still deficient in their reporting. In part, this may be caused by researchers first consulting these guidelines after the completion of experiments, at the time of publication. This review discusses factors that can (1) bias the outcome of experimental studies using animal models of osteoarthritis or (2) alter the quality of evidence for translation. We propose a checklist to consult prior to starting experiments; in the Design and Execution of Protocols for Animal Research and Treatment (DEPART). Following DEPART during the design phase will enable completion of the ARRIVE checklist at the time of publication, and thus improve the quality of evidence for inclusion of experimental animal research in meta-analyses and systematic reviews: "DEPART well-prepared and ARRIVE safely". Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis.

PubMed

Cross, A K; Haddock, G; Surr, J; Plumb, J; Bunning, R A D; Buttle, D J; Woodroofe, M N

2006-02-01

Experimental autoimmune encephalomyelitis (EAE) is an animal model of inflammatory demyelination, a pathological event common to multiple sclerosis (MS). During CNS inflammation there are alterations in the extracellular matrix (ECM). A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS)-1, -4 and -5 are proteases present in the CNS, which are able to cleave the aggregating chondroitin sulphate proteoglycans, aggrecan, phosphacan, neurocan and brevican. It is therefore important to investigate changes in their expression in different stages of EAE induction. We have investigated expression of ADAMTS-1, -4, -5 and tissue inhibitor of metalloproteinase (TIMP)-3, by real-time RT-PCR. We have also examined protein expression of ADAMTS-1, -4 and -5 by western blotting and immunocytochemistry in spinal cord from animals at different stages of disease progression. Our study demonstrated a decrease in ADAMTS-4 mRNA and protein expression. TIMP-3 was decreased at the mRNA level although protein levels were increased in diseased animals compared to controls. Our study identifies changes in ADAMTS expression during the course of CNS inflammation which may contribute to ECM degradation and disease progression.

Variation of lifespan in multiple strains, and effects of dietary restriction and BmFoxO on lifespan in silkworm, Bombyx mori.

PubMed

Song, Jiangbo; Tang, Dongmei; Li, Zhiquan; Tong, Xiaoling; Zhang, Jianfei; Han, Minjin; Hu, Hai; Lu, Cheng; Dai, Fangyin

2017-01-31

Established animal models have accelerated our understanding of the mechanisms involved in lifespan determination. However, more experimental animals are required to clarify the complex mechanisms behind the phenomena of aging and lifespan. In this study, we reported the variation of lifespan in nine distinct silkworm strains. Lifespan correlated significantly with BmFoxO gene expression in the representative silkworm strains tested (Xiafang, Dazao-N, and N4). In general, the female silkworm was longer lived than the male of the same strain. Dietary restriction extended the silkworm lifespan compared with that of silkworms fed ad libitum. The expression of BmFoxO was significantly elevated in the dietary restriction group on day 3 of the 4th instar and day 3 of the 5th instar, suggesting that BmFoxO contributes to dietary restriction-mediated lifespan extension. The RNA interference and overexpression of the BmFoxO gene significantly shortened and extended the silkworm adulthood, respectively. In conclusion, our findings suggest that the silkworm might serve as a promising experimental animal to explore the complex biological mechanisms of lifespan determination.

Immunocastration as an alternative to caponization: evaluation of its effect on body and bone development and on meat color and composition.

PubMed

Quaresma, M A G; Antunes, I C; Ribeiro, M F; Prazeres, S; Bessa, R J B; da Costa, P Martins

2017-10-01

Caponization is associated with some morbidity and mortality, which contributes to important economic losses. This practice is executed without any pain relief (neither anesthesia nor analgesia) and can be painful and without consideration of animal welfare. On the other hand, immunocastration accomplished by Improvac and Bovipriva in pigs and cattle represents a noninvasive procedure, and for that reason is regarded as an alternative with improved animal welfare. This study includes 4 experimental groups consisting of capons, slips, roosters, and birds submitted to the Improvac treatment. The administration of Improvac was associated with a considerable reduction in serum testosterone concentration (reduced by 79% compared to average serum testosterone of roosters). Regarding significant differences among experimental groups, birds from the Improvac group were intermediate between capons and slips with respect to abdominal fat pad weight and yield, breast meat water and protein contents, and femur length. Conversely, color parameters such as lightness, redness, and hue angle for Improvac birds were intermediate between roosters and capons. Thus, immunocastration with Improvac could represent an alternative solution to caponization, with considerable improvements in animal welfare. © 2017 Poultry Science Association Inc.

Baclofen reversed thermal place preference in rats with chronic constriction injury.

PubMed

Salte, K; Lea, G; Franek, M; Vaculin, S

2016-06-20

Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model.

Efficacy of pefloxacin in comparison with erythromycin in the treatment of experimental guinea pig legionellosis.

PubMed

Dournon, E; Rajagopalan, P; Vilde, J L; Pocidalo, J J

1986-04-01

Pefloxacin was compared to erythromycin in the treatment of guinea pigs severely infected with Legionella pneumophila. In this experimental model, two single intraperitoneal injections of either pefloxacin (10 mg/kg at 48 h and 5 mg/kg at 55 h) or erythromycin (40 mg/kg at 48 and 55 h) were administered 48 h post-infection (2 X 10(7) virulent L. pneumophila intraperitoneally). Counts of bacteria in blood monocytes and lungs of animals killed at different times after the completion of treatment, demonstrated a quick and highly significant reduction of the pretreatment bacterial load in pefloxacin-treated guinea pigs. Conversely, in erythromycin-treated animals the number of bacteria was only slightly reduced 17 h after the completion of the treatment and then multiplication up to pre-treatment levels occurred. The overall mortality was significantly lower in pefloxacin-treated animals with this therapeutic protocol. The remarkable results of pefloxacin in this model, were obtained with serum and lung levels of this drug lower than those achieved in man with the currently accepted regimens. Thus, pefloxacin appears to be a new promising antimicrobial agent for Legionnaire's disease.

Light pollution disrupts sleep in free-living animals.

PubMed

Raap, Thomas; Pinxten, Rianne; Eens, Marcel

2015-09-04

Artificial lighting can alter individual behaviour, with often drastic and potentially negative effects on biological rhythms, daily activity and reproduction. Whether this is caused by a disruption of sleep, an important widespread behaviour enabling animals to recover from daily stress, is unclear. We tested the hypothesis that light pollution disrupts sleep by recording individual sleep behaviour of great tits, Parus major, that were roosting in dark nest-boxes and were exposed to light-emitting diode light the following night. Their behaviour was compared to that of control birds sleeping in dark nest-boxes on both nights. Artificial lighting caused experimental birds to wake up earlier, sleep less (-5%) and spent less time in the nest-box as they left their nest-box earlier in the morning. Experimental birds did not enter the nest-box or fall asleep later than controls. Although individuals in lit nest-boxes did not wake up more often nor decreased the length of their sleep bouts, females spent a greater proportion of the night awake. Our study provides the first direct proof that light pollution has a significant impact on sleep in free-living animals, in particular in the morning, and highlights a mechanism for potential effects of light pollution on fitness.

Immune reactions and allergy in experimental anisakiasis

PubMed Central

Lee, Haneul Nari

2006-01-01

The third-stage larvae (L3) of the parasitic nematode, Anisakis simplex, have been implicated in the induction of hyperimmune allergic reactions in orally infected humans. In this work, we have conducted a review of an investigation into immune reactions occurring in animals experimentally infected with A. simplex L3. The patterns of serum antibody productions in the experimental animals against excretory-secretory products (ESP) of A. simplex L3 contributed to our current knowledge regarding specific humoral immune reactions in humans. In our review, we were able to determine that L3 infection of experimental animals may constitute a good model system for further exploration of immune mechanisms and allergy in anisakiasis of humans. PMID:17170569

Regenerative therapy in experimental parkinsonism: mixed population of differentiated mouse embryonic stem cells, rather than magnetically sorted and enriched dopaminergic cells provide neuroprotection.

PubMed

Tripathy, Debasmita; Verma, Poonam; Nthenge-Ngumbau, Dominic N; Banerjee, Meghna; Mohanakumar, Kochupurackal P

2014-08-01

The objective of the study was to develop regenerative therapy by transplanting varied populations of dopaminergic neurons, differentiated from mouse embryonic stem cells (mES) in the striatum for correcting experimental parkinsonism in rats. mES differentiated by default for 7 days in serum-free media (7D), or by enhanced differentiation of 7D in retinoic acid (7R), or dopaminergic neurons enriched by manual magnetic sorting from 7D (SSEA-) were characterized and transplanted in the ipsilateral striatum of 6-hydroxydopamine-induced hemiparkinsonian rats. Neurochemical, neuronal, glial and neurobehavioral recoveries were examined. 7R and SSEA- contained significantly reduced NANOG and high MAP2 mRNA and protein levels as revealed, respectively, by reverse transcriptase-PCR and immunocytochemistry, compared with 7D. Striatal engraftment of 7D resulted in a significantly better behavioral and neurochemical recovery, as compared to the animals that received either 7R or SSEA-. The 7R transplanted animals showed improvement neither in behavior nor in striatal dopamine level. The grafted striatum revealed increased GFAP staining intensity in 7D and SSEA-, but not in 7R cells transplanted group, suggesting a vital role played by glial cells in the recovery. Substantia nigra ipsilateral to the side of the striatum, which received transplants showed more tyrosine hydroxylase immunostained neurons, as compared to 6-hydroxydopamine-infused animals. These results demonstrate that default differentiated mixed population of cells are better than sorted, enriched dopaminergic cells, or cells containing more mature neurons for transplantation recovery in hemiparkinsonian rats. © 2014 John Wiley & Sons Ltd.

Quantity of IL-2, IL-4, IL-10, INF-γ, TNF-α and KC-like cytokines in serum of bitches with pyometra in different stages of oestrous cycle and pregnancy.

PubMed

Maciel, G S; Uscategui, R R; de Almeida, V T; Oliveira, Mef; Feliciano, Mar; Vicente, Wrr

2014-08-01

The occurrence of the pyometra is most common in the first half of the dioestrus when there is decreased cellular immunity associated with increased serum concentration of progesterone in females. The aim of this study was to determine the immunological profile of bitches with pyometra, studying serum levels of IL-2, IL-4, IL-10, IFN-γ, KC-like and TNF-α and comparing them with those of healthy bitches in anoestrus, dioestrus and pregnant. Forty females were divided into four experimental groups: group 1 (G1): with pyometra (n = 10); group 2 (G2): bitches in the second week of gestation (n = 10); group 3 (G3): in anoestrus (n = 10); and group 4 (G4): in dioestrus (n = 10). The serum levels for IL-2, KC-like, INF-γ and TNF-α were similar for all experimental groups. The values obtained for IL-10 were found increased (p < 0.001) in animals in dioestrus and pyometra compared with females in anoestrus and pregnant, and the levels of IL-4 observed were significantly greater (p < 0.001) in bitches with pyometra when compared with others. The cytokine profile in animals with pyometra is similar to bitches in dioestrus for IL-10 and had increase in IL-4 for bitches with pyometra, which represents an anti-inflammatory these cases. This suggests the presence of an immunosuppressive state in both cases, which may explain the propensity of bitches in dioestrus to be affected by pyometra and the severity of the disease on these animals. © 2014 Blackwell Verlag GmbH.

In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.

PubMed

Gutowski, Michal B; Wilson, Leslie; Van Gelder, Russell N; Pepple, Kathryn L

2017-03-01

We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

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.

Reduction in oxidative stress levels in the colonic mucosa without fecal stream after the application of enemas containing aqueous Ilex paraguariensis extract.

PubMed

Cunha, Fernando Lorenzetti da; Silva, Camila Morais Gonçalves da; Almeida, Marcos Gonçalves de; Lameiro, Thais Miguel do Monte; Marques, Letícia Helena Souza; Margarido, Nelson Fontana; Martinez, Carlos Augusto Real

2011-08-01

To evaluate the antioxidant effects of enemas containing aqueous extract of Ilex paraguariensis, comparing segments with and without fecal stream and correlating the segments with the duration of intervention. Twenty-six Wistar rats were subjected to a diversion of the fecal stream in the left colon by a proximal colostomy and distal mucosal fistula. The rats were distributed randomly into two experimental groups of 13 animals each based on the time of sacrifice after surgical procedure (two or four weeks). Each group was then divided into two experimental subgroups that received either second daily enemas containing 0.9% saline solution or aqueous extract of Ilex paraguariensis at 0.2g/100g. Colitis was diagnosed by histopathological analysis and the detection of oxidative tissue damage by measuring the levels of malondialdehyde. The Mann-Whitney test was used to compare the tissue levels of malondialdehyde between colon segments with and without fecal stream in each experimental group, and the Kruskal-Wallis test was used to verify the variance between the levels of oxidative stress according the duration of the irrigation; both tests determined significance at 5% (p<0.05). The levels of malondialdehyde in the animals subjected to intervention in the colon with saline with and without fecal stream after two and four weeks of irrigation were 0.05±0.006 and 0.06±0.006, and 0.05± 0.03 and 0.08 ±0.02, respectively. The malondialdehyde levels in the animals irrigated with Ilex paraguariensis with and without fecal stream after two and four weeks of irrigation were 0.010±0.002 and 0.02±0.004, and 0.03±0.007 and 0.04±0.01, respectively. After two and four weeks of intervention, the levels of malondialdehyde were lower in the animals irrigated with Ilex paraguariensis regardless of the time of irrigation (p=0.0001 and p=0.002, respectively). The daily rectal application of enemas containing aqueous extract of Ilex paraguariensis decreases oxidative tissue damage in the colon without fecal stream regardless of the time of irrigation.

Incorporation of the HIV-1 microbicide cyanovirin-N in a food product

PubMed Central

Li, Ming; Patton, Dorothy L.; Cosgrove-Sweeney, Yvonne; Ratner, Deena; Rohan, Lisa C.; Cole, Alexander M.; Tarwater, Patrick M.; Gupta, Phalguni; Ramratnam, Bharat

2012-01-01

An urgent need exists for HIV-1 microbicides. Here, we describe the in vivo testing of lactic acid bacteria bioengineered to secrete cyanovirin-N. We fed pigtail macaques a yogurt formulation that used bioengineered strains as a starter culture. Cyanovirin-N expression could be detected in the rectal vault during and immediately after feeding. Ex vivo viral challenge of rectal tissue biopsies revealed that peak viral burden was significantly lower in tissue obtained from experimental animals compared to control animals. Formulation of candidate compounds in lactic acid bacteria and their oral administration appears to be a feasible strategy for mucosal delivery of microbicides. PMID:21926631

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

PubMed

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

2012-07-01

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

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

PubMed Central

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

2012-01-01

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

A simple device to convert a small-animal PET scanner into a multi-sample tissue and injection syringe counter.

PubMed

Green, Michael V; Seidel, Jurgen; Choyke, Peter L; Jagoda, Elaine M

2017-10-01

We describe a simple fixture that can be added to the imaging bed of a small-animal PET scanner that allows for automated counting of multiple organ or tissue samples from mouse-sized animals and counting of injection syringes prior to administration of the radiotracer. The combination of imaging and counting capabilities in the same machine offers advantages in certain experimental settings. A polyethylene block of plastic, sculpted to mate with the animal imaging bed of a small-animal PET scanner, is machined to receive twelve 5-ml containers, each capable of holding an entire organ from a mouse-sized animal. In addition, a triangular cross-section slot is machined down the centerline of the block to secure injection syringes from 1-ml to 3-ml in size. The sample holder is scanned in PET whole-body mode to image all samples or in one bed position to image a filled injection syringe. Total radioactivity in each sample or syringe is determined from the reconstructed images of these objects using volume re-projection of the coronal images and a single region-of-interest for each. We tested the accuracy of this method by comparing PET estimates of sample and syringe activity with well counter and dose calibrator estimates of these same activities. PET and well counting of the same samples gave near identical results (in MBq, R 2 =0.99, slope=0.99, intercept=0.00-MBq). PET syringe and dose calibrator measurements of syringe activity in MBq were also similar (R 2 =0.99, slope=0.99, intercept=- 0.22-MBq). A small-animal PET scanner can be easily converted into a multi-sample and syringe counting device by the addition of a sample block constructed for that purpose. This capability, combined with live animal imaging, can improve efficiency and flexibility in certain experimental settings. Copyright © 2017 Elsevier Inc. All rights reserved.

The Microminipig as an Animal Model for Influenza A Virus Infection.

PubMed

Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Shibata, Masatoshi; Takahashi, Kenta; Sato, Yuko; Kiso, Maki; Yamayoshi, Seiya; Ito, Mutsumi; Enya, Satoko; Otake, Masayoshi; Kangawa, Akihisa; da Silva Lopes, Tiago Jose; Ito, Hirotaka; Hasegawa, Hideki; Kawaoka, Yoshihiro

2017-01-15

Pigs are considered a mixing vessel for the generation of novel pandemic influenza A viruses through reassortment because of their susceptibility to both avian and human influenza viruses. However, experiments to understand reassortment in pigs in detail have been limited because experiments with regular-sized pigs are difficult to perform. Miniature pigs have been used as an experimental animal model, but they are still large and require relatively large cages for housing. The microminipig is one of the smallest miniature pigs used for experiments. Introduced in 2010, microminipigs weigh around 10 kg at an early stage of maturity (6 to 7 months old) and are easy to handle. To evaluate the microminipig as an animal model for influenza A virus infection, we compared the receptor distribution of 10-week-old male pigs (Yorkshire Large White) and microminipigs. We found that both animals have SAα2,3Gal and SAα2,6Gal in their respiratory tracts, with similar distributions of both receptor types. We further found that the sensitivity of microminipigs to influenza A viruses was the same as that of larger miniature pigs. Our findings indicate that the microminipig could serve as a novel model animal for influenza A virus infection. The microminipig is one of the smallest miniature pigs in the world and is used as an experimental animal model for life science research. In this study, we evaluated the microminipig as a novel animal model for influenza A virus infection. The distribution of influenza virus receptors in the respiratory tract of the microminipig was similar to that of the pig, and the sensitivity of microminipigs to influenza A viruses was the same as that of miniature pigs. Our findings suggest that microminipigs represent a novel animal model for influenza A virus infection. Copyright © 2017 American Society for Microbiology.

EXPERIMENTAL ANIMAL MAINTENANCE

DOEpatents

Finkel, M.P.

1962-01-22

A method of housing experimental animals such as mice in individual tube- like plastic enclosures is described. Contrary to experience, when this was tried with metal the mice did not become panicky. Group housing, with its attendant difficulties, may thus be dispensed with. (AEC)

[Impact of streptozotocininduced hyperglycemia on anxiety level and physical fatigue of Wistar rats].

PubMed

Sidorova, Yu S; Shipelin, V A; Zorin, S N; Mazo, V K; Petrov, N A; Kochetkova, A A

2015-01-01

The aim of the study was to evaluate type 2 diabetes medicamental biomodel in 70-days experiment. Control group animals were provided with water ad libitum throughout the experiment, experimental group animals for the first two weeks were provided with 20% solution of fructose ad libitum instead of water. On the 15th day, experimental group animals (average body weight 257±8 g) were injected abdominally with streptozotocin (STZ) in dosage 40 mg/kg of body weight. For the next three weeks on the 22nd, 28th and 36th days, glucose level in blood taken from the tail vein was measured using portable electrochemical glucometer. On the 37th day animals with blood glucose level 11.0 mmol/L or higher were included in experimental group for further research. On the 44th and 60th day control measurements of glucose level were conducted. On the 70th day animals were taken out of experiment by decapitation under ether anesthesia. The concentration of glucose, glycosylated hemoglobin, triglycerides, cholesterine, HLD and LDL were measured in blood serum. Additionally anxiety level of animals was evaluated before and after STZ injection using Elevated plusmaze. The comparison of physical fatigue of control and experimental groups was performed using treadmill. On the 37th day blood glucose concentration of control group animals was 6.6±0.4 mmol/L. 33% of animals (13 of 40) with glucose level 11.0 mmol/L or higher formed the experimental group (average glucose level 16.2±1.3 mmol/L), other 27 rats had normal glucose level. The anxiety level of diabetic rats was higher than in control group. Diabetic rats showed significantly lower physical fatigue than control rats. On the 44th and 60th day of experiment glucose level in experimental rats from group 2 (15.5±1.4 и 14.8±1.2 mmol/L) was significantly higher than of control animals (7.0±0.5 и 6.8±0.3 mmol/L). Glycated hemoglobin level in blood serum of diabetic group (7.2±0.7%) was significantly higher than of control group (3.3±0.2%). This proves the progression of stable long-term hyperglycemia. According to results represented model can be used for initial experimental evaluation of tested antidiabetic biologically active substances.

Different views on ethics: how animal ethics is situated in a committee culture.

PubMed

Ideland, M

2009-04-01

Research that includes non-human animal experimentation is fundamentally a dilemmatic enterprise. Humans use other animals in research to improve life for their own species. Ethical principles are established to deal with this dilemma. But despite this ethical apparatus, people who in one way or another work with animal experimentation have to interpret and understand the principles from their individual points of view. In interviews with members of Swedish animal ethics committees, different views on what the term ethics really means were articulated. For one member, the difficult ethical dilemma of animal experimentation is the lack of enriched cages for mice. For another, the ethical problem lies in regulations restraining research. A third member talks about animals' right not to be used for human interests. These different views on "ethics" intersect once a month in the animal ethics committee meetings. There is no consensus on what constitutes the ethical problem that the members should be discussing. Therefore, personal views on what ethics means, and hierarchies among committee members, characterise the meetings. But committee traditions and priorities of interpretation as well are important to the decisions. The author discusses how "ethics" becomes situated and what implications this may have for committees' decisions.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

PubMed

Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

2010-06-01

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

RNA-Seq based transcriptome of whole blood from immunocompetent pigs (Sus scrofa) experimentally infected with Mycoplasma suis strain Illinois.

PubMed

do Nascimento, Naíla C; Guimaraes, Ana M S; Dos Santos, Andrea P; Chu, Yuefeng; Marques, Lucas M; Messick, Joanne B

2018-06-18

Pigs are popular animal models in biomedical research. RNA-Seq is becoming the predominant tool to investigate transcriptional changes of the pig's response to infection. The high sensitivity of this tool requires a strict control of the study design beginning with the selection of healthy animals to provide accurate interpretation of research data. Pigs chronically infected with Mycoplasma suis often show no obvious clinical signs, however the infection may affect the validity of animal research. The goal of this study was to investigate whether or not this silent infection is also silent at the host transcriptional level. Therefore, immunocompetent pigs were experimentally infected with M. suis and transcriptional profiles of whole blood, generated by RNA-Seq, were analyzed and compared to non-infected animals. RNA-Seq showed 55 differentially expressed (DE) genes in the M. suis infected pigs. Down-regulation of genes related to innate immunity (tlr8, chemokines, chemokines receptors) and genes containing IFN gamma-activated sequence (gbp1, gbp2, il15, cxcl10, casp1, cd274) suggests a general suppression of the immune response in the infected animals. Sixteen (29.09%) of the DE genes were involved in two protein interaction networks: one involving chemokines, chemokine receptors and interleukin-15 and another involving the complement cascade. Genes related to vascular permeability, blood coagulation, and endothelium integrity were also DE in infected pigs. These findings suggest that M. suis subclinical infection causes significant alterations in blood mRNA levels, which could impact data interpretation of research using pigs. Screening of pigs for M. suis infection before initiating animal studies is strongly recommended.

Public perceptions of animal experimentation across Europe.

PubMed

von Roten, Fabienne Crettaz

2013-08-01

The goal of this article is to map out public perceptions of animal experimentation in 28 European countries. Postulating cross-cultural differences, this study mixes country-level variables (from the Eurostat database) and individual-level variables (from Eurobarometer Science and Technology 2010). It is shown that experimentation on animals such as mice is generally accepted in European countries, but perceptions are divided on dogs and monkeys. Between 2005 and 2010, we observe globally a change of approval on dogs and monkeys, with a significant decrease in nine countries. Multilevel analysis results show differences at country level (related to a post-industrialism model) and at individual level (related to gender, age, education, proximity and perceptions of science and the environment). These results may have consequences for public perceptions of science and we call for more cross-cultural research on press coverage of animal research and on the level of public engagement of scientists doing animal research.

Remaining Sites Verification Package for the 100-F-54 Animal Farm Pastures, Waste Site Reclassification Form 2008-015

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

J. M. Capron

2008-04-17

The 100-F-54 waste site, part of the 100-FR-2 Operable Unit, is the soil associated with the former pastures for holding domestic farm animals used in experimental toxicology studies. Evaluation of historical information resulted in identification of the experimental animal farm pastures as having potential residual soil contamination due to excrement from experimental animals. The 100-F-54 animal farm pastures confirmatory sampling results support a reclassification of this site to No Action. The current site conditions achieve the remedial action objectives and the corresponding remedial action goals established in the Remaining Sites ROD. The results of confirmatory sampling show that residual contaminantmore » concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River.« less

Comparative value of blood and skin samples for diagnosis of spotted fever group rickettsial infection in model animals.

PubMed

Levin, Michael L; Snellgrove, Alyssa N; Zemtsova, Galina E

2016-07-01

The definitive diagnosis of spotted fever group (SFG) rickettsioses in humans is challenging due to the retrospective nature and cross reactivity of the serological methods and the absence of reliable and consistent samples for molecular diagnostics. Existing data indicate the transient character of bacteremia in experimentally infected animals. The ability of arthropod vectors to acquire rickettsial infection from the laboratory animals in the absence of systemic infection and known tropism of rickettsial agents to endothelial cells of peripheral blood vessels underline the importance of local infection and consequently the diagnostic potential of skin samples. In order to evaluate the diagnostic sensitivity of rickettsial DNA detection in blood and skin samples, we compared results of PCR testing in parallel samples collected from model laboratory animals infected with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia slovaca-like agent at different time points after infection. Skin samples were collected from ears - away from the site of tick placement and without eschars. Overall, testing of skin samples resulted in a higher proportion of positive results than testing of blood samples. Presented data from model animals demonstrates that testing of skin samples from sites of rickettsial proliferation can provide definitive molecular diagnosis of up to 60-70% of tick-borne SFG rickettsial infections during the acute stage of illness. Detection of pathogen DNA in cutaneous samples is a valuable alternative to blood-PCR at least in model animals. Published by Elsevier GmbH.

Wound-healing properties of the oils of Vitis vinifera and Vaccinium macrocarpon.

PubMed

Shivananda Nayak, B; Dan Ramdath, D; Marshall, Julien R; Isitor, Godwin; Xue, Sophia; Shi, John

2011-08-01

Vitis vinifera (grape) and Vaccinium macrocarpon (cranberry) are well known medicinal plants; most of the pharmacologically active phytochemicals have been isolated from the skin, fruit juice, fermented extract and alcohol fractions of the plants above. Here, the pharmacological properties of the phytochemical constituents present in oils of cranberry and grape were investigated. The oil of grape and cranberry has been evaluated for their wound healing activity by using an excision wound model in rats. The animals were divided into four groups of six each (n = 6). The experimental group 1 and 2 animals were treated topically with the grape and cranberry oil (100 mg/kg body weight), respectively. The controls were treated with petroleum jelly. The standard group of animals were treated with mupirocin ointment (100 mg/kg body weight). The healing was assessed by the rate of wound contraction and hydroxyproline content. On day 13, animals treated with cranberry oil exhibited a (88.1%) reduction in the wound area compared with grape-oil treated (84.6%), controls (74.1%) and standard group animals (78.4%) (p < 0.001). The hydroxyproline content of the granulation tissue was significantly higher in the animals treated with cranberry and the grape-oil (p < 0.000). Comparative investigation of the curative properties of the oils of V. vinifera and V. macrocarpon revealed a significant result which suggests their wound-healing potential. Copyright © 2011 John Wiley & Sons, Ltd.

Nonfeed application of rendered animal proteins for microbial production of eicosapentaenoic acid by the fungus Pythium irregulare.

PubMed

Liang, Yi; Garcia, Rafael A; Piazza, George J; Wen, Zhiyou

2011-11-23

Rendered animal proteins are well suited for animal nutrition applications, but the market is maturing, and there is a need to develop new uses for these products. The objective of this study is to explore the possibility of using animal proteins as a nutrient source for microbial production of omega-3 polyunsaturated fatty acids by the microalga Schizochytrium limacinum and the fungus Pythium irregulare. To be absorbed by the microorganisms, the proteins needed to be hydrolyzed into small peptides and free amino acids. The utility of the protein hydrolysates for microorganisms depended on the hydrolysis method used and the type of microorganism. The enzymatic hydrolysates supported better cell growth performance than the alkali hydrolysates did. P. irregulare displayed better overall growth performance on the experimental hydrolysates compared to S. limacinum. When P. irregulare was grown in medium containing 10 g/L enzymatic hydrolysate derived from meat and bone meal or feather meal, the performance of cell growth, lipid synthesis, and omega-3 fatty acid production was comparable to the that of culture using commercial yeast extract. The fungal biomass derived from the animal proteins had 26-29% lipid, 32-34% protein, 34-39% carbohydrate, and <2% ash content. The results show that it is possible to develop a nonfeed application for rendered animal protein by hydrolysis of the protein and feeding to industrial microorganisms which can produce omega-3 fatty acids for making omega-3-fortified foods or feeds.

Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give Something Back?

PubMed

Sanchez, Rick F; Daniels, Julie T

2016-04-01

Experimental animals have been used extensively in the goal of developing sight-saving therapies for humans. One example is the development of transplantation of cultured limbal epithelial stem cells (LESC) to restore vision following ocular surface injury or disease. With clinical trials of cultured LESC therapy underway in humans and a potential companion animal population suffering from similar diseases, it is perhaps time to give something back. Comparatively to humans, what is known about the healthy limbus and corneal surface physiology of companion animals is still very little. Blinding corneal diseases in animals such as symblepharon in cats with Feline Herpes Virus-1 infections require a basic understanding of the functional companion animal limbus and corneal stem cells. Our understanding of many other vision threatening conditions such as scarring of the cornea post-inflammation with lymphocytic-plasmacytic infiltrate in dogs (aka chronic superficial keratitis) or pigment proliferation with Pigmentary Keratitis of Pugs would benefit from a better understanding of the animal cornea in health and disease. This is also vital when new therapeutic approaches are considered. This review will explore the current challenges and future research directions that will be required to increase our understanding of corneal diseases in animals and consider the potential development and delivery of cultured stem cell therapy to veterinary ocular surface patients.

[Influence of enzymatic hydrolyzate of mussel meat on growth and some indicators of general adaptation syndrome in rats].

PubMed

Sidorova, Iu S; Seliaskin, K E; Zorin, S N; Abramova, L S; Mazo, V K

2014-01-01

The impact of the 15-day consumption of enzymatic hydrolyzate of the mussels meat as a part of semi-synthetic diet on some stress biomarkers and apoptosis activity in various organs of growing male Wistar rats have been studied. Enzymatic hydrolyzate of the mussels meat (EMM) was obtained in pilot conditions using the enzyme preparation "Protozim". The animals of control group 1 (n = 8 with initial body weight of 179.4 ± 5.9 g) and experimental group 2 (n = 8, 176.3 ± 4.5 g) received a semi synthetic diet; the animals of the experimental group 3 (n = 8, 177.6 ± 4.0 g) received the same semi synthetic diet in which 50% of the casein was replaced by the peptides of EMM. On the penult day of the experiment animals of groups 2 and 3 were subjected to stress exposure by electric current on their paws (current 0.4 mA for 8 seconds) and were placed in metabolic cages for the collection of daily urine. At the 15th day of the study, all control and test animals were killed by decapitation under ether anesthesia and necropsied. The content of prostaglandin E2 and β-endorphin in blood plasma was determined by ELISA test. The concentration of urine corticosterone was measured by HPLC. DNA damage and percentage of apoptotic cells (apoptotic index) were calculated in thymus by single-cell gel electrophoresis assay (Comet assay). The relative body weight increase of animals treated with EMM was significantly (p < 0.05) higher (68.2 ± 3.0%) than those in animals of groups 1 and 2 (57.2 ± 4.0 and 59.7 ± 2.8%, respectively). The apoptotic index in thymus cells of tested groups of animals (2 and 3) was significantly (p < 0.05) higher (1.13 ± 0.09 and 1.09 ± 0.01%) compared to intact animals of control group (1.04 ± 0.01%). Determination of β-endorphin and prostaglandin E2 levels did not shown any significant differences between the groups. Significantly (p < 0.05) lower concentrations of corticosterone was found in the daily urine of stressed animals from group 3 (452 ± 78 ng/ml), treated with EMM, compared to stressed animals of group 2 that received a casein diet (834 ± 167 ng/ml). It has been shown that consumption of EMM with a high content of short and medium peptides has an impact on effectiveness of body weight gain of growing laboratory animals, and restrict the increase of corticosterone level in rats blood, which is typical for general adaptation syndrome.

Histopathological study of experimental and natural infections by Trypanosoma cruzi in Didelphis marsupialis.

PubMed

Araujo Carreira, J C; Jansen, A M; Deane, M P; Lenzi, H L

1996-01-01

Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

[Occupational lung cancer. A comparison between humans and experimental animals].

PubMed

Adachi, S; Takemoto, K

1987-09-01

Many epidemiological and experimental studies have suggested that the respiratory tract is one of the most sensitive organs to environmental carcinogens. Nevertheless there is little evidence to determine the relationship between a specific environmental carcinogen and a cell type of lung cancer, because the cell types of lung cancer and their relative frequencies are highly complex compared with those of other organs and tissues. In the present paper, occupational lung-cancer characteristics, which are the clearest in the relation between cause and effect in human lung cancers, were reviewed in comparison with the results of animal experiments concerned with occupational lung carcinogens. Through accumulation of histopathological examinations of the lung cancer cases, the following relationships between cause and cell type were conjectured: chromium and squamous cell carcinoma; asbestos and adenocarcinoma; nickel and squamous cell carcinoma; beryllium and small cell carcinoma; bis (chloromethyl) ether and small cell carcinoma; mustard gas and squamous cell or small cell carcinoma; vinyl chloride and large cell or adenocarcinoma; radionuclides and small cell carcinoma. The relation pertaining to arsenic, benzotrichloride and tar could not be conjectured because of insufficient cases and information in the histological diagnosis. On the other hand, the carcinogenicity of these substances in occupational exposure has been confirmed by animal experiments administered intratracheally or by inhalation studies under relatively higher concentration. As a result of recent refinements of inhalation study, all-day and life-span exposure to extremely low concentrations, such as microgram/m3 orders, of certain substances has been possible. The characteristics of lung tumors occurring in these animals are rather different from those of human. For example, in mouse, almost all of the malignant lung tumors developed by carcinogens are adenocarcinomas and it is rare to find the squamous cell carcinoma. Moreover, small cell carcinoma and large cell carcinoma have not known to occur in the lungs of rats and mice. Therefore, future research should focus elucidating the specific relationship between cause and cell type of human lung cancer by means of animal experiments on lung cancer that give attention to the specificities of each experimental animal and the origin of the resultant lung tumor.

Ethical and Animal Welfare Considerations in Relation to Species Selection for Animal Experimentation

PubMed Central

Webster, John

2014-01-01

Simple Summary When making a choice of species for animal experimentation we must balance its suitability as a model for human medicine against the potential harms to the animals both from the procedures and the quality of their lifetime experience. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. Abstract Ethical principles governing the conduct of experiments with animals are reviewed, especially those relating to the choice of species. Legislation requires that the potential harm to animals arising from any procedure should be assessed in advance and justified in terms of its possible benefit to society. Potential harms may arise both from the procedures and the quality of the animals’ lifetime experience. The conventional approach to species selection is to use animals with the “lowest degree of neurophysiological sensitivity”. However; this concept should be applied with extreme caution in the light of new knowledge. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. A set of responsibilities is outlined for each category of moral agent. These include regulators, operators directly concerned with the conduct of scientific experiments and toxicology trials, veterinarians and animal care staff; and society at large. PMID:26479009

Ahimsa and alternatives -- the concept of the 4th R. The CPCSEA in India.

PubMed

Pereira, Shiranee; Tettamanti, Massimo

2005-01-01

The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) in India is one of a kind in the world. It is a statutory body of the government of India formed by an act of the Indian parliament. This body consists of nominated members and representatives from national regulatory agencies, Ministry of Health and Family Welfare, Ministry of Environment and Forests, national academic and research councils, premier research institutes, eminent scientists and animal welfare organisations. The CPCSEA draws its powers from the Prevention of Cruelty to Animals (PCA) Act of 1960 which states that the duty of the committee is "to take all such measures as may be necessary to ensure that animals are not subject to unnecessary pain or suffering before, during or after the performance of experiments on them". With the power to promulgate its own laws to ensure the humane and ethical use of animals in research and education, the CPCSEA in 1998 notified in the gazette of India the "Breeding of and Experiments on Animals (Control and Supervision) Rules 1998". The CPCSEA is unique in that the law in itself has enabled the creation of a common platform of discussion for scientists and animal activists for humane and progressive solutions for the use of animals in experimentation. In a country that is caught in a paradox of violence and rich cultural and religious traditions, India still draws a lot of its power from the concept of "Ahimsa" (the philosophy of non-violence). This concept is also pertinent to the use of animals in laboratories. Unethical, inhumane and unscientific practices, and ignorance of the use of alternatives were the way of science until 1999 when CPCSEA became functional. For four years CPCSEA has waged a battle, rescued thousands of animals from laboratories, fought legal battles to victory, enforced for the first time in the country good laboratory practice, designed guidelines for the use of animals in the production of immunobiologicals, introduced the credo of 3R principles, trained and taught scientific personnel the credibility of humane science and most importantly brought forward the concept of the fourth R, "rehabilitation" of used laboratory animals. Today CPCSEA has made it a national policy that personnel using experimental animals have a moral responsibility towards these animals after their use. Costs of after-care/rehabilitation of animals post experimentation are to be a part of research costs and should be scaled in positive correlation with the level of sentience of the animals. This paper is about the Indian law on animal experimentation and the success story of the CPCSEA in India in inculcating the credo of 4Rs -- Replacement, Reduction, Refinement, and Rehabilitation of animals used in experimentation.

Unripe Musa sapientum peel in the healing of surgical wounds in rats.

PubMed

Atzingen, Dênia Amélia Novato Castelli Von; Gragnani, Alfredo; Veiga, Daniela Francescato; Abla, Luis Eduardo Felipe; Cardoso, Lorraine Lorene Felix; Ricardo, Thiago; Mendonça, Adriana Rodrigues dos Anjos; Ferreira, Lydia Masako

2013-01-01

To assess the effects of unripe Musa sapientum peel on the healing of surgical wounds in rats. One hundred and twenty Wistar rats were divided into two treatment groups of 60 animals each: the control group (gel without the active ingredient) and experimental group (4% Musa sapientum peel gel). A 4 x 4 cm surgical wound was created on the back of each animal. The wound was cleaned daily with 0.9% saline, treated with 4% gel or natrosol gel (control), and covered with gauze. Animals from both groups were sacrificed after seven, 14 and 21 days of treatment; the tissue from the wound site was removed together with a margin of normal skin for histological analysis. No significant differences in wound contraction rates (p=0.982) were found between time points (seven, 14 and 21 days of treatment) in both groups. However, a significantly higher wound contraction rate was observed in the control group on day 21 compared with the experimental group (p=0.029). There were no significant differences in histomorphological features between groups. The experimental group showed an increased number of polymorphonuclear cells on day 7, with a significant reduction on day 21 (p=0.026). The use of 4% unripe Musa sapientum peel gel on surgical wounds in rats resulted in an increased number of polymorphonuclear cells on day 7, reduced wound contraction, reduced vascular proliferation and increased concentration of collagen fibers on day 21.

Quantitative detection of Toxoplasma gondii in tissues of experimentally infected turkeys and in retail turkey products by magnetic-capture PCR.

PubMed

Koethe, Martin; Straubinger, Reinhard K; Pott, Susan; Bangoura, Berit; Geuthner, Anne-Catrin; Daugschies, Arwid; Ludewig, Martina

2015-12-01

Magnetic-capture PCR was applied for the quantitative detection of Toxoplasma gondii in tissues of experimentally infected turkeys and retail turkey meat products. For experimental infection, three T. gondii strains (ME49, CZ-Tiger, NED), varying infectious doses in different matrices (organisms in single mouse brains or 10(3), 10(5), or 10(6) oocysts in buffer) were used. From all animals, breast, thigh, and drumstick muscle tissues and for CZ-Tiger-infected animals additionally brains and hearts were analyzed. Using the magnetic-capture PCR large volumes of up to 100 g were examined. Our results show that most T. gondii parasites are present in brain and heart tissue. Of the three skeletal muscle types, drumsticks were affected at the highest and breast at the lowest level. Type III strain (NED) seems to be less efficient in infecting turkeys compared to type II strains, because only few tissues of NED infected animals contained T. gondii DNA. Furthermore, the number of detected parasitic stages increased with the level of infectious dose. Infection mode by either oocyst or tissue cyst stage did not have an effect on the amount of T. gondii present in tissues. In retail turkey meat products T. gondii DNA was not detectable although a contact with the parasite was inferred by serology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

PubMed Central

Cheresiz, S. V.; Semenova, E. A.; Chepurnov, A. A.

2016-01-01

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

Evaluation of lipid peroxidation activity at intravenous administration of gold nanorods in rats with simulated diabetes and transplanted liver cancer

NASA Astrophysics Data System (ADS)

Bucharskaya, Alla B.; Dikht, Natalia I.; Afanasyeva, Galina A.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Zaraeva, Nadezhda V.; Khlebtsov, Nikolai G.; Khlebtsov, Boris N.

2014-01-01

In the experiment the white outbred rats with transplanted liver cancer (cholangiocarcinoma line PC-1) and simulated alloxan diabetes were treated by single intravenous injection of gold nanorods. State of lipid peroxidation was evaluated by the following parameters: the malondialdehyde, lipid hydroperoxide, the average weght molecules in the serum of animals by conventional spectrophotometric methods study using a spectrofluorometer RF-5301 PC (Shimadzu, Japan). In both experimental groups of animals the significant increasing of levels of lipid peroxidation products was noted compared with control group. After intravenous administration of nanoparticles in the group of animals with alloxan diabetes the activation of a free radical oxidation was not observed, in group with transplanted liver cancer the increasing of levels of lipid hydroperoxide, malondialdehyde was established.

Glycosaminoglycan synthesis in the mandibular condyle during growth adaptation.

PubMed

Kantomaa, T; Pirttiniemi, P; Tuominen, M; Poikela, A

1994-01-01

Condylar growth was studied after an operation simulating functional orthodontic appliances. Twenty-five rabbits underwent a surgical operation for the induction of premature synostosis to displace the glenoid fossa posteriorly during growth. Twenty-five control rabbits underwent sham operations. At the age of 15 days, 10 experimental and 10 control animals and, at the age of 20 days, 5 experimental and 5 control animals were killed. Their mandibular condyles were organ-cultured for 3 h in the presence of radiolabelled sulphur. The condyles were used for autoradiographic purposes. Digital image analysis of autoradiograms of histological sections showed synthesis of glycosaminoglycans to have increased from the anterior to the posterior direction. This increase was more marked in experimental animals than in the condyles of control animals. Ten experimental and 10 control animals were killed at the age of 15 days, and mandibular condyles were organ-cultured for 1, 4 and 7 days. Differentiation of proliferating prechondroblasts into hypertrophied chondrocytes continued under organ culture conditions. A marked decrease in the proliferating cell layer was noticed, especially in control condyles. Hypertrophy was faster and came closer to the surface of the condyle in the anterior region of the condyle. This was most marked in the condyles of experimental animals. The results indicate that a procedure carried out on the glenoid fossa with the same effect as functional appliances increases the synthesis of extracellular matrix in the posterosuperior region of the mandibular condyle.

Protective Effect of Selenium Against Cisplatin-Induced Ototoxicity in an Experimental Design.

PubMed

Doğan, Sedat; Yazici, Hasmet; Yalçinkaya, Esin; Erdoğdu, Halil Ibrahim; Tokgöz, Sibel Alicura; Sarici, Furkan; Namuslu, Mehmet; Sarikaya, Yasin

2016-10-01

Cisplatin is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. In the present study, we investigated the effect of selenium administration on lipid peroxidation (malondialdehyde [MDA]) and cisplatin-induced ototoxicity in rats. Healthy wistar albino rats (n = 21) were randomly divided into 3 groups: control (C), cisplatin (Cis), cisplatin and selenium (Cis+Se). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Hearing thresholds and lipid peroxidation (MDA) levels of the rats were recorded before injections and at the end of experimental protocol. The cochleas of animals were harvested for histologic and immunuhistochemical examinations. In biochemichal analyses, pretreatment with selenium prevented the elevation of MDA levels in Cis+Se group rats. Moreover, animals in Cis+Se group had better hearing threshold levels than animals in cis group. Samples obtained from the animals in Cis group revealed extensive loss of the normal microarchitecture of the organ of Corti. On the other hand, animals in Cis+Se group exhibited a preservation of the morphology of the organ of Corti and outer hair cells. In the immunohistochemical examinations of cochlear tissues stained with anti-caspase-3, a higher degree of immunopositivity was found in the Cis group. When Cis+Se group and Cis group were compared, significantly less immunopositivity occurred in the Cis+Se group (P < 0.05). Thus, it appears that pretreatment with selenium may reduce cisplatin-induced ototoxicity in rats.

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

PubMed

Bosmans, Joanna W A M; Moossdorff, Martine; Al-Taher, Mahdi; van Beek, Lotte; Derikx, Joep P M; Bouvy, Nicole D

2016-05-01

This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

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.

The transcriptional response of skin to fluorescent light exposure in viviparous (Xiphophorus) and oviparous (Danio, Oryzias) fishes.

PubMed

Boswell, Mikki; Boswell, William; Lu, Yuan; Savage, Markita; Mazurek, Zachary; Chang, Jordan; Muster, Jeanot; Walter, Ronald

2018-06-01

Differences in light sources are common in animal facilities and potentially can impact experimental results. Here, the potential impact of lighting differences on skin transcriptomes has been tested in three aquatic animal models commonly utilized in biomedical research, (Xiphophorus maculatus (platyfish), Oryzias latipes (medaka) and Danio rerio (zebrafish). Analysis of replicate comparative RNA-Seq data showed the transcriptional response to commonly utilized 4100K or "cool white" fluorescent light (FL) is much greater in platyfish and medaka than in zebrafish. FL induces genes associated with inflammatory and immune responses in both medaka and zebrafish; however, the platyfish exhibit suppression of genes involved with immune/inflammation, as well as genes associated with cell cycle progression. Furthermore, comparative analyses of gene expression data from platyfish UVB exposures, with medaka and zebrafish after exposure to 4100K FL, show comparable effects on the same stress pathways. We suggest the response to light is conserved, but that long-term adaptation to species specific environmental niches has resulted in a shifting of the wavelengths required to incite similar "genetic" responses in skin. We forward the hypothesis that the "genetic perception" of light may have evolved differently than ocular perception and suggest that light type (i.e., wavelengths emitted) is an important parameter to consider in experimental design. Copyright © 2017 Elsevier Inc. All rights reserved.

Histopathological comparative analysis of peri-implant soft tissue response after dental implant placement with flap and flapless surgical technique. Experimental study in pigs.

PubMed

Vlahovic, Zoran; Markovic, Aleksa; Golubovic, Mileta; Scepanovic, Miodrag; Kalanovic, Milena; Djinic, Ana

2015-11-01

The aim of this study was comparing the effect of flapless vs. flap technique of implant placement on inflammation degree of peri-implant soft tissue, through histopathological analysis. The experiment was conducted on five domestic pigs. Nine weeks after tooth extraction, implants were installed. Each animal received six implants in mandible. According to split-mouth design, randomly one side was used for flapless technique using mini-incision, while on the other side, flap was raised. After 7, 14, 21, 28, and 90 days, the experimental animals were sacrificed. Samples for histopathological analyzes were taken from the buccal side of peri-implant mucosa next to the neck of implants, from three levels. The degree of inflammatory response in the peri-implant soft tissue was estimated through ordinal scores from 0 to 3. In the flap group Score 3 indicating high degree of inflammation was present from day 7 to day 21, in contrast to flapless group where Score 3 was not recorded during the entire follow-up. Three months after implantation, there were no signs of inflammation neither around flap nor around flapless implants. Flapless surgical implantation technique using mini-incision decreases peri-implant soft tissue inflammatory reaction compared with flap surgery. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver

PubMed Central

Gaudio, Eugenio; Chaberek, Slawomir; Montella, Andrea; Pannarale, Luigi; Morini, Sergio; Novelli, Gilnardo; Borghese, Federica; Conte, Davide; Ostrowski, Kazimierz

2005-01-01

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl4-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl4-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research. PMID:16050897

Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

NASA Astrophysics Data System (ADS)

Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.

2011-05-01

It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental lumbar spinal cords. Taken together our results show that (1) rat motoneurons survived after 35-day antiorthostatic hind limb suspension and the changes in neurons had a mostly functional character, and (2) the increased immunoexpression of Hsp25 can be considered as the anti-apoptotic factor.

A statistical analysis of murine incisional and excisional acute wound models.

PubMed

Ansell, David M; Campbell, Laura; Thomason, Helen A; Brass, Andrew; Hardman, Matthew J

2014-01-01

Mice represent the most commonly used species for preclinical in vivo research. While incisional and excisional acute murine wound models are both frequently employed, there is little agreement on which model is optimum. Moreover, current lack of standardization of wounding procedure, analysis time point(s), method of assessment, and the use of individual wounds vs. individual animals as replicates makes it difficult to compare across studies. Here we have profiled secondary intention healing of incisional and excisional wounds within the same animal, assessing multiple parameters to determine the optimal methodology for future studies. We report that histology provides the least variable assessment of healing. Furthermore, histology alone (not planimetry) is able to detect accelerated healing in a castrated mouse model. Perhaps most importantly, we find virtually no correlation between wounds within the same animal, suggesting that use of wound (not animal) biological replicates is perfectly acceptable. Overall, these findings should guide and refine future studies, increasing the likelihood of detecting novel phenotypes while reducing the numbers of animals required for experimentation. © 2014 by the Wound Healing Society.

A statistical analysis of murine incisional and excisional acute wound models

PubMed Central

Ansell, David M; Campbell, Laura; Thomason, Helen A; Brass, Andrew; Hardman, Matthew J

2014-01-01

Mice represent the most commonly used species for preclinical in vivo research. While incisional and excisional acute murine wound models are both frequently employed, there is little agreement on which model is optimum. Moreover, current lack of standardization of wounding procedure, analysis time point(s), method of assessment, and the use of individual wounds vs. individual animals as replicates makes it difficult to compare across studies. Here we have profiled secondary intention healing of incisional and excisional wounds within the same animal, assessing multiple parameters to determine the optimal methodology for future studies. We report that histology provides the least variable assessment of healing. Furthermore, histology alone (not planimetry) is able to detect accelerated healing in a castrated mouse model. Perhaps most importantly, we find virtually no correlation between wounds within the same animal, suggesting that use of wound (not animal) biological replicates is perfectly acceptable. Overall, these findings should guide and refine future studies, increasing the likelihood of detecting novel phenotypes while reducing the numbers of animals required for experimentation. PMID:24635179

The dynamic genome of Hydra

PubMed Central

Chapman, Jarrod A.; Kirkness, Ewen F.; Simakov, Oleg; Hampson, Steven E.; Mitros, Therese; Weinmaier, Therese; Rattei, Thomas; Balasubramanian, Prakash G.; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G.; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M.; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E.; Putnam, Nicholas H.; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E.; Gee, Lydia; Kibler, Dennis F.; Law, Lee; Lindgens, Dirk; Martinez, Daniel E.; Peng, Jisong; Wigge, Philip A.; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R. H.; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M.; Wheeler, Benjamin M.; Peterson, Kevin J.; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A.; Strausberg, Robert L.; Venter, J. Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C. G.; Holstein, Thomas W.; Fujisawa, Toshitaka; Bode, Hans R.; David, Charles N.; Rokhsar, Daniel S.; Steele, Robert E.

2015-01-01

The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction. PMID:20228792

Organ culture as a technique for casual embryology and its application in radiobiology (in German)

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

BORGHESE, ELIO

1961-11-01

The classical methods of experimental embryology in amplubia are compared with the more recently introduced technique of culture in vitro of embryonic organs of warmblooded animals. Some isolation and recombination experiments carried out by means of organ culture are described. It is shown, by examples taken from research in progress, how this technique is applicable radiobiological experiments.

Morphometric analysis of small intestine of BALB/c mice in models developed for food allergy study.

PubMed

Coura Oliveira, Tatiana; Gouveia Pelúzio, Maria do Carmo; da Matta, Sérgio Luis Pinto; da Silveira Mezêncio, Jose Mário; Bressan, Josefina

2013-01-01

Although some animal models of food allergy in have already have been described, none of them uses the allergen in the animals' diet. This work describes the comparison between two developed models of food allergy in BALB/c mice, based in the administration of the allergen in the diet or by intragastric way. The experiment last for 28 days and the animals had been sensitized by means of subcutaneous injection in 1st and 14th days with in natura extract milk, bovine extract meat or frog extract meat. The experimental model that uses the allergen in the unbroken form presented morphometric alterations when compared with the one that used the heat treat allergen. It was noticed the existence of some more resistant proteins than others related to the denaturation, once compared the results of the two models; the differences had been more prominent for the milk and frog allergens. These results confirm the epidemiologic data of allergy incidence in the world's population. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

PubMed

Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

2017-04-01

Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

[Effect of probiotic product containing bifidobacteria and biogel from brown algae on the intestinal microflora and parameters of innate immunity in mice with experimental drug dysbacteriosis].

PubMed

Kuznetsova, T A; Makarenkova, I D; Koneva, E L; Aminina, N M; Yakush, E V

2015-01-01

The article represents the results of studying the effect of a new fermented product (FP) containing the probiotic strain Bifidobacterium bifidum 791 and Biogel from brown algae Laminariajaponica on the composition of intestinal microflora and parameters of innate immunity in mice with experimental dysbacteriosis, induced by administration of gentamicin in dose of 25 mg per kg body weight during 7 days. The experimental animals received for 6 weeks in addition to the diet FP, which was 2% of the average volume of feed intake. The FP influence was manifested by more rapid reduction of dyspepsia symptoms, restoration of body weight and balance the intestinal microbiocenosis (increasing of bifido- and lactobacteria, typical E. coli, reducing of the bacteria genus Proteus and Clostridium, elimination of S. aureus). As the results of FP administration we observed the statistically significant reduction of endogenous intoxication values and increasing of the phagocyte activity of neutrophils, related to effector cells of innate immunity, compared with animals not receiving FP. Identified effects of FP are due to both its probiotic properties through the presence of bifidobacteria and immunomodulating and enteral sorbtion activities of alginate component.

The disturbance of antioxidant/oxidant balance in fish experimentally infected by Aeromonas caviae: Relationship with disease pathophysiology.

PubMed

Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa; Leipnitz, Guilhian; Verdi, Camila Marina; Santos, RobertoC V; Stefani, Lenita M; Baldisserotto, Bernardo

2018-06-07

Aeromonas caviae is a Gram-negative bacterium rarely found in fish but it can be associated to high mortality of infected animals. The disease pathogenesis in fish associated to liver and kidney lesions directly linked to the initiation and progression of the disease remains poorly understood. Thus, the aim of this study was to evaluate whether A. caviae infection causes oxidative stress in liver and kidney of silver catfish Rhamdia quelen, and its involvement in disease pathogenesis. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels increased in liver and kidney of fish experimentally infected by A. caviae compared to the control uninfected group. On the other hand, non-protein sulfhydryl (NPSH) levels decreased in both tissues of infected animals, while the glutathione S-transferase (GST) activity decreased only in the hepatic tissue. No difference was observed between groups in both tissues regarding superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) activities and glutathione (GSH) levels. In summary, the disturbance of hepatic and renal antioxidant/oxidant equilibrium contributes to the pathophysiology of the disease in fish experimentally infected by A. caviae. Copyright © 2018 Elsevier Ltd. All rights reserved.

Refining animal experiments: the first Brazilian regulation on animal experimentation.

PubMed

de A e Tréz, Thales

2010-06-01

The very first law on animal experimentation has been approved recently in Brazil, and now is part of a set of the legal instruments that profile the Brazilian government's attitude toward the use of animals in experiments. Law 11794/08 establishes a new legal instrument that will guide new methods of conduct for ethics committees, researchers and representatives of animal protection societies. This comment aims to analyse critically the implications that this law brings to Brazilian reality. The link between it and the Russell and Burch's Three Rs concept is defined, and certain problems are identified. The conclusion is that the body of the law emphasises the refinement of animal experiments, but gives little importance to the principles of reduction and replacement.

Experimental animal studies of radon and cigarette smoke

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

Cross, F.T.; Dagle, G.E.; Gies, R.A.

Cigarette-smoking is a dominant cause of lung cancer and confounds risk assessment of exposure to radon decay products. Evidence in humans on the interaction between cigarette-smoking and exposure to radon decay products, although limited, indicates a possible synergy. Experimental animal data, in addition to showing synergy, also show a decrease or no change in risk with added cigarette-smoke exposures. This article reviews previous animal data developed at Compagnie Generale des Matieres Nucleaires and Pacific Northwest Laboratory (PNL) on mixed exposures to radon and cigarette smoke, and highlights new initiation-promotion-initiation (IPI) studies at PNL that were designed within the framework ofmore » a two-mutation carcinogenesis model. Also presented are the PNL exposure system, experimental protocols, dosimetry, and biological data observed to date in IPI animals.« less

Reconstruction of Canine Mandibular Bone Defects Using a Bone Transport Reconstruction Plate

PubMed Central

Elsalanty, Mohammed E.; Zakhary, Ibrahim; Akeel, Sara; Benson, Byron; Mulone, Timothy; Triplett, Gilbert R.; Opperman, Lynne A.

2010-01-01

Objectives Reconstruction of mandibular segmental bone defects is a challenging task. This study tests a new device used for reconstructing mandibular defects based on the principle of bone transport distraction osteogenesis. Methods Thirteen beagle dogs were divided into control and experimental groups. In all animals, a 3 cm defect was created on one side of the mandible. In eight control animals, the defect was stabilized with a reconstruction plate without further reconstruction and the animals were sacrificed two to three months after surgery. The remaining five animals were reconstructed with a bone transport reconstruction plate (BTRP), comprising a reconstruction plate with attached intraoral transport unit, and were sacrificed after one month of consolidation. Results Clinical evaluation, cone-beam CT densitometry, three-dimensional histomorphometry, and docking site histology revealed significant new bone formation within the defect in the distracted group. Conclusion The physical dimensions and architectural parameters of the new bone were comparable to the contralateral normal bone. Bone union at the docking site remains a problem. PMID:19770704

Light, time, and the physiology of biotic response to rapid climate change in animals.

PubMed

Bradshaw, William E; Holzapfel, Christina M

2010-01-01

Examination of temperate and polar regions of Earth shows that the nonbiological world is exquisitely sensitive to the direct effects of temperature, whereas the biological world is largely organized by light. Herein, we discuss the use of day length by animals at physiological and genetic levels, beginning with a comparative experimental study that shows the preeminent role of light in determining fitness in seasonal environments. Typically, at seasonally appropriate times, light initiates a cascade of physiological events mediating the input and interpretation of day length to the output of specific hormones that ultimately determine whether animals prepare to develop, reproduce, hibernate, enter dormancy, or migrate. The mechanisms that form the basis of seasonal time keeping and their adjustment during climate change are reviewed at the physiological and genetic levels. Future avenues for research are proposed that span basic questions from how animals transition from dependency on tropical cues to temperate cues during range expansions, to more applied questions of species survival and conservation biology during periods of climatic stress.

14 CFR § 1232.103 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... animal subjects. (a) Activity includes research, testing of hardware for animal use, flight experimentation, and any other tasks involving the use of animal subjects. (b) Animal is any live vertebrate....103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE...

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

PubMed Central

Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

Fear of predation drives stable and differentiated social relationships in guppies

PubMed Central

Heathcote, Robert J. P.; Darden, Safi K.; Franks, Daniel W.; Ramnarine, Indar W.; Croft, Darren P.

2017-01-01

Social relationships can have important consequences for fitness in animals. Whilst numerous studies have shown that individuals often join larger groups in response to perceived predation risk (i.e. fear of predation), the importance of predation risk in driving the formation and stability of social relationships within groups has been relatively ignored. We experimentally tested how predation threat influenced fine-scale social network structure using Trinidadian guppies (Poecilia reticulata). When perceived predation risk was high, individuals developed stable and more differentiated social ties compared to when perceived risk was low. Intriguingly, social differentiation coincided with shoals being somewhat smaller under high-perceived risk, suggesting a possible conflict between forming stable social relationships and larger social groups. Individuals most at risk of predation (large and bold individuals) showed the most exaggerated responses in several social measures. Taken together, we provide the first experimental evidence that proximate risk of predation can increase the intensity of social relationships and fine-scale social structure in animal populations. PMID:28150706

Fear of predation drives stable and differentiated social relationships in guppies.

PubMed

Heathcote, Robert J P; Darden, Safi K; Franks, Daniel W; Ramnarine, Indar W; Croft, Darren P

2017-02-02

Social relationships can have important consequences for fitness in animals. Whilst numerous studies have shown that individuals often join larger groups in response to perceived predation risk (i.e. fear of predation), the importance of predation risk in driving the formation and stability of social relationships within groups has been relatively ignored. We experimentally tested how predation threat influenced fine-scale social network structure using Trinidadian guppies (Poecilia reticulata). When perceived predation risk was high, individuals developed stable and more differentiated social ties compared to when perceived risk was low. Intriguingly, social differentiation coincided with shoals being somewhat smaller under high-perceived risk, suggesting a possible conflict between forming stable social relationships and larger social groups. Individuals most at risk of predation (large and bold individuals) showed the most exaggerated responses in several social measures. Taken together, we provide the first experimental evidence that proximate risk of predation can increase the intensity of social relationships and fine-scale social structure in animal populations.

A Protocol for Using Gene Set Enrichment Analysis to Identify the Appropriate Animal Model for Translational Research.

PubMed

Weidner, Christopher; Steinfath, Matthias; Wistorf, Elisa; Oelgeschläger, Michael; Schneider, Marlon R; Schönfelder, Gilbert

2017-08-16

Recent studies that compared transcriptomic datasets of human diseases with datasets from mouse models using traditional gene-to-gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. A major reason for the discrepancies between different gene expression analyses is the arbitrary filtering of differentially expressed genes. Furthermore, the comparison of single genes between different species and platforms often is limited by technical variance, leading to misinterpretation of the con/discordance between data from human and animal models. Thus, standardized approaches for systematic data analysis are needed. To overcome subjective gene filtering and ineffective gene-to-gene comparisons, we recently demonstrated that gene set enrichment analysis (GSEA) has the potential to avoid these problems. Therefore, we developed a standardized protocol for the use of GSEA to distinguish between appropriate and inappropriate animal models for translational research. This protocol is not suitable to predict how to design new model systems a-priori, as it requires existing experimental omics data. However, the protocol describes how to interpret existing data in a standardized manner in order to select the most suitable animal model, thus avoiding unnecessary animal experiments and misleading translational studies.

Electroencephalogram, circulation, and lung function after high-velocity behind armor blunt trauma.

PubMed

Drobin, Dan; Gryth, Dan; Persson, Jonas K E; Rocksén, David; Arborelius, Ulf P; Olsson, Lars-Gunnar; Bursell, Jenny; Kjellström, B Thomas

2007-08-01

Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on personal body armor. The protective vest may impede the projectile, but some of the kinetic energy is transferred to the body, causing internal injuries and occasionally death. The aim in this study was to investigate changes in electroencephalogram (EEG) and physiologic parameters after high-velocity BABT. Eight anesthetized pigs, wearing body armor (including a ceramic plate) on the right side of their thorax, were shot with a 7.62-mm assault rifle (velocity approximately 800 m/s). The shots did not penetrate the armor and these animals were compared with control animals (n = 4), shot with blank ammunition. EEG and several physiologic parameters were thereafter monitored during a 2-hour period after the shot. All animals survived during the experimental period. Five of the exposed animals showed a temporary effect on EEG. Furthermore, exposed animals displayed decreased cardiac capacity and an impaired oxygenation of the blood. Postmortem examination revealed subcutaneous hematomas and crush injuries to the right lung. The results in our animal model indicate that high-velocity BABT induce circulatory and respiratory dysfunction, and in some cases even transient cerebral functional disturbances.

Comparative analysis of numerical and experimental data of orthodontic mini-implants.

PubMed

Chatzigianni, Athina; Keilig, Ludger; Duschner, Heinz; Götz, Hermann; Eliades, Theodore; Bourauel, Christoph

2011-10-01

The purpose of this study was to compare numerical simulation data derived from finite element analysis (FEA) to experimental data on mini-implant loading. Nine finite element (FE) models of mini-implants and surrounding bone were derived from corresponding experimental specimens. The animal bone in the experiment consisted of bovine rib. The experimental groups were based on implant type, length, diameter, and angle of insertion. One experimental specimen was randomly selected from each group and was digitized in a microCT scanner. The FE models consisted of bone pieces containing Aarhus mini-implants with dimensions 1.5 × 7 mm and 1.5 × 9 mm or LOMAS mini-implants (dimensions 1.5 × 7 mm, 1.5 × 9 mm, and 2 × 7 mm). Mini-implants were inserted in two different ways, perpendicular to the bone surface or at 45 degrees to the direction of the applied load. Loading and boundary conditions in the FE models were adjusted to match the experimental situation, with the force applied on the neck of the mini-implants, along the mesio-distal direction up to a maximum of 0.5 N. Displacement and rotation of mini-implants after force application calculated by FEA were compared to previously recorded experimental deflections of the same mini-implants. Analysis of data with the Altman-Bland test and the Youden plot demonstrated good agreement between numerical and experimental findings (P = not significant) for the models selected. This study provides further evidence of the appropriateness of the FEA as an investigational tool in relevant research.

Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines.

PubMed

Hooijmans, Carlijn R; de Vries, Rob; Leenaars, Marlies; Curfs, Jo; Ritskes-Hoitinga, Merel

2011-03-01

Several studies have demonstrated serious omissions in the way research that use animals is reported. In order to improve the quality of reporting of animal experiments, the Animals in research: reporting in vivo experiments (ARRIVE) Guidelines were published in the British Journal of Pharmacology in August 2010. However, not only the quality of reporting of completed animal studies needs to be improved, but also the design and execution of new experiments. With both these goals in mind, we published the Gold Standard Publication Checklist (GSPC) in May 2010, a few months before the ARRIVE guidelines appeared. In this letter, we compare the GSPC checklist with the ARRIVE Guidelines. The GSPC describes certain items in more detail, which makes it both easier to use when designing and conducting an experiment and particularly suitable for making systematic reviews of animal studies more feasible. In order to improve not only the reporting but also the planning, design, execution and thereby, the scientific quality of animal experiments, we strongly recommend to all scientists involved in animal experimentation and to editors of journals publishing animal studies to take a closer look at the contents of both the ARRIVE guidelines and GSPC, and select the set of guidelines which is most appropriate for their particular situation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

PubMed Central

Wojnarowicz, Mark W.; Fisher, Andrew M.; Minaeva, Olga; Goldstein, Lee E.

2017-01-01

Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs”) from injury consequences (“outputs”) may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate clinical translation to benefit people affected by concussion, TBI, and CTE. PMID:28620350

Animal Watching: Outdoors and In.

ERIC Educational Resources Information Center

McLure, John W.

2001-01-01

Describes using domesticated, wild, or feral animals to teach students about nature and animal behavior. Connections can be made with psychology, economics, genetics, history, art, and other disciplines. The study of animal behavior provides opportunities for harmless student experimentation. (SAH)

The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Research.

PubMed

Morrissey, Bethny; Blyth, Karen; Carter, Phil; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

2017-01-01

While significant medical breakthroughs have been achieved through using animal models, our experience shows that often there is surplus material remaining that is frequently never revisited but could be put to good use by other scientists. Recognising that most scientists are willing to share this material on a collaborative basis, it makes economic, ethical, and academic sense to explore the option to utilise this precious resource before generating new/additional animal models and associated samples. To bring together those requiring animal tissue and those holding this type of archival material, we have devised a framework called Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) with the aim of making remaining material derived from animal studies in biomedical research more visible and accessible to the scientific community. We encourage journals, funding bodies, and scientists to unite in promoting a new way of approaching animal research by adopting the SEARCH framework.

The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Research

PubMed Central

Morrissey, Bethny; Blyth, Karen; Carter, Phil; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

2017-01-01

While significant medical breakthroughs have been achieved through using animal models, our experience shows that often there is surplus material remaining that is frequently never revisited but could be put to good use by other scientists. Recognising that most scientists are willing to share this material on a collaborative basis, it makes economic, ethical, and academic sense to explore the option to utilise this precious resource before generating new/additional animal models and associated samples. To bring together those requiring animal tissue and those holding this type of archival material, we have devised a framework called Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) with the aim of making remaining material derived from animal studies in biomedical research more visible and accessible to the scientific community. We encourage journals, funding bodies, and scientists to unite in promoting a new way of approaching animal research by adopting the SEARCH framework. PMID:28081116

Royal Jelly Promotes Ovarian Follicles Growth and Increases Steroid Hormones in Immature Rats

PubMed Central

Ghanbari, Elham; Khazaei, Mohammad Rasool; Khazaei, Mozafar; Nejati, Vahid

2018-01-01

Background Royal jelly (RJ) is a complementary diet widely prescribed by traditional medicine specialists for treatment of in- fertility. The aim of present study was to evaluate the effects of RJ on a set of reproductive parameters in immature female rats. Materials and Methods In this experimental study, thirty two immature female rats (30-35 g) were divided into four groups (n=8/group): three experimental groups and one control. The experimental groups received 100, 200 and 400 mg/kg/body weight doses of RJ daily for 14 days, and the control group received 0.5 ml distilled water interaperito- nealy (i.p). The treated rats were sacrificed and their ovaries were dissected for histological examination. The serum levels of ovarian hormones, nitric oxide (NO) and ferric reducing antioxidant power (FRAP) were evaluated, and the ratios of the ovarian and uterine weight to body weight were calculated. One-way ANOVA was used for data analysis. Results The body weights were significantly different (P=0.002) among the rat groups, with an increase in all RJ treated animals. Uterine and ovarian weights and the serum levels of progesterone (P=0.013) and estradiol (P=0.004) were significantly increased in experimental groups compared to the control group. In addition, a significant increase in the number of mature follicles and corpora lutea (P=0.007) was seen in RJ recipients compared to the controls. A significant increase in the serum levels of FRAP (P=0.009) and a significant decrease in NO level (P=0.013) were also observed. Conclusion RJ promotes folliculogensis and increases ovarian hormones. This product can be considered as a natural growth stimulator for immature female animals. PMID:29043701

Royal Jelly Promotes Ovarian Follicles Growth and Increases Steroid Hormones in Immature Rats.

PubMed

Ghanbari, Elham; Khazaei, Mohammad Rasool; Khazaei, Mozafar; Nejati, Vahid

2018-01-01

Royal jelly (RJ) is a complementary diet widely prescribed by traditional medicine specialists for treatment of infertility. The aim of present study was to evaluate the effects of RJ on a set of reproductive parameters in immature female rats. In this experimental study, thirty two immature female rats (30-35 g) were divided into four groups (n=8/group): three experimental groups and one control. The experimental groups received 100, 200 and 400 mg/kg/body weight doses of RJ daily for 14 days, and the control group received 0.5 ml distilled water interaperitonealy (i.p). The treated rats were sacrificed and their ovaries were dissected for histological examination. The serum levels of ovarian hormones, nitric oxide (NO) and ferric reducing antioxidant power (FRAP) were evaluated, and the ratios of the ovarian and uterine weight to body weight were calculated. One-way ANOVA was used for data analysis. The body weights were significantly different (P=0.002) among the rat groups, with an increase in all RJ treated animals. Uterine and ovarian weights and the serum levels of progesterone (P=0.013) and estradiol (P=0.004) were significantly increased in experimental groups compared to the control group. In addition, a significant increase in the number of mature follicles and corpora lutea (P=0.007) was seen in RJ recipients compared to the controls. A significant increase in the serum levels of FRAP (P=0.009) and a significant decrease in NO level (P=0.013) were also observed. RJ promotes folliculogensis and increases ovarian hormones. This product can be considered as a natural growth stimulator for immature female animals. Copyright© by Royan Institute. All rights reserved.

Value of the dorsal cutaneous guinea pig model in selecting topical antiviral formulations for the treatment of recurrent herpes simplex type 1 disease.

PubMed

Poli, G; Dall'Ara, P; Binda, S; Santus, G; Poli, A; Cocilovo, A; Ponti, W

2001-01-01

Recurrent herpes simplex labialis represents a disease still difficult to treat, despite the availability of many established antiviral drugs used in clinical research since 30 years ago. Although differences between the human disease and that obtained in experimental animal suggest caution in predicting an effective clinical response from the experimental results, some of the animal models seem to be useful in optimising the topical formulation of single antiviral drugs. In the present work the dorsal cutaneous guinea pig model was used to compare 5 different topical antiviral formulations with clinical promise (active molecule: 5% w/w micronized aciclovir, CAS 59277-89-3), using both roll-on and lipstick application systems. The aim being to evaluate which vehicle (water, oil, low melting and high melting fatty base) and application system (roll-on, lipstick) enhances the skin penetration and the antiviral activity of the drug, after an experimental intradermal infection with Herpes simplex virus type 1 (HSV-1). As reference, a commercial formulation (5% aciclovir ointment) was used. The cumulative results of this study showed that the formulation A, containing 5% aciclovir in an aqueous base in a roll-on application system, has the better antiviral efficacy in reducing the severity of cutaneous lesions and the viral titer; among the lipsticks preparations, the formulation D, containing 5% aciclovir in a low melting fatty base, demonstrates a very strong antiviral activity, though slightly less than formulation A. This experimental work confirms the validity of the dorsal cutaneous guinea pig model as a rapid and efficient method to compare the antiviral efficacy of new formulations, with clinical promise, to optimise the topical formulation of the active antiviral drugs.

Experimental evidence for inherent Lévy search behaviour in foraging animals.

PubMed

Kölzsch, Andrea; Alzate, Adriana; Bartumeus, Frederic; de Jager, Monique; Weerman, Ellen J; Hengeveld, Geerten M; Naguib, Marc; Nolet, Bart A; van de Koppel, Johan

2015-05-22

Recently, Lévy walks have been put forward as a new paradigm for animal search and many cases have been made for its presence in nature. However, it remains debated whether Lévy walks are an inherent behavioural strategy or emerge from the animal reacting to its habitat. Here, we demonstrate signatures of Lévy behaviour in the search movement of mud snails (Hydrobia ulvae) based on a novel, direct assessment of movement properties in an experimental set-up using different food distributions. Our experimental data uncovered clusters of small movement steps alternating with long moves independent of food encounter and landscape complexity. Moreover, size distributions of these clusters followed truncated power laws. These two findings are characteristic signatures of mechanisms underlying inherent Lévy-like movement. Thus, our study provides clear experimental evidence that such multi-scale movement is an inherent behaviour rather than resulting from the animal interacting with its environment. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Effect of mandibular distraction osteogenesis on the temporomandibular joint: a systematic review of animal experimental studies.

PubMed

Andersen, Kristian; Pedersen, Thomas Klit; Hauge, Ellen Margrethe; Schou, Søren; Nørholt, Sven Erik

2014-04-01

The present systematic review aimed to test the hypothesis of no effect of mandibular distraction osteogenesis on the temporomandibular joint. Animal experimental studies from January 1985 to August 2013 were included. Studies were searched in PubMed, Embase, Scopus, and the Cochrane Library. A total of 289 articles were identified, and 17 were included. Included studies were characterized by a high risk of bias and by inhomogeneity related to animal species, experimental procedures, and evaluation methods. Mandibular distraction osteogenesis within physiologic limits may be followed by adaptive changes in bone, disk, and cartilage. Increased daily rates and total activation length may influence the severity of the adaptive changes. Animal experimental studies indicate that mandibular distraction osteogenesis may induce adaptive changes in the temporomandibular joint. Adaptive changes may be influenced by increased daily rates and total length of distraction osteogenesis. Well-designed studies are needed before final conclusions can be drawn. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

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

Grams, M; Wilson, Z; Sio, T

Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons frommore » a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra.« less

Technical note: A method for assigning animals to treatment groups with unequal count per group that equalizes mean animal weight among groups.

PubMed

Epplin, F M; Haankuku, C; Horn, G W

2015-09-01

Pastures available for grazing studies may be of unequal size and may have heterogeneous carrying capacity necessitating the assignment of unequal numbers of animals per pasture. To reduce experimental error, it is often desirable that the initial mean BW be similar among experimental units. The objective of this note is to present and illustrate the use of a method for assignment of animals to experimental units of different sizes such that the initial mean weight of animals in each unit is approximately the same as the overall mean. Two alternative models were developed and solved to assign each of 231 weaned steers () to 1 of 12 pastures with carrying capacity ranging from 5 to 26 animals per pasture. A solution to Model 1 was obtained in which the mean weights among pastures were approximately the same but the variances among pastures were heteroskedastic, meaning that weight variances across pens were different (-value < 0.05). An alternative model was developed (Model 2) and used to derive assignments with nearly equal mean weights and homoskedastic variances among pastures.

Rhinosurgery in children: developmental and surgical aspects of the growing nose

PubMed Central

Verwoerd, Carel D. A.; Verwoerd-Verhoef, Henriette L.

2011-01-01

The anatomy of the nasal skeleton in newborns and adults are not alike. The complete cartilaginous framework of the neonatal nose becomes partly and gradually ossified during the years of growth and is more vulnerable to trauma in that period. Injury in early youth may have large consequences for development and may result in a nasal deformity which will increase during growth and reach its peak during and after the adolescent growth spurt. To understand more of the underlying problems of nasal malformations and their surgical treatment (septorhinoplasty) these items became the focus of multiple animal studies in the last 40 years. The effects of surgery on the nasal septum varied considerably, seemingly depending on which experimental animal was used. In review, however, the very different techniques of the experimental surgery might be even more influential in this respect. Study of one of the larger series of experiments in young rabbits comprised skeletal measurements with statistical analysis, and microscopic observations of the tissues. The behaviour of hyaline cartilage of the human nose appeared to be comparable to that of other mammals. Cartilage, although resilient, can be easily fractured whereas its tendency to integrated healing is very low, even when the perichondrium has been saved. Also surgical procedures – like in septoplasty – may result in growth disturbances of the nasal skeleton like recurrent deviations or duplicature. Loss of cartilage, as might occur after a septum abscess, is never completely restored despite some cartilage regeneration. In this article experimental studies are reviewed and compared. Still there remains a lack of consensus in the literature concerning the developmental effects of rhinosurgry in children. Based on their observations in animals and a few clinical studies, mostly with small numbers of patients but with a long follow-up, the authors have compiled a list of guidelines to be considered before starting to perform surgery on the growing midface in children. PMID:22073109

Using in vitro/in silico data for consumer safety assessment of feed flavoring additives--A feasibility study using piperine.

PubMed

Thiel, A; Etheve, S; Fabian, E; Leeman, W R; Plautz, J R

2015-10-01

Consumer health risk assessment for feed additives is based on the estimated human exposure to the additive that may occur in livestock edible tissues compared to its hazard. We present an approach using alternative methods for consumer health risk assessment. The aim was to use the fewest possible number of animals to estimate its hazard and human exposure without jeopardizing the safety upon use. As an example we selected the feed flavoring substance piperine and applied in silico modeling for residue estimation, results from literature surveys, and Read-Across to assess metabolism in different species. Results were compared to experimental in vitro metabolism data in rat and chicken, and to quantitative analysis of residues' levels from the in vivo situation in livestock. In silico residue modeling showed to be a worst case: the modeled residual levels were considerably higher than the measured residual levels. The in vitro evaluation of livestock versus rodent metabolism revealed no major differences in metabolism between the species. We successfully performed a consumer health risk assessment without performing additional animal experiments. As shown, the use and combination of different alternative methods supports animal welfare consideration and provides future perspective to reducing the number of animals. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pulmonary exposure to diesel exhaust particles induces airway inflammation and cytokine expression in NC/Nga mice.

PubMed

Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie; Ichinose, Takamichi; Shimada, Akinori; Yoshikawa, Toshikazu

2005-10-01

Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the effect of DEP on animal models with spontaneous allergic disorders has been far less intensively studied. The Nc/Nga mouse is known to be a typical animal model for human atopic dermatitis (AD). In the present study, we investigated the effects of repeated pulmonary exposure to DEP on airway inflammation and cytokine expression in NC/Nga mice. The animals were randomized into two experimental groups that received vehicle or DEP by intratracheal instillation weekly for six weeks. Cellular profiles of bronchoalveolar lavage (BAL) fluid and expressions of cytokines and chemokines in both the BAL fluid and lung tissues were evaluated 24 h after the last instillation. The DEP challenge produced an increase in the numbers of total cells, neutrophils, and mononuclear cells in BAL fluid as compared to the vehicle challenge (P<0.01). DEP exposure significantly induced the lung expressions of interleukin (IL)-4, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1alpha when compared to the vehicle challenge. These results indicate that intratracheal exposure to DEP induces the recruitment of inflammatory cells, at least partially, through the local expression of IL-4 and chemokines in NC/Nga mice.

Venous Shunt Versus Venous Ligation for Vascular Damage Control: The Immunohistochemical Evidence.

PubMed

Góes Junior, Adenauer Marinho de Oliveira; Abib, Simone de Campos Vieira; Alves, Maria Teresa de Seixas; Ferreira, Paulo Sérgio Venerando da Silva; Andrade, Mariseth Carvalho de

2017-05-01

To evaluate the expression of immunohistochemical markers of tissue ischemia (iNOS, eNOS, and HSP70) in a vascular damage control experimental model to determine if a venous temporary vascular shunt insertion leads to a better limb perfusion when compared with the ligature of the injured vein. Experimental study in male Sus Scrofa weighting 40 Kg. Animals were distributed into 5 groups: group 1 animals were submitted to right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2 animals were submitted to right EIA shunting and right EIV shunting; group 3 animals were submitted to right EIV ligation; group 4 animals were submitted to right EIV shunting; group 5 animals were not submitted to vascular shunting or venous ligation. Transonic Systems flowmeters were used to measure vascular flow on right and left external iliac vessels, and i-STAT (Abbot) portable blood analyzer was used for EIVs blood biochemical analysis. An initial baseline register of invasive arterial pressure, iliac vessels flow, and venous blood analysis was performed. Arterial pressure and iliac vessels flow were taken immediately after right iliac vessels shunting or ligation. Then, hemorrhagic shock was induced by continuous 20 mL/min blood withdraw from the external right jugular vein whereas arterial blood pressure and iliac vessels flow registers were taken every 10 min, and blood samples from EIVs were obtained every 30 min until the vascular flow through right EIA (or through the shunt inserted into the right EIV for group 4 animals) became inexistent or until the animal's death. After the end of the experiments, bilateral hind limb's biopsies were obtained for immunohistochemical analysis. Using image editing and analysis software, the expression of iNOS, eNOS, and HSP70 (3 well-known ischemic associated immunohistochemical markers) was assessed. The mean expression of each marker in the right hind limb was compared between groups. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. Immunohistochemical analysis showed no difference regarding the iNOS expression; nevertheless, both eNOS and HSP70 expression were statistically more intense (P < 0.05) on group 1 (eNOS = 1.32; HSP70 = 15.05) than on group 2 (eNOS = 0.018; HSP70 = 8.56). The higher expression of eNOS and HSP70 in the right hind limbs of group 1 animals (arterial shunt and venous ligature) than group 2 animals (arterial shunt and venous shunt) suggests that venous ligation is associated with more intense ischemic histological findings than venous shunting. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of Laser Photobiomodulation on Morphological and Functional Repair of the Facial Nerve.

PubMed

Buchaim, Daniela Vieira; Andreo, Jesus Carlos; Ferreira Junior, Rui Seabra; Barraviera, Benedito; Rodrigues, Antonio de Castro; Macedo, Mariana de Cássia; Rosa Junior, Geraldo Marco; Shinohara, Andre Luis; Santos German, Iris Jasmin; Pomini, Karina Torres; Buchaim, Rogerio Leone

2017-08-01

Evaluate the efficacy of low-level laser therapy (LLLT) on qualitative, quantitative, and functional aspects in the facial nerve regeneration process. Forty-two male Wistar rats were used, randomly divided into a control group (CG; n = 10), in which the facial nerve without lesion was collected, and four experimental groups: (1) suture experimental group (SEG) and (2) fibrin experimental group (FEG), consisting of 16 animals in which the buccal branch of the facial nerve was sectioned on both sides of the face; an end-to-end epineural suture was performed on the right side, and a fibrin sealant was used on the left side for coaptation of the stumps; and (3) laser suture experimental group (LSEG) and (4) laser fibrin experimental group (LFEG), consisting of 16 animals that underwent the same surgical procedures as SEG and FEG with the addition of laser application at three different points along the surgical site (pulsed laser of 830 nm wavelength, optical output power of 30 mW, power density of 0.2586 W/cm 2 , energy density of 6.2 J/cm 2 , beam area of 0.116 cm 2 , exposure time of 24 sec per point, total energy per session of 2.16 J, and cumulative dose of 34.56 J). The animals were submitted to functional analysis (subjective observation of whisker movement) and the data obtained were compared using Fisher's exact test. Euthanasia was performed at 5 and 10 weeks postoperative. The total number and density of regenerated axons were analyzed using the unpaired t-test (p < 0.05). Laser therapy resulted in a significant increase in the number and density of regenerated axons. The LSEG and LFEG presented better scores in functional analysis in comparison with the SEG and FEG. LLLT enhanced axonal regeneration and accelerated functional recovery of the whiskers, and both repair techniques allowed the growth of axons.

Systematic heterogenization for better reproducibility in animal experimentation.

PubMed

Richter, S Helene

2017-08-31

The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.

Geraniol attenuates fibrosis and exerts anti-inflammatory effects on diet induced atherogenesis by NF-κB signaling pathway.

PubMed

Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

2015-09-05

Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammation, immune responses, cell survival and cell proliferation. Tissue remodeling plays a significant role during the phase of inflammation and oxidative stress. In our study we have evaluated the effect of geraniol (GOH), a natural terpenoid on oxidative stress, inflammation and tissue remodeling in experimental animals. Experimental animals (hamsters) were divided into four groups; group 1 were control animals; group 2 were animals fed GOH alone (100mg/kg b.w. p.o); group 3 were animals fed atherogenic diet (standard pellet diet+10% coconut oil+0.25% cholesterol); group 4 animals were fed atherogenic diet as in group 3+GOH (100mg/kg b.w). At the end of the experimental period animals were killed and liver, heart and aorta tissues were analyzed for lipid peroxidation markers, non enzymic antioxidants and collagen distribution using histological studies like Milligan's trichrome and Picrosirius red staining. As inflammation plays a key role in tissue remodeling we also targeted the key inflammatory cytokine, NF-κB. GOH supplementation greatly prevented the remodeling of tissues by enhancing the free radical scavenging and anti-inflammatory effects. Thus in conclusion it can be suggested that GOH (100mg/kg b.w) prevents the atherogenic diet induced fibrosis in experimental hamsters. Copyright © 2015 Elsevier B.V. All rights reserved.

Establishment of a new pull-out strength testing method to quantify early osseointegration-An experimental pilot study.

PubMed

Nonhoff, J; Moest, T; Schmitt, Christian Martin; Weisel, T; Bauer, S; Schlegel, K A

2015-12-01

The animal study aims to evaluate a new experimental model for measuring sole the influence of the surface characteristics independent from implant macro-design on the level of osseointegration by registering the pull-out strength needed for removal of experimental devices with different surfaces from artificial defects. Seventy-two test bodies (36 with the FRIADENT(®) plus surface, 36 with the P15/HAp biofunctionalized surface) were inserted in six adult domestic pigs with artificial calvarial defects. The experimental devices were designed to fit in the defects leaving a gap between the test body and the local bone. After 21 days of healing, the animals were sacrificed and the test bodies were pulled out with a standardised reproducible pull-out device measuring the pull-out strength. The pull-out strength for both groups was compared. Twenty-one days after insertion a mean force of 412 ± 142 N for the P15/HAp group and 183 ± 105 N for the FRIADENT(®) plus group was measured for the removal of the specimens from the calvarial bone. The difference between the groups was statistically significant (p < 0.0001). The experimental set-up seems to be a suitable method when measuring the impact of implant surfaces on the early stage of osseointegration. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Histological evaluation of the influence of magnetic field application in autogenous bone grafts in rats

PubMed Central

Puricelli, Edela; Dutra, Nardier B; Ponzoni, Deise

2009-01-01

Background Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. Methods Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. Results The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. Conclusion The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field. PMID:19134221

A Selective Critique of Animal Experiments in Human-Orientated Biological Research.

ERIC Educational Resources Information Center

Webb, G. P.

1990-01-01

The advantages and justifications for using small animals in human-oriented research are reviewed. Some of the pitfalls of extrapolating animal-derived data to humans are discussed. Several specific problems with animal experimentation are highlighted. (CW)

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

Geraci, J.P.; Sun, M.C.; Mariano, M.S.

Dexamethasone (DEX) and captopril are effective drugs in the treatment of radiation nephropathy in experimental animals. The aim of the present study was to determine the relative effectiveness of the two drugs and to see if their combination is more effective than either drug alone. For this purpose both kidneys of 143 rats were exposed surgically and irradiated with 13-20 Gy {gamma} rays. The surrounding tissues, with the exception of a segment of lumbar cord, were shielded. Each group had free access to acidified drinking water containing either DEX (94 {mu}g/l), captopril (500 mg/l), DEX (94{mu}g/l) + captopril (500 mg/l)more » or drug-free water. Dexamethasone treatment was stopped after 90 days, but animals continued to receive captopril until death. At approximately monthly intervals the animals were weighed and renal function (PUN, hematocrit, {sup 51}Cr-EDTA retention) was measured. A side effect of treatment with DEX and DEX + captopril was a reduced increase in body weight. Paralysis of the hind limbs developed in nine animals that received captopril and/or DEX treatment. The classical histological lesions associated with radiation myelopathy were not evident in these paretic rats. It is therefore suggested that paralysis may be attributed in part to drug-induced neurotoxicity in animals with impaired renal clearance. Macroscopically and histologically, nearly all the animals that survived more than 400 days had evidence of renal tumor development. dexamethasone and/or captopril appear to selectively ameliorate glomerular compared to tubular damage, based on histological findings. All three experimental treatments delayed but did not stop the progression of lethal renal injury as measured by kidney function tests and survival time. Median survival times for nontreated and captopril-DEX- and DEX + captopril-treated animals exposed to 14.5 to 19.0 Gy kidney irradiation were 175,242,261 and 395 days, respectively. 33 refs., 8 figs., 4 tabs.« less

Comparative gastroprotective effects of natural honey, Nigella sativa and cimetidine against acetylsalicylic acid induced gastric ulcer in albino rats.

PubMed

Bukhari, Mulazim Hussain; Khalil, Javed; Qamar, Samina; Qamar, Zahid; Zahid, Muhammad; Ansari, Navid; Bakhshi, Irfan Manzoor

2011-03-01

Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). Experimental, case control study. Pharmacology and Pathology Department of King Edward Medical University, Lahore, from June to August 2007. The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines.

Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition.

PubMed

Woodward, Bill

2016-04-11

Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

"The Queen Has Been Dreadfully Shocked": Aspects of Teaching Experimental Physiology Using Animals in Britain, 1876-1986.

ERIC Educational Resources Information Center

Tansey, E. M.

1998-01-01

Reviews the impact of legislation on animal experimentation that has been in effect since 1876 in Great Britain. Focuses on the impact of these laws on the teaching of practical physiology to undergraduate students. Contains 26 references. (DDR)

77 FR 38199 - Propiconazole; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... group 12, except plum. Interregional Research Project Number 4 (IR-4) requested these tolerances under... experimental animals by the oral, dermal and inhalation routes. It is moderately irritating to the eyes, and... susceptible to its toxicity than rats. Decreased body weight gain in experimental animals was seen in...

The visual cliff's forgotten menagerie: rats, goats, babies, and myth-making in the history of psychology.

PubMed

Rodkey, Elissa N

2015-01-01

Eleanor Gibson and Richard Walk's famous visual cliff experiment is one of psychology's classic studies, included in most introductory textbooks. Yet the famous version which centers on babies is actually a simplification, the result of disciplinary myth-making. In fact the visual cliff's first subjects were rats, and a wide range of animals were tested on the cliff, including chicks, turtles, lambs, kid goats, pigs, kittens, dogs, and monkeys. The visual cliff experiment was more accurately a series of experiments, employing varying methods and a changing apparatus, modified to test different species. This paper focuses on the initial, nonhuman subjects of the visual cliff, resituating the study in its original experimental logic, connecting it to the history of comparative psychology, Gibson's interest in comparative psychology, as well as gender-based discrimination. Recovering the visual cliff's forgotten menagerie helps to counter the romanticization of experimentation by focusing on the role of extrascientific factors, chance, complexity, and uncertainty in the experimental process. © 2015 Wiley Periodicals, Inc.

[Possibilities and limitations of fibroblast cultures in the study of animal aging].

PubMed

Van Gansen, P; Van Lerberghe, N

1987-01-01

INTRODUCTION. Aging--the effect of time--occurs in every living organism. Senescence is the last period of the lifespan, leading to death. It happens in all animals, with the exception of a few didermic species (Hydras) having a stock of embryonic cells and being immortal. The causes of animal senescence are badly known. They depend both on genetic characters (maximal lifespan of a species) and on medium factors (mean expectation of life of the animals of a species). Animal senescence could depend on cell aging: 1) by senescence and death of the differentiated cells, 2) by modified proliferation and differentiation of the stem cells of differentiated tissues, 3) by alterations in the extracellular matrices, 4) by interactions between factors 1) 2) and 3) in each tissue, 5) by interactions between the several tissues of an organism. This complexity badly impedes the experimental study of animal senescence. Normal mammal cells are aging when they are cultivated (in vitro ageing): their phenotype varies and depends on the cell generation (in vitro differentiation); the last cell-generation doesn't divide anymore and declines until death of the culture (in vitro senescence). Analysis of these artificial but well controlled systems allows an experimental approach of the proliferation, differentiation, senescence and death of the cells and of the extracellular matrix functions. Present literature upon in vitro aging of cultivated human cells is essentially made of papers where proliferation and differentiation characteristics are compared between early ("young") and late ("old") cell-generations of the cultures. FIBROBLASTIC CELLS OF THE MOUSE SKIN. This cell type has been studied in our laboratory, using different systems: 1) Primary cultures isolated from peeled skins of 19 day old mouse embryos, 2) Mouse dermis analyzed in the animals, 3) Cultivated explants of skins, 4) Serial sub-cultures of fibroblasts isolated from these explants, 5) Cells cultivated comparably on plane substrates (glass, plastic, collagen films) and on tridimensional matrices (collagen fibres). Systems 2), 3), 4) and 5) have been obtained either from 19 day old embryos or from 6 groups of animals of different ages (from 1/2 till 25 month). In primary cultures (system 1) all the cell generations have been analyzed, including the last one until death of the culture. We have shown that many characters are varying with cell-generation: cell form and cell mass, rate of DNA replication and cell division, rate of RNA transcription, nature of the accumulated and of the synthetized proteins, organization of the cytoskeletal elements, organization of the extracellular matrix, type of cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Transcriptional profiles of pulmonary innate immune responses to isogenic antibiotic-susceptible and multidrug-resistant Pseudomonas aeruginosa.

PubMed

Tam, Vincent H; Pérez, Cynthia; Ledesma, Kimberly R; Lewis, Russell E

2018-04-01

The virulence of an isogenic pair of Pseudomonas aeruginosa strains was studied under similar experimental conditions in two animal infection models. The time to death was significantly longer for the multidrug resistant (MDR) than the wild-type strain. The transcriptional profiles of 84 innate immune response genes in the lungs of immune competent Balb/C mice were further compared. Significantly weaker expression of genes involved in production of soluble pattern recognition receptor and complement were observed in animals infected with the MDR strain. Altered patterns of innate immune system activation may explain the attenuated virulence in MDR bacteria. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Schistosoma haematobium infection in the opossum (Didelphis marsupialis): involvement of the urogenital system.

PubMed

Kuntz, R E; Myers, B J; Cheever, A W

1971-01-01

Investigations of experimental schistosomiasis haematobia have suffered for want of satisfactory mammals in which schistosome infections would establish host-parasite situations more or less comparable with those seen in man. As a consequence, mammals representing different major groups have been exposed to infection by Schistosoma haematobium (Iran strain) to determine their potential use as models for more detailed investigations. In preliminary studies, 8 American opossums (Didelphis marsupialis) were exposed to 1000 or 2000 cercariae. Macroscopic involvement of the urogenital tract was noted in 3 animals, one of which had a 1-cm fibrous plaque in the bladder. In another animal, multiple transitional cell papillomas were present in the bladder and in one ureter.

A methodology for estimating dog noise in an animal housing facility

NASA Technical Reports Server (NTRS)

Sierens, S. E.; Ingley, H. A.; Besch, E. L.

1977-01-01

A rectangular reverberation chamber was designed, constructed and calibrated for the experimental measurement of the sound power level (acoustic power) of a dog. Calibration of the chamber consisted of comparing the acoustic power measured for a random noise source in the chamber with that for the identical source in a free field environment. Data from dogs indicate that barking noise can be modeled as a square wave pattern with short duration and peak sound power levels in the 500 Hz octave band. A-weighted sound pressure levels of up to 114.7 dBA were absorbed, indicating a potential concern for both animals and man chronically exposed to such environments.

The Comparative Study of Metacognition: Sharper Paradigms, Safer Inferences

PubMed Central

Smith, J. David; Beran, Michael J.; Couchman, Justin J.; Coutinho, Mariana V. C.

2015-01-01

Results that point to animals’ metacognitive capacity bear a heavy burden given the potential for competing behavioral descriptions. This article uses formal models to evaluate the force of these descriptions. One example is that many existing studies have directly rewarded so-called “uncertainty” responses. Modeling confirms that this practice is an interpretative danger because it supports associative processes and encourages simpler interpretations. Another example is that existing studies raise the concern that animals avoid difficult stimuli not because of uncertainty monitored but because of aversion given error-causing or reinforcement-lean stimuli. Modeling also justifies this concern and shows that this problem is not addressed by the common practice of comparing performance on Chosen and Forced trials. The models and related discussion have utility for metacognition researchers and theorists broadly because they specify the experimental operations that will best indicate a metacognitive capacity in humans or animals by eliminating alternative behavioral accounts. PMID:18792496

The effect of animation on learning action symbols by individuals with intellectual disabilities.

PubMed

Fujisawa, Kazuko; Inoue, Tomoyoshi; Yamana, Yuko; Hayashi, Humirhiro

2011-03-01

The purpose of the present study was to investigate whether participants with intellectual impairments could benefit from the movement associated with animated pictures while they were learning symbol names. Sixteen school students, whose linguistic-developmental age ranged from 38?91 months, participated in the experiment. They were taught 16 static visual symbols and the corresponding action words (naming task) in two sessions conducted one week apart. In the experimental condition, animation was employed to facilitate comprehension, whereas no animation was used in the control condition. Enhancement of learning was shown in the experimental condition, suggesting that the participants benefited from animated symbols. Furthermore, it was found that the lower the linguistic developmental age, the more effective the animated cue was in learning static visual symbols.

Inflammation-induced preterm lung maturation: lessons from animal experimentation.

PubMed

Moss, Timothy J M; Westover, Alana J

2017-06-01

Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development.

PubMed

Kinter, Lewis B; DeGeorge, Joseph J

2016-12-01

Human discovery of pharmacologically active substances is arguably the oldest of the biomedical sciences with origins >3500 years ago. Since ancient times, four major transformations have dramatically impacted pharmaceutical development, each driven by advances in scientific knowledge, technology, and/or regulation: (1) anesthesia, analgesia, and antisepsis; (2) medicinal chemistry; (3) regulatory toxicology; and (4) targeted drug discovery. Animal experimentation in pharmaceutical development is a modern phenomenon dating from the 20th century and enabling several of the four transformations. While each transformation resulted in more effective and/or safer pharmaceuticals, overall attrition, cycle time, cost, numbers of animals used, and low probability of success for new products remain concerns, and pharmaceutical development remains a very high risk business proposition. In this manuscript we review pharmaceutical development since ancient times, describe its coevolution with animal experimentation, and attempt to predict the characteristics of future transformations. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Teaching neurophysiology, neuropharmacology, and experimental design using animal models of psychiatric and neurological disorders.

PubMed

Morsink, Maarten C; Dukers, Danny F

2009-03-01

Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to integrate the teaching of neurophysiology, neuropharmacology, and experimental design. For this purpose, seven case studies were developed in which animal models for several psychiatric and neurological diseases were described and in which neuroactive drugs used to treat or study these diseases were introduced. Groups of undergraduate students were assigned to one of these case studies and asked to give a classroom presentation in which 1) the disease and underlying pathophysiology are described, 2) face and construct validity of the animal model are discussed, and 3) a pharmacological experiment with the associated neuroactive drug to assess predictive validity is presented. After evaluation of the presentations, we found that the students had gained considerable insight into disease phenomenology, its underlying neurophysiology, and the mechanism of action of the neuroactive drug. Moreover, the assignment was very useful in the teaching of experimental design, allowing an in-depth discussion of experimental control groups and the prediction of outcomes in these groups if the animal model were to display predictive validity. Finally, the highly positive responses in the student evaluation forms indicated that the assignment was of great interest to the students. Hence, the currently developed case studies constitute a very useful tool for teaching neurophysiology, neuropharmacology, and experimental design.

Preventive Role of Hilar Parasympathetic Ganglia on Pulmonary Artery Vasospasm in Subarachnoid Hemorrhage: An Experimental Study.

PubMed

Araz, Omer; Aydin, Mehmet Dumlu; Gundogdu, Betul; Altas, Ender; Cakir, Murteza; Calikoglu, Cagatay; Atalay, Canan; Gundogdu, Cemal

2015-01-01

Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.

The effect of transfer factor on lymph node morphology in murine toxoplasmosis.

PubMed Central

Dundas, S. A.; Clark, A.

1986-01-01

Mice were infected intraperitoneally with a low virulence strain of Toxoplasma gondii (TO) and transfer factor (TF) was prepared from the spleens of infected (TFT) and uninfected control mice (TFC). Three experimental groups of 12 mice were given either saline, TFC or TFT, by intraperitoneal injection. After 24 h half of each group of these animals were infected by intraperitoneal injection of TO cysts. In three separate experiments animals were killed at 11, 28 and 35 days and the flank and axillary nodes removed for histological examination. There was generalized lymph node enlargement with cortical and paracortical expansion. In most animals there was diffuse infiltration of the nodes by clusters of histiocytes. Administration of TFC alone led to a mild increase in node size at 11 and 28 days. Administration of TFT alone had a moderate stimulatory effect on the mouse lymph nodes with a significant increase in size at 11 days due predominantly to expansion of the paracortex. Administration of TFT and TFC followed by inoculation of TO led to an increased and more consistent histiocyte response and an increased number of paracortical T blasts compared with animals given TO alone. TFT and TFC had no demonstrable protective effect in experimental murine toxoplasmosis as assessed by quantitation of toxoplasma brain cysts. The effect of transfer factor was not antigen specific in this system. Images Fig. 4 Fig. 5 Fig. 2 Fig. 3 Fig. 1 Fig. 6 PMID:2423107

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.

Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs

PubMed Central

Omobowale, Temidayo O.; Oyagbemi, Ademola A.; Oyewunmi, Oyefunbi A.; Adejumobi, Olumuyiwa A.

2015-01-01

Introduction: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Materials and Methods: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. Results: Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. Conclusion: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection. PMID:26130936

Translational pain assessment: could natural animal models be the missing link?

PubMed

Klinck, Mary P; Mogil, Jeffrey S; Moreau, Maxim; Lascelles, B Duncan X; Flecknell, Paul A; Poitte, Thierry; Troncy, Eric

2017-09-01

Failure of analgesic drugs in clinical development is common. Along with the current "reproducibility crisis" in pain research, this has led some to question the use of animal models. Experimental models tend to comprise genetically homogeneous groups of young, male rodents in restricted and unvarying environments, and pain-producing assays that may not closely mimic the natural condition of interest. In addition, typical experimental outcome measures using thresholds or latencies for withdrawal may not adequately reflect clinical pain phenomena pertinent to human patients. It has been suggested that naturally occurring disease in veterinary patients may provide more valid models for the study of painful disease. Many painful conditions in animals resemble those in people. Like humans, veterinary patients are genetically diverse, often live to old age, and enjoy a complex environment, often the same as their owners. There is increasing interest in the development and validation of outcome measures for detecting pain in veterinary patients; these include objective (eg, locomotor activity monitoring, kinetic evaluation, quantitative sensory testing, and bioimaging) and subjective (eg, pain scales and quality of life scales) measures. Veterinary subject diversity, pathophysiological similarities to humans, and diverse outcome measures could yield better generalizability of findings and improved translation potential, potentially benefiting both humans and animals. The Comparative Oncology Trial Consortium in dogs has pawed the way for translational research, surmounting the challenges inherent in veterinary clinical trials. This review describes numerous conditions similarly applicable to pain research, with potential mutual benefits for human and veterinary clinicians, and their respective patients.

Vestibular animal models: contributions to understanding physiology and disease.

PubMed

Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

2016-04-01

Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

Animals Used in Research and Education, 1966-2016: Evolving Attitudes, Policies, and Relationships.

PubMed

Lairmore, Michael D; Ilkiw, Jan

2015-01-01

Since the inception of the Association of American Veterinary Medical Colleges (AAVMC), the use of animals in research and education has been a central element of the programs of member institutions. As veterinary education and research programs have evolved over the past 50 years, so too have societal views and regulatory policies. AAVMC member institutions have continually responded to these events by exchanging best practices in training their students in the framework of comparative medicine and the needs of society. Animals provide students and faculty with the tools to learn the fundamental knowledge and skills of veterinary medicine and scientific discovery. The study of animal models has contributed extensively to medicine, veterinary medicine, and basic sciences as these disciplines seek to understand life processes. Changing societal views over the past 50 years have provided active examination and continued refinement of the use of animals in veterinary medical education and research. The future use of animals to educate and train veterinarians will likely continue to evolve as technological advances are applied to experimental design and educational systems. Natural animal models of both human and animal health will undoubtedly continue to serve a significant role in the education of veterinarians and in the development of new treatments of animal and human disease. As it looks to the future, the AAVMC as an organization will need to continue to support and promote best practices in the humane care and appropriate use of animals in both education and research.

The Effectiveness of Interacting with Scientific Animations in Chemistry Using Mobile Devices on Grade 12 Students' Spatial Ability and Scientific Reasoning Skills

NASA Astrophysics Data System (ADS)

Al-Balushi, Sulaiman M.; Al-Musawi, Ali S.; Ambusaidi, Abdullah K.; Al-Hajri, Fatemah H.

2017-02-01

The purpose of the current study was to investigate the effectiveness of interacting with animations using mobile devices on grade 12 students' spatial and reasoning abilities. The study took place in a grade 12 context in Oman. A quasi-experimental design was used with an experimental group of 32 students and a control group of 28 students. The experimental group studied chemistry using mobile tablets that had a digital instructional package with different animation and simulations. There was one tablet per student. A spatial ability test and a scientific reasoning test were administered to both groups prior and after the study, which lasted for 9 weeks. The findings showed that there were significant statistical differences between the two groups in terms of spatial ability in favour of the experimental group. However, there were no differences between the two groups in terms of reasoning ability. The authors reasoned that the types of animations and simulations used in the current study featured a wide range of three-dimensional animated illustrations at the particulate level of matter. Most probably, this decreased the level of abstractness that usually accompanies chemical entities and phenomena and helped the students to visualize the interactions between submicroscopic entities spatially. Further research is needed to decide on types of scientific animations that could help students improve their scientific reasoning.

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.

PubMed

Gardiner, T A; Anderson, H R; Degenhardt, T; Thorpe, S R; Baynes, J W; Archer, D B; Stitt, A W

2003-09-01

To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

Adolescent nicotine exposure disrupts context conditioning in adulthood in rats.

PubMed

Spaeth, Andrea M; Barnet, Robert C; Hunt, Pamela S; Burk, Joshua A

2010-10-01

Despite the prevalence of smoking among adolescents, few studies have assessed the effects of adolescent nicotine exposure on learning in adulthood. In particular, it remains unclear whether adolescent nicotine exposure has effects on hippocampus-dependent learning that persist into adulthood. The present experiment examined whether there were effects of adolescent nicotine exposure on context conditioning, a form of learning dependent on the integrity of the hippocampus, when tested during adulthood. Rats were exposed to nicotine during adolescence (postnatal days [PD] 28-42) via osmotic minipump (0, 3.0 or 6.0mg/kg/day). Context conditioning occurred in early adulthood (PD 65-70). Animals were exposed to an experimental context and were given 10 unsignaled footshocks or no shock. Additional groups were included to test the effects of adolescent nicotine on delay conditioning, a form of learning that is not dependent upon the hippocampus. Conditioning was assessed using a lick suppression paradigm. For animals in the context conditioning groups, adolescent nicotine resulted in significantly less suppression of drinking in the presence of context cues compared with vehicle-pretreated animals. For animals in the delay conditioning groups, there was a trend for adolescent nicotine (3.0mg/kg/day) to suppress drinking compared to vehicle-pretreated animals. There were no differences in extinction of contextual fear or cued fear between rats previously exposed to vehicle or nicotine. The data indicate that adolescent nicotine administration impairs context conditioning when animals are trained and tested as adults. The present data suggest that adolescent nicotine exposure may disrupt hippocampus-dependent learning when animals are tested during adulthood. (c) 2010 Elsevier Inc. All rights reserved.

Assessing the True Intraocular Pressure in the Non-human Primate.

PubMed

McAllister, Faith; Harwerth, Ronald; Patel, Nimesh

2018-02-01

For glaucoma patients, high intraocular pressure (IOP) is a risk factor for progressive neuropathy. Similarly, animal models used to study the disease are based on an experimental elevation of IOP. Thus, accurate IOP measurements are important in characterizing experimental models and resulting effects. The purpose of the present study was to investigate IOP measurements in a non-human primate model of experimental glaucoma by comparing clinical tonometry (Tono-Pen and TonoVet) to the true IOP from intracameral manometry. A total of 17 rhesus macaque eyes from 12 animals were used for this study. Eleven eyes had no previous experimental intervention, whereas six eyes were at varying stages of laser-induced experimental glaucoma. IOPs were adjusted by inserting a needle in the anterior chamber that was attached to a pressure transducer and syringe pump system. The anterior chamber IOP was adjusted to values between 10 and 50 mmHg and corresponding measures with Tono-Pen and TonoVet were taken. The IOPs by TonoVet and Tono-Pen were linearly related over the range of pressures tested (slope = 0.68 normal/healthy and 0.72 experimental glaucoma). For the most, TonoVet measures overestimated IOP at all anterior chamber pressure settings (mean difference of 3.17 mmHg, 95% CI 12.53 to -4.74 normal and 3.90 mmHg, 95% CI 12.90 to -6.53 experimental glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and underestimated at higher IOP (slope = -0.26 normal and -0.21 experimental glaucoma). The TonoVet and Tono-Pen tonometers that are often used to assess IOP in both clinical and experimental settings generally reflect the status of IOP, but the results from this study suggest that the instruments need calibration with true anterior chamber pressure for accurate measures in experimental models of glaucoma.

THE USE OF NON-TUMOR DATA IN CANCER RISK ASSESSMENT: REFLECTIONS ON BENZENE, BUTADIENE AND VINYL CHLORIDE

EPA Science Inventory

1.0 Introduction. Quantitative estimation of human cancer risk from exposure to chemicals has traditionally been almost exclusively based on tumor incidence in experimental animals. While improvements in carcinogenicity testing in experimental animals (1,2) and structure-...

[Some notes on the history of the experimental surgery laboratory. Reflections on its relevance in education and surgical research].

PubMed

de la Garza-Rodea, Anabel Sofía; Padilla-Sánchez, Luis; de la Garza-Aguilar, Javier; Neri-Vela, Rolando

2007-01-01

The progress of medicine has largely been due to research, and for surgery, in particular, the experimental surgical laboratory has been considered fundamental to the surgeon's education. In this study, a general view of experimental surgery is given in animal models based on bioethical norms as well as to design, create and apply different surgical procedures before performing in humans. Experimental surgery also facilitates surgical teaching and promotes the surgeon's scientific reasoning. Methods. This is a retrospective and descriptive study. Data were collected from direct and indirect sources of available publications on the historical, bioethical and educational aspects of medicine, focusing on surgery. The important facts corresponding to the field of experimental surgery and applicable in Mexico were selected. Concepts of experimental surgical models and of the experimental surgery laboratory were described. Bioethical considerations are emphasized for care of experimental animals. Finally, this work focuses on the importance of surgical experimentation in current and future development of the surgical researcher. Conclusions. Experimentation with animal models in a surgical laboratory is essential for surgical teaching and promotes development of the scientific thought in the surgeon. It is necessary for surgical research and is fundamental for making progress in surgery, treatment and medicine as science.

Light pollution disrupts sleep in free-living animals

PubMed Central

Raap, Thomas; Pinxten, Rianne; Eens, Marcel

2015-01-01

Artificial lighting can alter individual behaviour, with often drastic and potentially negative effects on biological rhythms, daily activity and reproduction. Whether this is caused by a disruption of sleep, an important widespread behaviour enabling animals to recover from daily stress, is unclear. We tested the hypothesis that light pollution disrupts sleep by recording individual sleep behaviour of great tits, Parus major, that were roosting in dark nest-boxes and were exposed to light-emitting diode light the following night. Their behaviour was compared to that of control birds sleeping in dark nest-boxes on both nights. Artificial lighting caused experimental birds to wake up earlier, sleep less (–5%) and spent less time in the nest-box as they left their nest-box earlier in the morning. Experimental birds did not enter the nest-box or fall asleep later than controls. Although individuals in lit nest-boxes did not wake up more often nor decreased the length of their sleep bouts, females spent a greater proportion of the night awake. Our study provides the first direct proof that light pollution has a significant impact on sleep in free-living animals, in particular in the morning, and highlights a mechanism for potential effects of light pollution on fitness. PMID:26337732

Bias in the reporting of sex and age in biomedical research on mouse models

PubMed Central

Flórez-Vargas, Oscar; Brass, Andy; Karystianis, George; Bramhall, Michael; Stevens, Robert; Cruickshank, Sheena; Nenadic, Goran

2016-01-01

In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other researchers can build on the results of such studies. Here we use text mining to study 15,311 research papers in which mice were the focus of the study. We find that the percentage of papers reporting the sex and age of mice has increased over the past two decades: however, only about 50% of the papers published in 2014 reported these two variables. We also compared the quality of reporting in six preclinical research areas and found evidence for different levels of sex-bias in these areas: the strongest male-bias was observed in cardiovascular disease models and the strongest female-bias was found in infectious disease models. These results demonstrate the ability of text mining to contribute to the ongoing debate about the reproducibility of research, and confirm the need to continue efforts to improve the reporting of experimental methods and materials. DOI: http://dx.doi.org/10.7554/eLife.13615.001 PMID:26939790

Bioavailability of soy isoflavones through placental/lactational transfer and soy food

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

Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov

2011-07-15

Isoflavones are non-nutritive components of soy responsible for estrogenic responses observed in vitro and in experimental animals. Possible beneficial effects (e.g., reduction of serum lipids, increased bone mineral density, relief of hot flashes and other menopausal symptoms, mammary and prostate cancer chemoprevention) in humans have been attributed to consumption of isoflavones but evidence for potential adverse effects (e.g., stimulation of estrogen-dependent mammary tumors and aberrant perinatal development) has also been reported in experimental animal models. Bioavailability from appropriate food matrices and exposure during different life stages are both critical determinants of isoflavone effects. For these reasons, it is important tomore » compare isoflavone bioavailability in adults to that in fetal and neonatal animals for a more complete understanding of potential susceptibility issues. Studies of the major soy isoflavone genistein were conducted in pregnant and lactating Sprague-Dawley rats to quantify placental and lactational transfer to plasma and brain to understand better biological effects observed in multigenerational studies. In addition, studies were conducted with genistein in adult Balb/c mice to define absolute bioavailability from both gavage and soy protein isolate (SPI)-containing food. The information derived from these studies makes it possible to predict internal exposures of children to genistein from soy infant formula, which is manufactured using SPI.« less

Comparing the Organs and Vasculature of the Head and Neck in Five Murine Species

PubMed Central

JAE KIM, MIN; YEON KIM, YOO; REN CHAO, JANET; SANG PARK, HAE; CHANG, JIWON; OH, DAWOON; JUN LEE, JAE; CHUN KANG, TAE; SUH, JUN-GYO; HO LEE, JUN

2017-01-01

Background/Aim: The purpose of the present study was to delineate the cervical and facial vascular and associated anatomy in five murine species, and compare them for optimal use in research studies focused on understanding the pathology and treatment of diseases in humans. Materials and Methods: The specific adult male animals examined were mice (C57BL/6J), rats (F344), mongolian gerbils (Merionesunguiculatus), hamsters (Syrian), and guinea pigs (Hartley). To stain the vasculature and organs, of the face and neck, each animal was systemically perfused using the vital stain, Trypan Blue. Following this step, the detailed anatomy of the head and neck could be easily visualized in all species. Results: Unique morphological characteristics were demonstrated by comparing the five species, including symmetry of the common carotid origin bilaterally in the Mongolian Gerbil, a large submandibular gland in the hamster and an enlarged buccal branch in the Guinea Pig. In reviewing the anatomical details, this staining technique proves superior for direct surgical visualization and identification. Conclusion: The anatomical details provided through these five species atlas will help experimental researchers in the future to select the most appropriate animal model for specific laboratory studies aimed to improve our understanding and treatment of diseases in patients.  PMID:28882952

Responses of arthropods to large-scale manipulations of dead wood in loblolly pine stands of the Southeastern United States

Treesearch

Michael D. Ulyshen; James L. Hanula

2009-01-01

Large-scale experimental manipulations of deadwood are needed to better understand its importance to animal communities in managed forests. In this experiment, we compared the abundance, species richness, diversity, and composition of arthropods in 9.3-ha plots in which either (1) all coarse woody debris was removed, (2) a large number of logs were added, (3) a large...

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

This report—the second of a series on codeine and its alternates for pain and cough relief—contains a detailed evaluation of experimental and clinical data on newer substances having analgesic properties comparable to and in approximately the same range as those of codeine. The data are discussed under the headings: analgesic effects in animals; clinical usefulness; side-effects with particular reference to dependence and abuse liability. PMID:4894737

[Antihyperalgesic activity of chlorimipramine and sodium phenytoin in an induced model of neuropathic pain in rats].

PubMed

Guevara-López, Uriah; Gutiérrez-Sougarret, Bernardo; López-Pavón, Lucy; Aldrete, J Antonio; Tamayo-Valenzuela, Antonio

2004-01-01

Neuropathic pain results from injury or impairment of the nervous system manifested by pain syndrome. Experimental models have been used to study its effects and how to suppress these. Tricyclic antidepressants (TCA) and anticonvulsant (AC) have been used for treatment. To evaluate the antihyperanalgesic efficiency of intraperitoneal (IP) chlorimipramine (CIP) vs IP phenytoine (DFH) for induced neuropathic pain in an experimental animal model. After making a surgical ligature of the sciatic nerve in the right leg of 18 male rats, the time of withdrawal of both claws immersed in hot (45 degrees C) and cold water (10 degrees C) was measured during a four week period before and after IP CIP, DFH, or placebo administered in a double blind study. Significant statistical differences were observed in the time of withdrawal with CIP as compared with DFH and when both groups were compared with placebo (as tested by the paw immersion in hot water). When the thermal stimulus was cold water, an increase of the time of withdrawal was seen with DFH. These findings suggest that CIP and FS are both effective in the treatment of neuropathic pain in an animal model, as well as for the treatment of secondary hiperalgesia.

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

PubMed

Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

2011-08-01

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Evoked potential recording during echolocation in a false killer whale Pseudorca crassidens (L)

NASA Astrophysics Data System (ADS)

Supin, Alexander Ya.; Nachtigall, Paul E.; Pawloski, Jeffrey; Au, Whitlow W. L.

2003-05-01

Auditory brainstem responses (ABRs) were recorded in a false killer whale while the animal echolocated a target. The ABR collection was triggered by echolocation clicks of the animal. In these conditions, the recorded ABR pattern contained a duplicate set of waves. A comparison of ABR wave delays recorded during echolocation with those recorded during regular external stimulation with experimenter generated clicks showed that the first set of waves may be a response to the emitted click whereas the second one may be a response to the echo. Both responses, to the emitted click and to the echo, were of comparable amplitude in spite of the intensity difference of these two sounds that may differ by more than 40 dB near the animal's head. This finding indicates the presence of some mechanism of releasing responses to echoes from masking by loud emitted clicks. The evoked-potential method may be productive to investigate these mechanisms.

Comparative study of hematopoietic stem and progenitor cells between sexes in mice under physiological conditions along time.

PubMed

Gasco, Samanta; Rando, Amaya; Zaragoza, Pilar; García-Redondo, Alberto; Calvo, Ana Cristina; Osta, Rosario

2017-12-01

Hematopoietic stem and progenitor cells (HSPCs) are attractive targets in regenerative medicine, although the differences in their homeostatic maintenance between sexes along time are still under debate. We accurately monitored hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs) frequencies by flow cytometry, by performing serial peripheral blood extractions from male and female B6SJL wild-type mice and found no significant differences. Only modest differences were found in the gene expression profile of Slamf1 and Gata2. Our findings suggest that both sexes could be used indistinctly to perform descriptive studies in the murine hematopoietic system, especially for flow cytometry studies in peripheral blood. This would allow diminishing the number of animals needed for the experimental procedures. In addition, the use of serial extractions in the same animals drastically decreases the number of animals needed. © 2017 International Federation for Cell Biology.

Part-body and multibody effects on absorption of radio-frequency electromagnetic energy by animals and by models of man

NASA Technical Reports Server (NTRS)

Gandhi, O. P.; Hagmann, M. J.; Dandrea, J. A.

1979-01-01

Fine structure in the whole-body resonant curve for radio-frequency energy deposition in man can be attributed to part-body resonances. As for head resonance, which occurs near 350 MHz in man, the absorptive cross section is nearly three times the physical cross section of the head. The arm has a prominent resonance at 150 MHz. Numerical solutions, antenna theory, and experimental results on animals have shown that whole-body energy deposition may be increased by 50 percent or more because of multiple bodies that are strategically located in the field. Empirical equations for SARs are also presented along with test data for several species of laboratory animals. Barbiturate anesthesia is sufficiently disruptive of thermoregulation that delta Ts of colonic temperature yield energy dose values in several mammals that compare quite favorably with those based on whole-body calorimetry.

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

Harkema, J.R.

The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have amore » good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway.« less

A Bayesian multi-stage cost-effectiveness design for animal studies in stroke research

PubMed Central

Cai, Chunyan; Ning, Jing; Huang, Xuelin

2017-01-01

Much progress has been made in the area of adaptive designs for clinical trials. However, little has been done regarding adaptive designs to identify optimal treatment strategies in animal studies. Motivated by an animal study of a novel strategy for treating strokes, we propose a Bayesian multi-stage cost-effectiveness design to simultaneously identify the optimal dose and determine the therapeutic treatment window for administrating the experimental agent. We consider a non-monotonic pattern for the dose-schedule-efficacy relationship and develop an adaptive shrinkage algorithm to assign more cohorts to admissible strategies. We conduct simulation studies to evaluate the performance of the proposed design by comparing it with two standard designs. These simulation studies show that the proposed design yields a significantly higher probability of selecting the optimal strategy, while it is generally more efficient and practical in terms of resource usage. PMID:27405325

Real-time speech-driven animation of expressive talking faces

NASA Astrophysics Data System (ADS)

Liu, Jia; You, Mingyu; Chen, Chun; Song, Mingli

2011-05-01

In this paper, we present a real-time facial animation system in which speech drives mouth movements and facial expressions synchronously. Considering five basic emotions, a hierarchical structure with an upper layer of emotion classification is established. Based on the recognized emotion label, the under-layer classification at sub-phonemic level has been modelled on the relationship between acoustic features of frames and audio labels in phonemes. Using certain constraint, the predicted emotion labels of speech are adjusted to gain the facial expression labels which are combined with sub-phonemic labels. The combinations are mapped into facial action units (FAUs), and audio-visual synchronized animation with mouth movements and facial expressions is generated by morphing between FAUs. The experimental results demonstrate that the two-layer structure succeeds in both emotion and sub-phonemic classifications, and the synthesized facial sequences reach a comparative convincing quality.

Administration of Substances to Laboratory Animals: Equipment Considerations, Vehicle Selection, and Solute Preparation

PubMed Central

Turner, Patricia V; Pekow, Cynthia; Vasbinder, Mary Ann; Brabb, Thea

2011-01-01

Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. The equipment selected to deliver substances to animals depends on the length of the study and the nature of the material being administered. This selection provides a significant opportunity for refining animal treatment. Similarly, when substances are administered as solutions or suspensions, attention should be given to selection of vehicles and methods used for preparing the solutions and suspensions. The research team, veterinarian, technical personnel, and IACUC members should be aware of reasons underlying selection of equipment for substance delivery and should consider carefully how substances will be prepared and stored prior to administration to animals. Failure to consider these factors during experimental planning may result in unintentional adverse effects on experimental animals and confounded results. PMID:22330706

Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data.

PubMed

Kosaka, Junko; Lankadeva, Yugeesh R; May, Clive N; Bellomo, Rinaldo

2016-09-01

The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models. MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015). We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury. We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings. We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was only found in models with low cardiac output and decreased renal blood flow (p < 0.0001). Only 21 studies (170 animals) assessed the prevalence of tubular cell apoptosis, which was reported in 158 animals (92.9%). The prevalence of tubular cell apoptosis was significantly higher in studies using small animals (p < 0.0001) and in peritonitis models (p < 0.0001). Simultaneous acute tubular necrosis and tubular cell apoptosis was rare (55 animals [32.4%]) and only seen with decreased cardiac output and renal blood flow. Nonspecific changes (vacuolization of tubular cells, loss of brush border, and tubular cell swelling) were each observed in 423 (39.9%), 250 (23.6%) and 243 (22.9%) animals, respectively. In models of experimental septic acute kidney injury in contemporary articles, acute tubular necrosis was relatively uncommon and, when present, reflected the presence of an associated low cardiac output or low renal blood flow syndrome. Tubular cell apoptosis seemed frequent in the few studies in which it was investigated. Nonspecific morphologic changes, however, were the most common histopathologic findings.

Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

NASA Astrophysics Data System (ADS)

Supriya, Ch.; Reddy, P. Sreenivasula

2015-06-01

Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

9 CFR 354.3 - Administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Administration. 354.3 Section 354.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... provisions of the regulations to permit experimentation so that new procedures, equipment, and processing...

RADIOLOGICAL STUDY OF MEGACOLON IN TRYPANOSOMA CRUZI INFECTED RATS

PubMed Central

FONTES, Carlos Edmundo Rodrigues; de ABREU, Ana Paula; GASPARIM, Aretuza Zaupa

2018-01-01

ABSTRACT Background: Researches on Chagas disease still use several animals and rats, due to size and susceptibility were preferred by many authors. Aim: To develop an experimental model of megacolon in rats inoculated with the strain Y of Trypanosoma cruzi. Methods: Thirty male Wistar rats were distributed in three groups inoculated with different inoculants: Group A: 600000, Group B: 1000000 and Group C: 1500000 blood trypomastigotes of T. cruzi. Animals were sedated intramuscularly at zero inoculation time (T0) and 60 days after inoculation (T60), to perform the barium enema in order to evaluate the dilatation of the different segments of colon in a comparative study of the measurements obtained, using a digital caliper. Evidence of infection was performed by blood smear collected from the animal’s tail 18 days after inoculation with observation of blood forms. Results: Comparing the intestinal diameter of the inoculated animals with 60,0000 trypomastigotes in the T0 of infection with T60 days after the inoculation, significant dilatation was observed between the proximal, medial and distal segments (p<0.01), indicating the establishment of the megacolon model. In addition, comparing intestinal diameter between the different segments, with in the T0 of infection and the T60 after inoculation, significant alterations were observed (p<0.05). Conclusion: The proposed model was possible for in vivo studies of alterations due to infection by T. cruzi and functional alterations of the colon. In addition, the changes manifested in the colon are not directly proportional to the size of the inoculum, but to the time of infection that the animals were submitted, since the animals inoculated with 60,0000 blood forms were the ones which presented the most significant alterations. PMID:29513802

Comparative development of Taenia solium in experimental models.

PubMed

Maravilla, P; Avila, G; Cabrera, V; Aguilar, L; Flisser, A

1998-10-01

Various mammals were evaluated as experimental models of adult Taenia solium. Suppressed and nonsuppressed hosts were used as experimental models. Infections were performed per os with cysticerci obtained from pigs; immunosuppression was induced with methyl prednisolone acetate at intervals of 10-14 days after infection. Tapeworms developed in hamsters, gerbils, and chinchillas but failed to develop in rabbits, cats, pigs, and rhesus monkeys. In infectable animals, treatment with the steroid facilitated maintenance and development of the parasite, and more tapeworms were obtained. Mature and some pregravid proglottids were recovered from hamsters and gerbils, whereas a gravid T. solium was obtained from a chinchilla at 12 wk postinfection. Eggs recovered from the chinchilla transformed into cysticerci in a pig 12 wk after oral infection. The T. solium-chinchilla experimental system seems to be an alternative definitive host for this parasite and thus the basis for a great diversity of studies.

Clever Hans and his effects: Karl Krall and the origins of experimental parapsychology in Germany.

PubMed

De Sio, Fabio; Marazia, Chantal

2014-12-01

Shortly before the outbreak of World War I, the so-called Elberfeld horses, the counting and speaking animals, were among the most debated subjects of the newborn comparative psychology. Yet, they have left little trace in the historiography of this discipline, mostly as an appendix of the more famous Clever Hans. Their story is generally told as the prelude to the triumph of reductionistic experimental psychology. By paying a more scrupulous attention than has so far being done to the second life of Hans, and to the endeavours of his second master, Karl Krall, this article explores the story of the Elberfeld horses as an important, if so far neglected, chapter in the history of experimental parapsychology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Standardised animal models of host microbial mutualism

PubMed Central

Macpherson, A J; McCoy, K D

2015-01-01

An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions. PMID:25492472

Preliminary study for small animal preclinical hadrontherapy facility

NASA Astrophysics Data System (ADS)

Russo, G.; Pisciotta, P.; Cirrone, G. A. P.; Romano, F.; Cammarata, F.; Marchese, V.; Forte, G. I.; Lamia, D.; Minafra, L.; Bravatá, V.; Acquaviva, R.; Gilardi, M. C.; Cuttone, G.

2017-02-01

Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and gamma index test. This work represents the first step towards the realization of a preclinical hadrontherapy facility at INFN-LNS in Catania for the future in vivo studies.

A Neospora caninum vaccine using recombinant proteins fails to prevent foetal infection in pregnant cattle after experimental intravenous challenge.

PubMed

Hecker, Yanina P; Cóceres, Verónica; Wilkowsky, Silvina E; Jaramillo Ortiz, José M; Morrell, Eleonora L; Verna, Andrea E; Ganuza, Agustina; Cano, Dora B; Lischinsky, Lilian; Angel, Sergio O; Zamorano, Patricia; Odeón, Anselmo C; Leunda, María R; Campero, Carlos M; Morein, Bror; Moore, Dadín P

2014-12-15

The aim of the present study was to evaluate the immunogenicity and protective efficacy of rNcSAG1, rNcHSP20 and rNcGRA7 recombinant proteins formulated with immune stimulating complexes (ISCOMs) in pregnant heifers against vertical transmission of Neospora caninum. Twelve pregnant heifers were divided into 3 groups of 4 heifers each, receiving different formulations before mating. Immunogens were administered twice subcutaneously: group A animals were inoculated with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) formulated with ISCOMs; group B animals received ISCOM-MATRIX (without antigen) and group C received sterile phosphate-buffered saline (PBS) only. The recombinant proteins were expressed in Escherichia coli and purified nickel resin. All groups were intravenously challenged with the NC-1 strain of N. caninum at Day 70 of gestation and dams slaughtered at week 17 of the experiment. Heifers from group A developed specific antibodies against rNcSAG1, rNcHSP20 and rNcGRA7 prior to the challenge. Following immunization, an statistically significant increase of antibodies against rNcSAG1 and rNcHSP20 in all animals of group A was detected compared to animals in groups B and C at weeks 5, 13 and 16 (P<0.001). Levels of antibodies against rNcGRA7 were statistical higher in group A animals when compared with groups B and C at weeks 5 and 16 (P>0.001). There were no differences in IFN-γ production among the experimental groups at any time point (P>0.05). Transplacental transmission was determined in all foetuses of groups A, B and C by Western blot, immunohistochemistry and nested PCR. This work showed that rNcSAG1, rNcHSP20 and rNcGRA7 proteins while immunogenic in cattle failed to prevent the foetal infection in pregnant cattle challenged at Day 70 of gestation. Copyright © 2014 Elsevier B.V. All rights reserved.

The route of administration drastically affects ivermectin activity against small strongyles in horses.

PubMed

Saumell, Carlos; Lifschitz, Adrián; Baroni, Renato; Fusé, Luis; Bistoletti, Mariana; Sagües, Federica; Bruno, Santiago; Alvarez, Gustavo; Lanusse, Carlos; Alvarez, Luis

2017-03-15

The goal of the current study was to evaluate the comparative efficacy of ivermectin (IVM) against small strongyles (cyathostomins) following its oral and intramuscular (IM) administration, in naturally parasitized horses. The parasitological data were complemented with the assessment of the plasma disposition kinetics of IVM. The trial included two different experiments. In experiment I, 40 horses naturally infected with small strongyles were randomly allocated into four experimental groups (n=10) and treated with IVM (0.2mg/kg) as follows: IVM oral paste, animals were orally treated with Eqvalan ® (IVM 1.87% paste, as the reference formulation) by the oral route; IVM oral solution, animals were orally treated with Remonta ® (IVM 2% solution, as a test formulation); IVM IM solution, animals were IM treated with the test product (Remonta ® IVM 2% solution); and control, animals were kept without treatment as untreated controls. In experiment II, 24 horses naturally parasitized with small strongyles were randomly allocated into the same four experimental groups (n=6) described for experiment I. Faecal samples were individually collected directly from the rectum of each horse prior (day -1) and at 7 and 15 (Experiment I) or 7, 15 and 21 (Experiment II) days after-treatment, to assess the eggs per gram (epg) counts and estimate the efficacy of the treatments. Additionally, the comparative plasma disposition kinetics of IVM in treated animals was assessed in experiment II. In both experiments, an excellent (100%) IVM efficacy was observed after its oral administration (test and reference formulations). However, the IM administration of IVM resulted in a low efficacy (36-64%). Similar IVM plasma concentration was observed after its oral administration as a paste or as a solution. The higher IVM plasma profiles observed after the IM administration accounted for an enhanced systemic availability. The improved IVM efficacy observed against adult cyathostomins after its oral administration can be explained by an enhanced drug exposure of the worms located at the lumen of the large intestine. These findings may have a direct impact on the practical use of macrocyclic lactones in horses. Copyright © 2017 Elsevier B.V. All rights reserved.

Activated carbon, a useful medium to bind chlordecone in soil and limit its transfer to growing goat kids.

PubMed

Yehya, Sarah; Delannoy, Matthieu; Fournier, Agnès; Baroudi, Moomen; Rychen, Guido; Feidt, Cyril

2017-01-01

Chlordecone (Kepone) (CLD) is a highly persistent pesticide which was extensively used in the French West Indies; high levels of CLD can still currently be found in large agricultural areas. As CLD transfers from soil to animals mainly via involuntary ingestion, the consumption of foodstuffs derived from animals raised in contaminated areas may significantly contribute to exposure of humans to CLD. The present study was designed to test the efficacy of two different activated carbons (ACs) sources in limiting CLD transfer from soil to animal. Three soils (ASs) were prepared according to the OECD guideline 207. One standard soil (SS) lacking AC, and two modified preparations of SS supplemented with 2% coconut-based activated carbon (ORBO), SSO or with 2% lignite-based one (DARCO), SSD. All three soils were spiked with 10 μg of kepone per g of dry matter and aged for three weeks. This study involved 15 goat kids randomly assigned to the 3 experimental groups (n = 5/group), which were fed the experimental matrices at an exposure dose of 10 μg CLD per kg of body weight per day. After 21 d of oral exposure, CLD in adipose tissue and liver were analysed by LC-MS-MS. A significant decrease of 63.7% and 74.7% of CLD concentrations in adipose tissue and liver, respectively, were obtained from animals exposed using SS containing DARCO as compared to those receiving only SS. Decreases in CLD levels of 98.2% (adipose tissue) and 98.7% (liver) were obtained for animals exposed using SS containing ORBO. This study leads us to conclude that (i) the presence of AC in CLD-contaminated soil strongly reduces CLD bioavailability, and (ii) the efficacy depends on the nature and characteristics of the AC used.

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.

Citrus pulp and wheat straw silage as an ingredient in lamb diets: effects on growth and carcass and meat quality.

PubMed

Scerra, V; Caparra, P; Foti, F; Lanza, M; Priolo, A

2001-04-01

Twenty "Merinizzata Italiana" lambs were introduced to two experimental diets. Ten animals (five males and five females, control group) received the traditional diet that is supplied by farmers in southern Italy, which comprised of oat hay ad libitum and commercial concentrate. The second group (the same number of lambs, silage group) received citrus pulp and wheat straw silage ad libitum and 70% of the commercial concentrate supplied to the control group. The animals were slaughtered after 80 days of feeding and carcass and some meat quality parameters were measured. No differences were observed for live weight between treatments, and carcass weights were similar for the two diets, but with obvious differences between sexes. Animals on silage produced carcasses with a better muscular conformation and with a lower fatness score (P<0.05). Subcutaneous fat colour was influenced by sex, being lighter in the female carcasses (P<0.05). Dissection of different anatomical parts showed a higher percentage of lean and a lower proportion of fat in silage samples compared to control ones. Ultimate pH was highly affected by sex being higher in the samples from male lambs (P<0.01), but was unaffected by diet treatment. Diet tended to affect meat shear force value which was lower in the silage samples, although, samples from all the animals were extremely tender. Meat from silage samples had a higher water content (P<0.05). Overall, in our experimental conditions, the use of citrus pulp silage seemed to be economically convenient for producing animals with substantially unmodified carcass and meat quality characteristics.

Sensitivity, specificity, and confounding factors of novel serological tests used for the rapid diagnosis of bovine tuberculosis in farmed red deer (Cervus elaphus).

PubMed

Buddle, Bryce M; Wilson, Tania; Denis, Michel; Greenwald, Rena; Esfandiari, Javan; Lyashchenko, Konstantin P; Liggett, Simon; Mackintosh, Colin G

2010-04-01

In this study, novel serological tests were used to detect tuberculosis (TB) in groups of farmed red deer (Cervus elaphus) varying in disease status or possible confounding factors. Groups of deer naturally or experimentally infected with Mycobacterium bovis and animals vaccinated against paratuberculosis were studied, as were uninfected animals and animals naturally or experimentally infected with Mycobacterium avium subsp. paratuberculosis. Sera were assayed using two rapid lateral-flow tests, Chembio's CervidTB STAT-PAK and DPP VetTB tests, and results were compared to those from tuberculin skin tests. Both serological tests had a high sensitivity, but specificity was adversely affected after animals had received a vaccine against paratuberculosis and were subsequently skin tested. The specificity of the DPP VetTB test was higher than that of the CervidTB STAT-PAK test, with natural infection with M. avium subsp. paratuberculosis adversely affecting the specificity of only the CervidTB STAT-PAK test. The sera from M. avium subsp. paratuberculosis-infected deer that produced false-positive reactions in the CervidTB STAT-PAK test were retested with a multiantigen print immunoassay (MAPIA), and some of these sera were shown to react with the MPB83 antigen. Combining the results from the serological tests and the skin tests showed only a slight increase in the sensitivity of detection of M. bovis-infected animals. It is concluded that both the CervidTB STAT-PAK and DPP VetTB tests offer rapid, convenient, and easy detection of bovine tuberculosis in deer, albeit with significant interference from paratuberculosis vaccination status and subsequent skin testing. The latter finding illustrates one of the limitations of currently available vaccines against paratuberculosis.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Meeting Report: Batch-to-Batch Variability in Estrogenic Activity in Commercial Animal Diets—Importance and Approaches for Laboratory Animal Research

PubMed Central

Heindel, Jerrold J.; vom Saal, Frederick S.

2008-01-01

We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research. PMID:18335108

Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets--importance and approaches for laboratory animal research.

PubMed

Heindel, Jerrold J; vom Saal, Frederick S

2008-03-01

We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research.

In vivo biodistribution of CNTs using a BALB/c mouse experimental model.

PubMed

Fufă, Mariana Oana Mihaela; Mihaiescu, Dan Eduard; Mogoantă, Laurenţiu; Bălşeanu, Tudor Adrian; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai; Bolocan, Alexandra

2015-01-01

Due to their unique behaviors, carbon nanotubes (CNTs)-based systems meet essential requirements for modern applications, such as electronics, optics, photovoltaics, fuel cells, aerospace engineering, military and biomedical applications. CNTs biocompatibility and toxic effects were assessed both in vitro and in vivo, in terms of hemocompatibility, cytocompatibility, immunoreactions and genetic behavior. The aim of this paper is to evaluate the in vivo biodistribution and biocompatibility of carbon nanopowder synthesized by plasma processing, using a BALB/c mouse experimental model. Three months old BALB/c mice were aseptically injected with 100 μL of 1 mg/mL dispersions. The obtained carbon-based nano-systems were dispersed in saline solution and subsequently sterilized by using a 30 minutes treatment with UV irradiation. The reference mice were injected with 100 μL of saline. The mice were kept under standard conditions of light, temperature, humidity, food and water (ad libitum) before the vital organ harvest. The animal welfare was daily monitored. At two and 10 days after the inoculation, the animals were euthanized under general anesthesia, for the sampling of internal organs (brain, myocardium, pancreas, liver, lung, kidney and spleen). No animal died during the experiment. Brain, myocardium and pancreas were histologically normal, with no tissue damage, inflammatory infiltrate or inorganic deposits. CNTs were evidenced only in hepatic, renal, pulmonary and spleen tissue samples. Increased amounts of inorganic granular structures were reported after 10 days of treatment, when compared to the short-term (two days) inoculation. Our BALB/c mouse experimental model was found to be useful for the in vivo assessment of biodistribution and biocompatibility of CNTs.

[The battery of tests for behavioral phenotyping of aging animals in the experiment].

PubMed

Gorina, Ya V; Komleva, Yu K; Lopatina, O L; Volkova, V V; Chernykh, A I; Shabalova, A A; Semenchukov, A A; Olovyannikova, R Ya; Salmina, A B

2017-01-01

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

PubMed

Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

2014-10-01

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

PubMed

Padilha, Gisele de A; Horta, Lucas F B; Moraes, Lillian; Braga, Cassia L; Oliveira, Milena V; Santos, Cíntia L; Ramos, Isalira P; Morales, Marcelo M; Capelozzi, Vera Luiza; Goldenberg, Regina C S; de Abreu, Marcelo Gama; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

2016-12-01

In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed. Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04). In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.

Hypolipidemic and antioxidant potentials of Xylopia aethiopica seed extract in hypercholesterolemic rats.

PubMed

Nwozo, Sarah O; Orojobi, Bosede F; Adaramoye, Oluwatosin A

2011-01-01

A short-term study was carried out on Wistar strain rats to determine the effects of Xylopia aethiopica extract on serum and postmitochondrial fractions (PMFs) of visceral organs in experimental hypercholesterolemia. Animals received normal diet and were administered cholesterol orally by intubations at a dose of 40 mg/kg/0.3 mL, plant extracts at 250 mg/kg, and cholestyramine (Questran®, Bristol-Myers Squibb, Hounslow, United Kingdom) at 0.26 g/kg five times a week for 8 consecutive weeks. Thereafter the hypolipidemic effects were assessed by measuring total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol, and triglycerides, whereas the extent of oxidative stress was assayed by measuring thiobarbituric acid-reactive substances and enzymatic antioxidants such as superoxide dismutase, catalase, and reduced glutathione (GSH) in serum and PMF of liver and kidney. We assayed two liver biomarkers-alanine aminotransferase and aspartate aminotransferase-for safety of X. aethiopica at the dose given in this experiment. Cholesterol feeding resulted in a significant increase (P < .05) in body weight of the hypercholesterolemic animals relative to control animals, and administration of X. aethiopica (250 mg/kg) caused a more than 60% reduction in body weight. Simultaneous treatment with X. aethiopica and Questran elicited 33.75% and 23.94% reductions, respectively, in serum cholesterol levels of hypercholesterolemic rats. In addition, the LDL-C level decreased significantly (P < .05) by 49.09% and 78.92% in serum and by 64.97% and 37.29% in the liver with cotreatment with the plant extract and Questran, respectively, compared to untreated hypercholesterolemic rats. X. aethiopica counteracted the decreases in enzymatic antioxidants, especially in GSH, where there was a greater than 300% increase compared with hypercholesterolemic animals. This study has shown that intake of X. aethiopica reduced the composition of lipids and produced a favorable lipid profile in the serum and PMF of visceral organs in experimental hypercholesterolemia.